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Contents

Editorial Advisory Board: Jose Luis Di Fabio, Technology and Health Services Delivery, PAHO Thomas Egwang, African Academy of Sciences Pamela Hartigan, Skoll Centre for Social Entrepreneurship Mohamed Hassan, African Academy of Sciences Calestous Juma, Harvard Mary-Louis Kerney, UNESCO Elil Renganathan, World Health Organization Padmanashree Sampath, IQSensato and African Technology Policy Studies Network Judith Sutz, Universidad de la República, Uruguay

Editorial Team: Charles A Gardner, Global Forum for Health Research Susan Jupp, Global Forum for Health Research Stephen A Matlin, Global Forum for Health Research Christine Mauroux, Global Forum for Health Research

Pro-Brook Publishing Team: Trevor Brooker, Pro-Brook Publishing Tim Probart, Pro-Brook Publishing Stephen Kemp-King, Pro-Brook Publishing Simon Marriott, Art Direction Jude Ledger, Copy Editor Pr Photo credits: WHO/PAHO/Carlos Gaggero WHO/TDR/Andy CraggsWyndeham Grang

The Global Forum Update on Research for Health Volume 6 is published for the Global Forum for Health Research by Pro-Brook Publishing Limited

Pro-Brook Publishing, 13 Church Street, Woodbridge, IP12 1DS, United Kingdom

Copyright Text © the Global Forum for Health Research 2009 Volume © Pro-Brook Publishing Limited 2009

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ISBN 978-2-940401-24-6 First published 2009

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e, Southwick, UK

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Contents

009 Foreword Gill Samuels

011 Introduction Charles A Gardner

Research and innovation in Cuba 014 Scientific research in the field of health in Cuba, based and oriented towards primary health care Dr José Ramón Balaguer Cabrera

020 Research in health from the Cuban international medical cooperation perspective Nestor Marimón Torres and Evelyn Martínez Cruz

024 Connecting immunology research to public health: Cuban biotechnology Agustin Lage

029 Development of Cuban biomedical technology and its impact in “Health for All” Ismael Clark Arxer

Social entrepreneurship 034 mothers2mothers: social entrepreneurship and public health – scaling innovation Gene Falk with Julia Coyner Robinson and Cynthia Schweer

039 African giant rats for tuberculosis detection: a novel diagnostic technology Bart J Weetjens with Georgies Mgode, B Witkind Davis, Christophe L Cox and Negussie W Beyene moting healt 043 Social innovation “pull” incentives Liza Kimbo

048 Promoting prevention-oriented approaches for chronic noncommunicable diseases Chorh Chuan Tan

Social innovation incentives: from “push” to people 054 Building global momentum for social innovation: accelerating systemic solutions through leadership networks François Bonnici and Mirjam Schöning

060 Innovative financing mechanisms – can they help to improve aid effectiveness for health systems development? Amrita Palriwala and Aarthi Rao

066 Healthful academic translations: cultivating Collaborative Doers as Innovation Managers for societal well-being Usha R Balakrishnan

072 The challenges of cardiovascular medicine in sub-Saharan Africa: opportunities for engagement between academia, industry and civil society Tembeka Mpako-Ntusi and Ntobeko BA Ntusi

080 Civil society engagement – a key strategy in research for health Sylvia de Haan with Samuel Anya, Ayo Palmer and Paul Bloch

083 Last mile delivery in health care and patient empowerment through technology: the case of “Telecommunication for Health” Roberto Tapia-Conyer and Rodrigo Saucedo

087 Community-directed intervention: replicating Japan’s health successes in Africa? Satoshi Omura and Andy Crump

091 Dragon Net: secret society or a network of health policy researchers? Toshihiko Hasegawa

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094 New approaches to health worker training, deployment and retention Mubashar Sheikh and Sigrun Møgedal

100 Brazil’s conception of South-South “structural cooperation in health” Celia Almeida with Rodrigo Pires de Campos, Paulo Buss, José Roberto Ferreira and Luiz Eduardo Fonseca

Technological innovation incentives: “push” and “pull” 110 Giving innovation a push: public and philanthropic R&D funding Mary Moran with Javier Guzman, Klara Henderson, Alina McDonald and Brenda Omune ealth research institutions and g 116 Government and philanthropic funding for technological innovation to develop new and better tools for neglected diseases Catherine M Michaud

119 Between pull and pools, where’s the “push” for global health R&D? Anthony D So

123 PDPs as social technology innovators in global health: operating above and below the radar Joanna Chataway with Rebecca Hanlin, Lois Muraguri and Watu Wamae

127 Innovation in life sciences Where do technologies come from? Vijay K Vijayaraghavan

131 Financing social entrepreneurship: innovation awards to cross the “Valley of Death” Charles W Wessner

138 Global health partnerships: a “pull” mechanism for innovation and new products Michel D Kazatchkine with Rifat Atun and Mary Ann Lansang

142 The pneumococcal Advance Market Commitment (AMC): innovative finance to help the poor Tania Cernuschi

147 Comparative advantages of push and pull incentives for technology development: lessons for neglected disease technology development Cheri Grace and Margaret Kyle

153 Emerging innovation practices and policies for the health-care needs of resource-poor people Raghunath Anant Mashelkar, with Bhushan Patwardhan and Shiladitya Sengupta

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Foreword

Innovation for health and health equity

Article by Gill Samuels Chair of the Foundation Council, Global Forum for Health Research, Switzerland

nnovation doesn’t just happen. It is a process driven by people with vision and with creative ideas that are often borrowed from across diverse sectors and disciplines. IWhether this involves social or technological innovation, or both, recognizing such people as innovators, applauding the new ideas that they often risk their reputations to champion, and helping them to scale up their efforts – this is how to change the world. This Global Forum Update on Research for Health focuses on incentives that drive people to innovate. For new technologies, we are generally familiar with “push” and “pull” incentives. Push incentives include public funding for research and tax breaks for private sector R&D. Pull incentives include intellectual property, private markets, public procurement and prizes for innovation. Policy-makers have a long menu of options to encourage technological innovation and to steer such innovation to improve health and health equity, addressing the needs of poor people. For social innovation, we are in less familiar territory. Perhaps funding social science research, social entrepreneurship and leadership training, and knowledge translation platforms are all “push” incentives for social innovation. Similarly, aid support for health services, increasing civil society and community participation, educating policy-makers on the value of evidence to inform policy decisions, new information and communications technologies and prizes can be seen as “pull” incentives. The Global Forum believes that the language of innovation (and concepts that surround it) may help build the bridges that are needed between researchers and implementers, and between those who focus on improving health technologies and those who focus on strengthening health systems. It may give us a common language for stakeholders to partner and cooperate more effectively to improve health services, products, methods, management practices and policies to bring better health for all. J

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Introduction

Introduction

Article by Charles A Gardner Global Forum for Health Research, Switzerland

he majority of papers in this edition of the Global Forum Update for Research Tfor Health focus on “push” and “pull” Technological innovation system incentives for innovation. Such incentives are most often discussed with regard to Possible incentives to improve global health equity technological innovation. Push Pull But technological innovation brings little Regulation Intellectual Procurement benefit unless it is linked to social innovation, Research Manufacture of safety & property & distribution including improvements in product and efficacy (products)

service delivery, and the management of •Government and global R&D funding •Fast-track regulatory approval vouchers people and information in health systems. Is •Tax breaks for private sector R&D •Transferable patent extensions there such a thing as a “social innovation •“Blended value” venture capital •Commercialization assistance system”? Can we think about “push” and •Liability protection for manufacturers •Global procurement and distribution funds •Patent pooling; open source innovation •Local pooled procurement “pull” incentives for social innovation? Do we •Entrepreneurship training •Advance Market Commitments (AMCs) gain any fresh insights by doing so? •University technology managers •Prizes for successful products Interestingly, a Google scholar search on 9 •Public-private product development partnerships (PDPs) October 2009 found 29,400 published papers containing the phrase “innovation sytem” (almost all focused on technological innovation), 595 papers containing the full phrase “technological innovation system,” Social innovation system? and only 20 containing the phrase “social innovation system.” J Possible incentives to improve global health equity Push Pull Slides adapted from Gardner CA, Acharya Delivery T and Yach D: “Technological and Social Research Knowledge Policy Practice & uptake Innovation: a Unifying New Paradigm in (products & services) Global Health,” Health Affairs, 26, no. 4 •Government and global R&D funding •Local and ODA funding for health services (2007): 1052-1061 •“Blended value” venture capital •Increase civil society & community participation •Social entrepreneurship training •Educate policy-makers on value of evidence •Research policy leadership training •Information and communications technologies •Encourage policy “experimentation” •Collect & share data from policy “experiments” •Professionalize “innovation managers” •Recognize and reward entrepreneurs; prizes

•Knowledge translation platforms

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Research and innovation in Cuba

014 Scientific research in the field of health in Cuba, based and oriented towards primary health care Dr José Ramón Balaguer Cabrera

020 Research in health from the Cuban international medical cooperation perspective Nestor Marimón Torres and Evelyn Martínez Cruz

024 Connecting immunology research to public health: Cuban biotechnology Agustin Lage

029 Development of Cuban biomedical technology and its impact in “Health for All” Ismael Clark Arxer

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Research and innovation in Cuba

Scientific research in the field of health in Cuba, based and oriented towards primary health care

Article by Dr José Ramón Balaguer Cabrera, Minister of Public Health, Cuba

n Cuba, since the triumph of the Revolution in 1959, the communities, such as Jaruco, San Cristobal, Colon and Isle State has taken the responsibility of health care of all its of Youth, just to mention a few, in which researchers, Icitizens, and in this way, puts into practice social, professionals and leaders of the community gather for the economic and medical actions to ensure the protection of idea of research and finding the best choices of solution, health. Principles include free access to all services, equal creating a space of interaction in which models of assistance rights and social justice, granting that the whole population, are validated with communal participation and intersectorial regardless where they live or work, and their income, may and that facilitate the achievement of the Projections of have equal opportunities to receive continuous health care Cuban Public Health for the Year 2015. starting from the family doctor and the nurse in the community up to the more complex forms of medical Primary assistance and research assistance from specialists of the highest rank and the more Since the triumph of the Cuban revolution 50 years ago, it advanced technology, if necessary. has been the political will of the government to release Scientific research is a principal element of this process policies directed towards the constant improvement of which has influenced the quality of life of the population, people’s well-being, achieving and consolidating the rights to resulting in health standards found in the developed world. health, education, sports, healthy recreation, and culture. All The System of Science and Improvement on Health is carried of these have contributed to the quality of life that expresses out by a wide group of institutions and facilities whose itself in such markers as the low infant mortality rate and principal target is the production, adaptation, transmission improved life expectancy in Cuba today, which are the main and widespread use of scientific and technical results, conquests of a socialist revolution in an underdeveloped achieved for the constant bettering of people’s health and country under a blockade. It has been the Cuban National well-being. The basis of this system is primary health care. Health System, unique, comprehensive and regionalized, Research within this system is oriented towards the totally free and accessible with coverage for all the problems and needs of the population as well as those of the population, the carrier of this political will. system of health itself; its performance involving not only the Primary health care (PHC) is the base of the Cuban Health research institutes but the whole National Health System, in System, of which it is the central function and the main core which the fundamental scenario is primary health care, that of the social and economic development of the community. It carries out the task of identifying the needs of the population constitutes the first element of a continuous process of health by means of the active field research work, during the clinical assistance, training of human resources and research. It tests of medicines, equipment and therapies, in the represents an essential element in providing services within assessment of the impact, both social as well as clinical, in the health system, with the characteristic of assisting healthy different environments, prevention (mainly vaccines) as well individuals as well as the sick. as curing (mainly medicines) and the development of It is here precisely where research plays a fundamental advanced equipment and technology for the network of role; it approaches a wide range of themes in the fields of polyclinics and family doctors offices of the health system, health and social sciences that go beyond traditional clinical giving an answer in a comprehensive way to the needs research in health services. The areas on which research is detected by means of local, territorial and national researches based in PHC in Cuba are, among others, the analysis of the and that today are regarded as the main causes of morbid- situation of health in the community (epidemiology, public mortality: noncommunicable diseases and their risk factors. health, detection, diagnosis, treatment and follow-up of the With that purpose exist projects in the different diseases), the individual (necessities, expectations, family,

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work and community environment), lifestyle (promotion of prenatal and neonatal tests for HIV, hepatitis, congenital health, prevention of disease), risk factors and medical care malformations, hypothyroidism and fenilcetonuria, as (integrating assistance process, satisfaction, quality, access, well as other tests to determine biotinidasa deficit, 17- equality). It could be said, therefore, that research in PHC hydroxiprogesterone for the diagnosis of adrenal applies its results directly on the population to whom it is congenital hyperplasia and galactosemia, genetic addressed, studying the early stages of a disease and diseases capable of compromising the health of the establishing a continuous relationship with patients, studying child. The task of the physician and the nurse in charge the natural history of a disease in its spectrum, in a of carrying out these tests has been vital, since the early continuous way and in situ. detection of these diseases allows treatment and avoids The Model of the Family Doctor with the specialist in the negative impact on the development and growth of Comprehensive General Medicine was introduced in 1984 in the infants, as well as the ones that apply to adults. the whole country, creating important transformations in the Techniques developed by the National Centre of Genetic health system of Cuba within the range of assistance, Medicine, oriented towards the prenatal diagnosis of teaching, research and direction, as well as in the structure congenital cardio-pathologies, as well as the creation of of the organization of ambulatory medical assistance, in the the Genetic Medicine Network that gives guidance and organization of the services, and in the health programmes, treatment to those with genetic diseases. which have contributed, beyond any doubt, to improve the Sickle-anaemia programme that applies to all pregnant markers of health standards of the Cuban population, women from the 9th to the 12th week of pregnancy. supreme and general objective of this new model of Pregnant women who carry the genes for the disease assistance and of the socialist system. and their husbands are both tested. If both are carriers This new professionalism brought about the approach to they are given counselling and informed of their choices medical assistance to individual, as a bio-psycho-social with the prenatal diagnosis. human being, regarding the influence of familiar, social and The National Centre of Neuro-Sciences (CNEURO) has environmental factors upon the individual’s health, with a developed as part of its strategy in neuro-diagnosis, a comprehensive approach, based on the promotion of health new system for the detection of hearing loss. Audix and the prevention of diseases and with the participation of equipment has been incorporated into the National individuals, families and the community. System of Health for this purpose. Others include It was in this decade when scientific research in the health Medicid and Neurotica. Tests for deviations in child field and the application of its results in the PHC neuro-development in Cuba include those for important strengthened its ties with the new research and production disorders such as mental disability, motor disability, centres that started to develop, along with the health language deficit, sensorial, visual and hearing problems. institutions, the material means, medicines, equipment, A programme of early detection of oral, breast and technologies, that responded to the needs of the population cervical cancer has been carried out for decades with and of the services, applying the results in an immediate models of assistance assessed in multiple investigations way, which was evidenced by health standard markers. by professionals in institutes of primary assistance. In the 1990s, despite the enforcement of the economic The Umelisa System for the assessment of the specific blockade and the collapse of socialist countries, scientific prostate antigen (PSA total and free) places Cuba in an research and human resources training were strengthened as advanced position for the diagnosis of prostate cancer, a a fundamental way to keep and improve the conquests of the disease that constitutes the second cause of death revolution in the field of health, which has granted our among the different types of cancer in men. researchers and professionals worldwide acknowledgment, Medicines for the treatment of cancer such as citostatics, making Cuba a power in this field and that in this new and products of bio-technology among which millennium achieved higher level of success in the combat monoclonal antibodies are relevant. against noncommunicable diseases that constitute the first Other biotechnology products like the eritropoyetine cause of morbid-mortality of Cuban population, which has a recombinant, the stimulator of colony growth (Leukocim) tendency towards ageing as a result of the social for the treatment of neutropenia associated to development achieved by Cuban public health. chemotherapy and radiotherapy, interferon and others. Some of the research applied during these years and that Tests for chronic kidney disease (CKD) and diabetes today enable us to continue improving the standards mellitus, since they are an increasing health problem in achieved have been: Cuba as in the rest of the world. They are also Antiretrovirals for the bi-therapy and tri-therapy treatment associated with other factors such as hypertension, heart of AIDS and, since 2001, the production of high- conditions, metabolic syndrome, children under age 5 efficiency generics (at present seven types are available) with low weight at birth, adults of age 60 and more, for the application of the tri-therapy or antiretroviral and pregnant women, all these being back-up with therapy. Today Cuba guarantees coverage of 100% of Cuban technology for diagnosis and treatment and for patients, including those who are HIV positive. the development of national generics by means of SUMA Citostatics for the treatment of cancer. technology. SUMA technology (UltraMicroAnalyticSystem), in the Remarkable in these years is the research “Psycho-social

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study of handicapped people and social, clinical, genetic as a fundamental tool for identifying the problem for research and psycho-pedagogical study of the mentally retarded in always by means of the proper use of human resources in the Cuba”. This was started on July 2001 by the area (doctors, nurses, technicians, students, health activists, appointment of Commander in Chief Fidel Castro and and others), properly trained with previous experience on the extended to April 2003, embracing the whole country. In subject of the search. it, the situation of people with mental disabilities and The training of human resources in the field of research other problems was characterized (according with the work must be organized by experts on the subject, with the criteria selected) on the basis of an exhaustive search participation of the three levels of the system, leading the through all possible sources of information and the patient up to the solution of the problems, with the previous application of the principle of research-action, in which approval of the government authorities, health authorities, the principal carriers were the professionals of primary and mass organizations of the area, evaluating with depth the health care. material resources available and the ones that are needed Development of vaccines and other medicines, not only before starting, and granting a system of information that for our country but also for our brothers in other permits knowing the results daily for making of decisions, developing countries. In Cuba, nine infectious-contagious including the possibility of organizing the solution of new diseases have been eliminated and another five are kept problems that may arise during the search. at low that impede their transmission. Examples are evidenced in the projects carried out in the municipalities of Isle of Youth, Cerro, San Cristobal, Colón These new technologies have been developed in the and Jaruco, to give and answer to the needs of the Cuban research centres of the West Scientific Town Centre (Polo population characterized by a state of health at the mercy of Científico) along with research institutes, hospitals and noncommunicable diseases, mainly cancer, diabetes clinics, and put into practice in communities. mellitus, hypertension, chronic kidney disease, heart and In the first decade of the new millennium significant brain diseases, that require technology and means for early transformations have been produced with the fast processes detection not only of the risks, but also of the main signs, of repair of clinics, with the need to bring to Primary Health even more by association among them, the high cost of Care, specialized services that were only given at hospitals, treatment and what they imply in the life expectancy of the producing a high technological transference to the clinics, Cuban population with a tendency to ageing. with the extension to the comprehensive services of This is how the principal method of work comes to be the rehabilitation, computerized libraries, increases in the active search of the population by means of the equipment needed for ultrasound, x-ray, electrocardiogram, “comprehensive check-up of the Cuban family”, which endoscopy, advanced vital support and trombolysis, constitutes a research-action programme carried out by all the chemotherapy, audiometer, and in delivery rooms and professionals and workers of the system, together with the municipal intensive care units. These improvements have research centres that provide the means and equipment helped clinics to bring services nearer to the population, required for the search and for the treatment of problems. contributing to an increase in patient satisfaction, improved Making reality the principle that research really responds to training of human resources and an increase in the research the needs of the population and the services, and by means carried out in these institutions, oriented mainly to of which the challenge that noncommunicable diseases noncommunicable diseases, which, as was said before, constitute may be faced since they are the first cause of constitute the principal cause of morbid-mortality in Cuba. morbid-mortality in our country and thus achieve the In these years, the National Health System and in Projections of the Cuban Public Health for the Year 2015. particular Primary Health Care has been constantly improving. The active search is included in a permanent and Conclusion systematic way for the identification and proper solution of The improvement of the health status and well-being as well the population’s health problems, as a State responsibility, as the increase of the level of satisfaction of the population fulfilling in this way one of the great ideas of Commander in with the services constitute the main purpose of the National Chief, expressed in his speech during the celebration of the Health System, for which it works in the bettering of the 26 of July 2006 in Granma Province, where he defines the activities and the programmes of the revolution among which active search as “the true diagnosis of the state of health of research has an outstanding position, strengthened mainly in the population and the greatest advance that can be thought primary assistance, since it allows us to achieve excellence in of to raise life expectancy of the human being at present”1. health services. This considerable impulse from the field of social advances Scientific research in primary health care constitutes by in the active search has taken into consideration its ethic, itself a very important and strategic element (of the future), economic, technological social and legal aspects, all of which not only from the political-economical point of view, but also under the concept of not only discovering the disease but of in the sphere of defence and for the social development of the identifying the persons with high risk, to diminish the mobility country. Thus, scientific research, the creating and and mortality specific thanks to the identification of the generalization of results are key elements in the economic greatest number of persons to whom an effective and proper efficiency and preconditions for development that make therapy may be offered, using the analysis of health situation essential the optimum use of capacities and resources

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devoted to it. Scientific research in health acquires a more also for those who claim to be the richest, but in many of outstanding meaning by the fact that it is addressed directly which live the poorest, the dispossessed, since, with few to the restoration and improvement of the health status of the material resources, but much dignity and political will from population, both of individuals and of the society as a whole, the government, with commitment of our men of science, and the principal scenario are our polyclinics, family doctors and who are, not only those in the big research centres, since and nurses. in Cuba science is made in the hospitals, polyclinics or The decrease of the mobility and mortality, mainly at the community, in all those places where there is a human expense of noncommunicable diseases that are their main resource trained for and committed to the social work that causes in our country, will be due to the early identification José Martí started and that our Commander in Chief Fidel of a greater number of patients to whom an effective and Castro Ruz has completed. adequate therapy may be offered, and to the contribution that Today we are an archipelago, a people “… a country of expensive technologies have in the prevention, control and men of science; of ideas…” as stated our Commander at the treatment available today for all the people due to the opening ceremony of the National Center of Scientific scientific development achieved in our country by scientists Research (CENIC) in the 1960s. and professionals. Cuba today is an example for developing countries and Dr José Ramón Balaguer Cabrera is Minister of Health in Cuba.

References

1. ‘1.Castro F. Discurso por la celebración del 26 de julio del 2006 en 15. Berraondo Z. y Col. Gestión por procesos en Atención Primaria. Vol 10 Granma. Periódico Granma, Ciudad Habana, 27 de julio del 2006. Número 2. Agency for Healthcare Research and Quality (AHRQ). Research agenda 04http://db.doyma.es/cgin/wdbcgie/doyma/mrevista.salta_a_ultimo?pident and areas of interest: Center for Primary Care Research. Rockville, M.D.: =34.2006. AHRQ;2001. 16. Caminal J, Sánchez E, Schiaffino A. El análisis por segmento de 3. Almarales B. Barreras que afectan la comunicación médico - paciente. población insatisfecha: una propuesta para optimizar la información de Hospital "Lucía Iñiguez Landín". 2002. Facultad de Ciencias Médicas las encuestas de satisfacción global. Revista Calidad Asistencial. "Mariana Grajales Coello". Holguín. Correo Científico Médico de Holguín 2002;17(1):4-10 2003; 7(2). Disponible en URL: 17. Cabrera N, Quiñones I, Álvarez AS, Gómez F. Resultados de investigación http://www.cocmed.sld.cu/no72/n72ori7.htm [Consultado: 31 de Octubre para el sector de la salud en Cuba, 2006. Rev. Cubana Salud del 2007]. Pública v.34 n.2 Ciudad de La Habana, abr.-jun. 2008. 4. Álvarez AS. Estudio de Caso de Cuba. 1ª Conferencia Latinoamericana de 18. Cabrera N, Álvarez AS y García A. La Investigación en el Sector Salud. Investigación e Innovación en Salud, PAHO, GFHR, COHRED, Ministerio Resultados de la Convocatoria 2007. Resultados de la convocatoria 2007 de Salud de Brasil. Río de Janeiro, Brasil, Abril de 2008. para investigaciones en el sector de la salud, Rev. Cubana Salud 5. Álvarez AS y Cabrera N. Financiamiento para la Investigación e Innovación Pública v.34 n.3, Ciudad de La Habana, Jul-Sept 2008. en Salud en Cuba. Artículo enviado al Global Forum for Health Research 19. Cabrera NJ. La Investigación y la Enseñanza en Salud Pública en Cuba. para su publicación en la Revista Financial Flows 2009, Ciudad Habana, Red Iberoamericana Ministerial de Aprendizaje e Investigación en Salud 2009. Pública – RIMAIS, 2007 6. Álvarez AS y Cabrera N. El Sistema de Ciencia e Innovación Tecnológica 20. Cappelaere P, Hoerni B. L’erreur d’Hippocrate. Bull Cancer. 2001;88(4) en Salud y su Universalización a todo el Sistema Nacional de Salud. Rev 21. Castell-Florit P. La intersectorialidad. Su beneficio social en el Sistema de Cubana de Educación Médica, Vol. 23 Nº 1, Autor Principal, C. Habana, salud de Cuba. Tesis para optar por el grado de Doctor en Ciencia de la 2009. Salud. La Habana, 2004. 7. Álvarez AS y Cabrera N. El Sistema Nacional de Ciencia e Innovacion 22. Castro F. Primer congreso del Partido Comunista de Cuba. Informe Tecnologica en Salud. I Taller Nacional de Investigaciones de la Red Central. Edit. DOR Comité Central PCC. La Habana, 1975. Nacional de Genética Médica, Teatro Centro de Convenciones Pedagógicas 23. Castro R. Discurso del Segundo Secretario del Comité Central del Partido de Cojímar, 25-26 de Junio 2008. y Ministro de las FAR, en la clausura del XIX Congreso de la Central de 8. Álvarez Sintes R, Álvarez R, Díaz G, Salas I, Lemus ER, Batista R. Temas Trabajadores de Cuba. Palacio de las Convenciones, Ciudad de La de Medicina General Integral. Vol. I .Capitulo1.La Habana: Editorial Habana, 27 de septiembre de 2006. Ciencias Medicas,2005:7-11 24. CIEM. Investigación sobre Ciencia Tecnología y Desarrollo Humano en 9. Andersen MR, Urban N, Ramsey S, Briss PA. Examining the cost- Cuba 2003. La Habana: CIEM; 2004. effectiveness of cancer screening promotion. Cancer. 2004;1;101(5 25. Colectivo de autores. Por la vida. Estudio psicosocial de las personas con Suppl):1229-38. discapacidades y estudio psicopedagógico social y clínico genético de las 10. Anderson A, Wagner E. Chronic illness management: what is the role of personas con retraso mental en Cuba. La Habana: Editorial Abril; 2003. primary care? Ann Inter Med. 2003;138:256-61 26. Documentos de trabajo y Declaración final de la I Cumbre 11. Arocha C. Centralización de los servicios de salud. Experiencia de la Iberoamericana de Medicina Familiar, Sevilla, España, 2002. Rev. Educ, salud pública cubana. Tesis para optar por el grado de Doctor en Ciencia del 2003. de la Salud. La Habana, 2006. 27. Fernández I. ¿Investigación en atención primaria? Aten Primaria. 2003; 12. Balaguer, JR. Discurso del Ministro de Salud Pública en la Reunión 31:281-4. Nacional de Rectores y Decanos del MINSAP, Ciudad Habana, 5 de junio 28. Fusté J, Bolíbar B, Castillo A, Coderch J, Ruano I, Sicras A. Hacia la de 2003. definición de un conjunto mínimo básico de datos de atención primaria. 13. Balaguer, JR. Discurso del Ministro de Salud Pública en la Graduación de Aten Primaria. 2002; 30:229-35. Ciencias Médicas Curso Académico 2003-2004, Ciudad Habana, Julio 29.Gilmore C y Moraes H. Gerencia de la calidad en salud. Tomado del 2004. libro Gerencia en Salud. Tomo I. ENSAP. Cuba. 1997. 14. Bencomo JF. La Red Nacional de Laboratorios SUMA: Soporte 30.Giocochea E. Experiencia en Medicina Familiar y Atención Primaria de Tecnológico en el Pesquisaje Seroepidemiológico del VIH-SIDA en CUBA. Salud RAMPA año 1 Vol Número 1 Julio- Sep pág. 1-86 DST-J Bras Doenças Sex Transm. 2003;15(4):5-11. http://www.idefiperu.org/RAMNRO1/RAMPA%20V1N1%20Completa1.pdf

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References continued

31.Gómez de la Cámara A. Investigación en atención primaria. Centro Salud. 45.MINSAP. Dirección de Ciencia y Técnica del MINSAP. Proyección 1994;2(7):531-3. Estratégica en Ciencia e Innovación Tecnológica en Salud para el periodo 32.González Cárdenas L. Segredo Pérez AM, Presno Labrador C, Fernández 2008-2010. Ciudad Habana, 2007. Díaz I, Alcance de la Atención Primaria de Salud en el mundo. En: CDS 46.MINSAP. Proyecciones de la Salud Pública Cubana hasta el 2015 (PSP- Dirección en Salud II. ENSAP, 2005. ISBN 959-7158-43-4. 2015). Ciudad Habana, Marzo de 2006. 33.Kalucy L, Beacham B, Raupach J, Dwyer J, Pilotto L. Priorities for 47.Montes de Oca R. Conquistar toda la justicia. La huella imperecedera de primary health care, research, evaluation and development in Australia. Celia. Departamento de Atención a la Población del Consejo de Estado. Primary Health Care Research and Information Service, Department of La Habana, 2007. General Practice. Adelaide (Australia): Flinders Press;2001 48.Muñiz Roque A M. Calidad en la interrelación Consultorio Policlínico – 34.Lafata JE, Simpkins J, Lamerato L, Poisson L, Divine G, Johnson CC. The Hospital en el Policlínico Docente Lawton. [ Tesis de Maestría ] Ciudad economic impact of false-positive cancer screens. Cancer Epidemiol. de la Habana: ENSAP; Enero 2004 Biomarkers Prev. 2004;13(12):2126-32. 49.OPS/OMS. El desarrollo de la evaluación de tecnologías en salud en 35.Lence JM. Repercusiones éticas de los programas de pesquisaje masivo América Latina y el Caribe. Washington, D.C.: OPS/OMS;1998. en el control del cáncer. Rev Cubana Salud Pública. 2007;33(1) (Programa de organización y Gestión de Sistemas y Servicios de Salud. 36.Los cuatros pilares de la medicina familiar. Rev Archivo de Medicina División de Desarrollo de Sistemas y Servicios de Salud). Familiar Vol 4 No 2 Abril- Junio 2004 50.Panerai R, Peña J. Evaluación de tecnologías en Salud. Metodologías para 37.Medicina Familiar en Cuba: Comienzo, presente y futuro. Rev. Atención países en desarrollo. Washington, D.C.: OPS-OMS;1990. Primaria 2007,39( 5):00-00 . España 51.Presno C. El médico de familia en Cuba. Rev. Cubana Med. Gen. Int., 38.Hatim Ricardo, Alberto. Modelo de desarrollo profesional: propuesta ene.-mar. 2006, vol.22, no.1, p.0-0. metodológica. Revista Cubana Educación Médica Superior, 52.Sancho-Garnier H. Problemes éthiques poses par les actions de 2003;17(1):47-52 prevention. Bull Cancer. 1995;82:468. 39.Hernández Elías R. Administración de Salud Pública. La Habana: 53.Showstack J, Anderson A, Hassmiller S. Primary care at a crossroads. Edición Ciencia y Técnica; 1971 Ann Intern Med. 2003a;138:242-3 40.MINSAP. Carpeta Metodológica de Atención Primaria de salud y Medicina 54.Showstack J, Lurie N, Larson EB, Anderson A, Hassmiller S. Primary Familiar. Folleto. La Habana, VII Reunión metodológica del MINSAP, care: The next renaissance. Ann. Intern. Med. 2003b;138:268-72. 2001. 55.Starfield B. Primary care: balancing health needs, services and 41.MINSAP. Documentos de archivo. Dirección Nacional de Servicios technology. Oxford (United Kingdom): Oxford University Press;1998 Ambulatorios 2002 – 2004 56.White KL. Fundamental research at primary care level. Lancet. 42.MINSAP. Fundamentación para el nuevo enfoque de la Medicina en la 2000;355:1904-6 Comunidad. La Habana, 1975: 3-26 57.WONCA Europe (The European Society of General Practice/ Family 43.MINSAP. Programa de atención Médica Integral a la familia y a la Medicine). The European definition of general practice/family medicine, comunidad. La Habana: MINSAP; 2004. 2002. Europa: Wonca Europe;2002 44.Ministerio de Salud Pública de Cuba. Anuario estadístico de Salud 2009. 58.World Health Organization (WHO). International Conference on Primary La Habana: MINSAP;2009.

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Research in health from the Cuban international medical cooperation perspective

Article by Nestor Marimón Torres (pictured), Head of International Public Health Department, Cuba and Evelyn Martínez Cruz, Instructor Professor at the National School of Public Health, Cuba

his paper describes the role of research in Cuban right” and “education of the population is a responsibility of medical cooperation as a working strategy, its role in the state” which are currently in force. Tthe cooperation and descriptive analysis of activities undertaken in this field, and its evolution, in keeping with The principle of international solidarity in health care transformation and advances made in Cuban medical The first solidarity action carried out in the field of health took international aid (currently in 76 countries and more than place in 1960 when Chile was hit by an earthquake and 38 000 health cooperators doing research in their brigades, Cuba sent an emergent medical brigade. Although aid was most of them located in communities in remote areas lacking dispensed on this occasion in response to the emergency, it basic health services). The main results achieved are is only on 23 May 1963, after sending the first medical described in qualitative and quantitative terms. The aim of brigade to Algeria, that Cuban International Medical this scientific research is to improve the work of the Cuban Cooperation is officially known as principle of health medical brigades, and in accordance with the main health internationalism, international solidarity of the Cuban health problems in the country in question, to develop human system, ethical fundament and profound humanism3. The resources in health and strengthen the national capacities of number of cooperators and countries where this aid is ministries of health given that this is the main purpose of this provided has increased over the years, as well as the aid and the only way to achieve an evident health diversification of this activity, specially in the teaching area development for those populations. and the number of medical faculties created abroad and the number of foreign students in Cuba. During 2007–2008, Introduction 10 241 students from 108 countries graduated in medicine, A change occurred in Cuba’s history in 1959: the success of dentistry, nursing and as health-related technicians. a revolution that generated political, economic and social In 49 years, a total of 132 849 heath cooperators provided transformations, to the benefit of the Cuban people. Before aid in 108 counties as follows: that period there was no experience in international health aid. Africa: 38 countries and 45 488 co-workers; At the time of the revolutionary victory in January 1959, America: 39 counties and 79 717 co-workers; the social and economic conditions were critical. To give an Eurasia and Middle East: 31 countries and 9644 exact idea of the situation: infant mortality stood at 60 per co-workers. 1000 live births, the hygienic and sanitary picture was full of communicable diseases, there was only one school of Currently there are more than 38 000 health workers in 76 medicine and two teaching hospitals. As to human resources, countries4,5,6. there were 6286 doctors, half of whom emigrated during the In all these countries, medical cooperation has been and is ensuing few years, which meant a hard blow for health provided on a totally disinterested basis, whose underlying authorities’ plans and a challenge for the Ministry of Health thinking can be summarized as follows: and medical education, which had to assume the massive Cooperation is a key element of Cuban foreign policy, as training of professionals needed to cover the lack of medical a route to true integration. services and professors. It is channeled through central and local government In order to overcome this situation, a national health looking for its sustainability. system was created composed of a network of higher medical It is arranged on the basis of the sum of the possibilities education facilities integrated in faculties, branches of of the two countries involved. medical sciences1,2 throughout the country. The doctors and paramedics sent from Cuba basically All this was possible due to profound changes in the provide primary health care services; serve the entire political, economic and social order all over the country population without distinction in terms of race, creed or supported in two important principles: “Health is a public ideology; do not involve themselves in matters of internal

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politics; and respect the laws and custom of the host SNo. Countries Scientific Papers symposia presented country. 1 Ecuatorial Guinea 38 30 Every effort is made to respond to the needs identified 2 Bissau Guinea 4 33 3 Mali 9 167 by the country receiving the aid. 4 Eritrea 5 139 By its institutional nature, it seeks the benefit of the 5 Zimbabwe 41 665 6 Nicaragua 2 54 largest possible number of people and operates in the 7 Belize 10 84 most remote and neglected areas7. 8 Guatemala 7 377 9 Honduras 10 628 10 Guyana 3 18 Just to give an example of the results obtained during the 11 Haiti 10 625 12 Bolivia 5 140 first 10 years of cooperation at the Comprehensive Health Total 144 2960 Programme, initiated in 1998 after the George and Mitch hurricanes in Central-America and the Caribbean, with Table 1: Number of scientific forums and papers presented per country specialists in comprehensive general medicine now spread in 43 countries, 544 020 359 medical consultations have Health System. To date, Cuba has 74 552 medical doctors. been carried out; 174 732 736 patients have been served in Of them, 32 289 are specialists in comprehensive general the place where they live; 1 052 975 deliveries have been medicine covering 100% of primary health care programmes made. As well as 3 583 994 surgical interventions, with and 24 faculties of medicine including the Latin-American 3 095 184 lives saved6,7. School of Medicine6,12. Reductions in the rates of infant and maternal mortality demonstrate the effectiveness of the work performed. In Research performed by medical brigades Guatemala, for example, infant mortality stood at 45 per Research activities as part of the teaching process, a crucial 1000 live births before medical cooperation’s arrival, and element for the professional training and study-work liaison, dropped to 16 in the area covered by the Cuban medical constitutes the premise for human resources development. team; in the case of Gambia, the reduction was from 121 per Research is also one of the working pillars carried out by 1000 live births to 40.6. As for reduction of maternal medical brigades when serving abroad, where scientific mortality rates in Haiti, the reduction was from 457 per methods of research are applied to improve working results, 10 000 live births to 285 per 10 000 live births; in Ghana benefiting different ministries of health. from 214 per 10 000 live births to 43 per 10 000 live The working approaches of a comprehensive health births6, 8, 9. programme are summarized as follows: Training activities in human resources: 534 305 persons human resources training; are involved, 220 729 participants in courses, 895 are hygiene/epidemiological control; graduated auxiliary technicians, 1054 are technicians and joint development of sanitary campaigns and mass 304 health professionals, of them, 278 physicians6. vaccination; There are other important cooperation programmes such advice to ministries of health; as: development of undergraduate and postgraduate Barrio Adentro in Venezuela launched on 16 April 2003 teaching, masters, courses, training etc.; – the most progressive and advanced scheme of its kind clinical and surgical assistance. (in terms of social services provided within a particular country) which is now part of ALBA, the “Bolivarian Research is the core work for medical brigades. The Alliance for the Americas”8. success of a final work is presented at scientific symposia in On 25 August 2005, the Henry Reeve contingent was regions and departments where brigades are located. The launched, an international corps of doctors trained to most relevant research results are presented in the Science deal with the aftermath of natural disasters and serious and Technology Forum in Cuba. epidemics. This contingent constitutes a new approach For the purposes of this study 12 countries involved in the for disaster medicine, although since 1960 this aid was Program were chosen from Africa, Latin America and the served by emergent brigades15. To date, of 10 000 Caribbean, some already have ten years of advances6,13. A Cuban cooperators, 4156 have served already in summary of the number of scientific study and papers Pakistan, Bolivia, Indonesia, Mexico, Peru and China presented according to the available data is shown in with important results11. Table 1. Operación Milagro (a programme aimed at curing eye The research topics are focused on the main causes of diseases through surgical intervention) was launched in morbidity and mortality of those countries and in 2004. To date, there have been 1 609 134 operations concordance with guidelines of ministries of health: analysis to patients from 34 countries, of them 268 077 took of health conditions; determining of the main causes of place in Cuba and 1 166 786 in ophthalmologic centres morbidity and mortality of those populations, especially created by Cuba in other countries6,12. communicable diseases such as malaria, tuberculosis, HIV/AIDS, leishmaniasis and Chagas disease; and the study The factors allowing this development were possible due to of noncommunicable diseases which coexist together. Other advances and strengthening achieved by the Cuban National topics are mother-and-child health; repairing and setting up

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of equipment in units where health professionals work; Ciriboya project to implement a health programme nursing personnel activities; training of personnel; and more contributing to improving health conditions of the recently Operación Milagro, in many of these countries where population and boosting comprehensive rural eye problems are another important part of country guidelines. development from inter-sector alliance in accordance The fact that these are developing countries with serious with the Garifuna population’s cultural patterns. political, economic and social problems, as a consequence of Joint Intibacá project with Ministry of Health consisting neo-liberal policies that have only contributed to increase the of the development of rural medicine. gap between rich and poor, increase poverty, exclusion and Solidarity Network Agreement sponsored by the first lady disparities among and within them, is always at the basis of of the country, aimed at decreasing poverty in very poor those analyses. For that reason, to demonstrate the impact on areas. these social determinants on health and seeking or proposing way of confrontation and solutions, the crucial aspects are the Guyana: joint research with local professionals being essence of medical brigades at the moment of integrating presented in Georgetown Public Hospital whose topics are medical attention-teaching and research. dengue, mental health affections, and protocol for diabetes This work approach agrees with Stephen A Matlin’s views foot applied at national level in public facilities. that studies may help identify the different types of barriers, Guatemala: according to a health situation analysis, whether they are economic, geographic, institutional, promotion and prevention actions were aimed at the political, social, cultural or technological, which prevent community level; TB and rabies protocols were modified after access to health and may also identify and validate actions to joint research as well as the evaluation of the country’s public improve equality and access to health for all13,14. hospital network by instruments designed by technicians and At the opening of the 11th Forum Professor Matlin made engineers specialized in medicine-linked equipment. reference to the importance and need for health care research Bolivia: a therapeutic guide to provide care to patients to focus on the main causes of death in developing countries suffering from dengue; an ambulance network project; a where communicable diseases are among the first causes, human resources training project and a sustainability especially in African countries; and to coinsider that a very proposal for emergency and disasters. small fraction of the funds allocated to health research are Belize: research together with local professionals on topics actually devoted to those issues, which are the main health such as mother and child care, diabetes mellitus and needs in those countries15. hypertension. The impact of positive research results embodies a Nicaragua: research on the health situation, actions to fundamental and essential objective for the work rendered by reduce maternal and infant mortality, and the application of cooperators because the quality of their services improves, new nursing techniques with the creation of models and national capacities increase, and the application of these procedures. policies at ministries of health is achieved. All this constitutes Guinea Bissau: joint research, papers presented on the a satisfaction and recognition to services provided by health incidence on mental disorders, and others dealing with professionals in brother countries where, as it has already training of human resources at events sponsored by the been said: Cuba does not give what it has left over, but it Ministry of Health. shares its main wealth: its human capital. Equatorial Guinea: researches; launching project of a Concrete examples can be seen as follows: medical sciences faculty; clinical and epidemiological Honduras: special research projects are developed as behaviour of malaria in children below five years of age in follows: Bata; incidence of human trypanosomiasis. Joint program with Ministry of Health to counteract the Haiti: project for comprehensive development in social HIV/AIDS epidemic. medicine in order to improve quality of life when intervening Siguateque project to promote a healthy lifestyle with the in social determinants. Other lines of work: strengthening of main main objective of preventing drug consumption and health facilities infrastructure and creation of new services, promotion of positive values in students. improvement of access to health system, human El Pantanal community. An extended project from the resources training and research on communicable and family support and psychological centre which aims at noncommunicable diseases13. improving the quality of life of inhabitants living in All these actions demonstrate that qualitative researches marginal areas of the capital through health promotion can be implemented with few resources aimed at solving actions and a comprehensive programme of educational problems that represent a high percent of the world and social assistance. population; actions that undoubtedly help to reduce the rift Communitarian intervention project on mental health at between the poor and the riches and to improve these Divina Providencia community. populations’ health indicators by coinciding with reviewed Governmental Victoria project consisting of re-establishing literature16. the physical and psychological health of people addicted to alcohol and drugs. Final considerations: Tawahka project, launched in 2001 aimed at improving Research is one of the medical brigades’ working this ethnic group’s quality of life. objectives. This activity allows us to gain in-depth

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knowledge of the sanitary conditions of a country and to value for the Cuban national health system, owing to the act accordingly in different scenarios and in neglected fact that new knowledge and experiences may be remote areas without medical services and economic presented in relevant national symposia or published in resources. local or international publications. Impact on human resources and development of undergraduate, postgraduate and research process is Nestor Marimón Torres has an MSc in public health and a first positive. It contributes to a scientific culture among degree in health administration. He is Associate Professor at the health professionals and favours the strengthening of National School of Public Health, Head of the International Public national capacities. Health Department and Director of International Relations at the Participation of local professionals and health authorities Ministry of Public Health. in research allows them to be aware of problems identified and their likely scientific solutions, to apply its Evelyn Martínez Cruz has an MSc in public health and results through therapeutic guides and protocols, which international health and a first degree in comprehensive general translates into better medical care and quality of services. medicine. She is an Instructor Professor at the National School of After a mission is implemented, the scientific and Public Health and a specialist in the Bilateral Department of technical quality, ethical and human values of health International Relations Direction at Ministry of Public Health. workers are reinforced. This fact serves as an added

References

1. Ministerio de Salud Pública, Cuba. Plan de Salud 1970–1980. In: 9. Anuario Estadístico MINSAP 2008. Recursos Humanos, 2004, No. 3. La Habana: MINSAP, p.20, p.23, 10. Delgado García G. La solidaridad internacional de la medicina cubana. p.35. Antecedentes, su desarrollo y trascendencia en la etapa revolucionaria. 2. Ministerio de Salud Pública, Cuba. Área de Docencia e Investigaciones. Cuadernos de Historia de la Salud Pública. Ciudad Habana; Consejo Objetivos para el año 2001. La Habana: MINSAP; 2001. Delgado García Nacional de Sociedades Científicas, 1987, Vol. 72, pp.137–49. G. Desarrollo histórico de la enseñanza médica superior en Cuba desde 11. Castro Ruz F. Discurso pronunciado en el encuentro con las fuerzas sus orígenes hasta nuestros días. Educ Méd Super, 2004, 18(1). medicas prometidas para apoyar al pueblo de Estados Unidos en regiones Disponible en: URL: htpp//bvs/ revistas/ems/indice.html. afectadas por huracán Katrina. Palacio de Convenciones. La Habana, 4 3. Delgado García G. Centenario del Ministerio de Salud Pública de Cuba September 2005. (1909–2009). Coloquio por el centenario del Ministerio de Salud Pública 12. Informes de Archivos. 1998–2009. Departamento Nacional de de Cuba, Instituto Superior de Ciencias Médicas de la Habana, Ciudad Estadísticas. MINSAP. Habana; Enero 2009. 13. Informes y reportes anuales de las Brigadas Médicas del Programa 4. Cooperación de Cuba en el mundo. Viceministerio de Cooperación Integral de Salud, Unidad Central de Cooperación Médica, 2009. Internacional, MINREX, La Habana, Cuba; May 2009. 14. Matlin S. Research contributions to improving equitable access to health 5. Informes de Archivos 1966–2009. Viceministerio de Docencia. Ministerio in developing countries. Global Forum update on research for health, de Salud Pública. ISBN 978-2-940401-01-7. Vol 4, 2008. 6. Informes de Archivos 1993-2009. Unidad Central de Colaboración 15. Matlin S. Equitable access. Research challenges for health in developing Médica. countries. A report on Forum 11. 29 October–2 November 2007. Beijing, 7. Jiménez Y. Cuba coopera. Conferencia en sede de la Organización People’s Republic of China. Panamericana de la Salud, Washington DC, October 2008. 16. Gray A. Equitable access to research capacity as a tool for health. Young 8. Marimón Torres N. La colaboración Medica Cubana en el siglo XXI: Una voices in research for health 2007. Global Forum for Health Research, propuesta para la sostenibilidad en Guinea Bissau. [tesis] Escuela October 2007, Geneva, Switzerland. Nacional de Salud Pública, 2006, p.10–15.

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Connecting immunology research to public health: Cuban biotechnology

Article by Agustin Lage, Director, Centre of Molecular Immunology, Havana, Cuba

he close connection between immunology and public one. Supporting the high health standards of Cubans are health has been successful in reducing infant mortality many social and economic determinants that guarantee wide Tand infectious diseases in Cuba. The next challenge is accessibility to and investment in the health system. Thus, it to find treatments for chronic diseases of adulthood and to is impossible to link the success of public health in Cuba to extend life expectancy. a single intervention. However, immunology research has How much immunology research does a small country certainly contributed to the reduction in infant mortality to require? The simple answer is “a lot”, if immunology research below 6 in 1000 newborns (the lowest in the region after is to have a tangible effect on people’s health. This is because Canada, and unique for countries in the tropical belt) and to the immune system functions as an informational system that an increased life expectancy of beyond 77 years. Cuban is shaped during a person’s life after exposure to pathogens. immunology research can also be attributed to the Not unexpectedly, immune interventions such as vaccines disappearance of several infectious diseases (such as that manipulate the “knowledge” of the immune system are polio, diphtheria, measles, rubella and mumps) and to a among the most cost effective in modern medicine. A substantial reduction in the occurrence of others (Table 1). “snapshot” of immunology research in Cuba shows a As notable examples, Cuba was the first country in community of more than 600 trained immunologists, 10 the Americas to eradicate polio and mumps, and an scientific institutions whose core research is immunology, outbreak of meningitis in 1982 was totally controlled annual congresses in the field, training systems for both basic (morbidity reduced by over 95%). Acute hepatitis B is also and clinical immunologists, a nationwide network of 137 disappearing in the population younger than 15 years of immunoassay laboratories, and several state-of-the-art age, dengue fever outbreaks have been controlled without manufacturing facilities for vaccines, cytokines, antibodies leaving the disease endemic, and the prevalence of infection and immunodiagnostic systems. with human immunodeficiency virus (HIV) remains below 0.1% of the population between 15 and 49 years of age Effect on public health (only 19 countries in the world have an infection rate Although remarkable for a country with only 11 million below this). people, the scale of scientific research in Cuba is not its most notable feature. The hallmark, or perhaps unique feature, of Biotechnology is the “connecting device” Cuban immunology research is its close connection with How was the connection between immunology research and public health. The effect of immunology on Cuban public public health built? The main “bridge” connecting health is clear: Cuba has the widest vaccination programme immunology and public health is biotechnology. This is not in the world1, including universal coverage of newborns with unexpected, given that 70% of worldwide biotech products vaccines against 13 diseases (in comparison, the World now in development are immunological. Of the 418 products Health Organization immunization programme has seven included in the 2006 survey published by the vaccines). In addition, epidemiological surveillance with Pharmaceutical Manufacturers Association (http://www. immunoassay screenings for more than 20 diseases is phrma.org/files/Biotech202006.pdf), antibodies, vaccines, routinely done, as are blood safety screens and prenatal immunomodulators and cytokines make up 289. The diagnoses for neural tube defects, congenital hypothyroidism biotechnology industry has allowed biological molecules to be and other diseases. Finally, hospitals regularly use interferon, manufactured with the purity, reproducibility and scalability of monoclonal antibodies, intravenous immunoglobulin, classic pharmaceuticals. This has aided drug discovery from cytokines and other immunotherapy products. The availability the vast array of biological molecules available, which began of interferon, for example, has enabled all cases of laryngeal very early in Cuba2. papillomatosis in Cuba to be treated. Although supported by two decades of education and Public health is a social achievement, not just a medical public health, as well as extensive training for young

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Disease Year of intervention Year of effect Result achieved Demographics and chronic diseases Poliomyelitis 1962 1962 Elimination Newborn tetanus 1962 1972 Elimination The structure of the Cuban population has Diphtheria 1962 1979 Elimination rapidly changed in the past three decades. Measles 1971 1993 Elimination German measles 1982 1995 Elimination At present, 15% of the population is over Parotiditis 1986 1995 Elimination 60 years old, and this figure is expected to Whooping cough 1962 1997 Elimination Syndrome of congenital 1986 1989 Elimination reach 29% by 2030. The target life German measles expectancy of 80 years is becoming Meningoencephalitis 1986 1989 Elimination after parotiditis a realistic possibility. Cardiovascular Tetanus 1962 1992 Rate <0.1 × 105 diseases and cancer are now the two Haemophilus influenzae 1999 2001 Rate <0.1 × 105 type B leading causes of death as the population ages. Autoimmune diseases and allergies Hepatitis B (<25 years 1992 2001 Rate <0.1 × 105 of age) are also increasing in frequency. This represents a new challenge for public Meningococcus, 1998 2001 <96% death rate; meningoencephalitis <93% morbidity health at large (not discussed here) and for immunologists in particular. More Table 1: Effect of the immunization programme in Cuba, 1962–2007 basic immunological research is required in this area, as globally immunotherapy scientists, the concerted effort to build a biotechnology for noncommunicable diseases is not showing the same industry really began in the early 1980s with the success achieved in fighting infection. In cancer construction of the West Havana Scientific Pole, an ensemble immunotherapy, for example, interferon treatment is limited of more than 40 organizations comprising about 12 000 to only a few malignancies, such as hairy cell leukaemia, employees, including 7000 scientists and engineers. Several lymphoma, melanoma and renal cell carcinoma, and of these organizations were deliberately designed to monoclonal antibodies that have entered the clinic have manufacture pharmaceuticals to drive the economic engine produced only minor increases in the survival of patients of the biotechnology industry in Cuba. Products are now with cancer. exported to over 40 countries. In addition, none of the 50 or more therapeutic vaccines Biotechnology filled the void between immunology being researched have reached registration4. Despite research and the health system. Eleven vaccines, more than considerable experimental advances in understanding 40 therapeutic biological compounds (including monoclonal immune tolerance, autoimmune diseases continue to be antibodies and recombinant proteins) and immunodiagnostic treated by nonspecific immunosuppression. Unfortunately, systems (including micro ELISA machines) are manufactured the substantial experimental data generated with animal in Cuba. The “pipeline” has 91 new potential products now models remain limited in their capacity to allow predictions being investigated. More than 60 clinical trials are ongoing, and guide clinical interventions. There are two reasons for with the participation of 65 hospitals. In total, Cuban this: the first relates to the complexity of the immune system, biotechnology centres own about 900 patents filed abroad. and the second relates to its evolution. Size, however, is not the only characteristic that should be considered. Scientific development requires good basic The barrier of complexity scientific research plus good connections, with close links During the past two decades, experts in complex networks among research, production, education and public health. have shown that the capacity to predict the activity of a For example, the first synthetic vaccine against Haemophilus system (despite the fact that complex networks are influenzae B was generated by Havana University3. It is macroscopically nonrandom and deterministic) based on the being manufactured at the Centre of Genetic Engineering and activity of its components is limited once the number of Biotechnology and is part of the Ministry of Health’s components reaches a certain threshold and when nationwide immunization programme. Such connections interactions among them become nonlinear. This challenges have been actively built and nurtured through diverse the reductionist approach, which has been the very essence management procedures such as regular meetings of of scientific research for the past 500 years. Experts of institutional directors, the creation of interinstitutional task complex dynamic systems are not only highlighting the teams for specific projects, and other tactics that promote problem but also providing ideas and methodologies for cross-institutional cooperation. dealing with this issue. Immunologists must take note of Although not without pitfalls, the triad formed by these solutions. immunology research, biotechnology and public health has The immune system should be considered a complex worked well for the control of infectious diseases, which now network, given that it consists of more than 200 cytokines account for 1.1% of the mortality rate. This relationship has and chemokines and contains millions of lymphocyte clones also reduced infant mortality. The next challenge for Cuban and billions of idiotopes and its macroscopic activity is immunology is to find treatments for chronic diseases of dictated by the interactions of all these components. How adulthood and to further increase life expectancy, which can complexity affects immunology is demonstrated by the no longer be raised by reducing the already low infant almost universal failure to predict the outcome of gene- mortality rate. inactivation experiments, the absence of effective vaccines

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for malaria and other parasites, tuberculosis or HIV, and the antibody targets the epidermal growth factor receptor and is context-dependent effects of some immunotherapy being used in 18 clinical trials covering various tumour interventions (which induce either tolerance or immunity). indications. Four other monoclonal antibodies are also in The complexity of the immune system, however, should not clinical trials. The Cuban cancer vaccine programme is the paralyze immunology research. The realization that the widest outside the USA, including eight therapeutic vaccines, immune system is a complex network has led to wider use of six of which are now undergoing clinical testing. New mathematical models for simulating its activity and testing adjuvants based on nanovesicles10 and cocleates11 derived hypotheses in silico. In addition, the introduction of high- from the outer membrane of Neisseria meningitidis are also throughput “omics” technologies for simultaneous being developed. measurement, as well as the exploration of combined But the issue is not just to have new products. Ongoing immunotherapy interventions, has become more common. efforts to make cancer vaccines, multi-epitope HIV vaccines12 The techniques of proteomics and the development of and new tuberculosis vaccines have emphasized the mathematical models are increasingly used by Cuban redundancy and robustness of control loops in the immune researchers. The proteomic map of one of the leading Cuban system. Simply generating new products is not sufficient. products (the meningitis B vaccine) has led to the Fundamental research is needed to determine what kind of identification of new putative protective protein components5. products need to be generated and how to use these products Cuban physicists have developed a mathematical model that to drive the immune system in the desired direction. describes the population dynamics of regulatory and effector The recognition that the immune response is diverse and T cell subpopulations. This has led to the prediction that the control loops are redundant has at least two practical unbound tumour growth can occur in two different ways, implications: the immune response needs to be focused, providing more clues for the rational design of new effective whereas feedback mechanisms must be dampened. The therapies6. Indeed, “Targeting Complexity” was precisely the former relates to antigen presentation. A tiny proteoliposome topic of the last 2006 Immunotherapy Meeting in Havana. is being developed that is able to induce dendritic cell maturation and to “condition” a T helper type 1 phenotype. Doing better than nature This is now being tested for cancer vaccines based on The complexity of the immune system has evolved as a result gangliosides10 and also prostate cancer and papilloma of adaptive pressure from infections balanced with the vaccines. Cochleate structures derived from N. meningitides11 need for a species to reproduce efficiently. Chronic that upregulate the expression of major histocompatibility noncommunicable diseases arise mainly at a complex class II and costimulatory molecules on human postreproductive age. Thus, there has been little or no dendritic cells and stimulate the production of interleukin 12 evolutionary pressure on diseases of late adulthood, and it is and interferon-γ are being investigated as adjuvants in likely that deleterious genes that are protective for vaccines for allergy as well as leishmania. A computer- antimicrobial immunity in the young but that create a chronic assisted algorithm for predicting epitopes of major inflammatory status in the elderly7, have been fixed. Such histocompatibility complex class II should also help identify chronic inflammatory conditions can lead to atherosclerosis, the molecular structures on which the immune response cancer and autoimmunity. Immunotherapy for such should be focused. conditions cannot simply imitate the way the immune system As for regulation, researchers must deal with negative normally reacts to infection, as is true for classic vaccines and feedback loops, which are often redundant and selected antibody therapy. Instead, immunotherapy for chronic mainly for rapid immune responses. An example is the dual noncommunicable diseases must make the immune system function of interleukin 2 in both the expansion and function in situations for which it has not been evolutionarily exhaustion of the immune response. An ongoing research selected. The success of organ transplantation shows that the project is exploring how this dual effect can be manipulated13. forces of nature can be overcome, but treatment of chronic Another example is regulatory idiotopes14, which are diseases of adulthood will require understanding of the probably not as widespread as previously thought but are molecular interplay of the immune system network and how particularly relevant in some antigenic systems, such as the various immune responses are terminated. This will be ganglioside vaccines. For cancer vaccines, tumour-induced fundamental for future immunology research. immunosuppresion is a formidable barrier, and one Cuban research group is delineating the function of gangliosides in The need for basic research downregulating CD4 expression15 and increasing release of The areas outlined above are the avenues that Cuban interleukin 10. Blocking the immunosuppressive activity of immunology research should explore if life expectancy is to be vascular endothelial growth factor is also being investigated16. extended beyond 80 years. The present projects of Cuban Immunologists should build theoretical foundations for the immunologists show how this is being tackled. Several new smart (and not serendipitous) design of combination monoclonal antibodies8 and therapeutic vaccines for cancer9, therapies. Chronic or repeated vaccination is difficult to AIDS and hepatitis B, as well as adjuvants10 and biologically imagine even today but should be explored, as should the active peptides, are now in development. Biotechnology is of counterintuitive scenario of vaccination in the context of course crucial in these and other projects, such as the immunosuppression. The results of the vaccine- humanized monoclonal antibody nimotuzumab8. This chemotherapy-vaccine lung cancer clinical trial with the

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Cuban epidermal growth factor vaccine suggest that this is environment. However, in terms of evolution, the human possible and even desirable. genome is designed to protect small, isolated human A corollary of chronic immunotherapy is the need to study populations in a relatively stable environment until just near the mechanisms of resistance, which will inevitably appear. the reproductive limit. In today’s world, the human genome Data from research on a Cuban antibody to epidermal growth cannot evolve as rapidly as lifestyles change. Careful factor receptor show how diverse such mechanisms can be: manipulation of the immune system, which is able to adapt some tumour cells resist such therapy by overexpressing in a person’s lifetime, could help tackle this problem. As the vascular endothelial growth factor17, whereas others world faces similar challenges, scientific research should downregulate the expression of major histocompatibility increasingly become an international endeavour. Cuba itself complex molecules. is now collaborating with many countries; some readers of On a different note, immunosenescence is being Nature Immunology probably identify themselves as part of characterized in an attempt to use it as a predictor of this network. response in clinical trials. In such trials, it is important to remember that human populations living in the tropical belt, Concluding remarks no matter how clinically healthy, are exposed to a microbial Immunology research is becoming an increasingly global burden that is different (in quality and quantity) from the affair, but the bridges linking science to public health (as well microbial burden that drives immunosenescence in more as the economy) are still mainly local. The process of temperate climates. building these local connections is neither spontaneous nor Multidisciplinarity is key, as shown by the increasing roles trivial, and it is in that sense that it deserves to be of other professionals in immunology research, such as emphasized here. mathematicians and physicists, who have generated theoretical models for handling complexity. These models Key messages may help create computer-assisted biological screens for therapies. For example, modelling how regulatory T cells Immunology has had, and will continue to have, an affect tumour biology has allowed the prediction of increasing role in population health. Immune differential responses to specific therapeutic combinations18. interventions, such as vaccines, are among the most cost-effective in modern medicine. The power of cooperation In the Cuban experience, the development of Chronic diseases of adulthood represent a new challenge for biotechnology, including manufacturing capacities immunologists, but previous successes in dealing with for bioproducts, acted as a “bridge” connecting infectious diseases will help in this. Despite a reduction in immunology research to public health. vaccine production by the market-driven pharmaceutical The challenge for the future is to repeat the industry worldwide, the Cuban biotechnology industry success in the control of infectious diseases, now continues to put more than half of its resources into disease for the control of the noncommunicable diseases prevention by generating vaccines. In addition to the of adulthood. To face this challenge will require optimization of vaccines already available, Dengue fever19, further basic scientific research in the complex cholera, tuberculosis, hepatitis C and HIV12 are new targets. mechanisms of the immune response, without Knowledge in these areas is beginning to cross-fertilize the weakening the connections between immunology development of immunotherapy for chronic diseases. For and public health. example, components of N. meningitidis are being used for cancer and allergy vaccines, and bystander stimulation by hepatitis B virus core antigens is being explored as a vaccine Dr Agustin Lage graduated in Medicine at Havana University in adjuvant20. Likewise, knowledge about regulatory feedback 1972, and carried out postgraduate studies on cancer and clonal exhaustion gathered from cancer vaccine trials biochemistry at the Pasteur Institute in Paris. He obtained a PhD will be instrumental in dealing with chronic infection. Close in 1979 in Cuba, at the National Institute of Oncology where he cooperation among scientific teams working in diverse areas worked as a scientific researcher and became Deputy Director for should help generate fresh ideas and techniques. In Cuba, Research in 1985. From 1991 to the present, he has worked as this sort of “knowledge recombination” strategy is actively Director-General of the Centre of Molecular Immunolgy in Havana. encouraged. A tremendous challenge will be to reinforce Dr Lage’s main field of research (with more than 100 papers priority for basic immunology research without weakening published) has been the changes in cell membranes in malignant the connections between immunology and public health, an transformation and cancer vaccines. He is a member of the Cuban important component of previous success stories. Parliament and of the Cuban Academy of Sciences. As the planet continues to “shrink”, humans are beginning to realize that everyone faces common challenges, both old and new. Some of the challenges are directly related to immunology. Everyone lives in a world of massive and highly mobile populations (both humans and microbes) and has a prolonged postreproductive lifespan in a rapidly changing

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References

1. Franco M et al. Pan American Journal of Public Health, 2007, 21, 11. Perez O et al. Immunology & Cell Biology, 2004, 82, 603–610. 239–250. 12. Cano CA. Genetic Analysis, 1999, 3–5, 149–153. 2. Limonta M. Annals of the New York Academy of Sciences, 1989, 569, 13. Montero E et al. Annals of the New York Academy of Sciences, 2007, 325–334. 1107, 239–250. 3. Verez-Bencomo V et al. Science, 2004, 305, 522–525. 14. Alfonso M. et al. Journal of Immunology, 2002, 168, 2523–2529. 4. Schlom J, Arlen PM, Gulley JL. Clinical Cancer Research, 2007, 13, 15. de Leon J., Fernandez, A., Mesa, C., Clavel, M. & Fernandez, L.E. Cancer 3776–3782. immunology. Journal of Immunotherapy, 2006, 55, 443–450. 5. Uli L et al. Proteomics, 2006, 6, 3389–3399. 16. Bequet-Romero M et al. Angiogenesis, 2007, 10, 23–34. 6. Leon K et al. Journal of Theoretical Biology, 2007, 247, 122–137. 17. Viloria-Petit A et al. Cancer Research, 2001, 61, 5090–5101. 7. Wick G et al. Experimental Gerontology, 2003, 38, 13–25. 18. Leon Ket al. Journal of Immunology, 2007, 179, 5659–5668). 8. Crombet T et al. Journal of Clinical Oncology, 2004, 22, 1646–1654. 19. Hermida L et al. Vaccine, 2006, 24, 3165–3171. 9. Lage A, Perez R, Fernandez LE. Current Cancer Drug Targets, 2005, 5, 20. Iglesias E, Muzio VL, Aguilar JC. Immunology & Cell Biology, 2006, 84, 611–627. 174–183. 10. Mesa C et al. Vaccine, 2004, 22, 3045–3052.

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Research and innovation in Cuba

Development of Cuban biomedical technology and its impact in “Health for All”

Article by Ismael Clark Arxer, President, Cuban Academy of Sciences

or many years and even today it has been widely Digital Research (with the initials CID in Spanish). Its first and admitted that “appropriate technologies”, for promotion basic aim was to achieve the development of a Cuban self Fand use in developing countries, should be characterized designed and produced digital computer. This initial task was by low cost and a relatively low degree of technical successfully accomplished and as a result, the first Cuban sophistication. For specific medical purposes, however, computer (identified as CID 201) came into work in April “appropriate technology” usually comes from developed 1970. From then on more than 100 computers (models 201 countries and is intended for us, developing countries. A and 201 B) were released for social uses in the country The matter is by no means a merely academic one as it between 1971 and 1979. Some years later, a new series of poses a critical question about the possibility of providing an minicomputers (CID 300/10) was developed and produced in adequate technological coverage to national systems oriented their hundreds taking advantages of COMECON standards to universal health-care access, i.e. “health for all” designed. and components available at that time, as Cuba had become I have sustained elsewhere that, for given purposes and a member of that international economic formation in the under proper conditions, as in the case of Cuba, an early 1970s. appropriate technology can be in fact the highest one Since its origins, the centre established close links with attainable by national scientific efforts, if oriented by definite other important Cuban scientific institutions, as is the case of social targets1. Indeed, government political will and social the National Centre for Scientific Research (with the initials committment with public health as a priority shows to be an CNIC in Spanish) and particularly with its Neurophysiologic essential driver of national scientific and technological Research Group. As a practical result of this early contribution to health system. cooperation, digital encephalograps started to be produced in In this communication I intend to briefly review and the early 1980s under the MEDICID brand name. CID comment on two successful Cuban examples of research and provided hardware and basic software; technical development (R&D) institutions supporting a sustained specifications and medical software were developed by the provision of advanced medical equipment to national health CNIC neurosciences group. Using a similar work scheme, programmes. According to their task, these R&D institutions CID developed and started in 1985 the production of its first run their own design teams and production installations. They digital electrocardiograph: CARDIOCID2. guarantee quality assurance and post selling services as well. In the early 1990s, at the time that Cuban foreign As a result, high performance equipment (although not economic relations had been abruptly disrupted as a necessarily of maximum sophistication) become affordable to consequence of the disappearance of the Soviet Union and wide public health uses. In the words of one of their leading political changes in Eastern Europe, the Cuban Government managers there is another key: solving health problems is as decided to strengthen the national production of medical much about how you apply the technology as it is about the equipment as a convenient supplier to the National Health technology itself. System and eventually a source of export items. In In any case, Cuban experience shows that an important accordance with this strategic decision, CID facilities and prerequisite is a clear political will directed to promote technical infrastructure were significantly enhanced, and new scientific and technical capacity building. In addition, Cuban skilled personnel recruited and intensively trained. By that achievements in this field have been particularly boosted by time, the institution adopted its current name as the Cuban the existence of a close and systematic cooperation among Institute of Digital Research (with the initials ICID RD centres, universities and public health institutions. in Spanish). Consequently a basic coverage of advanced performance Production of medical equipments: the ICID case equipment was produced and distributed between 1996 and This centre was organized in 1969 under the umbrella of 1999, destined for cardiology and intensive care units in Havana University and its original name was the Centre for about 200 health institutions throughout the country. Since

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then, ICID has been steadily producing specialized equipment for national purposes and more than 5600 of At present, all Cuban infants are tested at birth for these are now in use in hospitals and other health-care units. hypothyroidism, phenylketonuria, congenital adrenal Moreover, ICID equipment has been taken on Cuban medical hyperplasia, biotinidase deficiency and galactosemia. emergency missions abroad, as in Pakistan and Venezuela. These tests alone have been decisive in guaranteeing At present, more than 10 000 items of equipment produced a better quality of life for hundreds of Cuban children by ICID have been exported to Mexico, Venezuela, Spain, and their families Brazil, Algeria, South Korea, Columbia and other countries. The spectrum of current ICID output includes equipment for cardiology such as a portable electrocardiograph, systems for ambulatory monitoring of electrocardiographic signals or blood pressure, defibrillators and telemetric monitoring After several years of successful performance and in order systems. Pulse oymeters and monitors for physiologic to enhance the research and development activities as well parameters are also produced for special care units as well as the production facilities, a completely new centre with as other ingenious devices for electrical stimulation intended modern laboratories and powerful workshops was for physiotherapy or the prevention and heeling of trophic constructed and formally inaugurated in 1987 and named ulcers. A digital pletismograph originally developed by the the Immunoassay Centre (with the initials CIE in Spanish). Centre for Medical Biophysics is currently produced by ICID. At present, all Cuban infants are tested at birth for All of the pieces of equipment described are produced hypothyroidism, phenylketonuria, congenital adrenal according to precise quality requirements. ICID products hyperplasia, biotinidase deficiency and galactosemia. These were certified in 2006 as fulfilling ISO 9001:2000 tests alone have been decisive in guaranteeing a better standards3. quality of life for hundreds of Cuban children and their families. It should be mentioned that regular monitoring is A powerful tool for large scale diagnostic directed to diagnostic kits and reagents to ensure the programmes: the Immunoassay Centre accuracy of results, and all SUMA laboratories in Cuba and The starting nucleus in this important field developed as a Latin America participate in international monitoring, such as health oriented R&D group within CNIC at the end of the the US Centres for Disease Control Newborn Screening 1970s and its initial work showed the enormous potential of Quality Assurance Program’s proficiency testing panels. The this technology for large-scale screening programmes. Its first CIE is also responsible for protecting the country’s blood target was to develop an economical alpha fetoprotein supply, screening and certifying all blood donations. In all, screening test to detect foetal malformations, allowing some 50 million tests have been carried out with the CIE’s women and couples to make an informed decision about technology, which is decentralized in 181 laboratories continuing pregnancy, contributing both to a reduction in throughout the public health system, reaching every infant mortality and better medical attention for children born municipality in the country. Another 55 laboratories are with problems. located in research institutions and in armed forces Since then, they have developed 28 diagnostic tests and health facilities. 16 generations of equipment to screen for conditions ranging A few years ago, the Ministry of Public Health asked CIE to from congenital hypothyroidism and phenylketonuria (PKU) begin working on noncommunicable chronic conditions, in newborns, to HIV, hepatitis and dengue, their leading which are the main health problem in Cuba today. Some products being the ultramicroanalytic system (with the 49% of Cubans die from metabolic syndrome and another initials SUMA in Spanish) and reagent kits (UMELISA and 38% from cancer. Progress in early detection and control of UMTEST)4. These diagnostic tools are closely linked to public these illnesses will mean longer lives and better quality of life health programmes, such as maternal-child health, and to for millions of Cubans. One example is prostate cancer, epidemiological surveillance for infectious diseases. For responsible for the death of 2540 Cuban men in 2007. CIE example, in 1986, Cuba became the second country in the has now developed its own prostate specific antigen (PSA) Americas (after Canada) to provide full newborn screening test for early detection and is gradually extending its coverage for congenital hypothyroidism. availability across the country for annual testing of all men aged 50 and over. In other words, we now have a tool for mass screening as opposed to limited availability of the imported test, which was costing about US$ 14 apiece. Another example is colon cancer: a test to measure human The starting nucleus in this important field haemoglobin in faeces is now being work out, which is more developed as a health oriented R&D group within precise than the current test detecting any kind of blood in CNIC at the end of the 1970s and its initial works faeces. This will allow better early diagnoses of this cancer, showed the enormous potential of this technology which affects Cuban women more than men. About 1000 for large-scale screening programmes women in Cuba die annually from colon cancer, but approximately 80% could be saved if diagnosed early enough. In terms of other chronic conditions, currently being

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registered is a test for quantitative measurement of Key messages microalbuminuria, which is important for diseases associated with vascular damage, especially chronic kidney disease. Technology is to be considered as appropriate when Finally, a glucometer developed by CIE (SUMAsensor) is now it is accessible to the people who need it in any being introduced in Cuba and is being registered in Mexico particular country or region; when it increases and Argentina. CIE sells it very economically to the Cuban health-care coverage as efficiently as possible within public health system and internationally at about 60% of the the resources at hand. price of other similar equipment. The Cuban-developed Efficiency in technology also makes ethical sense: glucometer for diabetic patients is specially designed for health planners have to use resources in the most tropical climates (each dipstick is packaged separately with rational, optimal way in order to preserve the right an enclosed dehumidifier sachet) and can be regulated for to health for the greatest number of people. skin thickness (important for children). Test results appear in In Cuban experience, sustainable health depends 25 seconds. This exam offers a more integrated approach to more on health promotion and disease prevention – preventive care, taking into consideration genetic and including the application of technologies for broad environmental factors, and the glucometer is being included health coverage that are appropriate for the in the technology for this programme. Eventually, each severe socioeconomic environment – rather than on the diabetic will have their own glucometer at home. application of complex technologies or the latest CIE products are sold to the Cuban health system at models advertised by market-driven transnational reduced prices in local currency and to other countries at manufacturers. prices well below those charged by other manufacturers. The main commercial contracts are with Mexico, Colombia, Venezuela, Bolivia, Brazil, Argentina and China and the Ismael Clark Arxer received an MD degree from Havana University market is now being extended to Paraguay, Peru and Ecuador. in 1967. He specialized as a clinical biochemist at the National Centre for Scientific Research from 1967 to 1976. Linked to the Some final remarks Cuban Academy of Sciences since 1977, he has acted successively The experience of Cuban producers of biomedical technology as General Scientific Secretary, Vice-President for biology and sustains a number of plausible assertions, some of them medicine, and as its First Vice-President. When the Ministry for commented on recently by the founder and current director Science, Technology and Environment was created in 1994, Ismael of CIE5. was appointed as First Vice-Minister and eventually he became President of the Cuban Academy of Sciences two years later, when it was reorganized in 1996. References

1. Clark I, Piedra D. The role of advanced technologies (Hi Tech) as an Bimestre Cubana, vol. CII, no. 27, July–December 2007. option for development in Latin America and the Caribbean (original in 3. see http://www.combiomed.sld.cu Spanish). In: Memories of the event for the 30th anniversary of the 4. see http://www.tecnosuma.com Academy of Sciences of Cuba, 1992, Havana, Editorial Academia. 5. Yero JLF (MD, PhD, Director Immunoassay Center, Havana). Generating 2. Arrojas F. Cuban electronic medical equipments. The experience of the appropriate technologies for health equity. In: Reed G, ed. MEDICC Cuban Institute of Digital Research ICID (original in Spanish). Revista Review, winter 2009, vol. 11, no. 1.

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Social entrepreneurship

034 mothers2mothers: social entrepreneurship and public health – scaling innovation Gene Falk with Julia Coyner Robinson and Cynthia Schweer

039 African giant rats for tuberculosis detection: a novel diagnostic technology Bart J Weetjens with Georgies Mgode, B Witkind Davis, Christophe L Cox and Negussie W Beyene

043 Social innovation “pull” incentives Liza Kimbo

048 Promoting prevention-oriented approaches for chronic noncommunicable diseases Chorh Chuan Tan

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mothers2mothers: social entrepreneurship and public health – scaling innovation

Article by Gene Falk (pictured), Co-Founder and Executive Director, mothers2mothers, with Julia Coyner Robinson and Cynthia Schweer

others2mothers (m2m) was founded with the facilitate this conversation, m2m employs HIV-positive purpose of improving the outcomes of programmes women as “mentor mothers”, professional peer educators Mto reduce the vertical transmission of HIV, that is, who provide one-on-one and group education and support to programmes aimed at prevention of mother-to-child HIV-positive women in clinical PMTCT facilities. m2m was transmission (PMTCT). m2m employs new mothers living designed with a vision that this critical intervention could, with HIV as “mentor mothers”, professional peer educators and should, be part of standard services wherever there is who provide one-on-one and group education and support to PMTCT care. women like themselves in clinical facilities. In eight years, Innovation is simply a fancy word for trying something m2m has grown from a single support group in Cape Town different. It can be incremental, radical or revolutionary. While to a multinational nongovernmental organization (NGO) scientific advances have increased our potential to save lives operating in 546 sites in seven countries in southern and and improve quality of life in ways that were previously east Africa. unthinkable, the effectiveness of these treatments requires m2m addresses a problem that is two-fold. First, the increasingly extensive and complex involvement of both significant social, emotional and psychological barriers patients and health-care workers. To address this challenge, created by stigma and the lack of education and support m2m has developed an innovative response that aims to exacerbate the already daunting prospect of adhering to strengthen health-care systems by creating a new tier of PMTCT treatment regimens. Second, public health-care public heath professionals drawn from lay people, specifically systems in the developing world are simply too overburdened peer workers, who are uniquely positioned to improve PMTCT to provide these services to address these challenges. outcomes in resource-constrained environments. By Improving PMTCT outcomes requires solving both PMTCT combining best practices from both the public and private challenges and systemic issues simultaneously, which m2m sectors, m2m has created a simple, powerful, and endlessly aims to do. replicable programme model, as well as an innovative and The m2m intervention is specifically designed to address effective institutional system to support the model and ensure the issues preventing pregnant women and new mothers with its success in achieving scale. HIV from taking advantage of PMTCT services by using mothers who have recently experienced PMTCT programmes Background and context themselves as primary caregivers. Furthermore, m2m’s mothers2mothers (m2m) was founded in South Africa in model addresses the issue of chronic human capacity 2001 by Dr Mitchell Besser, a US-trained obstetrician with constraints within the existing medical system. Supporting extensive experience in PMTCT of HIV. During his this replicable model of peer support is m2m’s institutional involvement in establishing antenatal care programmes and model, which was designed with the intent to take the model coordinating services for HIV-infected pregnant women, new to scale. The combination of a simple, yet effective mothers, and infants in South Africa, Dr Besser became programme model and a leverageable institutional process familiar with the design, implementation and shortcomings of has allowed m2m to grow exponentially. PMTCT programmes. In the US, mother-to-child transmission mothers2mothers (m2m) was founded with the purpose of (MTCT) has been virtually eradicated; on the other side of the improving the outcomes of prevention of mother-to-child world, the situation was and continues to be very different. transmission (PMTCT) programmes providing care to HIV- While many of the same treatment options are available to positive pregnant women. m2m began with the simple women in sub-Saharan Africa, the uptake of treatment is hypothesis that the effectiveness of PMTCT can be significantly lower, and more than 90% of paediatric HIV significantly improved by providing opportunities for HIV- infections occur in these countries1. positive pregnant women to be mentored by mothers who As little as one dose of antiretroviral treatment (ART) as a have successfully and recently gone through PMTCT. To mother goes into labour and one dose for her baby after birth

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can decrease the rate of MTCT by half, and further medical interventions, including a longer ART regimen and specific infant feeding options, can lower the risk of MTCT even further2. With full medical intervention and PMTCT care, mother-to- child transmission of HIV can be reduced from 30% to less than 2%3. The consensus is that PMTCT is a global imperative. The Declaration of Commitment of UNGASS in June 2001 set a series of goals to reduce the proportion of infants infected by HIV by half by 20104. PMTCT is an element of three of the eight Millennium Development Goals5. The solutions are available and political will exists; so why is MTCT still so staggeringly high, resulting in nearly half a million HIV-positive babies born each year?6

Medicines don’t equal medical care Figure 1: m2m programme model Take a real and common situation: a young woman comes to a maternal health clinic. She is excited, since she developing world, fear, lack of knowledge and HIV stigma believes she is expecting a child. She sees a doctor, or more create significant social, emotional and psychological barriers likely a nurse, who confirms that she’s pregnant with a that exacerbate the inherent challenges in accessing and healthy baby on the way. And then the nurse asks: did you adhering to a treatment regimen. Second, on a systemic know that you have HIV? All too often, this is where the level, the public health care system simply does not have the conversation ends. Lack of education, disempowerment, resources to provide the support, education and counselling insufficient support and the very concrete consequences necessary to address these additional hurdles. Improving of stigma leave the young mother virtually deaf to anything PMTCT outcomes requires solving both issues that follows. simultaneously, which m2m aims to do. Without support, counselling and education, the availability of effective medical protocols can become Scaling innovation irrelevant. A woman may avoid enrolling in treatment, or she m2m’s stated goals are (1) to prevent babies from may not learn of the other steps she can take improve her contracting HIV through vertical (mother-to-child) baby’s chances of HIV-free survival, because the success of transmission; (2) to keep mothers with HIV healthy and these interventions depends on the very resource that is in promote HIV-free survival among their babies by increasing such short supply: human capacity. This is not unique to access to medical care; and (3) to empower mothers living PMTCT. Treatment for the world’s most intractable diseases is with HIV/AIDS to live positive and productive lives. increasingly people intensive and requires substantially more In the last several years, the term “social entrepreneurship” than a short course of pills or a simple vaccination. To ensure has emerged to describe innovative ventures that are initiated long-term efficacy, multi-step regimens require ongoing to respond to systemic social challenges. In their seminal behavioural as well as clinical interaction between health piece on the subject in the Stanford Social Innovation systems and patients. Review, Roger Martin and Sally Osberg write that one of the A recent article in AIDS, the journal of the International characteristics defining successful social entrepreneurship is AIDS Society, confirms these observations. Olive N “forging a new, stable equilibrium that releases trapped Nakakeeto and Lilani Kumaranayake write: potential or alleviates the suffering of the targeted group, and “When we set out looking at PMTCT, we were primarily through imitation and the creation of a stable ecosystem trying to answer the question whether reaching the UNGASS around the new equilibrium ensuring a better future for the 2001 goal – a 50% reduction in the incidence of HIV targeted group and even society at large”8. m2m is a textbook infection in infants – could be feasible. Our model suggests example of this precisely because we tap into the “trapped that these goals could be theoretically reached. However, potential” of a targeted group while simultaneously focusing using publicly available data on AIDS funding and human on its needs. resources, we found that the ability of countries to achieve The m2m intervention is specifically designed to address these goals is severely constrained. Human resource the issues preventing HIV-positive women from taking limitations would appear to be the most important constraint, advantage of PMTCT care by drawing on the most uniquely as only one country… was predicted to have sufficient qualified cohort as the front-line caregivers that can best human resources to fully scale up PMTCT and paediatric address the special needs of other pregnant women and new treatment up to 2015.”7 mothers – that is, by enlisting the mothers themselves. The problem is therefore two-fold. First, while PMTCT Furthermore, m2m’s model addresses the issue of chronic treatment is increasingly available to women in the human capacity constraints within the existing health

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are, by definition, new mothers with HIV who have recently Who will m2m focus on serving? Who will m2m provide? experienced PMTCT. From the

Always do Men who are not Medical start, we were aware that clients partners interventions Partners Couples while driven by programme Sometimes do counseling depending on local imperatives, this strategy would circumstances Primary support also ensure us of an exceptional networks Never do eg families, HIV+ Support groups staff: with few opportunities friends mother one-on-one PMTCT Disclosure and baby education referrals visits available to women in the developing world – and fewer Mobile clinics PMTCT facility Pre-nantal - still for HIV-positive new mothers 14 weeks – m2m is able to recruit from an Home visits extraordinary talent pool. The mentor mothers are Churches Community Schools outreach m2m’s most valuable resource, Community centres After 18 months and we choose to invest heavily

Where will the m2m intervention be focused? How long will m2m serve its clients in them. Substantial resources are dedicated to training and institutional learning. Each new Figure 2: Setting programmatic strategic boundaries mentor mother receives two full system. As professional, integrated members of PMTCT weeks of formal, curriculum-based training, and throughout health care teams, mentor mothers work alongside clinical her tenure she receives both on-the-job coaching and formal staff as the missing resource required to educate and support training updates. This training and development model allows pregnant women and new mothers, de-stigmatize HIV, and the organization to be highly responsive to advances in policy, empower other HIV-positive women to have hope and to take science and best practices, with new information and control of their social, economic and reproductive lives. curriculum enhancements rolling out on an ongoing basis. Peer support is hardly a new concept. Traditional peer m2m made an early, sometimes controversial commitment education programmes have shown positive results, yet their to paying staff a wage rather than using volunteers. Paying reach is often limited because many programmes are ad hoc workers is critical to m2m’s impact. By making staff or lack integration into clinical systems. Given the urgency of responsible and accountable for their work and compensating PMTCT, m2m’s challenge was to develop and support a peer- them commensurately for their performance, we are able to driven model that could be scaled effectively and efficiently. insist upon the high standards necessary to provide quality, m2m set out to create an organization that could take this professionalized service. Paying mentor mothers also simple and effective model of peer support to the wider reinforces their status within the system, ensuring that they population, ensuring quality, consistency and scalability. are viewed as professionals by their clinic colleagues as well Supporting this replicable model of peer support is m2m’s as by their clients. Furthermore, professionalizing this very “institutional model”, which was designed to provide the visible staff also offers significant benefits from a programme structures and processes that would take the programme standpoint, creating role models for other women, reversing model to scale. As highlighted in the article “Pathways to the worst assumptions about stigma and disempowerment, Social Impact” by Dees et al, new business models in the for- and enabling our clients to envision a positive future. In profit world often spread rapidly, but the corollary on the non- profit side is all too rare: “Many powerful programmes start with the idea of serving as a ‘pilot’ or ‘model’ that can be replicated around the country or the world, but frequently the replication fails to happen or is painfully slow. The cumulative effect is tragic”.9 m2m avoided this outcome by simultaneously developing a simple, replicable programme model and an effective institutional model, and then integrating them into a single enterprise that could be taken to scale. In implementing this scheme, m2m made a number of decisions to ensure that theory aligned with practice and strategy with implementation.

Drivers of scalability The m2m programme owes its success to the professionalized cadre of mentor mothers that operates on the front lines daily. At inception, m2m made the decision to be Figure 3: Growth targeted in its selection of employees and mentor mothers

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2009, our site staff will receive salaries totalling more than US$ 5 million. Nearly every cent will go directly into local economies, since our field staff acquires necessities such as A recent independent survey conducted by the food and secure housing for their families. Population Council’s Horizon Project and funded by From a logistical standpoint, m2m chose to work within USAID demonstrated that m2m has a positive impact existing health-care structures, aiming to strengthen them on efforts to prevent vertical transmission of HIV, and rather than to attempt to create parallel systems. Mentor that PMTCT-related indicators substantially improved mothers are situated within the clinical facilities that provide at sites after m2m services were introduced MTCT services, working whenever possible alongside the clinical staff and providing support from testing through antenatal care, delivery and postnatal service. Pregnant women who test positive are immediately referred to m2m top-tier management team and building robust processes to and a one-on-one education and support session is ensure effective implementation of policy and deployment of conducted on-site. As the pregnancy progresses, expectant resources. This extends to management processes at the mothers can visit m2m support sessions in conjunction with local, regional and national levels, systems of “command and their antenatal visits. Post-pregnancy, new mothers can control” that ensure the highest quality of service and the continue to attend support sessions as they go through the best possible outcomes are achieved consistently and process of accessing postnatal and infant care. effectively. The resulting organizational structure can then be While these basic elements will be present and consistent leveraged to sustainably and efficiently replicate our in all m2m sites, flexibility and adaptability is just as critical programme model. to the success of the model. To be effective, m2m’s programmes must be readily adaptable to geographic and Results and implications cultural variables and respond quickly to clinical and policy m2m’s model has gained wide acceptance. A recent developments in PMTCT care. Simultaneously, m2m’s site independent survey conducted by the Population Council’s staff must respond with care tailored to each set of unique Horizon Project and funded by USAID demonstrated that circumstances and sensitivities as well as the personal and m2m has a positive impact on efforts to prevent vertical psychosocial environment each woman inhabits. Rather than transmission of HIV, and that PMTCT-related indicators attempt to prescribe a dialogue between a mentor mother substantially improved at sites after m2m services were and her clients, mentor mothers are recruited selectively and introduced. Specifically, m2m has a significant impact on trained extensively in order allow them to best respond into key behavioural factors involved in preventing transmission, these variables. such as increasing the number of women and infants who Sometimes m2m may vary which services mentor mothers accepted and adhered to treatment regimens during and after provide, whom they serve, for how long they work with birth, increasing the rates of disclosure of status to family clients, and where they engage clients. However, within each members, increasing adherence to an exclusive feeding of these categories, m2m has also defined boundaries that choice, and increasing the use of family planning after guide the limits of the programme model’s flexibility. pregnancy10. m2m’s success has led to our incorporation in Therefore, m2m allows room for local adaptation while still official government guidelines about PMTCT, and initiatives informing where we can have the most impact given our are underway to develop the national scale-up of m2m’s capabilities, by where our resources can be most effectively programmes in multiple countries. allocated, and by consideration of what other organizations The combination of a simple, yet effective programme are already doing. model and an effective and leverageable institutional model At the same time, m2m is steadfastly disciplined in its has allowed m2m to grow exponentially. At the end of 2007, focus and does not hesitate to decline funders’ and partners’ m2m had 121 South African sites and had just begun its first requests for expansion into areas beyond PMTCT or to non- operations outside of South Africa, with 34 sites in Lesotho. strategic locations. m2m has made a conscious effort to Eighteen months later, m2m has 546 sites in seven define its operations by both what we do and what we don’t countries in sub-Saharan Africa. Over the course of 2008, do (Figure 2). Simple programme models are constantly m2m conducted over one million client encounters, reaching under threat. Funding is enticing and donors are apt to 150 000 HIV-positive pregnant women and new mothers. In believe that if you can do one thing well, you may be able to 2009, m2m is projected to conduct more than two million do other things well too. There have been numerous client encounters, enrolling 300 000 HIV-positive pregnant opportunities to expand m2m services beyond PMTCT care, women and new mothers. J rather than expand services to more women. However, it is hard to do both at the same time. Profit-seeking Gene Falk left a long-standing career as a senior media companies understand this well and will only diversify executive in New York and moved to Cape Town to oversee the product and service offerings when the core business rollout and expansion of m2m. Gene has a history of activism for has been established. HIV/AIDS and gay and lesbian civil rights. He was a founding Finally, on top of our commitment to our site staff, m2m national board member of the Gay and Lesbian Alliance invests significantly in people and systems, recruiting a Against Defamation, and provided support and direction to

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HIV/AIDS groups including Treatment Action Group and Gay focusing on obstetric fistula in Sierra Leone and has studied in Men’s Health Crisis. Senegal. She graduated magna cum laude from Columbia In his professional role with m2m, Gene has received numerous University with a BA in African History. awards and citations, including both the Skoll and the Schwab Foundation’s Award for Social Entrepreneurship. He holds a BA Cynthia Schweer is a Fellow with LGT Venture Philanthropy, a cum laude, from Williams, and an MBA from the Wharton School fund investing in organizations focused on raising quality of life of the University of Pennsylvania. around the world, including mothers2mothers. Previously, she was CEO (USA) of the Starfish Greathearts Foundation, a foundation Julia Coyner Robinson is a Fellow in the Office of the Executive providing grants to community-based organizations caring for Director at mothers2mothers. In 2008–2009, she was the orphaned and vulnerable children in South Africa. Cynthia holds a volunteer Acting Administrator at a women’s health programme BA from Georgetown University and an MBA from INSEAD.

References

1. Towards universal access: scaling up priority HIV/AIDS interventions in Available at: www.who.int/hiv/topics/mtct/en/index.html. Accessed 1 the health sector. World Health Organization, April 2007, p.6. August 2009. 2. Prevention of mother-to-child transmission briefing note. World Health 7. Nakakeeto ON, Kumaranayake L. The global strategy to eliminate HIV Organization, 1 October 2007, p.4. infection in infants and young children: a seven-country assessment of 3. HIV/AIDS and pregnancy. Avert, 2009. Available at: costs and feasibility. AIDS, 15 May 2009, Vol. 23, Issue 8:987–995. http://www.avert.org/pregnancy.htm. Accessed 25 August 2009. 8. Martin RL Osberg S. Social entrepreneurship: the case for definition. 4. Declaration of commitment on HIV/AIDS. United Nations General Stanford Social Innovation Review. Spring 2007, p.35. Assembly Special Session on HIV/AIDS, 25–27June 2001, p.21. 9. Dees J, Gregory BA, Wei-Skillern J. Pathways to social impact: strategies 5. About MGDs. Millennium Project. 2006. Available at: for scaling out social innovations. Duke-Fuqua School of Business CASE http://www.unmillenniumproject.org/goals/index.htm. Accessed 1 August Working Paper Series, August 2002, p.1. 2009. The three UN Millennium Development Goals addressed by 10. Horizons Report. Horizons Program, Population Council, June 2007. PMTCT are Goal 4: Reduce child mortality; Goal 5: Improve maternal Available at: http://www.m2m.org/images/downloads/ health; Goal 6: Combat HIV/AIDS, malaria, and other diseases. Horizons_Report_2007.pdf. Accessed 1 August 2009. 6. Mother-to-child transmission of HIV. World Health Organization, 2009.

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African giant rats for tuberculosis detection: a novel diagnostic technology

Article by Bart J Weetjens (pictured), Founder and Director Development, APOPO with Georgies Mgode, B Witkind Davis, Christophe L Cox and Negussie W Beyene

uberculosis (TB) continues to be a major public health To alleviate this diagnostic problem in sub-Saharan Africa, problem especially in developing countries. More than Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling T2 billion people (i.e. one third of the world’s total (APOPO) came up with a novel technology: training and population) are infected with TB bacilli (Mycobacterium utilizing African giant pouched rats (Cricetomys gambianus) tuberculosis, the bacteria causing TB). One in every 10 of for TB diagnosis. This paper reports the successes achieved those people will become sick with active TB in their lifetime. so far with this novel technology, the ongoing research People with HIV/AIDS have more risks of TB infections. activities, the way forward and the challenges to be overcome Globally, there were 1.77 million deaths from TB in 2007, to finally make the technology fully operational. To this effect, including 456 000 people infected with HIV, which is nearly a case study conducted on samples collected from selected 4800 deaths per day1. urban health centres in Tanzania that resulted in a significant HIV has caused TB incidence to triple in sub-Saharan increase in TB case detection, as well as demonstrating Africa, where in some countries 80% of TB patients are detection of difficult sputum smear negative specimens, is co-infected with HIV. Thirteen out of the 15 countries with the presented. highest TB burden are in Africa1. Despite TB killing more APOPO is an award-winning social enterprise5 that people with HIV than any other disease, in 2008 only 1% of researches, develops and deploys detection rat technology for people with HIV had a TB screening. This is a drawback and humanitarian purposes. It utilizes a local resource, the African major challenge to the global efforts towards achieving the TB rats, for its detection technology. Using these rats as detectors control targets as well as the UN Millennium Development is advantageous due to their efficiency in this role, and their Goals for 20152. Although there are more sophisticated acute sense of smell. Other benefits include their low cost for methods in the developed world, the diagnosis of TB in husbandry and maintenance, ease of transport and their wide affected countries is mainly based on microscopic availability. It has also been shown that once trained, they examination of TB bacilli (Acid-fast bacilli-AFB) in sputum can reliably carry out repetitive tasks. Moreover, it is an smears stained by the Ziehl Neelsen (ZN) method. Other appropriate tool since it does not depend on high tech rarely used methods include fluorescent microscopy (FM) and equipment or highly skilled labour, increasing its accessibility culture (gold standard) that requires laboratory facilities that in the countries of operation6. Initially, APOPO proved the are not readily available in resource-limited areas. For concept of its innovative technology for the detection of example, Tanzania has only three TB culture laboratories landmines and this result is currently operational in some serving nearly 40 million people2. This makes the ZN method countries seriously affected by landmines6,7. As an extension (microscopy) a vital tool for TB control in developing of its knowledge and as a separate wing of its research countries. The case detection rate in these countries (e.g. activities, APOPO envisaged a completely new idea of using Tanzania) is around 47%, far below the global target of its technology for the benefit of the larger poor: rats detecting 70%3. This is attributed to the poor sensitivity of the method; TB! This idea is based on the fact that the mycobacteria emit the huge workload, which causes fatigue to the microscopist specific volatile organic compounds8,9, that are likely to be and may result in significant number of false-negatives detected by the rats through olfactory perception and the (misdiagnosis); and to difficulties in diagnosing TB in patients proof of this concept was recently published10. co-infected with HIV because most of them produce negative To explain the training and evaluation procedure briefly, smear results which delays the diagnosis and treatment in the beginning at the age of four weeks rats learn to associate the absence of culture facilities1,4. Therefore, a fast, simple and pop sound of a metal clicker, made by the trainer, with a more efficient diagnostic system is highly demanded. reward of food (peanuts or banana pulp). They learn to

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25.0%

20.0%

15.0%

DOTS + (%) 10.0% APOPO + (%)

5.0%

0.0% Amana Magomeni Mwanyamala Tandale

Figure 1: Cassettes containing sputum samples for TB detection Figure 2: Tuberculosis case detection in the four selected DOTS (a), a sniffer rat is being rewarded after positive indication of a centres in Dar es Salaam (microscopy) and APOPO trained African tuberculosis sample in the evaluation line cage (b). giant pouched rats (Cricetomys gambianus) (n = 15 041 patients).

indicate positive samples by keeping their nose in the smear microscopy from the DOTS centres and APOPO’s “sniffing holes” of a specially designed cage, under which the microscopy as well as rats’ detection. target samples are placed (see video at www.herorat.org or APOPO’s research outputs so far asserted that sniffer rats www.apopo.org). The rat ignores sniffing holes with negative can analyse sputum samples faster and reliably with high samples after sniffing for less than a second, and proceeds to sensitivity and specificity10. Furthermore, it demonstrated that sniff the next hole in a row until it “hits” a positive hole where rats can analyse an average of 70 sputum specimens in 20 it keeps the nose fixed for five seconds. The training and minutes whereas an average of 20 specimens can be evaluation set-up for the analysis of sputum samples consists analysed by a microscopist in a day of eight working hours. of a configuration (cage), in which samples are lined up to Hence, using rats for detection reduces workload significantly be sniffed by the trained rats, to indicate positive targets in in the TB diagnosis centres and improves the quality of return for a food reinforcer (Figure 1a and b). The samples results, which diminishes with increasing workload. The use are inserted into cassette-carriers containing 10 samples of rats can also reduce transmission/spread of TB bacilli from each, which are placed under corresponding sniffing holes in infected patients who are undetected or misdiagnosed due to the cage. The sniffing holes are covered with metal plates in various reasons including workloads in laboratories and HIV between testing to keep headspace vapour in the air above status11. For example, the new 577 patients who were the sputum and to allow systematic sniffing of the samples detected by rats but missed/undetected in the DOTS centres by the rats. The trainer uncovers the sniffing holes, such that would have been able to transmit TB to between 5770 and the rats have to sufficiently sniff a sample first before the 8655 people per year if they had remained undetected (one lid of the next sample is opened. This set-up allows untreated person can transmit TB to between 10 and 15 processing (analysis) of 140 sputum samples in one session people per year2,12. This shows the potential use of sniffer rats of 15–20 minutes. as a first-line screening tool in active case finding and A recent case study conducted on sputum samples referring suspected patients to DOTS centres for confirmation collected from four selected Direct Observation Treatment and early treatment. Similarly, culture laboratories could Short-Course (DOTS) centres in Dar es Salaam, Tanzania benefit from dealing with screened suspect positive samples (namely: Amana, Mwananyamala, Magomeni and Tandale) only, which may improve work in these laboratories as well from January 2008 to May 2009 demonstrates the as the drug susceptibility testing facilities (DST). These may advantage of APOPO’s technology over the conventional ZN contribute to achieving the Global Plan to Stop TB and the microscopy. The rats screened samples systematically, target to save 14 million lives and achieve the proper indicating positive specimens by keeping the nose in the treatment of 50 million people. sniffer hole for five seconds while scratching paws on the Current research activities are geared towards further cage floor. Positive indications were confirmed by microscopy improvement of the sensitivity and specificity of rats’ (ZN) and the positive findings for patients undetected/missed detection; refining sample collection, transport and pre- by microscopy in DOTS centres were communicated to DOTS treatment procedures so as to avoid any cue the process centres for tracing and further confirmation by the DOTS might leave for the sniffer rats; automation of the evaluation centres. Out of 15 041 patients the DOTS centres (ZN cage so that any human error (bias from animal trainers) microscopy) detected a total of 1838 (12.2%) patients could be minimized; and installing a quality assurance and whereas sniffer rats detected 2415 patients (16.1%) with internal accreditation scheme for individuals or groups of increased case detection in all four DOTS centres (Figure 2). trained rats. We are also planning to launch a clinical trial in The cases detected by rats but missed by DOTS centres (n = Cape Town, South Africa where TB as well as TB-HIV co- 577) increased TB detection by 31.4% which is found to be infection is rampant but the expertise and the technology to statistically significant (p<0.001). Statistical tests also run the confirmatory tests are present. Due to the relative confirmed the agreement between results of the positive technological advances in South Africa, the accreditation

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procedure is in place and we anticipate swift accreditation Key messages once we successfully finish the clinical trial. Once we gain experience there, we may transfer this knowledge to Tanzania Using African giant pouched rats for TB detection where the accreditation procedure is non-existent, assist our significantly increases case detection including Tanzanian colleagues to establish one, and seek accreditation detection of sputum smear negatives mostly missed to implement the technology. The last steps will pave the way by microscopy. for seeking international accreditation to be officially part of Utilizing sniffer rats reduces the time required to the tool to curb the TB burden worldwide. screen for TB (less than 6 minutes are needed to Access to funding remains the main challenge for APOPO’s analyse an average of 20 specimens which may innovative technology to be embraced in the global fight require 8 hours for examination by microscopy) against TB. So far a number of organizations and foundations in turn reducing the workload in DOTS centres, (such as The World Bank Development Marketplace, UBS which is directly related to the quality of Optimus Foundation and the US National Institutes of Health) diagnostic results. have provided funding for this project. But as explained in the There are a number of steps to pass through to preceding paragraph we have a long way to go and numerous reach to the ultimate goal of using APOPO’s new research activities to conduct to reach our ultimate goal. technology for the global fight against TB and the APOPO looks forward to continued partnering with interested main challenge for the accomplishment of this task parties as we work towards containing the spread of TB. is funding.

Acknowledgements Antwerp University (Belgium); Sokoine University of biostatistics at the Tufts University School of Medicine in Boston, Agriculture (SUA); National Institute for Medical Research USA. Prior to APOPO, Wit worked for the International Fund for (NIMR); National Tuberculosis and Leprosy Programme Animal Welfare responding to international disasters and (NTLP); Ministry of Health and Social Welfare (Tanzania); the overseeing scientific documentation and policy development. Wit Direct Observation Treatment Strategy (DOTS) centres in Dar holds an MSc from the Tufts University School of Veterinary es Salaam, Tanzania; and Max Planck Institute for Infection Medicine and a BSc from Bates College. She maintains a long- Biology, Berlin, Germany as well as The World Bank standing commitment to identifying ways where animals and Development Marketplace (USA), UBS Optimus Foundation people can improve each other’s health and welfare. (Switzerland) and National Institute of Health (NIH/NIAID, USA) are kindly acknowledged for collaboration and Christophe Cox is a Belgian national who has an MSc in product funding respectively. development and an MSc in development cooperation. He obtained three years’ grassroots experience working in Kenya as a volunteer Bart Weetjens is a product development engineer with a focus in a rural community development project between 1994 and on appropriate technologies for developing countries. In 1998, 1997. He then joined APOPO at the start of the project. Having Bart initiated the use of HeroRATS: trained giant African pouched been involved in all aspects of the development of APOPO, rats as an alternative and sustainable landmine detector, in Christophe gained knowledge in animal behaviour, chemistry and response to the global landmine challenge. Since 2000 APOPO olfaction, as well in financial and administrative management. He has addressed humanitarian detection challenges in Africa: the was appointed CEO of APOPO in 2008. detection of landmines and screening for TB. HeroRATS have received much international recognition. Bart is an ASHOKA Fellow Negussie Beyene, PhD, is APOPO’s analytical chemist seconded and a SCHWAB Fellow, and a permanent member to the Global by GICHD to manage APOPO’s analytical explosives chemistry lab Agenda Councils. In 2009, he won the SKOLL Awards for social at SUA, in support of the REST research programme. He was an entrepreneurship. Bart is a Zen Buddhist monk and lives with his assistant professor at Addis Ababa University, Ethiopia before wife and two daughters in Tanzania. resuming his current post. Negussie has conducted research in laboratories in Austria, South Africa and Spain. His prior Georgies Mgode is pursuing his PhD study at the Max Planck experience as a clinical chemist and head of the Regional Public Institute for Infection Biology, Berlin, Germany. He has a Bachelors Health laboratory in Ethiopia, lectureship of clinical chemistry and degree in zoology/botany from the Open University of Tanzania, and research experience in the development of sensors and biosensors a Masters degree in zoology from the University of Pretoria, South for compounds of biomedical importance has lead to a keen Africa. At Sokoine University of Agriculture, Tanzania, Georgies has interest in biomedical sciences and to his active contribution in been involved in research on rodent-transmitted diseases of public APOPO’s TB project. health and veterinary importance (such as plague and leptospirosis), as well as rodent taxonomical studies. He is currently investigating the target compounds from TB organisms detected by the trained African giant pouched rats.

B Witkind (Wit) Davis is a volunteer for APOPO as part of her Masters of Public Health coursework in epidemiology and

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References

1. World Health Organization (WHO) report 2009. Global tuberculosis minefield. Journal of Mine Action, 2006, 9.2. control: epidemiology, strategy, financing. 8. Fend R et al. Prospects for clinical application of electronic-nose 2. http://www.stoptb.org technology to early detection of Mycobacterium tuberculosis in culture and 3. Minion J, Zwerling A, Pai M. Diagnostics for tuberculosis: what new sputum. Journal of Clinical Microbiology, 2006, 44:2039–2045. knowledge did we gain through The International Journal of Tuberculosis 9. Phillips M et al. Volatile biomarkers of pulmonary tuberculosis in the and Lung Disease in 2008? International Journal of Tuberculosis and breath. Tuberculosis, 2007, 87:44–52. Lung Disease, 2009, 13(6):691–697. 10. Weetjens BJ et al. African pouched rats for the detection of pulmonary 4. Pai M, Kalantri S, Dheda K.New tools and emerging technologies for the tuberculosis in sputum samples. International Journal of Tuberculosis and diagnosis of tuberculosis: part II. Active tuberculosis and drug resistance. Lung Disease, 2009, 13:737–743. Expert Review of Molecular Diagnostics, 2006, 6:423–432. 11. Davies PD, Pai M. The diagnosis and misdiagnosis of tuberculosis. 5. Awarded by Ashoka, Skoll Foundation, Schwab Foundation, and the World International Journal of Tuberculosis and Lung Disease, 2008, Bank’s Development Marketplace Global Competition. 12:1226–1234. 6. http://www.herorat.org 12. http://www.etharc.org/faq/faqtb.htm 7. Verhagen R et al. Rats to the rescue: results of the first tests on a real

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Social innovation “pull” incentives

Article by Liza Kimbo, Regional Director, Academy for Educational Development, Kenya

hallenges to quality provision of health-care services in “despite no official user fees at government facilities, two low-income countries include poor geographical thirds of children with fever were taken to drug shops/private Caccess to health facilities and low investment in clinics as the first source of care outside the home”. needed physical infrastructure; inconsistent supply of health Rutebemberwa et al recommend that government support products; inadequate numbers of trained health workers; and needs to extend beyond the public health facilities and insufficient funding and mechanisms to assure quality in both include the private sector5. public- and private-sector facilities. Social franchising is an In Tanzania, plans are underway to convert close to 8000 option for low income countries in delivery of needed health informal drug shops into licensed and certified outlets through care services to under-served populations. Social franchising the Accredited Drug Dispensing Outlets (ADDOs) programme. has been defined as a franchise system, usually run by a While accreditation schemes on their own do not fit into the nongovernmental organization (NGO), which uses the definition of social franchises, these types of programmes structure of a commercial franchise to achieve social goals1. provide an economically viable alternative for regulation and Social franchising differs from commercial franchising in that control of pharmaceutical provision in the private sector. The it aims to provide equitable services, accessible to the poor. ADDO programme, now managed by the Ministry of Health Key elements of the social franchise are a business format and Social Welfare through the Tanzania Food and Drug that defines the services being provided, the brand that is Administration provides a training programme and annual advertised to consumers as an indication of high quality, licensing of drug shops. Managed using a decentralized affordable services, and quality assurance mechanisms that system, drug shops owners have an incentive to voluntarily assure training and support2. apply to become formal drug sellers due to training provided Experiences with various forms of franchising span over 10 and an expansion of their drug list to include simple years, and unlike commercial franchising, clear definition of antibiotics. Donors are attracted to this programme as it what constitutes a proper social franchise is still under provides a large network of outlets based in rural and urban debate. A meeting of leaders of major clinical social communities that can provide rapid access to medications. franchises from around the world held in November 2008 However, its success will be dependent on investment in broadly defined characteristics of clinical social franchises to brand advertising, strengthening of its quality assurance include operator owned outlets; payments to outlets based on mechanisms and systematized continuing training and services provided, standardized services and clinical services education programmes. Accreditation is an important first offered3. A compendium of clinical social franchises step towards national support for social franchising developed after the meeting lists 33 programmes globally that programmes. The ADDOs programme highlights the need for broadly fit their definition of clinical social franchise, an continuous training of providers on current treatment increase from just four such programmes in 20014. guidelines and assurance that both subsidized but also good While this decade has seen the growth of social franchising quality pharmaceuticals reach the outlets. programmes, the next decade will test various models for This may still not be sufficient to assure that subsidized scale-ability and sustainability. The prevailing circumstances drugs get to rural customers. Goodman et al found that high of low-income countries also present certain opportunities for antimalarials’ prices in the study districts in Tanzania were investment in these innovative programmes. These include likely to be an important factor in the low proportion of availability of retired but capable health workers in addition to careseekers obtaining appropriate treatment, and recommend trained but unemployed professionals. Most low-income that policy-makers expand the number of drug shops countries have both legal and illegal distribution systems that distributing antimalarials with recommended retail prices6. deliver pharmaceuticals of varying quality to small towns and While informal drug shops provide a large pharmaceutical villages, through private providers that fall through the market, quality control rests not just in initial registration of regulatory mechanisms. A recent study in Uganda found that product, but in subsequent supply and close monitoring of

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franchising, is the difficulty and complexity it presents in controlling the quality and price of services2. A key requirement for franchising is brand recognition, Social franchising is now being trialled by governments in and attendant significant investment in development public facilities. A recent evaluation study by Ngo on the of a recognizable brand supported by quality launch of a social franchise network of reproductive health standards and consistency in services services through community public health clinics in Vietnam, suggests that significant improvement in reproductive health care service quality can be achieved through adaptation of the social franchise model to public sector7. quality of pharmaceuticals available for sale in such outlets. For this reason, social franchises provide the benefit of An enabling environment assured quality of pharmaceuticals through controlled Countries need to provide the enabling legal and regulatory procurement, supply and controlled prices. environment for social franchising and accreditation schemes A key requirement for franchising is brand recognition, and to flourish. This extends to legal protection for brands, and attendant significant investment in development of a enforcement of franchise contracts. Governments can choose recognizable brand supported by quality standards and to provide budgetary support to coordinating structures of consistency in services. The business format franchising in accreditation and social franchise schemes as this can also health care presents certain challenges for standardization of offset their efforts to provide access and quality for health treatment and quality provision. Experiences with the Child care8. It is also necessary to embrace the private sector in and Family Wellness (CFW) clinics in Kenya show that policy formulation, include them in programmes for nurses applying for a franchise could present with up to four continuing education and new treatment guidelines, and different nursing qualifications, and in addition hold other enable access to drugs according to latest guidelines. Most qualifications e.g. in midwifery. Standardization of treatment social franchises aim to fill a gap brought about by lack of across a range of diseases has proven to be difficult due in national health standards and support mechanisms for part to the varying qualifications of providers and the need to provision of a regulated health-care services industry with provide for professional latitude in diagnosis. Nurses already reliable enforcement. established in private practice are attracted to the franchise Low-income countries may apply licensing requirements option principally due to training opportunities and access to that are incongruent with current health worker training and assured quality drugs. However, they invariably are the most qualifications levels. Health workers who could provide basic difficult to convert as they already have clientele and may services may find themselves unemployed due to the barriers perceive that the franchise brand did not contribute placed by over-stringent licensing requirements, and policy significantly to growth in their business. CFW clinics found guidelines that are not in tune with existing capacity e.g. a that greater adherence to franchise standards is achieved country with less than one pharmacist for every 20 000 with nurse practitioners who rely on financing and people should not have statutes that make it illegal for other other support from the centralized organization to establish health workers to dispense basic essential drugs. At the same their clinics, rather than those converted from time, “competition” from unqualified providers due to poor existing businesses. regulatory control and enforcement impedes the growth and The CareShop model in Ghana also works on a conversion success of legitimate businesses. Support for accreditation model, taking existing drug shops (chemical sellers) and through professional networks is also recommended, accrediting them to form a social franchise. The central especially in the form of recognition of and publicity for management function in this model faced challenges such schemes. working with experienced business owners and seeking to find incentives for them to adhere to franchise principles for Funding constraints improved quality provision. This effort is especially Successful social franchises are reliant on long-term assured challenging where there is not the required national level funding, as the very nature of such programmes calls for an support for accreditation and enforcement, and implementation timeframe in excess of five years. Currently noncompliant outlets continue to flourish. only a few donors have made the sizable commitments Fractional franchises take existing businesses and add on required to establish and nurture the growth of social a franchised service or product. Examples such as the family franchises. In order for the social franchise to be viable, it is planning models provide greater scope for professional freedom, with incentives provided through additional training and product supply. The oldest and best known fractional social franchise is the Greenstar Network which was Successful social franchises are reliant on long- established in 1995 for distribution of family planning term assured funding, as the very nature of such products in Pakistan. This model builds on existing capacity programmes calls for an implementation and infrastructure in the private sector to rapidly scale up timeframe in excess of five years delivery of specific services. However the main disadvantage of this model of franchising, just as in the business format

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necessary for each unit in the franchise to be profitable; the Key messages organization needs the requisite managerial capability and in addition, economies of scale are built to provide sufficient This has been the decade of interest and growth of returns to the central infrastructure. This is a challenge in the social franchising in developing countries, and the resource-poor settings targeted by social franchises. Social coming decade will provide the real test for franchises that build a large network of outlets that cannot sustainability and scaleability of these initiatives. sustain themselves will consume donor funds and are sure to Low-income countries may reap benefits from fail once the funding comes to an end. The pressure to providing a conducive and supportive regulatory achieve large scale very quickly can also lead to business environment, accreditation programmes for health- failure, as the social enterprise Aspire found when it scaled care providers and facilities, and by defining up a business that was not founded on a viable concern9. provision at the levels of the available trained Success for social franchises can be defined in various health-care workers. ways. Enabling access to products and services that could not New funding mechanisms with longer funding time- reach the population is one sure way, but the focus on NGOs frames are required to overcome the currently and lack of sustainability of central management structures constrained financing environment which leads to may mean that social franchise programmes will be seen as the stifling of growth in the private health sector. temporary solutions without scale up capability. Success in social franchises will be undeniable only when we can show self-sustaining models operating at national scale. This is our developing country spans 15 years. This includes the challenge for the next decade. establishment of a private-sector chain of retail pharmacies and management of a nurse-owned clinic franchise with 63 outlets in Liza Kimbo is currently the Regional Director for East and Kenya. Liza has chaired two national advocacy groups for increased Central Africa for the Academy for Educational Development (AED) access to essential drugs, and strengthening civil society based in Nairobi, Kenya. Her experience in the management of representatives for malaria to participate in policy-making and retail pharmaceutical companies and social franchises in a national funding for the disease.

References

1. Montagu D. Franchising of health services in developing countries. Health Journal, 2009, Vol 8:45. Policy and Planning, 2002, 17(2), pp.121–130. 6. Goodman C et al. Concentration and drug prices in the retail market for 2. McBride J, Ahmed R. Social franchising as a strategy for expanding malaria treatment in rural Tanzania. Health Economics, June 2009, access to reproductive health services: a case study of the Greenstar 18(6):727–42. service delivery network in Pakistan, 2001. 7. Ngo A et al. Developing and launching the government social franchise 3. Montagu D, Decker M. Report on a multicountry social franchise model of reproductive health care service delivery in Vietnam. Social meeting. UCSF Global Health Group, 2008. Marketing Quarterly, March 2009, Vol. 15(1):71–89. 4. Montagu D et al. Clinical social franchising: an annual compendium of 8. Bishai et al. Social franchising to improve quality and access. Harvard programs, 2009. San Francisco: The Global Health Group, Global Health Health Policy Review, Spring 2008, Vol. 9 (1):184–197. Sciences, University of California San Franciso, 2009. 9. Tracey P, Jarvis O. Case study. An enterprising failure: why a promising 5. Rutebemberwa E et al. Utilization of public or private health care social franchise collapsed. Stanford Social Innovation Review, Stanford providers by febrile children after user fee removal in Uganda. Malaria Graduate School of Business, Spring 2006.

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Promoting prevention-oriented approaches for chronic noncommunicable diseases

Article by Chorh Chuan Tan, President, National University of Singapore

ost countries of the world, developed and education and counselling which is difficult to achieve in developing, are experiencing a growing epidemic of practice. In addition, it is often not easy to convince patients Mchronic noncommunicable diseases. In Singapore, to modify their current lifestyles and have long-term treatment for example, the prevalence of diabetes, hypertension and for the sake of preventing a possible medical complication in hypercholesterolaemia, conditions which are major causes of the future. coronary heart disease, stroke, kidney failure and blindness, Second, most health-care systems are compartmentalized is still high even though intensive health promotion and largely focused on the treatment of acute, severe illnesses programmes appear to have had some positive impact (Table in hospitals. This creates structural, funding and 1). Coronary heart disease, stroke and cancer account for organizational impediments to modes of care delivery which more than 60% of all deaths and a high burden of disability are much more prevention-focused, and which cross and health-care cost1. In 2004, diabetes mellitus, ischaemic community, primary care and hospital care sectors. heart disease and stroke were the top three leading causes of premature death and ill-health in Singapore, and together Health Services Development Programme accounted for 28% of the total disease burden (in disability This paper describes two initiatives undertaken in Singapore adjusted life years)2. which indicate that targeted prevention-oriented programmes The high prevalence of chronic noncommunicable diseases can significantly improve clinical outcomes, while reducing and the severe medical complications associated with them, utilization of expensive hospital resources. This paper also represent predictable and serious challenges for health briefly considers some of the key factors which were essential systems in the future. Clearly, we need new health-care for the successful implementation of these programmes. delivery approaches that focus on preventing advanced and The two initiatives, the Singapore National Asthma severe disease, and achieve better overall clinical outcomes Programme (SNAP) and the Early Psychosis Intervention more cost-effectively. However, it has been difficult to make Programme (EPIP), were developed as part of a larger Health progress on developing effective new approaches for two Services Development Programme (HSDP), driven and main reasons. funded by the Singapore Ministry of Health since 2001. The First, the optimal management of most chronic diseases, HSDP provides a new stream of health-care funding for such as diabetes and hypertension, requires patients to have innovative proposals from the public health system to address a good understanding of their medical problems and practical important health-care issues. knowledge about how best to manage them. Very importantly, patients must also be motivated to modify their Example 1: Singapore National Asthma Programme lifestyles and to comply with treatment and a regular regime (SNAP) of monitoring. This often requires intensive and repeated The problem defined In the year 2000, asthma was assessed to be a significant 1992 1998 2004 public health problem in Singapore. Apart from the high and Diabetes 8.6% 9.0% 8.2%* rising asthma prevalence in the population (4% in adults and Hypertension 22.2% 27.3% 24.9%* 20% in school children)4, of particular concern was the Total cholesterol >6.2 mmol/l 19.4% 25.4% 18.7%* Obesity (BMI >30 kg/m2) 5.1% 6.0% 6.9% problem of severe asthma. Severe or poorly controlled asthma Smoking > 1 cigarette/day 18.3% 15.0% 12.6%* accounted for an estimated 20 000 emergency department

* Significant difference (p<0.05) in age-standardized rates between 1998 and 2004. attendances and up to 100 deaths each year during the period 1986–19935. With effective long-term control of their Table 13: Prevalence of diabetes, hypertension, asthmatic condition, most of such patients could have largely hypercholesterolaemia, obesity and smoking in Singaporeans avoided acute or severe attacks requiring emergency aged 18–69 years department attendances and hospitalization. However, a local

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study in 1996 reported that of patients presenting with population in 2000 to 0.14 per 100 000 in 2006. asthma at one public sector emergency medicine department, only 23% were on maintenance inhaled Further developments steroids and half of the patients had had an emergency The success of the asthma programme in acute hospitals led medicine department visit in the preceding six months. to its logical extension to four government-subsidized primary care polyclinics. HSDP funding was continued and increased The proposed approach to the current level of about 3 million Singapore dollars per This problem had been identified by senior respiratory year. The longer-term objective is to achieve excellent asthma physicians in Singapore for some time. The call for proposals control at the primary care level so as to minimize hospital under the Ministry of Health’s HSDP in 2001 provided a attendances and admissions for severe, poorly-controlled strong impetus for physicians from all six public hospitals in asthmatic attacks. Singapore to submit a joint proposal for a Singapore National Asthma Programme. Briefly, the proposal covered three main Example 2: Early Psychosis Intervention Programme areas: The problem defined Intensive public education stressing the following main It is estimated that 3 out of 100 persons will suffer from a messages: psychotic disorder in their lifetime8. Worldwide, psychoses – acute asthma attacks can be life-threatening; are among the most disabling conditions and impose an – acute asthma attacks can be prevented; enormous burden in economic cost and human suffering – optimal treatment usually with preventor medication will with no less than 25% of the total “burden of disease” being help to prevent worsening of the disease and improve attributed to neuropsychiatric conditions9. In Singapore, the outcomes; bulk of care for psychoses is provided by a single institution, – low-dose inhaled steroids are safe, even for children. the Institute of Mental Health. Intensive physician education including new clinical Late diagnosis and treatment of psychosis is a major factor practice guidelines targeted mainly at primary care contributing to substantial morbidity, a higher degree of physicians. disability and the need for hospitalization, both acute and The centrepiece of the proposal was for all high-burden long-term10,11. In Singapore, patients with first episode asthma patients presenting with severe acute asthmatic psychosis had an average duration of untreated psychosis of attacks to the six public hospitals to be referred to 32.6 months and a median of 12 months12. Factors that special clinics supported in part by HSDP funds. These contributed to this delay include stigma, ignorance about clinics have dedicated nurses who would educate early psychosis, and particularly in this part of the world, the patients about asthma and teach a simple way of misattribution of psychosis to supernatural causes13. assessing its severity and the proper use of inhalers, as well as case-managers who would track the patients’ The proposed approach progress and contact defaulters. For needy patients who In 2001, the Early Psychosis Intervention Programme (EPIP) require second-line, non-standard drugs to control their was accepted for funding by HSDP. The aims of the EPIP asthma optimally, subsidies are provided for such drugs were to: within these clinics. The individual programmes at raise awareness of the early signs and symptoms of these six hospitals are coordinated centrally by the psychosis, and reduce the stigma associated with programme director, who is a senior physician in one psychosis; of the hospitals. establish strong links to primary health-care providers to work as partners in the detection, referral and SNAP was approved for funding under HSDP in 2001, at a management of those with psychosis including right- cost of approximately 1.5 million Singapore dollars per year. siting of care; improve the outcome for these patients and reduce the Outcomes burden of care associated with the disease. The outcomes of this programme have been excellent. Hospital admissions from asthma fell by 20%, from 125 per EPIP has been described in detail elsewhere14 but briefly, 100 000 population in the year 2000 to 100 per 100 000 has the following key components. EPIP developed a wide population in 2004. There was a nearly a five-fold reduction network of partners which enabled it to identify potential in reported absenteeism rates from work or school due to cases of early psychosis very effectively. The programme asthma – one third of patients had reported missing work or established extensive links with general practitioners, school before enrollment into the programme and this figure counsellors in higher education institutions, police and the dropped to 6–7% after enrolment into SNAP. As for asthma armed forces through a multiplicity of approaches: media, mortality, the long-term trend in Singapore showed that total newsletters, DVDs, posters in public places, talks, seminars and age specific rates had already begun to fall in the late and workshops. This comprehensive outreach was selected 1990s. Following the introduction of SNAP, asthma mortality as a model by WHO which included a description of it in a continued to decline. For example, asthma mortality for special publication. patients aged 5–34 years dropped from 0.45 per 100 000 Cases identified by this broad network are referred for

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evaluation to dedicated clinics run by the Institute of Medical Key messages Health (IMH). Patients diagnosed to have early psychosis benefit from clinical intervention and treatment initially in the The two initiatives described in the article IMH. When stabilized, the patients are referred back to (Singapore National Asthma Programme and Early general practitioners as part of a shared care programme. Psychosis Intervention Programme) indicate that targeted prevention-oriented programmes can Outcomes significantly improve clinical outcomes for chronic, The programme has significantly reduced the time it takes for noncommunicable diseases while reducing patients with psychosis to be diagnosed and treated. EPIP utilization of expensive hospital resources. has also achieved a much lower rate of default, and superior The successful implementation of these programmes clinical outcomes (symptom reduction, improvement in required strong and visionary physician leadership, functioning and employment rate, very low suicide rate), and empowered by funding and support from the a high rate of patient satisfaction. Ministry of Health. Intensive public and medical The benefits from reduced morbidity and mortality and professional education, and the forging of extensive improved patient productivity have been sizable, to both the partnerships within the health care system are key patients as well as the community at large. Cost-effectiveness elements. analysis showed that the programme became more cost- This approach represents a feasible way to gradually effective with time. In recognition of the substantial and shift health care systems which are traditionally positive impact that it has achieved, EPIP was awarded the over-weighted towards hospital-based tertiary care, WHO State of Kuwait Prize for Research in Health Promotion. towards more cost-effective disease management models of care delivery. Further developments EPIP has received continued funding from the Ministry of Health (MOH). Its success in attaining clearly articulated very extensive network of partners to help detect possible outcome indicators provided convincing evidence for policy cases of psychosis very early. makers in the MOH that the early detection and treatment of Fourth, the case histories illustrate the stepwise manner by psychosis must remain a central focus in the National Mental which significant change can be introduced and entrenched Health Blueprint which was formulated in 2007. within the health-care system. SNAP’s initial focus was on severe asthma in acute hospitals as this was, as it were, an Key lessons obvious and “low-hanging fruit” that could be tackled by The two case histories provide several valuable learning reorganization of hospital resources. The success of this points regarding the development of prevention-oriented phase provided the impetus for the extension of a similar programmes for chronic noncommunicable diseases. approach into the government-subsidized polyclinic system. First, strong and visionary physician leadership is a critical Following this, the next logical step would be to extend it into factor in initiating and implementing substantive changes in the entire primary care sector, but a major consideration here care delivery. The clear definition of the specific clinical issues is that the bulk of this sector in Singapore comprises private to be addressed and the articulation of the rationale of the practitioners who receive relatively little in government proposed approaches are extremely important. However, subsidies and who are unlikely to have the resources to these cannot proceed without mechanisms that empower provide the counselling services necessary. In addition, the such leadership. In this regard, the HSDP provides the use of expensive preventor drugs would, under the current impetus and funding support that encourages and supports financing framework, be covered for mainly by out-of-pocket physicians and other health-care professionals to work payments, which may limit the full extent of its indicated together on challenging and worthy clinical and public health usage. Nevertheless, the success of SNAP provides the problems. As part of HSDP, the Ministry of Health also plays impetus for these challenges to be looked at critically, and a major facilitatory role to ensure effective implementation. a basis for designing an approach which may address The establishment at the outset, of clear and agreed goals these effectively. and outcomes is a vital part of this process. Second, both case histories illustrate the crucial importance Conclusion of education of the public, primary care physicians and These case histories suggest that it is feasible to administrators, as well as the engagement of key systematically identify a number of key clinical and public stakeholders. This education needs to be accompanied by the health problems that contribute most to the overall burden of development and popularization of targeted tools, e.g. simple chronic disease, and to design and implement prevention- scoring systems to assess asthma severity, and clinical oriented programmes that improve clinical outcomes while practice guidelines. reducing severe or advanced disease that increases the Third, extensive partnerships are essential for the consumption of expensive hospital resources. In my view this programmes to have the necessary scale to make a significant would be a feasible way to gradually shift health-care systems impact. In the case of SNAP, all the public hospitals in which are traditionally over-weighted towards hospital-based Singapore participated in the programme. EPIP relied on a tertiary care, towards more cost-effective disease

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management models of care delivery. At the same time, we Ministry of Health, (2000–2004); NUS Provost, then Senior should in parallel, greatly increase efforts focused on health Deputy President (2004–2008); and Deputy Chairman of the promotion to reduce the incidence of chronic Duke-NUS Graduate Medical School Governing Board noncommunicable diseases. (2004–2007). Professor Tan has been a key leader in Singapore’s Biomedical Acknowledgements Sciences Initiative since its inception in 2000, for which he was I would like to thank Professor Lim Tow Keang, Associate awarded the National Science and Technology Medal in 2008. He Professor Chong Siow Ann and Dr Chew Suok Kai for their also received the Public Service Star (2003) for his leadership role kind assistance with this manuscript. in overcoming the SARS epidemic, the Public Administration Gold Medal (2004), the Albert Schweitzer Gold Medal from the Polish Professor Tan Chorh Chuan was appointed President of the Academy of Medicine (1998), and the Singapore Youth Award National University of Singapore (NUS) in 2008. Concurrently, he (1996). serves as Deputy Chairman of Singapore’s Agency for Science, Professor Tan is a member of the World Economic Forum’s Technology and Research (A*STAR). Global University Leaders Forum, and is also currently Chair of the A renal physician, he has held appointments as Dean, NUS International Alliance of Research Universities, a consortium of 10 Faculty of Medicine (1997–2000); Director of Medical Services, leading research-intensive universities.

References

1. Ministry of Health. Health Facts, Singapore, 2008. Schizophrenia Bulletin, 1996, 22:327–345. 2. Phua HP et al. Singapore’s burden of disease and injury 2004. Singapore 11.Larsen TK, Johannessen JO, Opjordsmoen S. First episode schizophrenia Medical Journal, 2009, 50(5):468–78. with long duration of untreated psychosis. British Journal of Psychiatry 3. Ministry of Health, Singapore National Health Survey, 2004. 1998, 172(Suppl 33):45–52. 4. Chew FT, D Goh YT, LEE BW. The economic cost of asthma in Singapore. 12.Chong SA, S Mythily, Verma S. Reducing the duration of untreated Australian and New Zealand Journal of Medicine, 1999, 29(2):228–33. psychosis and changing help-seeking behaviour in Singapore. Social 5. Chew FT, LEE BW. Utilization of healthcare resources for asthma in Psychiatry Psychiatric Epidemiology, 2005, 40:619–21. Singapore: demographic features and trends. Asian Pacific Journal of 13.Chong SA et al. Determinants of duration of untreated psychosis and the Allergy and Immunology, 1998, 16:57–68. pathway to care in Singapore. International Journal of Social Psychiatry 6. Abisheganaden J, Sin Fai Lam KN, Lim TK. A profile of acute asthma 2005, 51:55–62. patients presenting to the emergency room. Singapore Medical Journal 14.Chong SA et al. The Early Psychosis Intervention Programme in 1996, 37(3):252–254. Singapore: A balanced scorecard approach to quality care. Journal of 7. Registrar-General of Births and Deaths, Singapore. Singapore Report on Mental Health, 2008, 17:79–91. Registration of Births and Deaths from 1995 to 2007. 15.Chong SA, Bird L. Spreading the word: The outreach programme of the 8. Jablensky A et al. Psychotic disorders in urban areas: an overview of the Early Psychosis Intervention Programme, Singapore. In: Saxena S, Study on Low Prevalence Disorders. Australian and New Zealand Journal Garrison PJ, eds. Mental health promotion: case studies from countries, of Psychiatry, 2000, 34:221–236 2004, Joint Publication of the World Federation for Mental Health and the 9. Murray CJL, Lopez AD, eds. The Global Burden of Disease Project. World Health Organization. Harvard: Harvard University Press, 1996. 16.Chong Siow Ann, personal communication. 10.McGlashan TH. Early detection and intervention in schizophrenia.

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054 Building global momentum for social innovation: accelerating systemic solutions through leadership networks François Bonnici and Mirjam Schöning

060 Innovative financing mechanisms – can they help to improve aid effectiveness for health systems development? Amrita Palriwala and Aarthi Rao

066 Healthful academic translations: cultivating Collaborative Doers as Innovation Managers for societal well-being Usha R Balakrishnan

072 The challenges of cardiovascular medicine in sub-Saharan Africa: opportunities for engagement between academia, industry and civil society Tembeka Mpako-Ntusi and Ntobeko BA Ntusi

080 Civil society engagement – a key strategy in research for health Sylvia de Haan with Samuel Anya, Ayo Palmer and Paul Bloch

083 Last mile delivery in health care and patient empowerment through technology: the case of “Telecommunication for Health” Roberto Tapia-Conyer and Rodrigo Saucedo

087 Community-directed intervention: replicating Japan’s health successes in Africa? Satoshi Omura and Andy Crump

091 Dragon Net: secret society or a network of health policy researchers? Toshihiko Hasegawa

094 New approaches to health worker training, deployment and retention Mubashar Sheikh and Sigrun Møgedal

100 Brazil’s conception of South-South “structural cooperation in health” Celia Almeida with Rodrigo Pires de Campos, Paulo Buss, José Roberto Ferreira and Luiz Eduardo Fonseca

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Building global momentum for social innovation: accelerating systemic solutions through leadership networks

Article by François Bonnici (pictured), Head of Africa, and Mirjam Schöning, Senior Director, Schwab Foundation for Social Entrepreneurship

t is impossible to ignore the profound impact of ill health, refine, adapt and reapply models in designing effective disease and premature death on our world – from personal solutions and reforms to these systems in order to improve Ihuman suffering, substantial economic costs to issues of the delivery of quality health care for all. In recent years, new global security. Unprecedented gains in public health and life strategies have been initiated by governments, donors, expectancy were made in the 20th century due to advances academic institutions and foundations to allow technological in science, medicine and policy; yet, these have not been and social innovators to grow and develop their ideas to equitably distributed. Despite substantial increases in research, promote global health – by holding up incentives, mobilizing funding and collaboration during the last decade towards talent, focusing communities, stimulating product these inequities and towards addressing preventable disease development partnerships and providing awards and prizes to and deaths, significant barriers and complexity remain in the accelerate progress4. provision of appropriate quality, affordable health care for all1. The wider adoption of successful social innovations and The use of the term “innovation” in global health has broader paradigm shifts in health care, however, are still slow recently been emphasized to broadly encompass all the processes. One approach to accelerate this process is by phases from conception to outcome for new products, promoting innovations through leadership networks. In services, practices and policies, and to strip off the association 2000, Professor Klaus Schwab and Hilde Schwab recognized of the term with invention alone and patent protection this opportunity in the network of leaders in the communities practices by corporations. The emphasis falls simultaneously of the World Economic Forum that Professor Schwab founded on the need for both technological innovation (e.g. for drugs, in 1971. They established the Schwab Foundation for Social equipment, vaccines) and social innovation (e.g. management Entrepreneurship to identify excellent social innovations; of resources, organization of systems, stakeholder involvement) recognize these through prestigious awards; build a as key strategies to improve health-care systems2. community of leading social entrepreneurs as peers of other By nature, on the one hand, public policy development global leaders; enable access to funders; and provide a high- relies on due process and the review of evidence within an profile platform to bring the ideas to the attention of the existing educational and institutional paradigm, potentially largest networks of global decision-makers – such as those hindering innovation and delaying the uptake of novel and participating in the World Economic Forum Annual Meeting5. radical solutions to complex health challenges. On the other A recent review of the role of philanthropic prizes for social hand, innovation in the corporate sector has typically innovation describes six types of approaches, or archetypes sustained health inequities as private health care provision of (exemplar, exposition, network, participation, market care and health products excludes the majority of global stimulation and point solution)6. The work of the Schwab citizens in gaps known as market failures by economists3. Foundation uses the first of these three approaches by Such risk-averse policy development and commercial focusing attention or influencing the perceptions of social systems can thus stifle social experimentation in the interests entrepreneurs and their models (exemplar); highlighting a of citizens and patients. In a time of great need for fresh range of best practices, ideas and opportunities within the solutions, innovators are ironically deprived of the resources field of social entrepreneurship (exposition); and celebrating and recognition that would maximize their potential to and strengthening a community of pre-eminent social strengthen collective efforts. entrepreneurs (network). The Schwab Foundation’s unique interaction with the Spurring social and technological innovation through World Economic Forum facilitates its dual objectives: (1) to leadership networks provide unique opportunities to accelerate the efforts of social It is, therefore, necessary to learn how to facilitate the work entrepreneurs through interaction with decision-makers at the of technology and social innovators who experiment, fail, highest level (CEOs of business, ministers of government,

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etc.) within the World Economic Forum community and (2) Narayana Hrudayalaya and the Aravind Eye Care System to expose the incumbent leadership to totally new are two further examples of revolutionary approaches to approaches to dealing with the current economic and social increasing the quality and quantity of health-care provision. challenges on national, regional and global agendas. The Both have emerged from India in the last two decades. The social entrepreneurs are thus integrated as peers into this delivery model of the Narayana Hrudayalaya Institute of community of world leaders to provide their unique insights Medical Sciences in Bangalore strives to make sophisticated and contributions to current and future issues on the global health care available to all by drastically reducing expenses agenda, in proactive, innovative and entrepreneurial ways. through innovative cost-saving methods, high volumes and Through multiple interactions over several years, momentum effective management of human resources and technologies. for paradigm shifts is built by creating global leaders out of Through these savings, it can provide 60% of treatments grassroots innovators. below cost, or for free. The institute also has a network of 39 We have been privileged to interact with some of the telemedicine centres reaching out to patients in remote rural world’s leading social innovators in health, tackling the gaps areas and two health insurance programmes covering leading to poor performance and inadequate coverage of 2 million farmers at Rs 120 per year (US$ 3)7,11. Meanwhile health care systems7. Six such gaps have been outlined by in Madurai in South India, Aravind grew from an 11-bed eye the World Economic Forum’s Global Health Initiative: clinic into one of the largest and most productive eye care information gap, awareness gap, infrastructure gap, delivery facilities in the world. Aravind Eye Care System treats over gap, funding gap and innovation gap8. Outstanding social 2.3 million patients each year, two-thirds for free or at a entrepreneurs have been recognized by the Schwab steeply subsidized fee, by taking its services to the rural Foundation for successful experiments in bridging some of villages to identify those in need of treatment or surgery. The these critical gaps, leading the way for similar models or hospital is an international resource and training centre that policy development. They have been promoted and is revolutionizing hundreds of eye care programmes in many sponsored to join captains of the health-care industry and other countries. With less than 1% of the country’s ministers of health during their discussions at several ophthalmic manpower, Aravind performs about 5% of all sequential World Economic Forum Annual Meetings to bring cataract surgeries in India. Since its inception, Aravind has these new paradigms to a global audience. performed close to 3 million surgeries and handled over 25 million outpatient visits7,12. Social entrepreneurs as a new generation of global By understanding that disease is exacerbated by socio- leaders economic factors, the Association Saúde Criança Renascer The Soul City Institute for Health in South Africa recognized in Brazil developed a system to provide post-hospitalization that to bridge the awareness gap in health education and assistance for families and children from the lowest-income promotion, it had to use mass media communication communities who were recently discharged from hospital. At strategies and technologies appropriate to our modern world. a large public hospital in Rio de Janeiro, paediatric Soul City is now an international, multimedia “edutainment” readmissions dropped by 68% in 2007 because of these initiative that seeks to positively impact people’s lives by efforts. The model has proven to be easily transferable and integrating health and development issues into serialized has spread as a complementary care system adjacent to 23 prime-time television programmes, radio dramas, easy-to- hospitals in Brazil; it has served 26 000 people to date7,13. read booklets and mobile phone interactive messages. The Even in the most developed countries, such as the USA, most evaluated “edutainment” programme in the world, Soul significant gaps in service delivery and health financing City reaches 79% of South Africa’s 47 million people and remain, but by being creative with human resources, these has been replicated in eight countries in Southern Africa and can be addressed. With an ageing population and exorbitant two in Latin America7,9. costs of institutional care, home-based care is under- In developing and emerging economies, the infrastructure recognized as an effective care solution. This is being and delivery gaps are often the most apparent as citizens of transformed by Cooperative Home Care Associates (CHCA), these nations struggle to overcome multiple barriers to access the first worker-owned home health-care agency in the health care. BRAC (formerly the Bangladesh Rural United States. Like BRAC, CHCA recognized latent capacity Advancement Committee) is one of largest and most and trained individuals who were mostly dependent on respected NGOs in the world, particularly because of its welfare to become empowered as home health-care workers impact on the health of children and women in the context to deliver high-quality services. CHCA has 1100 workers and of a highly inadequate public health-care system. Instead of has succeeded in cutting the turnover of health aides to bringing new resources to the challenges, BRAC assists poor approximately 20% annually as compared to the 40% communities to self-organize and to develop their untapped industry average. In 1991, CHCA established the potential to empower themselves and improve their own Paraprofessional Healthcare Institute (PHI) to demonstrate quality of life. Its health programmes alone reach over the model in other settings and to catalyse national debate on 10 million people, far more than many public health-care the quality of paraprofessional jobs and long-term care7,14. In systems around the world, while its non-formal schools this publication, you will also find a description of provide education to 1.3 million children (70% of whom mothers2mothers, using a similar highly scalable model of are girls)7,10. training new mothers living with HIV to empower, mentor

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and counsel pregnant women who are newly diagnosed with service delivery programmes and building management HIV to prevent mother-to-child transmission of the virus (see capacity in overburdened health-care systems19. article by Gene Falk on page 36). Finally, the World Economic Forum has recently developed Significant innovation and funding gaps exist in the a new global system to support existing governance structures development of new and appropriate pharmaceuticals and and international institutions. For 68 of the most pressing technologies for which no attractive market exists for global issues (six of which are global health issues), the traditional health-care companies. Two organizations, the Forum has created a Global Agenda Council of experts Program for Appropriate Technology in Health (PATH) and the selected by peer review including scientists, economists, Institute for OneWorld Health, have pioneered models for academics, business and civil society leaders20. While there is research and development of drugs or technologies, significant value in bringing together the foremost experts on challenging the existing paradigms and demonstrating how each of these issues, the real breakthrough has been the new models could be established within or through cross-interactions between experts from different disciplines partnerships with these industries. PATH’s innovative and sectors given the interlinked nature of the challenges. strength is not only in tailoring health technologies to be Social entrepreneurs stand at the nexus of many of these relevant in low-resource settings, but also in collaborating issues and can readily provide key insights as they have with the private sector to get the technologies manufactured proven solutions that have already been implemented at and distributed at reasonable costs, and with governments to significant scale where many programmes and international adopt and implement them7,15. The Institute for OneWorld agencies have failed in the past. In addition to a dedicated Health was the first non-profit pharmaceutical company Global Agenda Council on Social Entrepreneurship, the managing complex drug development projects for safe, Schwab Foundation has strategically positioned social effective and affordable new medicines for neglected entrepreneurs as experts in other councils, including those on diseases, working with universities and pharmaceutical health-related issues such as the ageing society; chronic companies to apply unused intellectual property for non- diseases and malnutrition; health-care systems; HIV/AIDS; commercial gain7,16,17. These result in private sector resources pandemics; and welfare of children. By doing so, these social applied to the public good and sustainable solutions in the entrepreneurs can connect experts and global decision- long run. makers to the practicalities of innovating at the grassroots level, but with systemic change and scale in mind. Further leadership networks in the World Economic Forum to accelerate innovation Building a global momentum for change In addition to the pre-eminent social innovators within the The organizations described above have achieved significant Schwab Foundation’s community described above, the World impact through extraordinary work. Importantly, these social Economic Forum has established several additional avenues entrepreneurs have proven that health delivery systems can to accelerate innovative ideas, the Technology Pioneers be reorganized to rapidly increase the quantity of service community, The Forum of Young Global Leaders and, more delivery while improving the quality of care. By innovative recently, a major initiative, the Global Agenda Councils. actions and models, they have powerfully contributed to the Since 2003, the Technology Pioneers Programme has debate on the business model used by the pharmaceutical, recognized companies all over the world, which design and diagnostics, devices and vaccine industries to produce their develop exciting and potentially disruptive technologies in the products. They have shown how policies and commercial fields of health and biotechnology, science and information systems can be improved or transformed to bridge the gaps in technology. mPedigree, a Ghanaian technology company improving health for all. There is therefore a need to: recognized as a Technology Pioneer in 2008, developed the understand that current systems and policies can hinder first system SMS-based service through which consumers social and technological innovation for public good; and patients can instantly verify the source of a purchased recognize those social and technological innovations that pharmaceutical at no cost, at the point of purchase, using have potential for massive scale; standard mobile phones18. integrate these innovators as experts or leaders into The Forum of Young Global Leaders is a unique, policy development processes in order to build multistakeholder community of the world’s most extraordinary momentum towards the widespread acceptance of such leaders under 40 years of age, creating a diverse, new approaches. multistakeholder network of the top young leaders in the world who bring fresh and collaborative thinking on the key We believe that, by promoting these social innovators and issues facing our world. Ernest Darkoh, Founding Partner and their organizations as global leaders, they can start to change Chairman of Broadreach Healthcare, joined this group of the paradigms that make global health challenges seem young leaders and began to influence his peers on the impossible to conquer. challenges of HIV/AIDS in Africa. Broadreach led Masa, Botswana’s national ARV treatment programme, the largest in Dr François Bonnici is currently Head of Africa for the Schwab Africa, in partnership with the Bill & Melinda Gates Foundation for Social Entrepreneurship and recently graduated as Foundation, Merck and the government of Botswana, and has a Global Leadership Fellow of the World Economic Forum, where he since established itself as an expert in the design of efficient was the Associate Director of the Global Health Initiative.

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Originally trained as a physician in South Africa, he also read for entrepreneurship as a key element to advance societies and a Masters degree in Public Health (London) and an MBA (Oxford) address social problems in an innovative, effective manner. She as a Rhodes Scholar. He has worked in clinical paediatrics, joined the Foundation at inception in 2000, after three years at managed public health programmes, worked as a consultant to Bain & Company, and is currently its Director. She holds a Masters UNICEF, country governments and social enterprises and as a in Public Administration from Harvard University’s Kennedy researcher in the Clinical Trials Unit at Oxford University. School of Government, an MBA from St Gallen University, Switzerland, and an International Business Diploma from ESADE, Mirjam Schöning heads the Schwab Foundation for Social Spain and the Stockholm School of Economics. Her fields of Entrepreneurship whose mission is to raise awareness on social expertise include social entrepreneurship, microfinance and social investing. References

1. Becker GS, Philipson TJ, Soares RR. The quantity and Quality of life and 0&stype=0 (accessed 4 August 2009). the evolution of world inequality. American Economic Review, 2005, 12. Profile of Thulasiraj Ravilla, Aravind Eye Hospital. 95(1):277–291. http://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index.htm?sna 2. Gardner CA, Acharya T, Yach D.Technological and social innovation: me=152628&sorganization=0&sarea=0&ssector=0&stype=0 (accessed a unifying new paradigm for global health. Health Affairs, 2007, 4 August 2009). 26(4):1052–61. 13. Profile of Vera R Cordeiro, Associação Saúde Criança. 3. Bator Francis M. The anatomy of market failure. The Quarterly Journal of Renascerhttp://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index Economics, 1958, 72(3):351–379. .htm?sname=117989&sorganization=0&sarea=0&ssector=0&stype=0 4. Bays J, Goland T, Newsum J. Using prizes to spur innovation. The (accessed 4 August 2009). McKinsey Quarterly, 2009. 14. Profile of Rick Surpin, Cooperative Home Care Associates, http://www.mckinseyquarterly.com/Using_prizes_to_spur_innovation_2396 Paraprofessional Healthcare Institute and Independence Care System. #top (accessed 3 August 2009). http://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index.htm?sna 5. World Economic Forum Annual Meetings take place in Davos-Klosters, me=141899&sorganization=0&sarea=0&ssector=0&stype=0 (accessed Switzerland every year in January. 4 August 2009). http://www.weforum.org/en/events/AnnualMeeting2010/index.htm 15. Profile of Christopher J Elias, Program for Appropriate Technology in (accessed 4 August 2009). Health. http://www.schwabfound.org/sf/SocialEntrepreneurs/ 6. Bays J, Goland T, Newsum J. 2009. And the winner is….capturing the Profiles/index.htm?sname=167425&sorganization=0&sarea=0&ssector= promise of philanthropic prizes. 0&stype=0. http://www.mckinsey.com/clientservice/socialsector/And_the_winner_is.pdf 16. Profile of Victoria G Hale, Institute for OneWorld Health. (accessed 3 August 2009). http://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index.htm?sna 7. Schwab Foundation for Social Entrepreneurship, 2009. Outstanding me=141822&sorganization=0&sarea=0&ssector=0&stype=0 (accessed Social Entrepreneurs, 2009. 4 August 2009). 8. World Economic Forum. Strengthening the management of health systems 17. Hale V. Seeking a cure for inequity in access to medicines. Innovations, in sub-Saharan Africa: working with governments, 2007. 2007, 2(4):59–71. 9. Profile of Garth Japhet, Soul City Institute for Health and Heartlines. 18. Profile of mPedigree, Technology Pioneer of the World Economic Forum http://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index.htm?sna 2009. me=111292&sorganization=0&sarea=0&ssector=0&stype=0 (accessed http://www.weforum.org/en/Communities/Technology%20Pioneers/Selected 4 August 2009). TechPioneers/index.htm (accessed 4 August 2009). 10. Profile of Fazle H. Abed, BRAC. 19. Profile of Ernest Darkoh, Broadreach Healthcare. http://www.schwabfound.org/sf/SocialEntrepreneurs/Profiles/index.htm?sna http://www.weforum.org/en/Communities/Young%20Global%20Leaders/W me=115798&sorganization=0&sarea=0&ssector=0&stype=0 (accessed howeare/Search/index.htm?Keywords=ernest&isSearch=true 4 August 2009). 29. The Network of Global Agenda Councils. 11. Profile of Dr Devi P Shetty, Narayana Hrudayalaya Institute of Medical http://www.weforum.org/en/about/GlobalAgendaCouncils/index.htm Sciences. http://www.schwabfound.org/sf/SocialEntrepreneurs/ (accessed 4 August 2009). Profiles/index.htm?sname=168496&sorganization=0&sarea=0&ssector=

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Innovative financing mechanisms – can they help to improve aid effectiveness for health systems development?

Article by Amrita Palriwala (pictured), Program Officer, Results for Development Institute, with Aarthi Rao, Program Associate, Results for Development Institute

evelopment assistance for health (DAH) has The proposed framework substantially expanded in the past two decades. A While there are many possible ways to examine health Drecent account shows that the total amount almost financing tools in terms of their contribution to the quadrupled from US$ 5.6 billion in 1990 to US$ 21.8 billion effectiveness of DAH, we would argue that four dimensions in 20071. Most of this increase has focused on the prevention are especially important to consider. Specifically, we suggest and treatment of the three major diseases – HIV/AIDS, that innovative financing will be most helpful in improving tuberculosis and malaria – with only a modest portion going DAH effectiveness if it leads to: to health systems support. Enhanced predictability and stability of funding for In response to a growing concern that the 49 poorest recipients – current DAH in the form of grants from countries need to invest more in health systems in order to public sources tends to be short-term (less than five reach the Millennium Development Goals (MDGs) for health2 years, often shorter) and unpredictable5. This makes it by 2015, the Taskforce on Innovative International Financing difficult for grant recipients (whether developing for Health Systems, led by Prime Minister Gordon Brown of countries, research and development (R&D) the United Kingdom and Robert Zoellick, President of the manufacturers or multilateral organizations responsible World Bank3, has called for an additional US$ 10 billion per for channelling funds) to plan and commit to their year4. A range of new and innovative financing mechanisms investments in health and achieve programme objectives have been proposed to mobilize essential funds for basic supported by that funding. Can innovative mechanisms health and nutrition services, and related human resources help to provide more long-term, predictable and stable and infrastructure. funding to its recipients? While these new financing mechanisms may help to raise Increased coordination and reduced transaction costs additional billions for health systems, less attention has been for countries – historically, the proliferation of assistance paid to assessing whether they will help to improve the overall channels has led to fragmentation in DAH, including effectiveness of development assistance for health, or will end from bilateral agencies, nongovernmental organizations up exacerbating some of the current weaknesses in DAH. and foundations, and a growing number of multilateral At present, DAH exhibits a number of weaknesses and institutions and global programmes. Can innovative inefficiencies, including unpredictable and unstable flows of mechanisms help coordinate and simplify funding from funding; lack of incentives for achieving key health outcomes different sources, for example by combining and utilizing on the ground; high transaction costs for countries, related to existing channels? multiple processes for planning, procurement, reporting, etc; Stronger incentives for achieving health results in and limited effectiveness in helping poor households achieve countries – results-based financing is not a new concept more rapid access to life-saving health products and services. for DAH, and developing countries and donors have Will the innovative financing instruments now being adopted many measures that link the availability of considered to augment funding for health systems actually funding to concrete, measurable results on the ground6. help to resolve these weaknesses and inefficiencies in DAH, Can the new financing mechanisms create or promote or will they make them worse? clear incentive structures so that aid leads to tangible In this paper, we propose a framework for assessing results for its primary recipients and ultimately countries? innovative financing tools for health systems in terms of their Direct positive impact on access to health services and impact on DAH effectiveness, and then apply this framework products for poor households and low-income countries to four of the most prominent new financing instruments – innovative financing mechanisms are intended to be being considered. catalytic and accelerate access to existing or new health

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Innovative Provides predictable, Incentivizes recipient Links to Improves coordination, Speeds up access mechanism stable funding for recipient results country results lowers transaction costs to health products for countries and services

Debt2Health ** ** ** * * AMCs *** *** * ** *** IFF2 *** ? * ** *** AMFm ** * ** ***

Table 1: Summary of health systems financing innovations

services and products for developing countries that creditor have reached a joint agreement. The mechanism would otherwise not be possible through traditional aid. could potentially help the long-term financial sustainability of One novel feature of some recent innovative approaches the fight against AIDS, TB, and malaria if it indeed stimulates is “frontloading,” whereby additional funds are countries to create additional fiscal space for health. A similar committed immediately for health, but donors pay for scheme could be developed to channel resources for health them in the future. Can these kinds of approaches system strengthening initiatives. For example, donors could generate more health benefits for the poor sooner, cancel debt if the indebted country provided counterpart helping to reduce poverty and speed up overall financing for scaling up its human resources for health through socioeconomic development? a related programme offered by other multilateral institutions.

Assessing recent health systems financing Advance market commitments (AMCs) innovations The AMC concept was developed during 2004–2006 as a Using the four dimensions of improved DAH described way to accelerate R&D by creating a secure market for new above, we have carried out a preliminary assessment of four drugs and vaccines, usually legally binding commitments of the most widely discussed health systems financing from developed countries to subsidize the prices of these new innovations – debt swaps, advance market commitments, health products when ordered by low-income-country the International Financing Facility, and the Affordable governments. AMCs are intended to motivate firms to Medicines Facility. Table 1 summarizes our findings. develop and supply new products tailored to the needs of developing countries11. A pilot AMC for vaccines against Debt2Health pneumococcal disease is about to be launched to encourage Debt2Health, a debt swap instrument offered by the Global manufacturers to develop vaccines that would cover the Fund, encourages channeling the resources of developing pneumo viral strains most prevalent in low-income countries countries away from debt repayment towards investments in and to scale up manufacturing rapidly for these markets12. A health. This innovative financing mechanism enables the group of donors has agreed to pay US$ 1.5 billion to support creditor to cancel a fraction of the publicly held debt if the sales of the vaccine for an initial period in return for promises recipient government repays the remainder with at least a from manufacturers to offer a lower long-run price to partial transfer to the Fund’s programmes for increasing health developing countries13. spending in that country7. To date, Germany has forgone a The AMC concept offers highly predictable financing to total amount of 90 million euros in debt to Indonesia and recipient manufacturers because donors have already made Pakistan in return for their total spending of 55 million euros commitments that include an adequate return on investment on respective approved programmes8. In May 2009, Australia for the development of the vaccine. Because AMCs are joined the initiative as a second creditor to Indonesia. designed as a “pull mechanism,” whereby they pay for By the Global Fund acting as a third-party facilitator, the outputs rather than inputs, manufacturers are rewarded only recipient country faces potentially lower transaction costs if the vaccines are purchased by developing countries, thus related to debt conversion than it would negotiating with incorporating a performance-based measure. It is difficult for various bilateral governments independently. Countries could AMCs, however, to directly incentivize developing countries reduce their transaction costs further if a critical mass of debt to deliver on tangible health outcomes as they have the could be consolidated across donors. As it stands, freedom to choose the amount of vaccines to purchase, and Debt2Health does not directly incentivize recipient countries no performance targets are defined at the country level. to deliver on specific health results but is aligned with the Resources from the pilot AMC for pneumo will be channeled Fund’s performance-based disbursement and review process through GAVI’s national programmes for new vaccine for approved programmes9. One possible modification that support so no additional transaction costs are expected for could make the current design of the scheme more results- countries. Further, AMCs help to accelerate adoption of new, focused is to require donors to cancel debt in installments as costly vaccines in the developing world by offering an the recipient country reaches its defined programme targets affordable price for these life-saving products. over time, similar to the way “buy-downs” have been implemented to increase vaccination coverage rates for polio A second International Financing Facility for health in Nigeria and Pakistan10. Debt2Health offers few benefits in systems terms of predictable financing, as the resource envelope is A stream of promised future grant payments by donors could defined once both the individual recipient country and be used to secure bond financing, thus “front-loading”

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funding for health systems. The International Financing donors commit to providing a long-term global subsidy. By Facility for Immunization (IFFIm), which has generated reducing the average price to US$ 0.05 per treatment for additional resources, channeled through GAVI, to pay for both first-line public and private buyers, the AMFm can vaccines that are already on the market but are underused in increase availability of ACTs in the private sector, where over developing countries, works in this way14. To date, seven 60% of patients have access to antimalarial treatments but donor governments have made pledges to contribute US$ 5.3 only 5% of ACTs are provided currently22. Because the degree billion over 20 years15. The Task Force on Innovative of competition in private drug markets can differ across International Financing for Health Systems has proposed a countries, it may take longer for the private supply chain to second IFF concept to be used for broader health-system pass the savings from the global subsidy on to the consumer purposes beyond immunizations16. To do so, donors would in less competitive markets. Nevertheless, there appears to have to make additional grants for financing this second IFF. be little doubt that the savings generated from the subsidy will Further, if some funds were channeled through organizations reach the consumers. The post-subsidy results of a pilot study other than GAVI, the structure and governance for this IFF conducted by the Clinton Foundation in Tanzania showed that would need to be altered as these channels might have the price for ACTs was low and comparable to that of older different allocation and decision processes. drugs, and the proportion of customers purchasing ACTs Such bond financing can be predictable and long-term increased from 1% to 44%23. There are no direct because pledges have been made by donors, creating a performance-based incentives associated with the AMFm, defined overall resource envelope that can be accessed and several complementary interventions beyond those that quickly during the frontloading period. There is no address affordability would be required to ultimately have a performance-based measure linking health outcomes to the positive impact on malaria prevalence or drug resistance. bond financing mechanism. However, GAVI, as the recipient Countries receiving grants for procurement and purchase of and channel of the IFFIm, applies a performance-based AMFm co-paid ACTs and supportive interventions by the mechanism to provide immunization services support to poor Global Fund will be subject to its performance-based funding countries, rewarding those that surpass the country’s target system. The Global Fund will engage in negotiations with number of immunized children17. For the second IFF, one of manufacturers directly and no additional transaction costs are the selection criteria for host organization(s) might be whether expected to be borne by countries. Finally, the AMFm it applies a performance-based funding system to incentivize presents a way to create an attractive and affordable market improvements in health systems. A major benefit of the IFFIm for effective malaria treatment in developing countries, is that the frontloading feature enables many more children to enabling the poor to access these important drugs faster than have access to vaccines early in the funding cycle than if it were left to global markets. otherwise would have been available. Frontloading has its costs – an estimated 3.5% of the total commitments are lost Conclusions to interest and commissions for borrowing on capital markets As our preliminary assessment above suggests, a number of and additional outlays to the World Bank which serves as the the new financing tools being proposed for expanded support financial intermediary. Overall, however, long-term returns for to health systems have the potential to not only mobilize low-income countries from the IFFIm are expected to be large. additional resources but also contribute positively to the overall effectiveness of DAH. In particular, the innovative Affordable Medicines Facility-Malaria (AMFm) mechanisms we looked at (debt swaps, AMCs, a second IFF, The AMFm idea originated in 2004 as a way to offer a global and the AMF) are likely to help make DAH more predictable public subsidy for an artemisinin-based combination therapy and generate more stable funding flows for recipients, and (ACT) through public and private supply channels to crowd also contribute positively to accelerated and wider access to out medically inadequate or inappropriate monotherapies and essential health services and products for the poor. deliver a more effective and inexpensive treatment in malaria- On the other hand, it is much less clear whether the endemic countries18. The AMFm concept provides a co- innovative financing instruments being considered at present payment in the form of a cash subsidy to the manufacturer will help to incentivize better results on the ground or improve that would ultimately reduce the retail price to the consumer aid coordination and lower administrative and other buying an ACT at a shop from US$ 6–10 to US$ 0.20–0.50, transaction costs. allowing for standard mark-ups for drugs, and be competitive An important lesson from our analysis is that detailed with prices of available monotherapies19. In four years of design decisions about how the newly generated funds are technical and political dialogue among a multitude of key channeled down to the country and health facility level will stakeholders, the AMFm has moved from a novel idea to be critical in determining whether the effectiveness of DAH is implementation so its effects are yet to be proven21. The improved or undermined – the source of the additional Global Fund has agreed to host and manage the first phase funding alone tells us little about this issue. Incremental of AMFm for 11 countries, with approved support of about resources from a second IFF, for example, could be directed US$ 190 million from DfID and UNITAID. The AMFm is to countries through an existing global institution, or could be expected to process its first orders for ACTs in early 2010. scattered across many separate multilateral and bilateral The AMFm could provide predictable financing to recipient programmes. The impact on coordination and transaction manufacturers and low-cost ACTs for consumers if a group of costs would be dramatically different under these two distinct

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approaches. The same can be said for the issue of results- and the Congressional Budget Office, Washington, DC. She also focus. Additional funding from an IFF2, for example, could worked at The Advisory Board Company, a best practices research be used to reward countries, facilities and households that and consulting firm in Washington, DC, to advise senior make significant progress in health outcomes, or the funding executives at US hospitals and health-care systems on strategy could simply be used for more health inputs. The impact on and operations. incentives for results would be completely different Amrita Palriwala holds an MSc with merit in health economics depending on the design choice. jointly from the London School of Economics and the London School of Hygiene and Tropical Medicine (2008) and a BA in Acknowledgements economics from Brandeis University, Massachusetts (2003). The authors are grateful to Robert Hecht for this opportunity and for his contributions and advice. Aarthi Rao joined the Results for Development Institute as a program associate in June 2009. She works across various Amrita Palriwala is a program officer at the Results for projects including the Ministerial Leadership Initiative, the Review Development Institute, where she is working on a growing portfolio of the GAVI Alliance Eligibility Policies, and the Health Financing of projects on health financing and improving R&D, and access to Task Force. Aarthi Rao has worked in both India and Nepal and new health technologies in developing countries. also in domestic nonprofit organizations. She holds a BA in Public She has professional experience in economics with the Health from the Johns Hopkins University, USA where she studied Organisation for Economic Co-operation and Development, Paris public health and international development.

References

1. N. Ravishankar et al., “Financing of global health: tracking development 2008, http://www.brookings.edu/projects/global- assistance for health from 1990 to 2007,” The Lancet 373, Issue 9681: health/~/media/Files/Projects/globalhealth/healthsnapshots/vaccines.pdf 2113 – 2124 (20 June 2009). (accessed 6 January 2009); and O. Barder, M. Kremer, and R. Levine, 2. Health Millennium Development Goals refer to MDG 1c (malnutrition), 4 Making Markets for Vaccines: Ideas to Action, 2005, (child mortality), 5 (maternal health), 6 (HIV, malaria and other diseases), http://www.cgdev.org/doc/books/vaccine/MakingMarkets-complete.pdf and 8e (essential drugs). (accessed 12 January 2006). 3. Taskforce on International Innovative Financing for Health Systems, 12. Because these vaccines are already in very late-stage development, the http://www.internationalhealthpartnership.net/en/taskforce (accessed 10 main aim of the pneumo AMC will be to ensure adequate supply to August 2009). developing countries at an affordable price. 4. Taskforce on International Innovative Financing for Health Systems, “More 13. GAVI Alliance, "Saving Lives with New Vaccines: Advanced Market money for health and more health for the money” (Main report), 2009, Commitments," 2007, http://www.internationalhealthpartnership.net/CMS_files/documents/taskfor http://www.vaccineamc.org/files/AMC_FactSheet_v2.pdf (accessed 6 ce_report_EN.pdf (accessed 10 August 2009). January 2009). 5. R. Hecht and R. Shah, “Recent Trends and Innovations in Development 14. Brookings Institution, "International Finance Facility for Immunization," Assistance for Health,” Disease Control Priorities Project: 13, 2008, http://www.brookings.edu/projects/global- http://www.dcp2.org/pubs/DCP/13/FullText (accessed 10 August 2009). health/~/media/Files/Projects/globalhealth/healthsnapshots/iffim.pdf 6. Including output-based aid, results-based loan buy-downs, conditional (accessed 6 January 2009). cash transfers, provider payment incentives, vouchers, and performance- 15. IFFIm, “About IFFIm,” http://www.iff- based rewards immunisation.org/01_about_iffim.html (accessed 10 August 2009). 7. Brookings Institution, “Debt2Health: Debt Conversion for the Global Fund 16. Taskforce on International Innovative Financing for Health Systems, to Fight AIDS, Tuberculosis, and Malaria,” 2008, “Raising and Channeling Funds” (Working Group 2 Paper), 2009, http://www.brookings.edu/projects/global- http://www.internationalhealthpartnership.net/pdf/IHP%20Update%2013/ health/~/media/Files/Projects/globalhealth/healthsnapshots/debtconversion Taskforce/Johansbourg/Taskforce%20Working%20Group%202%20Report. .pdf (accessed 10 August 2009). pdf (accessed 10 August 2009). 8. The Global Fund, “Basic Information on Debt2Health,” 17. Global Alliance for Vaccines and Immunization, “Immunization Services http://www.theglobalfund.org/documents/innovativefinancing/Factsheet_d2 Support (ISS),” http://www.gavialliance.org/support/what/iss/index.php h_en.pdf (accessed 10 August 2009). (accessed 10 August 2009). 9. The Global Fund, “Performance-based Funding,” 18. Brookings Institution, “Affordable Medicines Facility - Malaria (AMFm),” http://www.theglobalfund.org/en/performancebasedfunding/?lang=en 2008, http://www.brookings.edu/projects/global- (accessed 10 August 2009). health/~/media/Files/Projects/globalhealth/healthsnapshots/amfm.pdf 10. The Bill and Melinda Gates Foundation, “Financial Innovation Will Buy (accessed 6 January 2009). Vaccine To Help Eradicate Polio Worldwide,” 19. The Global Fund, “Affordable Medicines Facility - malaria (AMFm)” http://www.gatesfoundation.org/press-releases/Pages/eradicate-polio- http://www.theglobalfund.org/en/amfm/ (accessed 10 August 2009). worldwide-030429.aspx (accessed 10 August 2009); The Bill and 20. Including the World Bank, RBM Partnership, Gates Foundation, DFiD, the Melinda Gates Foundation, “Bill Gates Visits Nigeria to Boost Global Fight Dutch government, UNICEF, WHO and the Global Fund Against Polio,” http://www.gatesfoundation.org/press-releases/Pages/fight- 21. R. Laxminarayan and H. Gelband, “A Global Subsidy: Key to Affordable against-polio-in-nigeria-090202.aspx (accessed 10 August 2009); and Drugs for Malaria,” Health Affairs 28, no.4, (2009): 949-961. The World Bank, “WB’s Additional Support for Pakistan’s Polio 22. The Global Fund, “AMFm Frequently Asked Questions,” 2009, Eradication Initiative US $21.14 million,” 2007, http://www.theglobalfund.org/documents/amfm/AMFmFAQs_en.pdf http://siteresources.worldbank.org/INTPAKISTAN/Resources/Polioeradicatio (accessed 10 August 2009). n.pdf, (accessed 10 August 2009). 23. William J. Clinton Foundation, Tanzania Pilot ACT Subsidy: Report on 11. Brookings Institution, "Advance Market Commitments for Vaccines," Findings (New York: Clinton Foundation, 2008).

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Healthful academic translations: cultivating Collaborative Doers as Innovation Managers for societal well-being

Article by Usha R Balakrishnan, President, CarthaGlobal Ventures & Consulting, Iowa City, USA

cience and technology have the potential to transform licensing offices in the United States are furnished from the practices that can save and improve the lives of so earned royalty/licensing income in their intellectual property Smany millions in underprivileged and vulnerable portfolios. Further, because of narrowly-crafted missions, populations. Meeting this vision, however, requires that severely-limited resources, and pressure to show short-term science and technology be translated into innovative products results to shareholders or funders, most employers find it and services, so as to ensure relevance, appropriateness and difficult to capitalize on the intrinsic motivations of their high- sustainability for use to benefit the intended populations. This aspiration employees to contribute into broader communities- paper argues that as academic research tends towards of-practice. Finally, with the ongoing economic crisis, collaborations that are global, interdisciplinary and inter- academic technology managers confront significantly sectoral, a corollary need emerges to develop the requisite increased pressure to generate licensing revenue to support leadership and managerial abilities to create and enhance their own functions and their parent organizations. Not partnerships which translate these academic advancements surprisingly, there is little choice but to defer their aspirational into (social and/or technological1) innovations to achieve goals of being social entrepreneurs. increased effectiveness in terms of public health outcomes. In The problem of benign neglect is compounded because particular, I argue for the development of a cadre of bridging immediate financial incentives are often missing in numerous professionals from academe and the field – “Collaborative academic innovations, particularly when such innovations Doers”2 – who could act as fundamental cogs in the process confer significant societal benefits over the long term. Case of connecting, activating and leveraging the stores of studies 1 and 2 showcase how valuable innovations might institutional resources, human capital, and scientific and have still languished but for the evangelical efforts of some of technological prowess to advance global good. By the players involved. highlighting opportunities to cultivate academic-practitioner What happens versus what can happen is the core issue networks of Collaborative Doers, I hope to spur attention and when dealing with global health-related innovations as well dialogue among various stakeholders to create the resource as technologies which cry out for assuring and activating capacity needed for promoting the human competencies that humanitarian access. Recently, such concern has gained can help improve health access and equity. centre stage because of the emergence of a global health Currently, academic technology managers oversee some industry spurred by increased funding into research and the aspects of innovation diffusion in the context of academic spawning of global public-private partnerships6. Related discoveries that promise commercial potential or local issues that affect health – food security, water resources, economic development. Bridging the worlds of science, law sanitation, climate change, environmental and energy and business, these managers make the deals that move sustainability – have expanded the stakeholder groups and academic ideas into development by the private sector. There the scope of roles for scientists and managers alike within a are no schools to attend or degree to obtain before one global good industry. Naturally we find numerous papers7 and becomes a university technology manager. Rather, one learns calls-to-action8 for optimizing health research architecture from on-the-job experience as well as training programmes of and innovation systems, a new generation of problem- organizations like the Association of University Technology solvers9 and academic leadership for organizational and Managers (AUTM)3. programmatic transformations10,11. Moreover, academic technology transfer has typically been To meet these calls, we need “bridging professionals” tied to financial incentives by way of commercialization of because the worlds inhabited by the various stakeholder research-based innovation and entrepreneurship. Indeed, the communities – academics, nongovernmental organizations, operating budgets (including salaries) at most technology corporations, “philanthropoids” and parliamentarians (or

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CASE STUDY 1: Sprinkles4

Stanley Zlotkin is Division Head of GI/Nutrition at The Hospital for Sick Children, and Professor of Pediatrics & Nutritional Sciences at the University of Toronto. Stan invented Sprinkles, which are sachets (like that of sugar) that contain a blend of micronutrients in powder form, and can be used to fortify any homemade food. Sprinkles is inexpensive to manufacture and easy to distribute. Importantly, Sprinkles does not change the taste or appearance when mixed into children’s food, making it more likely to be used. Sprinkles addresses malnutrition issues among children, especially iron deficiency anaemia which is the most prevalent nutrient deficiency in the world today. Over a decade ago, at the time Stan came up with the idea for Sprinkles, he did not find support from his organization’s technology transfer group since intellectual property protection would likely not garner significant licensing revenues. Stan, a model collaborative doer, had to configure alternate pathways to make his vision come true. Despite the barriers, he proceeded to test the efficacy of Sprinkles in diverse settings, and teamed up creatively with a willing commercial partner. Today, the Sprinkles Global Health Initiative – a nonprofit launched with the support of his institution – is linked up in numerous partnerships and making a difference in so many parts of the world. The health impact of the programme has been demonstrated in Bangladesh and Mongolia. Partners in the initiative have included UNICEF, USAID, World Bank and CIDA, and many others. Stan is also building a global network through grassroots mothers’ groups that provide essential health education for distributing Sprinkles. Stan has won numerous awards for his work. The question to ponder is what happens if an innovator does not have the skills and grit of a Stan Zlotkin? Stan’s dogged efforts inspire us to configure new pathways to support academic inventors whose work may some day make a huge difference.

members of Congress) – are very different12. The denizens of In sum, there is limited recognition that the impact of an these worlds have their individual cultures and languages13 innovation-driven global good industry depends upon the meaning that we need boundary-spanners who can bridge availability of a suitably-trained workforce that can bring these various cultures and forge new partnerships. But disparate parties together and bridge often conflicting finding meaningful partnership opportunity occurs only upon interests. Clearly, we need new training models and familiarity with the various languages of practice and spheres professional development programmes that can help of influence among the bridging zones. No single person can connect, contextualize, and engage effectively those within be expected to possess sufficient familiarity required to work and outside of academia, within and outside of health among these multiple constituencies. Thus, boundary sciences to fulfill the workforce needs of this industry. Thus, spanning work can only thrive with trustful networks of the question is: how can we encourage the birth of a new Collaborative Doers who are sufficiently capable and willing profession of knowledge managers globally who can help to work together with the personal will to do good and the shepherd social and technological innovations out of the professional humility to execute their tasks14 over the short, university settings where they often arise and into the real mid, or long term as may be required. These traits are world where they are needed? particularly relevant because any such bridging professional needs to relate with sensitivity and care to issues of the poor Building a network of Collaborative Doers and the vulnerable in our society; indeed, routine business In this section, I share a few examples of CARTHA training models may not only be inappropriate but even programmes that have helped identify Collaborative Doers unethical and exploitative of the poor. from a variety of disciplines, sectors and regions. The

CASE STUDY 2: The Ponseti Method5

Clubfoot affects nearly 150 000 newborns annually, with 80% of them in impoverished nations. Clubfoot causes a baby’s feet to turn inwards and downwards; if not corrected, a child is unable to walk or move properly. Over nearly five decades, Ignacio Ponseti (Professor Emeritus of Orthopedic Surgery at the University of Iowa Hospitals and Clinics) developed and practised the revolutionary Ponseti Method for clubfoot treatment as an alternative to surgery. Early in his career, Ponseti realized that surgical approaches did not fully correct clubfoot and/or created problems later in life, such as severe arthritis or even requiring more surgery. He set out to develop a non-surgical treatment that made the most of babies’ flexible ligaments. Although the method was initially met with some opposition, it is now endorsed by numerous organizations, including the American Academy of Pediatrics and the World Health Organization. In addition to the improved physical outcomes, the Ponseti Method is less expensive and can be taught to non-physician health-care providers, which is useful in areas with few or no doctors. In 2008, the University of Iowa launched the Ponseti International Association for the Advancement of Clubfoot Treatment. In partnership with CURE International, Christian Blind Missions and an anonymous donor from North Carolina, orthopaedic specialists from the University of Iowa and elsewhere are now training local health-care workers (doctors, nurses, midwives) in 10 countries. To supplement in-person training, materials are provided through the e-granary digital library (www.widernet.org/digitallibrary/) and online education (https://globalcampus.uiowa.edu). Prominent Iowa City Rotarians are advocating for further outreach, linkages and support of these activities. This is a glowing example of global partnerships that help spread academic innovations to help the disadvantaged. However, a natural question is whether an earlier launch of such initiatives could have been undertaken for improving the lives of so many more children?

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programmes utilize the C2G2 Training Model: Building Forming a professional society and developing Collaborative Competence (C2) within Multisector certifications: Collaborative Doers need to share their Partnerships for Global Good (G2), shown in Figure 1. It is learning-by-doing perspectives and gain new particularly relevant to note that these programmes (see competencies through cross-sector, transnational training http://cartha.org/programs/index.htm) aim to add the social platforms and exchange portals. Utilizing in-person dimension and have been designed and executed with all- training programmes and IT-based environments (social volunteer teams of Collaborative Doers to build and enhance media, new media and other learning platforms), new Collaborative Competence skill sets (see Figure 2). Finally, curricula and certification programmes that supplement with humility, I present these early pilots as anecdotal traditional education and training in academe could be evidence of what can be done (and to imagine what more established to provide viable structures for development could be done) as we seek to collectively build on of Innovation Managers. professionalizing a cadre of Collaborative Doers to serve as Innovation Managers. Promoting tangible mechanisms for social change through portfolio assignments and resource allocations Initiating thought leadership dialogues in professional for Innovation Managers: Innovation Managers require society meetings to promote continuous interaction time, travel support, seed funding and fundraising talent between technology managers and academic scholars to put into practice what they learn through professional and researchers from different regions of the world: development programmes to: (a) alter patterns of seeking from 2001 on, several groups within and outside the new academic research and innovations that can be Association of University Technology Managers began translated; (b) hone frameworks and methods used to raising awareness for global health issues in the context evaluate such innovations; and (c) craft appropriate of intellectual property management. Evolving from the regional/transnational, multi-sector alliances and deals work of the Technology Managers for Global Health15, that can produce better health equity outcomes. several networking events and training programmes have Community leaders and institutions (e.g., community been promoted in conference settings and campus foundations) could serve as useful vehicles in this regard seminars. These dialogues, in part, continue to help at the localized levels to support the development of identify how academic licensing policies and younger generations of Collaborative Doers. management practices might be refined. For example, it has now become more common to consider Inducing new research and evaluation centres: we need institutionalizing policies for use of humanitarian trained scholars and researchers to observe, study and licensing provisions in patent licensing agreements.16 report on the work of Collaborative Doers and the use of collaborative competence skill sets in various settings. Fostering transnational alliance-building and advocacy They can help develop the suitable metrics to through contextualization: it is obvious that independently track and assess the work and health de facto ambassadorial behaviours are required among equity impact of Collaborative Doers serving as Collaborative Doers operating at the intersection of socio- Innovation Managers. Such metrics may lead to positive cultural norms and bridging diverse groups of academics transformations in the culture of innovation itself. and practitioners from different regions of the world. Measuring global health equity impacts could (a) Such ambassadors empower and inspire themselves and rejuvenate certain “neglected” research sectors (e.g., others by creating a “glocalizing” network aimed at social sciences and humanities); and (b) strengthen inducing these diverse groups to cooperate and craft human resources policies and compensation practices human-centred approaches to addressing problems of the with regard to Collaborative Doers and their functional most-disadvantaged sections of our society. We recognize roles within organizational hierarchies and external however that a lack of routine communication and outreach responsibilities. advocacy training for academics and technology managers has been generally lamented in public The primary benefit of “collaborative doing” is to increase engagement realms17. Therefore, such “glocalizing” the probability of reaping the societal benefits associated with networks intentionally embed filmmakers, documentary currently neglected academic innovations. Subsidiary benefits producers, writers and other creative artists who can help are likely to be realized in the areas of formulating policy as Collaborative Doers reach wider publics. well as building a global community (adept at tapping into locally-resident talent and knowledge resources) with the Developing fellowships, speaker series and exchange shared goal of advancing global good. Thus, well-trained, programmes: we draw upon the motivations of high- well-networked Collaborative Doers will (a) share, utilize and aspiration individuals by inviting contributions from disseminate resources in more thoughtful, more equitable younger and older generations from different regions. ways than currently observed; and (b) usefully guide the Existing platforms offered by social service clubs (such formulation of better policies for the future (rather than sole as Rotary or Lions) can greatly benefit such outreach reliance on past data to dictate future policy). and engagement.

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Cultivating collaborative doersSM A conundrum CARTHA’s comprehensive C2G2SM framework enables the formulation and Education and training programmes implementation of solutions to create greater equity and reduce economic and social requiring transcontinental exchanges disparities in local and global settings. We provide models for understanding, of academics and professionals are facilitating and communicating the work of Collaborative Doers. costly and time-consuming. Who could or should be funding these CARTHA programming overview programmes for the development of Building Collaborative Competence (C2) Collaborative Doers, particularly Within Multisector Partnerships for global good (G2) because the benefits of their actions accrue beyond any single Provide tools for Study current organization? In light of the vast innovators practice benefits to be gained, I argue that it is reasonable to invest an additional Conduct training Build collaborative and development competence small percentage of research expenditures towards training and mechanisms geared towards professionalizing the management of C2G2SM Training Model innovations within and outside of Building Collaborative Competence (C2) the academic sectors to improve Within Multisector Partners hips for Global Good (G2) global health equity outcomes. Such a cadre of Collaborative Doers could “GLOBAL GOOD” also act as Innovation Managers for LEADERS research and development (R&D) investments anticipated into New Provide Study other areas (e.g., climate change academic- tools for current New and climate adaptation; water- practitioner innovators practice organizations initiatives related technologies, etc.) which Collaborative increasingly require cross-sector Doers approaches, involve large-scale funding for large-scale alliances and New Formulation of Conduct Build approaches directly affect the global health new problems training and collaborative to traditional landscape. and development competence challenges challenges However, what “paid jobs” exist currently or will arise in the “GLOBAL GOOD” future for such professionals? In METRICS essence, beyond any personal satisfaction derived from being a good global citizen or the prestige of being recognized by CARTHA Programming others for one’s good works, what Components of C2G2 SM Training Model Development is the core economic rationale for any academic or professional to be Provide tools for Technology Study current C2G2SM Roles or seek further education and innovators Measures practice Contexts training to become a Collaborative Doer? Philanthropies and funding Web-based Online Empathy Metrics agencies could be more vigilant Learning Community Governance Outcomes about how their grant making Platforms Networking Leadership Reporting positively or adversely affects the birthing, development and maintenance of Collaborative Training and Fellows Build collaborative Academics Competence traits in the people development Interns competence Professionals and partners affiliated with their grantees. Academics and Career Case Studies Conferences Donors practitioners acting within these Development Immersive Grantees Workshops purposeful endeavours need Counseling Media Organizations Learning appropriate mechanisms, training, and networks to continuously Figure 1: CARTHA’s C2G2SM training model and programming overview align the impact of their daily

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The skill sets and traits outlined below were gathered on behalf of CARTHA with the pooled experiences of over 55 volunteers in 2007.

Collaborative Doers require Collaborative Competence skill sets l Cultural translation skills in fluid and complex situations l Ability to proactively reach out with empathy and fairness l Talent of bridging across people, organizations and networks l Aptitude to involve, engage and leverage resources across different generations and cultures l Capacity to spur individual and collective thinking towards collective doing for collective benefit

Collaborative Doers: TRAITS l Include local talent and passion on local projects l Anticipate new ideas and innovations to come from any corner of the globe l Work with dignity and respect for local community to solve problems they identify l Rely on nuances from oral, written and digital cultures before defining a community problem l Share and gain new channels and platforms for innovation development, transfer and dissemination l Engage young people to give creative input and also allow them to gain early advantage of learning by doing

Collaborative Doers: OUTCOMES l Serve as transformative and resilient thought leaders l Identify, share and leverage various resources for collective benefit l Negotiate partnerships and manage expectations to arrive at a better balance in terms of social, environmental and economic impacts

© 2006-2009 CARTHA. All Rights Reserved.

Figure 2: Collaborative CompetenceSM Skill sets

professional work to benefit larger interests of society over the Key messages short and long term. Bridging professionals (Collaborative Doers) with Conclusion leadership traits and managerial skill sets As global linkages between academic-practitioner (Collaborative Competence) are needed to serve as communities proliferate, there is a growing need to understand Innovation Managers to help shepherd academic academic research translation and innovation management- (social and/or technological) innovations to produce related frameworks as well as research, training, and practice increased public health outcomes. environments from a variety of perspectives, including Filling this unmet workforce need for an innovation- mechanisms that bridge academic disciplines. To advance driven global health industry requires multiple global health causes, academic Innovation Managers need to stakeholders to thoughtfully create the resource collaborate with academic scientists to understand their capacity for birthing (a) “glocalized” academic- aspirations for advancing societal impact: formulating practitioner networks of Collaborative Doers, and (b) interdisciplinary, sustainable solutions through an enhanced a cadre of professional Innovation Managers who understanding of the complexity of global health problems can in turn help form the partnerships to connect, and their determinants; raising awareness for the need to activate and leverage key additional resources in share experiences and perspectives from novel collaborative timely ways that move a broader set of potentially structures and new managerial roles among the partnering useful ideas into policy and action. stakeholders; and helping bring attention to these topics CARTHA’s “C2G2 Training Model” and early pilots among wider publics. Of course, those persons possessing offer some possibilities for what can be – and what the impulse to creatively connect and invent with others in more could be – done to advance “health equity entrepreneurial ways for larger societal causes will likely impacts” of such a bridging workforce. pursue bridging work as Collaborative Doers with or without support and recognition. But, because of the accelerating complexities and scope of global health issues, it is neither As global awareness leads to increased appreciation for the wise nor practical to rely on such passion or voluntarism global good, the least we can do as a concerned community alone to resolve the wide-ranging effects of increased income, of stakeholders is to spur the formulation, implementation social and health disparities. Tangible support and recognition and evaluation of alternate paths to vary the patterns of health of the work of Collaborative Doers may get us to attaining equity outcomes we expect from and want to promote with greater heights of excellence in more timely ways in the hope increased financing for academic R&D-induced innovations. of creating a more equitable world. It is time to professionalize a cadre of Collaborative Doers that A cadre of Collaborative Doers serving in a network of can serve as Innovation Managers for societal well-being. Innovation Managers – speaking the languages of academics, nongovernmental organizations (NGOs), policy-makers, Acknowledgments philanthropic donors and the private sector – can fulfill some I thank Robert S Bar, R Luke Evans, Paul Greenough, and of the workforce needs of the global health industry. Building Ramji Balakrishnan for their comments. Collaborative Competence will help leverage multisector partnerships, deal-making and resources to move a broader Usha R Balakrishnan is President of CarthaGlobal Ventures & set of potentially useful ideas into policy and action. Consulting in Iowa City and volunteers her time as Founder & Chair

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of CARTHA (www.cartha.org), a 501c3 nonprofit organization included directing corporate partnerships, fostering economic launched in 2006. She led the formation of Technology Managers development-related outreach, and managing inventions, patent for Global Health in 2003 and has organized numerous thought licensing and technology transfer functions. She has a BCom from leadership dialogues and seminars in the USA and abroad. Her Bombay University and an MBA from the University of Iowa. 15-year academic administration career at the University of Iowa

References

1. Gardner CA, Acharya T, Yach D, Technological and social innovation: A in personal email correspondence dated May 2008 from Charles A unifying new paradigm for global health, Health Affairs, 2007, 26 Gardner who served on CARTHA’s founding Board of Directors from (4):1052–1057. 2006–2009. 2. See www.cartha.org; CARTHA’s tagline is Cultivating Collaborative Doers. 13. Balakrishnan U, Ramamoorti S. Contrasting inhabitants of distinct 3. See www.autm.net. Several AUTM-like networks have now arisen: ACCT cultures: Towards an academic-practitioner dialogue for real world (Canada), ProTon (Europe), FORTEC (Brazil), SARIMA (Africa), ATMT problem-solving & decision-making. accessible at (Taiwan), Knowledge Commercialisation Australasia, STEM (India), etc. www.cartha.org/WorkingPaper/. 4. Excerpted from www.sghi.org; www.cihr-irsc.gc.ca/e/32709.html; 14. This is an intentional play on words. While leadership excellence in the http://www.ashoka.org/fellow/ and Zlotkin SH et al. Micronutrient social sector surely needs a combination of personal humility and sprinkles to control childhood anemia. PLoS Medicine, 2005, Jan; professional will (as stated by Jim Collins who also interestingly points out 2(1):e1. Also see Silversides A, Long Road to Sprinkles, Canadian “why business thinking is not the answer” in the subtitle of his 2005 Medical Association Journal, 26 May 2009, 180 (11):1098. monograph titled “Good to great and the social sectors”), these traits are 5. Excerpted from www.uihealthcare.com and www.ponseti.info/pia/. simply insufficient to raise awareness for or helpfully address the immense 6. Many of these public-private product development partnerships and scale or social and cultural underpinnings of dire economic consequences programme transformations in global health research have been spurred and human suffering due to poverty-driven health disparities. and supported by funding either directly or indirectly by entities such as 15. Technology Managers for Global Health (www.tmgh.org) formed in 2003 The Rockefeller Foundation; Bill & Melinda Gates Foundation; national initially as an AUTM Special Interest Group in partnership with MIHR, a governments and international development agencies. Also see Koplan, nonprofit initiated by the Rockefeller Foundation. Also see Balakrishnan U, JP et al. Towards a common definition of global health, Lancet, 2009, Troyer L, Brands E. Surveying the need for “Technology Management for 373: 1993–1995. Global Health” training programs. Journal of the Association of University 7. Mahoney RT, Morel CM. A global health innovation system (GHIS), Technology Managers, 2006, 18 (2):53–68. Innovation Strategy Today, 2006, 2(1):1–12. 16. Stevens, AJ, Effort, AE. Using Academic Licensing Agreements to promote 8. See Article 18 of The Bamako Call to Action on Research for Health: global social responsibility. Les Nouvelles – Journal of the Licensing Strengthening research for health, development, and equity, from the Executives Society International, 2008, 43 (2):85–101. See also Global Ministerial Forum on Research for Health, Bamako, Mali, Nov. www.iphandbook.org; and AUTM Better World Report 2009 Innovations 2009. from academic research that positively impact global health at 9. McArthur J, Sachs J. Needed: a new generation of problem solvers. The www.betterworldproject.net. Chronicle of Higher Education, 26 June 2009. 17. Advocacy in science and related training programmes have been topical 10. Skorton DJ. Higher education: special interest or national asset? The themes examined by the Committee on Scientific Freedom, Responsibility Chronicle of Higher Education, 21 November 2008. and the Law of the American Association for the Advancement of Science, 11. See Higher education and collaboration in global context: building a see www.aaas.org and also Leshner AI. “Glocal” Science Advocacy, global civil society. a UK-US Study Group report, July 2009, accessible Editorial in Science, vol. 319, 15 February 2008. See also Haney JM, at Cohn A. Public relations and technology transfer offices: an assessment of http://www.international.ac.uk/our_research_and_publications/index.cfm. US universities’ relations with media and government. Industry & Higher 12. I gratefully acknowledge the contribution of the language for this section Education, 2004, 18 (4):227–234.

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The challenges of cardiovascular medicine in sub-Saharan Africa: opportunities for engagement between academia, industry and civil society

Article by Tembeka Mpako-Ntusi (pictured), Director, Research Development and Technology Promotion, Cape Peninsula University of Technology, Cape Town, South Africa and Ntobeko BA Ntusi, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

lready, cardiovascular disease accounts for 30% of the spectrum from communicable diseases and malnutrition to global burden of disease, with 80% of this CVD and cancer3. In 2001, CVD was the leading cause of Acardiovascular burden occurring in developing death worldwide, with the exception of sub-Saharan Africa countries. By the year 2020, cardiovascular disease will be (SSA), where human immunodeficiency virus/acquired the commonest cause of death in all regions, including sub- immunodeficiency syndrome (HIV/AIDS) was the leading Saharan Africa. Cardiovascular disease in sub-Saharan Africa cause of overall death, with CVD being the second is unique in that it is largely non-ischaemic, predominantly commonest cause of death in this region4. It is predicted that affects the young, and infections remain an important by the 2020, CVD will be the leading cause of death in all contributor to its aetiology. Because cardiovascular disease in regions of the world, including SSA5. Hypertension, stroke, Africa mostly affects the young, it has the potential to cardiomyopathy and rheumatic heart disease (RHD) have undermine national productivity. Therefore policy planners emerged as the dominant forms of CVD in SSA6–9. have to invest in the health of its citizens, particularly in the Unlike in the industrial nations where the epidemiology of management of cardiovascular disease, if Africa is to realize cardiovascular disease is well-understood, there are no economic development. Important causes of cardiovascular community-based studies of the incidence and prevalence of disease on the African continent include hypertension, heart CVD in SSA6,8,10. Most of the information about CVD on the failure, stroke, diabetes, and emerging problems of obesity African continent is obtained from studies on hospitalized and smoking. The phenomenology of cardiovascular disease patients. These studies highlight three significant and in sub-Saharan Africa is intricate and demands a cohesive, intriguing observations related to the epidemiology of CVD in multi-faceted and multi-level approach. The challenge of SSA. Firstly, common cardiovascular disorders in Africa like cardiovascular health in Africa provides opportunities for hypertension11, stroke12, peripartum cardiomyopathy13, collaboration between policy-makers, nongovernmental rheumatic heart disease14, and endomyocardial fibrosis15 organizations, professional societies, academics, health present predominantly in the young6,16. This is in contrast to professionals, research funding organizations, pharmaceutical industrial nations where coronary artery disease, heart failure companies and related industries, and civil society at large. and other forms of CVD are diseases of the elderly17. Secondly, the causes of CVD in SSA remain largely non-ischaemic. The Introduction observation that the diagnosis of myocardial infarction was At the beginning of the 20th century, cardiovascular disease made in only 0–10% of cases admitted to African hospitals (CVD) was responsible for less than 10% of all deaths for heart disease confirms that ischaemic heart disease globally. The last century witnessed a rise in the rates of CVD remains uncommon in black Africa, although indications are that coincided with industrialization and urbanization, which that it is on the increase6,18. With the exception of were closely associated with increased levels of hypertension, hypertension, risk factors for coronary artery disease remain diabetes and dyslipidaemia1. Already in the early part of the low throughout most of SSA19,20. Thirdly, infections remain a 21st century, CVD accounts for approximately 30% of deaths significant cause of CVD in Africans. Cor pulmonale and worldwide, with 80% of this cardiovascular burden in the pericarditis, largely due to tuberculosis, account for developing world2. The epidemiological transition occurring in approximately 10% of causes of heart failure in Africa6. Africa has the consequence of economic and social Pericardial disease, whose burden has increased in the transformation, resulting in dramatic shifts in the disease advent of the HIV/AIDS epidemic, is mainly due to

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tuberculosis; and cor pulmonale, is most commonly children affected by RHD globally live on the continent. RHD secondary to post-tuberculous lung disease21. Syphilitic heart accounts for a major proportion of all CVD in children and disease, which previously accounted for substantial young adults in African countries33. The incidence of acute morbidity on the African continent, is now much less rheumatic fever in developed nations has dropped common22. However, HIV has replaced syphilis in SSA, and precipitously to below 1 in 100 000, but in Sudan it exceeds affects about 30 million Africans23. HIV-related cardiac 100 in 100 00034. RHD accounts for 17–43% of all disease includes tuberculous pericarditis, HIV cardiovascular disease in SSA16. The disease causes cardiomyopathy, HIV-associated pulmonary hypertension, 400 000 deaths annually, mainly among children and young and metabolic complications of highly active antiretroviral adults living in developing countries33. At least 12 million therapy (HAART), which comprise dyslipidaemia, diabetes, people are estimated to be currently affected by rheumatic accelerated atherosclerosis, and early coronary artery heart disease with two million patients requiring repeated disease, all of which significantly contribute to cardiovascular hospitalization and 1 million requiring, often unaffordable, morbidity in SSA24,25. heart surgery in the next 5 to 20 years35. Of great concern is the fact that the early presentation of Idiopathic dilated cardiomyopathy (DCM) contends with heart disease in Africans has the potential to undermine RHD and hypertension as the leading causes of heart failure national productivity, as a consequence of the number of in Africa36, accounting for 10–17% of all cardiac conditions active life years lost by the most productive segment of the encountered at autopsy in South Africa and Uganda37. In population6,10. In a report titled A race against time: the SSA, DCM occurs commonly in the third and fourth decades challenge of cardiovascular disease in developing countries, of life, with men affected twice as commonly as women38. Leeder and colleagues estimated that in five developing Peripartum cardiomyopathy (PPCM) shares many countries (Brazil, India, China, South Africa and Mexico), at common features with other forms of non-ischaemic least 21 million years of future productive life are lost cardiomyopathy10. However, women with PPCM are younger, annually because of cardiovascular disease26. However, while have a higher rate of spontaneous recovery of left ventricular the disease burden and the societal and health care costs of function, and have better survival than patients with CVD are high in SSA, the resources devoted towards health idiopathic DCM39. In the USA, the incidence of PPCM is 1 care are extremely scarce3. per 4000 births40, while in South Africa it is estimated to be In this paper, the current challenges to CVD in SSA will be 1 per 1000 births41. Endomyocardial fibrosis (EMF) has reviewed. Clearly, CVD in SSA is a complex phenomenon that previously been shown to be the commonest cause of heart demands a comprehensive, multi-faceted and multi-level disease in Ugandan hospitals, accounting for nearly 20% of approach. Possible approaches to the predicament of CVD in cases referred for echocardiography42. EMF has been found Africa are explored, with a particular focus on the possibilities to predominate in children and young adults, with a peak for collaboration between all levels of society. incidence at the ages of 11 and 15 years in both sexes; with women showing a second peak between 26 and 30 years43. The nature of the problem: the state of Hypertrophic cardiomyopathy has been shown to occur cardiovascular health in sub-Saharan Africa commonly among Africans, and is an important cause of 1. Hypertension – high blood pressure has a prevalence of heart failure44,45. up to 30% in SSA27. There were approximately 80 million patients with hypertension in SSA in 2000 and projections 3. Stroke – stroke is common in SSA, affecting based on current epidemiologic data suggest that this figure predominantly the young, with a high morbidity and will rise to 150 million by 202528. The increase in the mortality12. A recent systematic analysis of the burden of incidence of hypertension appears to be closely correlated stroke in SSA revealed that: (1) although the absolute with ageing of the population as well as with the growing number of stroke deaths remains low as a result of the number of overweight and obese persons29. The association population structure of SSA (about 44% of people are under of arterial hypertension with type 2 diabetes is particularly 15 years of age), the age-adjusted stroke mortality among deleterious30. Contemporary trends show regional variations adults in sub-Saharan Africa appears similar to that occurring with prevalence being associated with the rate of in high-income regions, and is increasing; (2) although urbanization and westernization of lifestyle31. In black Africans, comparable community-based case-fatality studies are perhaps due to delayed and/or inadequate therapeutic lacking, the available case-fatality data from hospital-based management and to a likely genetic predisposition, organ- prospective studies reveal a rate of about 30% at one month related complications are more common and occur earlier. – a value much higher than the 20% reported for much older Stroke, heart failure and renal failure are frequent populations in the industrial world; (3) the stroke incidence complications in young hypertensive African patients, with from hospital-based studies is lower than that in community- significant social and economic implications32. based studies in high-income regions, but it is higher in people younger than 65 years of age; and (4) the prevalence 2. Heart failure – hypertension, cardiomyopathy and of disabling stroke in sub-Saharan Africa is at least as rheumatic heart disease (RHD) account for over two thirds of high as in high-income areas despite the fact that the cases of heart failure in SSA6. Whereas Africa has 10% of the prevalence of stroke in SSA is less than half that found in world’s population, as many as half of the 2.4 million high-income regions46.

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4. Diabetes – type 2 diabetes is the predominant form of infarction increased with higher income and education levels diabetes in SSA, accounting for over 90% of cases. Type 1A in the black African group, in contrast to the findings in other (autoimmune type 1) and type 1B (idiopathic type 1) or racial groups such as whites and coloureds (mixed ancestry)20. alternatively ketosis-prone type 2 diabetes constitute the remainder47. Both the IDF and WHO predict a rise in the Possible solutions for the challenges to CVD in SSA: number of people with diabetes to 380 million by 202548,49. opportunities for engagement between academia, Low- and middle-income countries will bear the burden of industry and civil society this increase, and Africa will contribute significantly to this CVD in SSA is well established as a significant cause of rise. A recent publication from South Africa, reported that morbidity and mortality. Furthermore, CVD in SSA has a large undiagnosed diabetes was present in 20% of indigenous economic impact. Hence, debate has emerged on what Africans with angiographically proven coronary artery should be the appropriate cardiovascular agenda for SSA. We disease50. It is very probable that diabetes-related CAD and believe that the challenges that face CVD in SSA also present ischaemic left ventricular dysfunction contributes significantly opportunities for various stakeholders within African society to the rising tide of IHD in SSA. to come together and explore interventions that lead to a decrease in the suffering and death from CVD in the region. 5. Metabolic syndrome – although the risk factors for atherosclerosis have traditionally been low in Africans, with 1. Reliable data on, and risk factors for CVD at a the exception of hypertension, the picture is changing rapidly, population level does not exist in SSA58. We need population- with the prevalence of diabetes, dyslipidaemia, overweight based studies on the incidence and prevalence of CVD and obesity in most African countries increasing markedly morbidity and mortality. It is only when we understand the over the past 20 years. A recent study from South Africa magnitude of the problem that we can better develop showed that the metabolic syndrome could be diagnosed in strategies to deal with it. Large-scale epidemiological and up to 25.5% of urbanized women51. The prevalence of clinical research is needed in order to provide local answers obesity in Nigeria has recently been found to be as high as to the challenges of CVD in SSA. Importantly, CVD needs 31.7%52. In this study, obese Africans tended to be female to be understood within a local explanatory framework and young, with strong predictors of obesity being a family of culture. history of obesity and a sedentary lifestyle. This rising tide of the metabolic syndrome in SSA is further worsened by the 2. Limited resources are allocated to health services in double burden of HIV/AIDS. HAART for treatment of HIV low-income countries. Cardiovascular diseases have to infection produces a spectrum of metabolic complications, compete with other significant burdens like infectious which include dyslipidaemia, insulin resistance and changes disease, malnutrition and high infant and maternal mortality. in body fat compartmentalization53. Health planners need to prioritize cardiovascular health in Africa because of its high clinical burden and social impact. 6. Ischaemic heart disease – numerous reviews and reports have highlighted the rarity of coronary artery disease 3. Health systems need to re-orient their planning, so that (CAD) in SSA. In a study conducted in 1960, CAD was they not only focus on acute care, but imperatively, also on shown to be “extremely rare” in Africans54, and, in fact, in a care of chronic CVD. Facilities and infrastructure should be later study, Africans were declared to be “virtually free” from improved, and there is a great need for adequately trained CAD55. Reports from SSA hospitals indicate that African personnel to manage CVD in SSA47. patients with CAD tend to be younger, with males outnumbering females, and that the clinical and laboratory 4. There is a greater need for focusing on prevention features and complications of CAD are similar to those in the strategies for CVD in SSA. These strategies would ideally white population56. The reported rarity of CAD in SSA must be initiate and promote tobacco control programmes, improve accepted cautiously, as the evidence is not strong enough to blood pressure control, improve diabetic control, lower serum confirm that ischaemic heart disease was rare, without lipids, and promote healthy lifestyles – increased exercise, accounting for misdiagnoses, limited access to and lack of moderate use of alcohol, and a diet rich in fruits and facilities for making the appropriate diagnosis6. More recently, vegetables and low in saturated fats58. however, a South African study indicated that modifiable risk factors for atherosclerosis were high, with 56% of patients 5. It is an imperative requirement to have improved being hypertensive, 44% obese, and only 13% had no risk access to health care facilities throughout the African factors for CAD18. Furthermore, 10% of patients studied were continent, particularly in rural areas. It is common for people diagnosed with CAD. This is the first study to report evidence in Africa to travel hundreds of kilometers to reach the nearest of strong epidemiological transition occurring in urban healthcare facility. There is a need to develop and maintain Africans. The major modifiable risk factor for CAD in Africa appropriate infrastructure to deal with the double burden of is hypertension, with an incredible odds ratio of 6.9920. infections, malnutrition and chronic diseases of lifestyle. Other identified risk factors for CAD in SSA include high salt intake, increased body weight and physical inactivity57. In 6. At a primary health level, there is a lack of education the INTERHEART African study, the risk of acute myocardial and screening for many cardiovascular disorders and their

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complications. Planners need to put in place strategies to Key messages prevent, improve early detection and treatment of CVD. CVD in SSA is common, and will continue to increase 7. In many SSA countries, with the notable exception of in the foreseeable future. By the year 2020, CVD will South Africa and Namibia, payment for medication is the account for major morbidity and mortality on the responsibility of the patient. The cost of drugs needed for African continent. management of CVD is often beyond the reach of most CVD in SSA is unique in that: patients. Hence, simple treatments need to be cheaper and 1. it predominantly affects the young; more available for patients in SSA. 2. it is largely non-ischaemic; 3. infections remain an important cause of CVD 8. In order to achieve the goal of low-cost, affordable in Africa. drugs, pharmaceutical and related industries should also Because CVD in SSA affects the young, it has the participate in the continental effort to fight CVD. potential to undermine national productivity. SSA has to invest in the health of its citizens, particularly 9. Few centres in SSA have the infrastructure and in the management of CVD, if it is to realize expertise to conduct large-scale epidemiologic research. economic development. The culture of research is often non-existent in many medical CVD in SSA is a complex phenomenon that demands schools and universities. There is a need for a coordinated a comprehensive, multi-faceted and multi-level national and continental plan for research, as well as approach. The challenge of CVD in Africa provides improving existing regulatory frameworks for research on opportunities for collaboration between policy- the continent. makers, nongovernmental organizations, professional societies, academics, health 10. Funding and capacity is a great challenge for professionals, research funding organizations, researchers, academics and professional organizations that pharmaceutical and related industries, and civil plan and conduct studies, clinical trials, and programmes society at large. A systems approach to addressing for CVD in SSA. Such funding is needed to improve not only the challenges presented by CVD in SSA has a the investigation of heart disease, but also to improve service high success potential, especially when all the provision, refurbishment of facilities, remuneration and relevant subsystems perform various integrated training of personnel. There is an opportunity for increased functions focusing on both prevention and collaboration between public and private partners, to enable management strategies. facilities to provide optimal cardiovascular services and support.

11. Various segments of society need to raise awareness 14. Most Africans still consult both traditional and about the public health hazards of smoking, excessive western medicine practitioners. There are often conflicting alcohol use, physical inactivity, obesity, high glycaemic load, messages and explanatory models of disease. In order to and a diet high in saturated fats. Furthermore, planners improve the care of people with CVD, there needs to be need to put in place strategies to improve access to greater communication and collaboration between the reasonably priced fruit and vegetable products, and well as various providers within the health sector in SSA. safe and accessible recreational facilities to encourage participation in exercise. 15. Although there is a plethora of guidelines for clinical care in many industrialized societies, it is not the case for 12. Most secondary forms of prevention for CVD (like SSA. There is an urgent need for the development and aspirin, statins, B-blockers and ACE-inhibitors) have been implementation of clinical guidelines from academics and evaluated in populations in industrial nations. There is professional bodies for improved prevention and flagrant lack of data from SSA. The establishment of management of CVD in SSA. collaborative registries of common CVD on the continent will go a long way in rectifying this situation58. 16. Policy planners in Africa must adopt a life course approach to the epidemiology of CVD in SSA. The life 13. There is a need to improve efficiency in implementing course approach studies the long-term effects on chronic existing and currently expended programmes on CVD disease risk of physical and social exposures during prevention and management on the continent. When policy gestation, childhood, adolescence and later adult life. Thus, planners propose relevant strategies, their implementation is planners should focus on investigation of biological, often constrained by inadequate human and financial behavioural and psychological pathways that operate across resources. There is also a need for an integrated approach for an individual’s life-course, as well as across generations, to promoting and sustaining CVD prevention and management. influence the development of chronic diseases59. Hence, all segments of society should be involved in both planning and implementation of relevant programmes.

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Conclusion physician based at Groote Schuur Hospital and the University of CVD in SSA is common, and its prevalence is predicated to Cape Town. He has an interest in clinical cardiology, clinical increase dramatically in the future. To quote from Reddy, research, medical education, and the interface of cardiovascular “Epidemics of cardiovascular disease in non-Western medicine with public health. His research concerns lie in the fields countries present complex challenges but also great of hypertension, non-ischaemic cardiomyopathies and opportunities. Seldom in the history of human health have inflammatory heart disease. His research focuses on the use of we been endowed with such foresight about our destiny and non-invasive imaging modalities to study the pathogenesis of the forearmed with such power to change it. It is a challenge to afore-mentioned clinical entities. human intellect and enterprise to apply our knowledge creatively and cost-effectively to minimize the burden of Dr Tembeka Mpako-Ntusi is the Director of Research and cardiovascular disease throughout the world60”. Technology Promotion at the Cape Peninsula University of The future of cardiovascular health in SSA is at a Technology. Her major responsibility is the coordination of research crossroads, and health and policy planners can contribute activities and the provision of strategic leadership for academic substantially by seizing the opportunity to act now to ensure research. Her research focus area is on gender issues and women’s a healthy future for Africa. studies. She is passionate about the promotion of research to provide solutions for social problems and to improve the quality of Dr Ntobeko BA Ntusi Bsc (Hons), MB ChB FCP (SA), is a life of women and children.

References

1. Yusuf S et al. Global burden of cardiovascular diseases: part I: general in rural Tanzania. International Journal of Epidemiology, 1993; 22:651– considerations, the epidemiologic transition, risk factors, and impact of 659. urbanization. Circulation, 2001; 104:2746–2753. 20. Steyn K et al. Risk factors associated with myocardial infarction in Africa: 2. Mathers CD et al. Deaths and disease burden by cause: Global burden of the INTERHEART Africa study. Circulation, 2005; 112:3554–3561. disease estimates for 2001 by World Bank country group. Working Paper 21. Ntsekhe M, Hakim J. Impact of human immunodeficiency virus on 18, 2002, Bethesda, Maryland USA: Disease Control Priorities Project. cardiovascular disease in Africa. Circulation, 2005; 112:3602–3607. 3. Gaziano TA. Cardiovascular disease in the developing world and its cost- 22. Watson-Jones D et al. Syphilis in pregnancy in Tanzania II: The effective management. Circulation, 2005; 112:3547–3553. effectiveness of antenatal syphilis screening and single-dose benzathine 4. Rodgers A, Vaughan P. World Health Report 2002: Reducing risks, penicillin treatment for the prevention of adverse pregnancy outcomes. promoting healthy life. Geneva, Switzerland: World Health Organization. Journal of Infectious Diseases, 2002; 186:948–957. 5. Murray CJL, Lopez AD (eds). The global burden of disease: a 23. Merson MH et al. The history and challenge of HIV prevention. Lancet, comprehensive assessment of mortality and disability from diseases, 2008; 372:475–488. injuries, and risk factors in 1990 and projected to 2020, 1996. Boston, 24. Magula NP, Mayosi BM. Cardiac involvement in HIV-infected people living Mass: Harvard School of Public Health. in Africa: a review. Cardiovascular Journal of South Africa, 2003; 6. Ntusi NBA, Mayosi BM. Epidemiology of heart failure in sub-Saharan 14:231–237. Africa. Expert Review of Cardiovascular Therapy, 2009; 7:169–180. 25. Nzuobontane D, Blackett KN, Kuaban C. Cardiac involvement in HIV 7. Lemogoum D, Degaute J-P, Bovet P. Stroke prevention, treatment and infected people in Yaounde, Cameroon. Postgraduate Medical Journal, rehabilitation in sub-Saharan Africa. American Journal of Preventive 2002; 78:678–681. Medicine 2005; 29;95–101. 26. Leeder S et al. A race against time: the challenge of cardiovascular 8. Seedat YK, Rosenthal T. Meeting the challenges of hypertension in sub- disease in developing countries, 2004. New York, NY: Trustees of Saharan Africa. Cardiovasc Journal of South Africa, 2006; 17:47–48. Columbia University. 9. Muna WFT. Cardiovascular disorders in Africa. World Health Statistics 27. Seedat YK. Hypertension in black South Africans. Journal of Human Quarterly, 1993; 46:101–107. Hypertension, 1999; 13:96–103. 10. Mayosi BM. Contemporary trends in the epidemiology and management 28. Ezzati M et al. Selected major risk factors and global and regional burden of cardiomyopathy and pericarditis in sub-Saharan Africa. Heart, 2007; of disease. Lancet, 2002; 360:1347–1360. 93:1176–1183. 29. Fourcade L, Paule P, Mafart B. Arterial hypertension in sub-Saharan 11. Opie LH, Seedat YK. Hypertension in sub-Saharan African populations. Africa. Update and perspectives. Médicine Tropicale, 2007; Circulation, 2005; 112:3562–3568. 67:559–567. 12. Mensah GA. Epidemiology of stroke and high blood pressure in Africa. 30. Kengne AP, Amoah AG, Mbanya JC. 2005. Cardiovascular complications Heart 2008; 94:697–705. of diabetes mellitus in sub-Saharan Africa. Circulation, 2005; 112:3592– 13. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet, 2006; 3601. 368:687–693. 31. Poulter NR et al. Determinants of blood pressure changes due to 14. Essop MR, Nkomo VT. Rheumatic and nonrheumatic valvular heart urbanization: a longitudinal study. Journal of Hypertension – Supplement, disease: epidemiology, management, and prevention in Africa. Circulation, 1985; 3:S375–S377. 2005; 112:3584–3591. 32. Dzudie A et al. Chronic heart failure, selected risk factors and co- 15. D’Arbela PG et al. Survival after first presentation with endomyocardial morbidities among adults treated for hypertension in a cardiac referral fibrosis. British Heart Journal, 1972; 34:403–407. hospital in Cameroon. European Journal of Heart Failure, 2008; 16. Damasceno A et al. Heart failure in sub-Saharan Africa: time for action. 10:367–372. Journal of the American College of Cardiology, 2007; 50:1688–1693. 33. Rheumatic fever and rheumatic heart disease: report of a WHO expert 17. Wenger NK. The graying of cardiology: implications for management. consultation: Geneva, 29 October–1 November 2001. WHO Technical Heart, 2007; 93:411–412. Report Series, 2001; 923. 18. Sliwa K et al. Spectrum of heart disease and risk factors in a black urban 34. Community control of rheumatic disease in developing countries: a major population in South Africa (the Heart of Soweto Study): a cohort study. public health problem. WHO Chronicle, 1980; 34:336–345. Lancet, 2008; 371:915–922. 35. Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary 19. Swai ABM et al. Low prevalence of risk factors for coronary heart disease prevention of acute rheumatic fever: a meta-analysis. BMC Cardiovasc

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References continued

Disorders 2005; 5: 11-. 49. Roglic G, Unwin N, Bennett PH, et al. The burden of mortality 36. Akinkugbe OO, Nicholson GD, Cruickshank JK. Heart disease in blacks of attributable to diabetes: realistic estimates for the year 2000. Diabetes Africa and the Caribbean. Cardiovasc Clin 1991; 21: 377–391. Care 2005; 28: 2130–2135. 37. Steenkamp JH, Simson IW, Theron W. Cardiovascular causes of death at 50. Ntyintyane LM, Panz VR, Raal FJ, et al. Metabolic syndrome, Tshepong Hospital in 1 year, 1989–1990: a necropsy study. S Afr Med J undiagnosed diabetes mellitus and insulin resistance are highly prevalent 1992; 81: 142–146. in urbanised South African blacks with coronary artery disease. 38. Chetty S, Mitha AS. Arrhythmias in idiopathic dilated cardiomyopathy: a Cardiovasc J S Afr 2006; 17: 50–55. preliminary study. S Afr Med J 1990; 77: 190 –193. 51. Schutte AE, Schutte R, Huisman HW, et al. Classifying Africans with the 39. Ntusi NBA, Mayosi BM. Aetiology and Risk Factors of Peripartum metabolic syndrome. Hom Metab Res 2009; 41: 79-85. Cardiomyopathy: A Systematic Review. Int J Cardiol 2009; 131: 168- 52. Siminialayi IM, Emem-Chioma PC, Dapper DV. The prevalence of obesity 179. as indicated by BMI and waist circumference among Nigerian adults 40. Cetta F, Michels VV. The natural history and spectrum of idiopathic attending family medicine clinics as outpatients in Rivers State. Niger J dilated cardiomyopathy, including HIV and peripartum cardiomyopathy. Med 2008; 17: 340-345. Curr Opin Cardiol 1995; 10: 332 –338. 53. Samaras K, Wand H, Law M, et al. Prevalence of metabolic syndrome in 41. Desai D, Moodley J, Naidoo D. Peripartum cardiomyopathy: experiences HIV-infected patients receiving highly active antiretroviral therapy using at King Edward VIII Hospital, Durban, South Africa and a review of the the International diabetes Foundation and Adult Treatment Panel III literature. Trop Doct 1995; 25: 118–123. criteria. Diabetes Care 2007; 30: 113-119. 42. Freers J, Mayanja-Kizza H, Ziegler JL, et al. Echocardiographic diagnosis 54. Shaper AG, Williams AW. Cardiovascular disorders at an African hospital of heart disease in Uganda. Trop Doct 1996; 26: 125–128. in Uganda. Trans Roy Soc Trop Med Hyg 1960; 54: 12-32. 43. Rutakingirwa M, Ziegler JL, Newton R, Freers J. Poverty and eosinophilia 55. Vaughan JP. A brief review of cardiovascular disease in Africa. Trans R are risk factors for endomyocardial fibrosis (EMF) in Uganda. Trop Med Int Soc Trop Med Hyg 1977; 71: 226-231. Health 1999; 4: 229- 235. 56. Bertrand E. Coronary heart disease in black Africans: an overview. East 44. Amoah AG, Kallen C. Aetiology of heart failure as seen from a national Afr Med J 1995; 72: 37-41. cardiac referral centre in Africa. Cardiology 2000; 93: 11–18. 57. WHO Report. Cardiovascular disease: prevention and control. 2007. 45. Abegaz B. The impact of echocardiography in the diagnosis of 58. Yusuf S, Vaz M, Pais P, et al. Tackling the challenge of cardiovascular hypertrophic cardiomyopathy. East Afr Med J 1990; 67: 556 –567. disease burden in developing countries. Am Heart J 2004; 148: 285- 46. Connor MD, Walker R, Modi G, et al. Burden of stroke in black 293. populations in sub-Saharan Africa. Lancet Neurol 2007; 6: 269–278. 59. Ben-Shlomo Y, Kuh D. A life course approach to chronic disease 47. Levitt NS. Diabetes in Africa: epidemiology, management, and healthcare epidemiology: conceptual models, empirical challenges and challenges. Heart 2008; 94: 1376-1382. interdisciplinary perspectives. Int J Epi 2002; 31: 285-293. 48. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: 60. Reddy KS. Cardiovascular disease in non-western countries. New Engl J prevalence, numerical estimates, and projections. Diabetes Care 1998; Med 2004; 350: 2438-2440. 21: 1414–1431.

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Civil society engagement – a key strategy in research for health

Article by Sylvia de Haan (pictured), Head of Projects and Programmes, Council on Health Research and Development, with Samuel Anya, Ayo Palmer and Paul Bloch

he ultimate test of any research or intervention is the for health”, which includes sectors beyond health (such as extent to which it makes a difference in the lives of agriculture, housing and environment) that have a direct Tthose it is designed to benefit. For some research, impact on the health of populations. especially operational or applied research, the expectation is that it can directly contribute to better health or better health Selected case studies of CSO involvement in research services. For other, more basic or fundamental research, for health several years may pass and additional research may be There are good examples of CSOs contributing to research for needed before the findings have an impact on health. health and the health research process in their respective However, findings from research may not necessarily lead to countries. The examples vary from influencing specific health improvement of services delivered to a community, or to programmes and health policies (the examples of the Centre changes in health policies that have positive effects on the for Science and Environment and the Integral Health health of populations. Research in developing countries is Coordination Programme) to attempting to influence national particularly challenging due to weak research capacity, weak health research policies and systems (the examples of policy-making processes, and a social and political context Research!America and the Public Health Research & that is frequently not conducive to the meaningful Development Centre). participation of all stakeholders in research1. Besides, The Centre for Science and Environment (CSE) in India is research agendas are often influenced and directed by the an independent, public interest organization that aims to priorities of funding agencies leading to research that has no increase awareness on issues related to science, technology, direct link to the priorities of the country and its people. environment and development. CSE played an important role The participation and engagement of civil society and civil in providing evidence that Endosulfan residues, a pesticide society organizations (CSOs) in research is increasingly seen sprayed aerially on cashew nut plantations, were over several as a key strategy that can contribute to a better targeting of hundred times the residue limit in the blood of the population research, improve the quality of research and increase the in a village in Kerala. Subsequently, the affected community utilization of research results. The contextual knowledge of used this evidence in court to successfully secure a ban of the civil society is a reason for ensuring their participation in use of the pesticide in the state1. research that affects national and local practices and policies. In Bolivia, the Integral Health Coordination Programme Researchers, health professionals and civil society collectively (PROCOSI), an umbrella nongovernmental organization can produce “better” research, that is, research of higher (NGO), was involved in a programme focusing on the methodological and ethical quality, that responds better to prevention of Chagas disease, primarily through the community needs, that produces findings which are more improvement of housing conditions. The vector causing the relevant to practical decisions made by the community, that disease was seen as a good luck omen by the community, is presented in more accessible formats, widely disseminated, rather than as a public health risk. Research with the and that more appropriately influence policy and practice2–5. community to understand this situation helped to jointly set Furthermore, civil society participation can help increase priorities for health improvement. This was combined with accountability of researchers and funding institutions towards education of the use of local resources (i.e. a tiled roof) the population they are meant to serve with their research. against the vector1. This may help to create an involved community that is better Research!America is a public education and advocacy informed and recognizes the value of research and the alliance focusing on making research to improve health a research process 2,5,6. higher priority in the United States of America. The involvement of stakeholders from various sectors and Research!America succesfully lobbied for an increase in the disciplines – including civil society organizations – is needed National Institutes of Health (NIH) budget. It aims to increase especially in the transition from “health research” to “research funding for health research and to motivate and empower the

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public to actively support research. It uses public opinion Box 1: The Call for Civil Society Engagement in Research for Health surveys as a tool to achieve its objectives. The findings of The Call for Civil Society Engagement in Research for Health these surveys illustrate the supportive attitude of Americans calls on all stakeholders to: towards health research. For example, 67% of Americans are Acknowledge the importance of research for improving willing to pay US$ 1 more per week in taxes for additional health for all, and to recognize the contribution CSOs can medical research, and 95% indicated that it is important to make to support the broad scope of research for health, with a focus on health, development and equity. conduct health research to understand and eliminate health Build and nurture partnerships with CSOs around common disparities in the population7. concerns on national and global priorities in research for The Public Health Research and Development Centre health, and to base these partnerships on the principles of (CIAM) in the Gambia plays, as an NGO, a supportive role in mutual respect, fairness, inclusiveness, transparency and strengthening the governance of the health research system trust and with a multidiscipline approach. in the country. With links to government, academia and other Create environments at national and global levels in which NGOs, it is well placed to play an advovacy role in the area CSOs can exercise their legitimate roles in research for of health research policy development and health research health, by providing financial, infrastructural development agenda setting in the country, and support the Ministry of and institutional capacity building support to CSOs. Health in developing an effective and sustainable health Provide funding which is long-term and flexible, based on research system8. fair contracting principles, thus strengthening CSOs to engage in participatory processes, build their institutional capacity, and becoming a strong partner in developing and Strategies to increase the role of CSOs in research implementing research strategies at local, regional and for health global levels. Despite the evidence from the literature, and the case studies Value additional and creative means of communicating described above and elsewhere, civil society and CSOs still research, using a variety of channels and languages, and to often play only a marginal role in national health research acknowledge the role CSOs can play in raising awareness of and in strengthening health research systems. To change this research, in increasing engagement in research, in situation and to draw the attention to the potential of transforming research findings into action, and in engaging CSOs in health research, CIAM, the Centre for communicating this to the public, thus helping build public Health Research and Development (DBL, Denmark) and the trust in research. Council on Health Research for Development (COHRED) Jointly identify indicators and methodologies for evaluating the impact and contribution of all stakeholders, including jointly organized an international consultative process prior to CSOs, in research for health. the Ministerial Forum on Research for Health (Bamako, November 2008). This consultation resulted in a Call for Civil Society Engagement in Research for Health9, which was subsequently presented and debated in Bamako, and helped Research institutions to: to put CSO engagement in research for health high on the – adjust institutional policies to facilitate CSO agenda of the Bamako Forum. The acknowledgement of the engagament within their institutions and research role of CSOs in research for health is reflected in the three programmes; outputs from Bamako – the Ministerial Plan of Action, the – provide training for researchers and CSO partners; Bamako Communique, and the Call for Civil Society – develop clear partnership arrangements that allow Engagement. participation to become collaborative and empowering, The high-level political recognition obtained at the Bamako rather than consultative only; Forum now needs to be translated into action to ensure CSO – play a key role in developing the research agenda, engagement in research as a standard practice , especially in and work with CSOs in this process. the South. Government, academia, funding institutions and Funding institutions and development agencies to: development agencies, and CSOs can undertake one or more – provide planning grants, training grants and long-term of the following actions to work towards strengthening CSO funding, so that the ability of CSOs to participate in engagement in research for health: research can be strengthened throughout projects and programmes; Governments to: – set funding criteria that ensure a focus on – develop legal and policy directions that specify collaboration with CSOs for part of their funding citizen’s rights to have a say in research. Such schemes. frameworks facilitate action by CSOs to demand these Civil society organizations to: rights; – develop networks of CSOs to create a stronger voice – coordinate the other actors in research and provide to influence policies, strategies and agendas of other the corner stones of a research system through which actors; interaction and partnership building between actors is – engage with media to disseminate information to the strengthened; public about the benefits of research and the – facilitate inclusive agenda setting for research and importance of involving civil society therein; encourage CSO input to this process. – highlight priorities and real needs of populations, and

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use this to contribute and influence the agenda setting Sylvia de Haan MSc, MPH is a health scientist. She worked for process; several years in public health research, and environmental and – identify their own capacity building needs and ensure occupational health research in the Netherlands, Niger and staff training where needed. Tanzania. She is currently the Head of Projects and Programmes For all actors to monitor and document progress made with the Council on Health Research for Development (COHRED) with moving towards CSO engagement in research for and is based in Geneva, Switzerland. Sylvia de Haan has over ten health. Monitoring and reporting will allow re-direction of years of experience in supporting health research system strategies and approaches to ensure that research development in the South and is leading COHRED’s work around increasingly becomes a tool for health development of civil society engagement in research for health. those most in need. Samuel Anya MBBS, MRCOG has been Director of CIAM – Public Over the past two to three decennia there has been a shift Health Research & Development Centre in the Gambia since 2009. away from regarding the community as a subject of research His work focuses on building a sustainable health research system to working with civil society and CSOs in partnership and in the Gambia and facilitating evidence-based decision-making. dialogue in research. The strategies described in this paper He also reviews health and M&E systems of the principal recipients are a first step in proposing how CSOs could become more of Global Fund grants in Ghana, Liberia and Sierra Leone. Samuel involved in research for health. What remains is to spell out Anya led the obstetrics and gynaecology programme at the further details of how each strategy would be implemented so University of The Gambia until July 2008. that the expected impact of CSO engagement can be meaningfully assessed within a context in which all actors Ayo Palmer MRCP, MSc is Senior Technical Coordinator at CIAM. involved in research for health reinforce their involvement by She previously served as Director of CIAM from 2004 to 2009. Ayo building upon their individual strengths. Palmer is a paediatrician and public health practitioner with extensive experience of working in the health-care system in the Key messages Gambia. She has designed and implemented operational studies to address implementation constraints, set up national monitoring Research for health takes a broader view than health and evaluation systems for health programmes, and worked as a research. It includes sectors beyond health (such as consultant in countries in the sub-region to review the health, agriculture, housing and environment) that have a monitoring and evaluation components of grants funded by the direct impact on the health of populations. To Global Fund to fight AIDS, TB and malaria. ensure an effective move towards research for health, the involvement of stakeholders from various Paul Bloch MSc, PhD is a senior scientist and technical adviser sectors and disciplines – including civil society in the field of health systems research and capacity building at the organizations (CSOs) – is needed. Centre for Health Research and Development, University of CSOs can play a key role in all aspects of the Copenhagen, Denmark. He has worked in the interface between research process, from developing a research operational research and development in Africa for almost 20 years agenda that responds to the needs and concerns of and is currently mainly occupied with action research on fair the public, to conducting research and transforming priority setting and decision-making processes within district research findings into action. health systems in Kenya, Tanzania and Zambia, and with health Key strategies have been developed that can be research systems strengthening and policy advocacy in the Gambia. used by governments, academia, funding bodies, development agencies and CSOs to further strengthen CSO engagement in research for health.

References

1. Can communities influence national health research agenda’s? Record 6. Minogue V et al. The impact of service user involvement in research. Series Paper 3, Geneva: Council on Health Research for Development International Journal of Health Care Quality Assurance Incorporating (COHRED), 2006a. Leadership in Health Services, 2005, 18(2–3), 103–112. 2. Summary statement on consumer and community participation in health 7. Woolley M, Propst SM. Public attitudes and perceptions about health- and medical research. Canberra: National Health and Medical Research related research. Journal of the American Medical Association, 2005, Council (NHMRC) and Consumers Health Forum of Australia, 2002. 294(11), 1380–1384. 3. O’Fallon L, Dearry A. Community-based participatory research as a tool to 8. Palmer A, Anya S, Bloch P. The political undertones of building national advance environmental health sciences. Environmental Health health research systems – reflections from the Gambia. Health Research Perspectives, 2002, 110(Supp. 2), 155–159. Policy and Systems, 2009, 7:13. 4. Oliver S et al. Involving consumers in research and development agenda 9. A Call for Civil Society Engagement in Research for Health. Towards a setting for the NHS: developing an evidence-based approach. Health Post-Bamako Action Plan. Input to the Global Ministerial Forum on Technology Assessment, 2004, 8(15), 1–148, III–IV. Research for Health. Bamako, November 2008. Available at: 5. Shea B et al. Consumer-driven health care: building partnerships in http://www.cohred.org/main/Assests/PDF/Bamako_web.pdf research. Health Expectations, 2005, 8(4), 352–359.

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Last mile delivery in health care and patient empowerment through technology: the case of “Telecommunication for Health”

Article by Roberto Tapia-Conyer (pictured), Director-General, Carso Health Institute – Carlos Slim Foundation, Mexico, and Rodrigo Saucedo, Researcher, Carso Health Institute – Carlos Slim Foundation, Mexico

he epidemiologic profile of the population in Latin America has hospital-based interventions with community participation. been continuously changing for the last 30 years. The second major turnaround refers to the degree of TNoncommunicable diseases have emerged as the main burden involvement of patients with respect to their own disease. It is of national health systems, shifting the pattern from the youngest estimated that only 50% of patients comply with their population to the eldest e.g. diabetes, cardiovascular diseases and physicians’ prescription irrespective of the disease or their obesity. The average mortality rate from diabetes mellitus (DM) in Latin age10. Treatment of chronic diseases requires an intake of America1 is 35 with the extreme cases of Mexico (83.1) and several doses of medication on a daily basis, and there is an Uruguay (14)2,3. The International Diabetes Federation inverse linear relation between the number of doses and the estimated that in 2007 there were 20.7 million people with levels of compliance11. Additionally, people discontinue their DM and impaired glucose tolerance whereas in 2025 there will medicine intake within a period of time; patients suffering from be 41.2 miliion people; this is a 99.2% growth rate. In fact, hypertension generally discontinue their medication intake in WHO estimates that in 2030 nine out of the ten main causes 90 days12. On the other hand, the ageing of the population of death will be attributable to noncommunicable diseases4. plays a key role. In Latin America life expectancy at birth has Research into causes of this increase does not point a linear increased from an average 61.1 years for the 1970–1975 cause. A sedentary lifestyle and bad diet have been pointed to period to 73.8 in 2005–2010, and it will increase to 77.3 as the main driving forces5. On the other hand, cognitive and years in 2025–2030, as Figure 1 shows13. This scenario is motivation factors play a key role too6. immersed in a context of globalization and immigration, which Nevertheless, some communicable diseases are present in limits the capacity of national health systems to provide people’s entire lives such as HIV/AIDS. The number of people continuous and sustained health treatment. Health systems living with HIV/AIDS in Latin America has grown from 1.3 must be able to provide mobile health care, either with mobile million in 2000 to 1.6 million in 2007; a 20.9% growth rate7. health units or through patients’ remote management. Thus, the analysis is now between acute and chronic diseases8. As a consequence, complications related to disease arise, The centre of the analysis in public health is now on morbidity increasing the direct and indirect costs associated to it and rather than on mortality9. At the Carso Health Institute, an driving national health costs in both developed and developing initiative of the Carlos Slim Foundation, we argue that chronic countries. In the US, for diabetes alone, the total cost of diseases are conditions of life and an effective strategy must treatment and complications was 132 billion in 2002, and it integrate health services through multiple bidirectional 80 channels of communication so that the patient, the physician 78 and the health system can continuously interact. 76 74 For the strategy to be effective, we believe that a major 72 turnaround is required at two different levels: at the health 70 68 system-level and at the patient-level. First, there must be a 66 change in the way traditional health services are provided. The 64 62 current system is hospital-centric, it works on a one-to-one 60 interaction and it is limited in the time of interaction between the physician and the patient. Patients are still passive recipients of vertical and reparative interventions. This limits 1970-1975 1975-1980 1990-1995 1985-1990 2010-2015 1980-1985 1995-2000 2015-2020 2005-2010 2025-2030 2020-2025 follow-up of the patient’s health conditions and therefore limits 2000-2005 Source: UN Population Division the success of any treatment. It is necessary to shift from acute Figure 1: Life expectancy at birth in Latin America, 1970–2030 discrete interventions to preventive continuous care, integrating

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will grow at an annual rate of 3.3% to 192 billion in 202014. 400 In the UK, National Health Service expenditure will grow at an 350 average real rate of 4.2 to 5.1% by 202215. Turning to Latin 300 America, the cost of treatment for diabetes was US$ 7 667 250 million in 2007 and it will grow at an annual rate of 3.8% to 200 Millions 16 US$ 28 080 million in 2025 . 150 Thus, governments are now struggling to find a new way to 100 approach chronic diseases. We believe that technology is the 50 agent of change for the current paradigm in the delivery of 0 health services. In Latin America the use of technology is 1990 2000 2001 2002 2003 2004 2005 2006 2007 2008 increasingly becoming a part of people’s everyday lives. In 1999 there were 62.7 million fixed phone lines in Latin Fixed phone lines Mobile phone users America, increasing to 99.4 in 2008. With respect to mobile Source: ITU 2008 phone users, there were 19 million in 1999, and it Figure 2: Number of fixed lines and mobile phone users in Latin dramatically increased up to 374.9 million in 2008 for an America, 1999–2008 average of 80 mobile phone users per 100 inhabitants (Figure 2). Some factors explain this. Firstly, mobile phones require 200 wireless infrastructure only. Secondly, mobile phones can be 180 160 purchased without any credit conditions. 140 With respect to personal computers (PCs), in 1999 there 120 were 18.6 million PCs in Latin America, increasing to almost 100 Millions 87 million in 2008, a growth rate of 368% in only 9 years. 80 Nevertheless, the trend is much steeper for Internet users. 60 40 There were 9.97 million Internet users in 1999, increasing to 20 183.5 million in 2008, 17.4 times the number of users in 0 1999. Two possible factors explain this. Firstly, a single PC 1990 2000 2001 2002 2003 2004 2005 2006 2007 2008 may be used by more than one person in a household; secondly, the number of public Internet kiosks has risen Number of PCs Internet users Source: ITU 2008 dramatically since 2000, as is the case in Mexico17. Figure 3: Number of PCs and Internet users in Latin America, The use of technology to deliver health services is now a 1999–2008 current practice. Scholars and project designers have even created some terms to define them: eHealth, telemedicine, decline of between 33 and 50% in missed appointments given telehealth or mHealthi. Furthermore, there has been a large the SMS reminders24. movement about the benefits of it; yet only a few studies Nevertheless, SMS may not be the most effective way to provide solid evidence to support this argument. address chronic diseases given that the elderly group uses the Some systematic reviews have been performed but phone a lot less frequently compared to younger groups, unfortunately some methodological limitations in the projects especially in developing countries, where the use of mobile evaluated impede their replication and escalation18,19,20. phones is mainly by adolescents and young adults. Therefore, Furthermore, almost all mHealth projects are designed to an integral strategy must consider the use of the Internet, the improve health system efficiency, or to improve efficiency in fixed phone line and community-based participation. As some the way physicians allocate their time. Finally, none of the studies have proved, phone-based interventions have studies found in the literature refer to projects implemented in demonstrated positive results among persons with low Latin America. To our knowledge, those projects are only found socioeconomic status19. in grey literature, i.e. research and technical papers, With this scenario, at the Carso Health Institute we created government reports, surveys, etc21. Telecommunication for Health in which the mobile phone, the Nevertheless, the very few studies that performed controlled Internet and the fixed phone converge in a unique studies or clinical trials provide interesting insights worth a technological platform created to provide strategic integral deeper analysis. Within all the technologies the most studied is bottom-up services to the individual and achieve last mile the mobile phone. In a recent study, Fjeldsoe found out that delivery. If users have access to multiple communication 93% of SMS-based interventions delivered positive behaviour platforms, we expect an increase in the extent to which users changes22. He found that dialogue initiation, continuous are informed and willing to treat and control their disease. interactivity and customization of SMS were highly effective; Furthermore, users can test themselves at home, and then this is consistent with a 2003 WHO study in which motivation send the results through the channel that is most convenient and behavioural skills were described as the main drivers of to them, either at home through the 01-800 telephone compliance23. Furthermore, mobile phones were not used for number, at their personalized website or through their mobile information sharing only. Some studies have demonstrated a phones. For us, mHealth does not refer to the use of mobile devices to provide a health service; it refers to mobilizing the i Hereafter we will refer to this movement as mHealth. health resources to wherever the user goes, literally following

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him and enhancing the probability of a treatment succeeding. Key messages With Telecommunication for Health it is the user that demands Chronic diseases are conditions of life and an results from the health system, setting a new bidirectional effective strategy must integrate health services channel of communication and empowering him to take further through multiple bidirectional channels of action. These innovations are available even in the poorest communications, setting the patient at the centre communities. of the analysis. To our knowledge, this is the first scalable project that uses a It is necessary to change the current paradigm of bottom-up approach that places the person in the centre of the provision of health services, from acute discrete strategy. Some studies have demonstrated that remote interventions to continuous preventive care, management of chronic diseases decreases the number of integrating hospital-based interventions into a hospitalizations by up to 32%, the number of emergency room nonspatial environment. visits by 40%, the number of hospital admissions by 63% and The current view of patients as passive recipients of the number of hospital bed days of care by 60%25. care must be shifted to a full partnership in health Shifting the current paradigm means changing the focus of care, where patients are informed, are aware of their care, from discrete services to integral continuous services that diseases, and are empowered to take further action place prevention as the main approach, considering the to control and manage their health. community as a strategic player in addressing health needs. It also means setting a turnaround in the location of care, from hospital-based interventions to nonspatial interventions, where and the Mexican Public Health Society, which he chaired in 1997. health care is present everywhere. Finally, it implies shifting the Roberto Tapia-Conyer holds a Master of Public Health degree from balance of responsibility, transforming the traditional view in Harvard University and a Doctorate in Sciences conferred by the which patients are passive recipients of care towards a full University of Mexico. partnership in their management of health. It is when patients are aware and empowered to act that the strategy may Rodrigo Saucedo is a researcher at the Carso Health Institute. He succeed. is actively involved in the design of technology-intensive health projects, as well as the strategic positioning of the various health Roberto Tapia-Conyer is the Director-General of the Carso Health projects. He has been a consultant for the Mexican Ministry of Institute. Prior to that, he served as the Vice-Minister of Prevention Health, the Mexican Ministry of Social Development and the Centre and Health Promotion for 12 years. He also chaired the Strategic for Research and Development in Economics in Public Finance, Technical Advisory Group of WHO’s TB Programme and has been Financial Protection in Health and sustained public policies. Rodrigo appointed a member of the Influenza Global Action Plan Advisory Saucedo holds a Bachelor in Economics from CIDE in Mexico, Group. He is an active member of the Mexican Academy of Sciences, specializing in Public Finance and has taken courses in Management the Mexican Academy of Medicine, the Mexican Academy of Surgery and Corporate Finance.

References

1. Latin America refers to Argentina, Belize, Bolivia, Brazil, Chile, Colombia, 15. Chauhan D et al. The upward trend in healthcare spend. In: The role of Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, mobile phones in increasing accessibility and efficiency in healthcare. Nicaragua, Panama, Paraguay, Peru, Uruguay and Venezuela. Vodafone Policy Paper Series 4, 2006. 2. There was no information for Belize, Bolivia and Honduras. 16.Diabetes Atlas, 3rd ed. Brussels, International Diabetes Federation, 2008. 3. Basic Health Indicators 2008. Geneva, World Health Organization, 2009. 17.World Telecommunication/ICT Indicators Database online. Geneva, 4. World Health Statistics 2008. France, World Health Organization, 2008. International Telecommunications Union. http://www.itu.int/ITU-D/ict/ (last 5.Mobile health: the potential of mobile telephony to bring health care to the accessed 3 August 2009). majority. Washington, Inter-American Development Bank, 2009. 18.Whitten P. Systematic review of cost-effectiveness studies of telemedicine 6. Tackling obesities: future choices – project report. Scotland, UK interventions. British Medical Journal, 2002, 324:1434–1437. Government, 2007. 19.Krishna S et al. Healthcare via cell phones: a systematic review. 7. Report on the global AIDS epidemic. Geneva, UNAIDS/WHO, 2008. Telemedicine and e-Health, 2009, 15(3):231–240. 8. Frenk J. Reinventing primary health care: the need for systems integration. 20.Guide to regional good practice: eHealth. Brussels, IANIS, 2007. Lancet, 2009, 374: 170–173. 21.Two projects are the Andean e-Health Initiative 9. Frenk J et al. La transición epidemiológica en América Latina. Bol. of (www.andeanehealthhomestead.com) and the Cell PREVEN project in Sanit Panam 1991, 111(6):485–496. Peru (www.perupreven.org). 10.Bloom B. Daily regimen and compliance with treatment. British Medical 22.Fjeldsoe et al. Behavior change interventions delivered by mobile Journal 2001, 323:647. telephone Short Message Service. American Journal of Preventive 11.Bloom B. Direct medical costs of disease and gastrointestinal side effects Medicine, 2009, 36(2):165–175. during treatment for arthritis. American Journal of Medicine, 1988, 23.Adherence to long term therapies: Evidence for action. Geneva, World 84(2a):20-24. Health Organization, 2003. http://www.who.int/chp/knowledge/ 12.Bloom B. 2001, ídem. publications/adherence_report/en/index.html (last accessed 3 August 2009). 13.2008 World Population Prospects. Geneva, UN Population Division, 24.Rifat A. A review of the characteristics and benefits of SMS in delivering 2009. http://esa.un.org/unpp/index.asp (last accessed 3 August 2009). healthcare. In: Vodafone Policy Paper, The role of mobile phones in 14.Rifat A et al. Use of mobile technologies to enhance control of type 1 increasing accessibility and efficiency in healthcare. Vodafone Policy diabetes in young people: economic evaluation. In: The role of mobile Paper Series 4, 2006. phones in increasing accessibility and efficiency in healthcare. Vodafone 25.Technology trends: how technology will shape future care delivery. San Policy Paper Series 4, 2006. Francisco, Health Tech Report, 2008.

Global Forum Update on Research for Health Volume 6 85 Treatment, Training and Surveillance

Technology Transfer for access to Drugs

Awareness and Prevention

Research for new TB drugs

Community Support and Patient Advocacy

Multidrug-resistant tuberculosis Lilly and its Partners are working hard to support the goal of saving 14 million lives from TB and MDR-TB by 2015

The Lilly MDR-TB Partnership, care workers, raises awareness a public-private undertaking, and promotes prevention, while mobilizes 18 partners on five providing support for communities continents in the battle to stop and advocating on behalf of people the spread of MDR-TB and save living with TB and MDR-TB. The lives. The Lilly initiatives all have partners work together closely, one thing in common: improved sharing knowledge, expertise and care for some of the world’s most research in the quest to contain vulnerable people. The public- and conquer one of the world’s private partnership provides oldest diseases. access to medicines, transfers The Lilly MDR-TB Partnership is manufacturing technology to about more than the transfer of resource-constraint countries, technology and know-how conducts research, trains health — it’s the Transfer of Hope.

For more information visit www.lillymdr-tb.com 87-90 omura + crump:gf6 23/10/09 14:25 Page 87

Social innovation incentives: from “push” to people

Community-directed intervention: replicating Japan’s health successes in Africa?

Article by Satoshi Omura (pictured) and Andy Crump, Kitasato Institute, Kitasato University, Tokyo

mproving health and well-being, nationally and population lived in rural areas. Furthermore, the indigenous internationally, is a major challenge for all institutions and population were wary of the governing authorities, which had Iauthorities providing leadership in the field. Today, there is been installed by the occupying power. Nevertheless, the ample evidence that what is required is holistic, country swiftly created the infrastructure, skills and resources multidisciplinary, multisector, inclusive engagement and needed to dramatically improve health and well-being, ownership of the process if it is to be successful. Ultimately, alleviate poverty and stimulate and sustain development. individuals are the only true agents of change, so the process Within two decades, Japan drastically reduced infant and must encompass health workers, affected communities, maternal mortality rates, eradicated malaria, leprosy, researchers, clinicians and academics, as well as schistosomiasis, filariasis and other infectious diseases, the coordinated participation of governmental and markedly reduced the impact of tuberculosis, established a nongovernmental agencies. To be successful and sustainable, thriving economy, and produced world-leading living the process must be people centred. According to the World standards and social welfare systems for its entire Health Organization, “as societies modernize, people demand population3. Initially, some technical assistance and more from their health systems, for themselves and their medications were provided from overseas but several basic families, as well as for the society in which they live. Thus, medicines, such as penicillin, were not made available, there is increasingly popular support for better health equity forcing the Japanese to simply devise a means of making and an end to exclusion; for health services that are centred their own4. on people’s needs and expectations; for health security for the The remarkable postwar health and standard-of-living communities in which they live; and for a say in what affects improvements were accomplished through a holistic, their health and that of their communities”1. community-based approach that included school-based Globally, health services have tended to be restricted to health programmes, improved nutrition, provision of safe urban areas and to be primarily accessible only to the water and sanitation, community involvement, creation of relatively wealthy minority. However, the Orient has long been institutional capacity, cohesive operation of research and a source of innovative health interventions best suited to fit control programmes, and via the development of effective and the prevailing conditions in and needs of affected reliable health systems and health insurance5. Most communities, especially when the communities lie in remote, significantly, a key component of the multisector and rural areas. The most successful of these have been multidisciplinary operation was the creation of a network of controlled, governed by or orchestrated within the public health centres throughout the nation, with the goal of communities themselves. Probably the best-known example one centre per 100 000 inhabitants. The centres linked and is China’s Barefoot Doctors programme, which operated from coordinated community resources (clinics, hospitals and 1965, providing free, timely health services to over 500 schools) with human resources (public health nurses, million rural dwellers. It was recognized internationally as a midwives, Livelihood Extension Workers and community fine example of the key element necessary for improving groups), which together with specialist input from local health worldwide, namely the equitable and sustainable medical associations, universities and research institutes, provision of primary health care (PHC)2. allowed critical problems to be identified and customized What is less well known is that, beginning in the late- solutions to be found. By 1958, the centres accounted for 1940s, Japan’s astonishing health improvements were also 23.5% of the nation’s health budget, reflecting the intensive made possible by community-directed interventions. In post- focus on community-driven health activities6. Utilizing World War II Japan, conditions were similar to those efficient, scientific approaches to identify problems and witnessed in many of the sub-Saharan Africa countries today. solutions, the centres did not actually provide medical Resources were scarce, infectious diseases were rife, effective services but instead concentrated on prevention, early medications were in poor supply or lacking and 70% of the detection and community education. Efforts initially focused

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on maternal and child health care, parasitic disease control WHO-based Special Programme for Research and Training in and tuberculosis control, the most pressing health issues at Tropical Diseases (TDR), found the drug to be a safe and the time. effective treatment for river blindness in humans. In turn, this Some 30 years after the start of Japan’s health led to the world’s first, longest running and most successful improvement “miracle”, by which time the successes had drug donation programme, with ivermectin being made become globally apparent, the 1978 Alma Ata Declaration of available free of charge for the treatment of onchocerciasis for “Health for All by the year 2000” stated “primary health care as long as it was required, all those with a financial interest is essential health care based on practical, scientifically in the compound foregoing their income. By 2008, an sound and socially acceptable methods and technology estimated US$ 2.7 billion worth of tablets had been made universally accessible to individuals and families in the donated10. In order to ensure that the drug reached those community through their full participation and at a cost that most in need, predominantly people living in impoverished, the community and country can afford to maintain at every remote rural parts of Africa, TDR pioneered research on a stage of their development, in the spirit of self-reliance and new system of delivery, named Community-Directed self-determination”. The five fundamental principles of PHC Treatment (ComDT). Ivermectin was such a safe drug that it were defined as fairness and equality, community could be given by nonmedical volunteers following just a few participation, appropriate technology and a multisector, days of training11. The African Programme for Onchocerciasis multidisciplinary, diversified and integrated approach. Control (APOC), established in 1995, has the goal of Enshrined in the Declaration is the principle that “people eliminating Onchocerciasis from Africa using ivermectin have the right and duty to participate individually and alone, distributed via the highly-innovative ComDT collectively in the planning and implementation of their mechanism. In Africa alone, some 54.6 million people are health care”7. receiving ivermectin tablets annually, with 127 000 Unsurprisingly, Japan’s Overseas Development Aid communities involved in the ComDT scheme. It is envisaged programmes are driven by the concept of “Village Living” that that by 2010, some 90 million people will be receiving has served the nation so well over the past 50 years or so, ivermectin annually through sustainable ComDT operations. bestowing on the entire population the prospect of a long and The ComDT approach has brought substantial achievements healthy life. This philosophy is the driving force behind the for river blindness control. In 2007, one million disability- assistance that Japan is offering to Africa and its Asian adjusted life years (DALYs) were averted by community- neighbours8. It is a philosophy that has a long and proud directed treatment with ivermectin, representing more than history in Japan. 55% of all DALYs that would otherwise have been lost in In 1878, Shibasaburo Kitasato, the founder of Serotherapy APOC member countries without treatment12. According to and one of the world’s pre-eminent microbiologists, first UNESCO, the success in fighting onchocerciasis is “the most outlined the fundamental belief that governed his life’s work triumphant public health campaign ever waged in the and those who have followed him, namely that “the basis of developing world”13. Community-directed health interventions medicine should be the prevention of diseases, and that represent a new model of delivering primary health care achievements obtained by medical research should be swiftly which incorporates the dual benefits of community and actively applied and widely used to improve public empowerment and health system support. It is now widely health”. Ever since he established the Kitasato Institute in accepted that community and end-user involvement and Tokyo in 1914, its scientists, such as Kiyoshi Shiga empowerment, from the initial stages onwards, together with and Hideyo Noguchi, have maintained and promoted the engagement of civil society, in collaboration with that philosophy. government authorities can greatly enhance disease control The story of ivermectin, complete with its Japanese and health improvement programmes14. origins, provides a perfect encapsulation of the Kitasato Over the past two decades or so, the world has slowly philosophy and the positive impact of community-driven realized that combination therapy is the best way to combat health care in realizing the ultimate goal of improving health many infectious diseases – witness the multi-drug therapy for and quality of life – especially in Africa. It has provided a leprosy, tuberculosis, HIV/AIDS and malaria. What APOC has perfect guideline for the world to follow to help improve proved within the past few years is that combination delivery, health and living standards in under-resourced or outlying when organized by affected communities, is the best means communities. to ensure maximum impact of most health intervention Discovered by scientists from the Kitasato Institute, the programmes in Africa. Streptomyces avermectinius found in Japanese soil remains Analysis of the ivermectin story indicates that given the only source of avermectin ever found9. In the early- international collaboration, multidisciplinary involvement and 1970s, an innovative partnership set up with the private equitable partnerships; health products that are safe, sector, in the shape of the US-based Merck & Co. Inc., led to effective, appropriate and affordable; political will and the discovery of a di-hydro derivative of avermectin. The commitment of suitable resources; and most crucially, the compound, ivermectin (the world’s first endectocide), quickly engagement of affected communities in the planning and became the world’s market leading drug in animal health, a management of health interventions, most diseases and position it maintained for over 20 years. In the mid-1980s, conditions that are plaguing the world’s poorest communities collaboration with the public sector, in the form of the can be effectively tackled – and even eliminated. Where the

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intervention involves health products provided free or at Key messages significantly subsidized costs, to not make full use of the scheme, which heralds a potential revolution in African health Community-driven health interventions have the care, would be sheer folly. best outcomes and provide a model for Africa to The evidence for using a community-driven system to bring follow. health care to Africa, where two thirds of the population still Japan’s world-leading health improvements, based live in remote rural areas, is irrefutable. TDR has recently on experience of community-driven published a report of a field study of Community-directed multidisciplinary, multisector interventions, can be interventions (CDI) in Africa that covered 2.35 million people, duplicated in Africa and elsewhere. based on expansion of APOC’s ComDTi system. The study Evidence and policy must be put into practice and evaluated the incorporation into existing ComDTi of several individuals empowered to accomplish widespread individual interventions; malaria treatment, malaria health equity and improved living standards. prevention (via insecticide-impregnated bednet (ITN) distribution), Vitamin A supplements; directly-observed treatment (short-course) – or DOTS – for tuberculosis; as well Determinants of Health (CSDH), which had the task of as fully integrated delivery of all interventions. The CDI identifying means to overcome health inequalities. In 2008, approach proved to be much more effective than currently the CSDH concluded that, in order to succeed it is necessary operating health-care delivery mechanisms for all to fully understand the circumstances and environments in interventions, except DOTS. CDI was also much more which people are born, grow, live, work and age; to rectify efficient and reduced costs, with no specific technical inequitable distribution of power and money; to ensure limitations limiting the delivery of combined interventions. availability of adequate and sustainable resources at The only restrictions were social constraints, notably international, national and local levels; and that all problems increased workload for community volunteers, and problems need to be accurately identified and quantified – preferably by associated with ensuring supplies of necessary products via those directly affected – in order to determine effective, the health system. In communities covered by CDI, more acceptable and affordable solutions and to integrate their than twice as many febrile children received appropriate effective implementation19. antimalarials; possession and utilization of ITNs was twice as In China, despite making huge advances against infectious high; Vitamin A coverage was significantly higher, and diseases and providing basic free primary health care (PHC) ivermectin coverage was increased by 10%15. Various other to most citizens, the Barefoot Doctors scheme ostensibly studies across Africa have confirmed the potential and collapsed in the mid-1980s and virtually nothing was put in positive impact of combining delivery of basic health care its place. Earlier this year, perhaps mindful of recent global using the CDI approach16,17. developments and Japan’s enviable and sustained successes, Africans have enthusiastically embraced the CDI health China indicated that it had again recognized the value of intervention approach and many see it as a key to improving engaging and empowering communities to tackle their own health and raising living standards across the continent. At an health problems, especially with respect to underprivileged intergovernmental meeting of health ministers in June 2009, rural populations. It announced a major three-year health the Nigerian Minister of State for Health called for the care reform plan that aims to provide equitable health care for introduction of the philosophy and principle of CDI into the the nation’s 1.3 billion population by 2020. The US$ 124 training curriculum of all African health-care professionals. Dr billion plan involves basic health insurance cover for over Uche Amazigo, APOC’s current Director and one of the 90% of the population, provision of essential drugs, improved pioneers of community-directed interventions echoed this PHC facilities, equitable access to health services and reform sentiment, declaring “if Africa’s health workers of tomorrow of state-run hospitals. Notably, to ensure that China’s huge are to make a significant improvement in the health of the rural population is properly catered for, at least one new clinic poor and rich alike, policy- and decision-makers in health will be established in each of the nation’s 700 000 villages need a new health strategy – one that acknowledges the to improve community-level health. At the township level, 29 people as the heartbeat of the health system. All clinical and 000 hospitals will be built, augmented by 2000 more at the preventive programmes should be people-oriented”. Indeed, county level. Some 1.37 million health-care practitioners will the African Union’s first four-year implementation plan for its be trained to staff the clinics, along with 500 000 more for Africa Health Strategy (2007–2015) stipulates that medical centres at the township and municipal levels20. The “Community empowerment for effective participation in all new Chinese initiative reflects the Kitasato philosophy, priority programmes is needed… Communities need to be Japan’s post-war experience and WHO’s current policy actively involved in programme planning and implementation guidance, as explained by the Chinese Minister of Health, instead of being perceived as recipients of services only”18. Zhu Chen. “By applying the policy of prevention first, focusing Indeed, global realization of the need to re-evaluate health on rural and grassroots level service, and paying equal inequalities and movement towards a more holistic, attention to both Western medicine and traditional Chinese evidence-based, people-centred approach to health has been medicine, we should be able to pave a cost-effective way for burgeoning since the mid-1990s when APOC was formed. In health-care development”. It is a way forward that Africa 2005, the WHO launched the Commission on Social should be encouraged and empowered to follow.

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Satoshi Omura is a world leader in bioorganic chemistry, Andy Crump is an international multimedia communications particularly in the discovery of antibiotics and other useful specialist with expertise in the fields of environment, development chemicals derived from naturally-occurring microorganisms. and global health. He has produced, published and broadcast During his 40-year career, he has discovered over 410 novel books, articles, photos, TV and video, CD-rom, websites and bioactive compounds, including ivermectin, one of the world’s training materials extensively around the world. Initially a research most important and successful animal and human medicines, biologist at Imperial College, London, he has worked at the Panos discovered and developed through a collaborative research Institute (London), for several UN agencies and nongovernment programme with Merck & Co. Inc. (USA). He is currently President organizations, and extensively for the UN’s Special Programme for Emeritus of the Kitasato Institute in Tokyo, Japan. He is also Max Research & Training in Tropical Diseases (TDR) in Geneva. He is Tishler Professor of Chemistry at Wesleyan University (USA) and currently working as a consultant and is Visiting Professor in Professor Emeritus of Chemistry at Kitasato University in Tokyo. science communication at Kitasato University in Tokyo.

References

1. World Health Report: Primary health care (now more than ever). WHO, Nature Reviews Microbiology, 2004, 2 (12);984–989 Geneva, 2008. Downloadable from: 12. The African Programme for Onchocerciasis Control (APOC). Revitalising http://www.who.int/whr/2008/en/index.html health care delivery in sub-Saharan Africa, 2007, (36pp). Downloadable 2. Zhang D, Unschuld PU. China’s barefoot doctors: past, present, and from: future. Lancet, 2008, 372;1865–1867. http://www.who.int/apoc/publications/EN_HealthCare07_7_3_08.pdf 3. Takeuchi T, Nozaki S, Crump A. Past Japanese successes show the way to 13. UNESCO World Science Report 2005. p.198. UNESCO, 2005, Paris. accomplish future goals. Trends in Parasitology, 2007, 23;260–267. 14. Doyle C, Patel P. Civil society organizations and global health initiatives: 4. Kumazawa J, Yagisawa M. The history of antibiotics: the Japanese story. Problems of legitimacy. Social Science and Medicine, 2008, Journal of Infection and Chemotherapy, 2002, 8;125–133. 66;1928–1938. 5. A comprehensive review of Japan’s successful postwar health successes 15. TDR. Community-directed interventions for major health problems in can be found in: Japan’s experiences in public health and medical Africa, 2008 (132pp). Downloadable from: systems. Japan International Cooperation Agency (JICA), 2005, Tokyo, http://apps.who.int/tdr/svc/publications/tdr-research- Japan, publications/community-directed-interventions-health-problems http://www.jica.go.jp/english/publications/reports/study/topical/health/. 16. Homeida M et al. APOC’s strategy of community-directed treatment with 6. Annual Report on Health and Welfare (in Japanese). Ministry of Health ivermectin (CDTI) and its potential for providing additional health services Labour and Welfare, 1963, Tokyo, Japan. to the poorest populations. Annals of Tropical Medicine and Parasitology, 7. WHO and UNICEF (1978) Downloadable from: 2002, 96 (supplement); S93–104. http://www.who.int/hpr/NPH/docs/declaration_almaata.pdf+%22Alma+At 17. Amazigo U. The African Programme for Onchocerciasis Control (APOC). a+Declaration%22&hl=en. Annals of Tropical Medicine and Parasitology, 2008, 102;19–22. 8. Crump A, Yamamoto T. Japan’s health revolution to be bestowed on 18. African Union. The Africa Health Strategy Implementation Plan, 2008. Africa. Real Health News, 2006, 6;28–31. MIN/Sp/AU/CAMH3/3 Downloadable from: http://www.africa-union.org 9. Mura S. Ivermectin: 25 years and still going strong. International Journal 19. Closing the gap in a generation: health equity through action on the of Antimicrobial Agents, 2008, 31;91–98. social determinants of health. Final Report of the Commission on Social 10. Mandavilli A. Free to fight disease. Nature Medicine, 2008, 14 Determinants of Health, 2008, WHO, Geneva. (6);594–597. 20. Chen Z. Launch of the health-care reform plan in China. Lancet, 2009, 11. Omura S, Crump A. The life and times of ivermectin – a success story. 373;1322–1323.

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Dragon Net: secret society or a network of health policy researchers?

Article by Toshihiko Hasegawa, Director, Department of Health Policy and Management, Nippon Medical School

ragon Net is a network of health policy researchers Since then, Dragon Net symposia have been held about once who have developed and supported the core policies a year by various conveners in several countries, as shown in Dof the health sector in six Asian “dragon” countries, Table 1 below. including four “little dragons” (Hong Kong, Korea, Singapore The network’s discussions have focused on middle-income and Taiwan), a “growing dragon” (Thailand) and the “old countries, mainly represented by the four “little dragons”, dragon” (Japan). although Thailand and Japan have benefited from them The spirit of the network began to develop at a meeting in as well. Researchers from all six countries have been active 1989 when Taiwan organized the International Symposium from the inception of the network, and recently researchers for Health Care Systems to advance universal coverage of from Malaysia and mainland China have also joined and health insurance. When a review and evaluation of the actively participated. national health insurance system of Taiwan was held in After hosting the 1998 meeting at which the network was 1996, most of the current members of the Dragon Net were named Dragon Net, Japan did not host the meeting again invited to participate and to present their own countries’ until 2009. Table 1 shows the meetings that Dragon Net has health insurance programmes and institutions. Similar large organized over the years: meetings were organized in 1997 in Japan, involving not only the dragon countries but also many colleagues from Membership and organization other less developed countries in Asia such as Mongolia, The members who participated in the first so-named Laos, the Philippines, etc. The symposium was entitled Dragon Net Meeting of Tokyo in 1998 are listed in Table “Health transition and health sector reform in Asia”. Again, 2 along with their 1998 academic or public administration many of the Dragon Net members attended. affiliations. At the request of health policy researchers in the dragon The network is a voluntary group in its spirit and in its countries, an international research meeting and policy financing. In principle, the participants pay their own air fare dialogue, focusing on health sector reforms in the four “little and the conveners share the costs of the meeting unless dragon countries”, was held in Tokyo in 1998. During that sponsors or research grants are found. The topic and meeting, the network was named “Dragon Net” by Dr Serdar objectives of the meeting are decided by the convener after Savas from Turkey, who was then a WHO-Europe official. extensive discussion with other members.

Symposium Year Venue Convener/Institution Pre Dragon Network Meetings International symposium on health care system 1989 Taipei, Taiwan Taiwanese government East Asia consortium on health care systems 1994 Seoul, Korea Ok Ryun Moon International symposium for health care system 1996 Taipei, Taiwan Chih-Liang Yaung Symposium on health care reforms 1997 Taipei, Taiwan Taiwanese government Comparative health transitions in Asian countries 1997 Tokyo, Japan T Hasegawa Official Dragon Network Meetings Health sector reform in East Asia: designing of the welfare state in four little tigers 1998 Tokyo, Japan T Hasegawa 2nd Dragon Net meeting 1999 Hong Kong G Lieu, 3rd Dragon Net meeting 2000 Taipei & Hualien CL Yaung & T Chiang 4th Dragon Net meeting 2002 Chiangmai Sanguan N 5th Dragon Net meeting 2003 Seoul, Korea OR Moon Towards evidence-based policy-making in health systems 2003 Kuala Lumpur R Hussein Comparative health systems and policies in Asia 2004 Singapore PK Hong 7th Dragon Net meeting 2005 Beijing, China Chih-Liang Yaung Health services management – four little dragons’ perspectives 2007 Hong Kong P Yuen

Table 1: Dragon Net meetings

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Four little dragon countries (Korea, Singapore, Taiwan and Hong Kong) Describe the existing social security and health insurance Dr Phua Kai Hong National University of Singapore Dr Lim Meng Kin Health Corporation of Singapore systems in the four little dragons, Thailand and Japan. Dr Ok Ryun Moon Seoul National University Compare and contrast the systems, to identify and list Dr Soonman Kwon Seoul National University cross-cutting issues and concerns affecting the structure Dr Chih-Liang Yaung National Taiwan University Dr Tung-Liang Chiang National Taiwan University and performance of these systems in terms of the Mr Geoffrey Lieu Hospital Authority, Hong Kong following domains: Dr Peter P Yuen Hong Kong Polytechnic University – financing of health care;

Old dragon (Japan) – delivery systems; Prof Yoshinori Hiroi Chiba University – roles and operations of health insurance; Prof Shuzo Nishimura Kyoto University – designing an Asian-values-based welfare state. Prof Naruo Uehara Tohoku University Dr Masaki Muto National Hospital of Nagano Identify the basic components of a health-care system Dr Toshihiko Hasegawa National Institute of Health Services for incorporation into the new design for the welfare Management state of the 21st century for Asia based on Asian values

Growing dragon (Thailand) and within an Asian context. Dr Sanguan Nitayarumphong Ministry of Public Health, Thailand Identify the lessons learned from the present experiences of the four little dragons, Thailand and Japan, and make Observer Dr Seder Savas WHO Regional Office for Europe recommendations and proposals for reform of health insurance and social security in the participating Later jointed active member countries. Prof Yasuo Uchida Kobe University Prof Tomohiro Hirao Kagawa University Prof Tomonori Hasegawa Toho University Achievement of the network The uniqueness of the group is that it is the only multi- Table 2: Membership and organization country health policy researchers’ network in Asia and particularly in dragon countries. It provides an invaluable Goal and objective of network opportunity for participants and their countries to learn from At the end of 20th century, the four little dragons in East each other, particularly when we reflect on the fact that due Asia, standing at the threshold of evolution towards a welfare to language barriers Japanese policy development has not state during the 21st century, were experiencing been shared with others on an ongoing basis. The network considerable hesitation on three accounts: includes two Japanese members who are in charge of First, the forerunners and proponents of a welfare state, generating evidence for health policy within the Ministry of i.e. OECD countries, were in the process of undertaking Health and another who has been advising the Koizumi and major reforms of the welfare state, including a re- subsequent cabinets, so that members have had the examination of the basic principles underpinning the welfare opportunity to listen to first-hand information regarding state and of the changing role of the government in the experiences and developments in Japan. In Thailand, Dr operation of a welfare state. Sanguan Nitayarumphong played a very important role in the Second, the basic principles of the welfare state, as “30 baht treat all diseases” scheme, and he hosted developed in Europe, had been based on a value system that the Dragon Net meeting several times in the form of may differ significantly from the value system or systems international symposia. operating in Asia. The other achievements of Dragon Net include ongoing Third, the health issues in the four little dragons exchange of information and its function as a pool of human included the relatively swift emergence of a rapidly ageing resources for other projects. For example, in 2004 the population, coinciding (even more so now) with severe Japanese team invited Dr Sanguan to Sri Lanka to advise Sri economic stress. Lankan officials on health sector reform. The receiving The dragon countries’ policy focus on industry and officials were quite impressed with the health financing of production sectors had proved wildly successful. Suddenly, Thailand, and the visiting team succeeded in changing their however, these dragons faced the rapid ageing of their mindset. Although individual members of the network have populations, requiring a well structured and sustainable published books and some papers, no publication has been welfare system. Welfare had not been a top priority in policy- submitted by the network itself. The next challenge is to making in the traditional colonial settings of Singapore and develop more formal information generation and Hong Kong, and in the special situation in Taiwan. dissemination activities. The objectives of Dragon Net, as set by the members’ Korean, Singaporean and Japanese colleagues have their consensus were to re-examine the basic principles own health policy views based on their participation in underpinning the structure and operations of a welfare state network activities. Hong Kong colleagues had major roles in and to compare and contrast the experiences of the four little developing and advancing the health sector reform proposal dragons vis-à-vis the assumptions of the European models of submitted to the Hong Kong government in 2007. Taiwan a welfare state, all in the context of existing Asian values and colleagues have been very active in health policy reform Asian development. Core objectives of associated research activities there, and recently Dr Chih-Liang Yaung became project(s) were as follows. Minister of Health.

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Lessons from the experience of Dragon Net other countries that share similarities in terms of economic In the development of a new policy framework, it is growth, culture, society, historical background and so on, an impossible to refine the framework through experimental important and effective means to improve a country’s health planning and implementation because there is no chance to policy. Such interactions have also provided a context for recover from the failure of the experiment. That situation ongoing concurrent sharing of extremely relevant action makes learning together about and from the experiences of research throughout its planning, implementation and evaluation phases. Key messages Dragon Net provides a new form of knowledge sharing and transformation for health policy researchers. It would be The importance of information sharing among exciting to see the development of similar networks in other countries of similar economic development and parts of the world in this bottom up fashion, and if such cultural background because it is impossible to networks could interact, new knowledge, and perhaps new experiment with new policies in a real setting. forms of knowledge, could be generated. Dragon Net is such a network of health policy researchers who have developed and supported the Toshihiko Hasegawa, MD, MPH, PhD, is the Director of the core policies of the health sector in six Asian Department of Health Policy and Management at Nippon Medical “dragon” countries, including four “little dragons”. School. He graduated with an MPH degree from Harvard School of In the ten-year history of Dragon Net, there have Public Health and from Osaka University Medical School as MD. been many achievements in each membership He has carried out research on health policy; health sector reform; country, including the development of real policies. planning and evaluation of health programmes such as cancer, It would be exciting to see the development of hypertension, accident and asthma; hospital strategic management similar networks in other parts of the world in this including marketing, customer satisfaction, quality management bottom up fashion. Then further worldwide and patient safety; and international health. He has also had a long interaction can be possible. career in Japanese government including development of elderly care policy and management of Japanese national hospitals.

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New approaches to health worker training, deployment and retention

Article by Mubashar Sheikh (pictured), Executive Director, Global Health Workforce Alliance, and Sigrun Møgedal, Chair, Global Health Workforce Alliance

mproving global health and achieving global health equity as reducing maternal and child deaths and the impact of urgently requires a new era of innovation in health worker HIV/AIDS, but also those goals that can only be achieved by Itraining, deployment and retention. “Business as usual” stable, healthy societies, such as reducing poverty and approaches to the management of human resources for increasing access to education. Virtually every MDG is health (HRH) have created large and growing health threatened by the ongoing lack of access to quality health care. disparities between rich and poor nations and regions that The Alliance promotes innovative and holistic approaches present an enormous threat to global health and to: development. Disparities in access to care must be increase health worker training and ensure that that aggressively addressed through new and innovative training meets real world needs; approaches that strengthen health systems and increase improve the retention of trained health workers by access to a trained and motivated health workforce. improving health worker support and supervision; Created in May 2006, the Global Health Workforce Alliance address the global economic pressures that skew the (the “Alliance”) is a common platform for joint action to health workforce marketplace; address the training, support and management of health promote new approaches to increase health worker and workers worldwide. Acting as a partnership of some 250 health system organization, to make health systems members including national governments, civil society, function more effectively for all. international agencies, finance institutions, researchers, educators and professional associations, the Alliance is the To achieve these vital objectives, Alliance partners work leading global advocate promoting innovative approaches to with a wide range of local, national and international identifying, implementing and advocating for solutions to advocates and decision-makers, serving as a collaborative reverse the massive global shortage of trained health workers. platform for action to: Today, more than one billion people have no access to any build the evidence base needed to develop, support and type of health care at all, due largely to the shortage of 4.3 promote innovative approaches to reversing the HRH million trained health workers. This crisis is directly related to crisis; high rates of unsafe childbirth, maternal and child mortality, develop and build support for innovative frameworks for and failure to meet basic development objectives such as action to improve access to a trained, supported and reducing hunger and extreme poverty and increasing access motivated health workforce; to education. support effective advocacy to focus international attention The World Health Organization (WHO) has declared that on the strong link between health workforce capacity and the lack of access to a trained health workforce has reached development. a crisis level in 57, mostly poor countries. This crisis, however, is not limited to the countries most directly affected, Collecting evidence, building knowledge and sharing but is truly global. Its roots are found not only in deficiencies information in health workforce training, management and support in The first step to understanding and addressing the factors that poorer countries, but also in the economic pressures exerted shape and deepen the health workforce crisis is bringing by wealthier countries that are also not producing a sufficient together diverse stakeholders to share information on how the supply of trained health workers to serve their domestic crisis impacts different segments of society, examine the health needs. factors that contribute to the health workers shortage, and Disparities in access to health present some of the greatest address the systemic obstacles that have frustrated previous challenges to achieving the Millennium Development Goals attempts to build a sufficient and sustainable core of trained (MDGs). Lack of quality health care not only inhibits our and motivated health workers. The Alliance does this by ability to achieve those MDGs related directly to health, such convening partners and institutions of various competencies,

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capabilities and constituencies to work together under a trusted, accountable, transparent and agreed platform for action. Recognizing the need for action is only the beginning, however. Promoting awareness of and building commitment to address the global HRH crisis requires an intensive process of gathering and validating reliable information. Recognizing that a number of well-intentioned efforts to boost health workforce capacity have been hampered by a critical lack of quality baseline data, information and analysis, the Alliance prioritizes the collection of vital evidence and the promotion of knowledge building and sharing as key to efforts to develop, support and promote innovative approaches to address the HRH crisis. Specifically, it: Works with multilateral institutions, development partners, academia, civil society and other private and Figure 1: Health workers examining a child © Naomi/WHO, 2008 public sector actors to scale up investment in information collection and the sharing of best practices in health workforce policy and management at the country and regional levels. Commissions original research to address key gaps in knowledge. Promotes evidence-informed action to address global policy challenges such as the insufficient and inefficient use of health workforce resources; fiscal restraints on health sector spending; and health workforce migration. Works with countries to develop standardized indicators and strengthen statistical capacity for labour market analysis, policy development and health workforce management, along with robust frameworks for health workforce monitoring and evaluation. Promotes intra-country collaboration, including regional and international exchanges among academic Figure 2: Briefing on maternal health © Joydeep/WHO, 2008 institutions and the development of strong regional and subregional academic centres, to establish data and evidence to promote innovative HRH policies. Facilitates information sharing and access to global knowledge networks across countries, including through the exchange of technical expertise between Ministries of Health, with an emphasis on South-South collaboration. Supports health information centres for health professionals in rural areas. Provides a Journal Watch and searchable database on HRH issues. Works in partnership with institutions such as the WHO Health Metrics Network (HMN) to build reliable country profiles and define global HRH indicators; the World Bank in building the capacity of HRH managers in French-speaking countries such as those in West Africa Figure 3: Health worker talks to a patient © Lopes/WHO, 2008 and Haiti; and the International Labour Organization (ILO) to address health risks to workers and to the lack of occupational health services for the vast majority of requires the active and ongoing collaboration of private and the global workforce. public sector partners, including nongovernmental organizations (NGOs) and others whose work directly or Supporting innovative frameworks for action indirectly impacts the health workforce crisis. National governments cannot solve the HRH crisis alone. The Alliance develops and supports partnership Building sustainable support for country leadership to train, mechanisms designed to identify and address policy and deploy and support sufficient numbers of health workers implementation bottlenecks to innovative HRH policies.

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Alliance-supported Task Forces and Working Groups address redistribution of specific tasks, where appropriate, from key areas impacting the global health workforce shortage, highly qualified health workers to health workers with including migration, retention, financing and scaling-up shorter training, in order to make more efficient use of education and training, producing vital evidence to support the available human resources for health. WHO the development of national HRH action strategies. recommendations emphasize that task shifting can be an On the government and academic levels, innovation means extremely efficient approach to increasing human bringing together Ministries of Health, Education, Public resources for health, but that it must be accompanied by Service and Labour, among others, along with leaders of significant investment in additional changes in worker public and private education institutions, to determine the training and support, as well as regulatory systems. skill mix of health workers needed for each country, and to Promoting positive practice environments, including institute coordinated policies to address immediate, medium providing a safe working environment and positive and long-term training, management and support needs with organizational culture for health workers. Factors at least a 10-year planning horizon. Specifically, the Alliance contributing to health worker satisfaction and reduced helps governments, educational and training institutions, and rates of attrition may include a commitment to flexible professional associations to: working hours, opportunities for professional Align training programmes with country health priorities development, and improved communication between and with efforts to reduce staff and student attrition. management and staff. Establish quality standards for service, accreditation Supporting the development of strong national, regional systems for education and training, appropriate regulatory and international institutions such as professional frameworks for public and private sector health worker associations providing fellowship, peer oversight and education and reliable indicators of country-level progress. promotion of professionalism for the health workforce. Promote innovative and pragmatic approaches to Supporting innovative financing strategies, including a developing and utilizing new and existing faculty, new taskforce on Innovative Financing for Health, infrastructure and partnerships to significantly increase launched by the UK, Norway, WHO, the World Bank and education, training and research capacities. others to help fund more than one million health workers Ensure an appropriate focus on pre-service education by 2015; efforts to bring ministries of health and other and in-service training as integral components of partners together to develop financial risk sharing and education, training and professional growth. performance-based financing mechanisms to provide more predictable, productive financing for health Innovation also means providing new tools that offer workforce and health system development; and efforts to practical guidance to country-level efforts to improve their better align the health funding efforts of public and HRH capacities. One such product developed by the Alliance, private donors, foundations, partnerships and initiatives. the Resource Requirements Tool (RRT), helps countries Promoting Health Workforce Observatories, cooperative estimate the financial resources needed to meet their HRH mechanisms of public and private institutions that plans. RRT addresses a range of factors including the specific provide a forum for partnership, experience sharing, health needs of the country; current health worker distribution networking and advocacy to support HRH development and gaps; training requirements and crossover between and improvement. public and private health services, and allows users to adjust Supporting a Code of Practice for the international their plans to address changing conditions and economic recruitment of health personnel, as developed by WHO circumstances. and the Alliance-convened health Worker Migration Alliance partners are leading in developing and Initiative. Health worker migration is one of the implementing innovative approaches to reverse the global fundamental issues to be addressed for the resolution of health workforce crisis through holistic approaches that the health workforce crisis. While acknowledging that increase health worker training, improve health worker health worker migration has both positive and negative support, address migration pressures and, importantly, impacts, the Code calls on countries to put appropriate maximize the capacity of trained health workers by re- mechanisms in place to shape the health workforce thinking and, where appropriate, revising old models of market in favour of retention. Under the Code, countries health service delivery. The partners of the Alliance are drawing health workers, often called “destination working to promote innovation in health workforce education, countries,” would commit to supporting and enhancing training and retention by: the education and training of health workers both at Exploring new ways to develop and utilize new and home and in source countries. existing faculty, infrastructure and partnerships to enable well balanced and significant increases in education, Alliance partners are also working on other innovative training and research. approaches to improve health system efficiency, such as the Supporting investment to improve health workforce development of new therapies for neglected diseases and information systems and quality monitoring and the implementation of long-distance and eHealth improvement. approaches that can improve both patient care and health Promoting task shifting, which involves the planned worker utilization.

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Building a global advocacy movement Key messages The global health workforce shortage is central to global health and development disparities. Human resources for The Global Health Workforce Alliance (the “Alliance”) health issues have not yet achieved the full prominence on is the leading global advocate for increased action the global health agenda that is needed to affect broad and to address the health worker crisis. The Alliance is lasting change. That situation is changing. a partnership of some 250 members, including The Alliance has been instrumental in supporting the national governments, civil society, international passage of and in advocating for the full implementation of agencies, finance institutions, researchers, the groundbreaking Kampala Declaration and Agenda for educators and professional associations dedicated Global Action, which provides the international framework to to identifying, implementing and advocating for strengthen human resources for health over the next decade. solutions to the health workforce crisis. The Kampala Declaration was developed and approved Health workers are the cornerstones of health through a highly-consultative, evidence-based process systems. About one billion people worldwide lack designed to ensure support from the broad array of even simple health care, because of the critical constituencies, including the international community, shortage of trained health workers. Lack of trained government, funders, civil society and health workers health workers blocks efforts to meet basic themselves, that must be intimately and actively involved to development goals such as improving maternal and affect lasting change on HRH issues. child health, reducing extreme poverty and Much more is known today about the centrality of the increasing access to education. Closing the global health workforce crisis to human development than health worker gap now is essential to meeting the was understood even just a few years ago. In the three years Millennium Development Goals by 2015 – and other since its founding in 2006, the Alliance has dedicated its development targets. efforts to building the evidence and advocacy base for a Increased political commitment and funding are worldwide effort to revamp how health workers are trained, producing significant progress in efforts to address deployed and supported. This vision includes access to a the complex issues underlying the global health trained health workforce for all, based on health systems that workforce crisis. include more cost-effective services, products and methods; Success will require the collaboration of all sectors: management practices and policies designed to improve national and donor governments, civil society, the health outcomes; effective national health innovation private sector and international organizations all systems; and an emphasis on social entrepreneurship have vital roles to play in resolving this crisis. for health. The 250 partners of the Global Health Workforce Alliance are committed to supporting innovative new approaches to Coordinator of the UN system as well as Representative for FAO. reverse a health workforce crisis created and supported by He has served on various committees and task forces at the outdated models of health workforce training and support, as national, regional and international levels. Dr Sheikh is the author well as economic models that see access to health as a of numerous policy documents, training manuals and guidelines. short-term economic commodity, rather than as a long-term human right. Dr Sigrun Møgedal is Chair of the Global Health Workforce Alliance and Ambassador of HIV/AIDS and Global Health Dr Mubashar Sheikh is Executive Director of the Global Health Initiatives for Norway since 2005. She is a medical doctor with Workforce Alliance. He has a Masters of Public Health from Yale professional and diplomatic engagement in the global health and University, is a Fellow of the College of Physicians and Surgeons HIV/AIDS response, partnership development, global and national in Pakistan, and is a specialist in health system policy and health architecture, and reform and global health challenges to planning. Dr Sheikh started his career with the Pakistan Institute foreign policy. She also works on issues of development policy, of Medical Sciences in Islamabad. From 1993 to 1998, he international health policy analysis, human resources for health, managed the Primary Health Care Department at the Ministry of health systems development and reform. Health in Pakistan. During this time he also designed, Dr Møgedal is currently a board member of the Global Fund to implemented and led a nationwide community-based childcare Fight against Aids, TB and Malaria (GFATM), the Global Alliance and reproductive health network under the “Lady Health Workers” for Vaccines and Immunization (GAVI) and UNITAID. From initiative, which has had an important positive impact on the 2000–2001 she was the State Secretary of the Ministry of Foreign health status of mothers and children in some of the remotest Affairs for international development. She has also served as the parts of the country. In 1998, Dr Sheikh joined the Eastern Senior Executive Adviser, for Global Initiatives at NORAD, and as Mediterranean Office of the World Health Organization as Senior Policy Adviser to the Executive Director of UNAIDS. She is Regional Adviser in the Health Systems department, responsible a founding member of Board, Global Forum for Health Research, for the promotion of a Primary Health Care approach among the and a member of various committees as well as the Norwegian member states. Research Council. In 2004, Dr Sheikh was assigned to the WHO office in Iran as During the 1970s and 1980s, Dr Møgedal was Director of Country Representative, where he also served as Resident various health programmes in Nepal.

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Brazil’s conception of South- South “structural cooperation in health”

Article by Celia Almeida (pictured), Senior Researcher and Professor, National School of Public Health, with Rodrigo Pires de Campos, Paulo Buss, José Roberto Ferreira and Luiz Eduardo Fonseca

t the dawn of the new millennium, poor countries’ important long-term foreign policy issues of our time”, and health needs had not diminished, but may have declared the urgent need to broaden foreign policy and to Achanged for the worse. This shocking lack of progress create new paradigms of cooperation, outlining the linkages was due to a complex interplay among many factors, internal between foreign policy and health4. and external to the health sector, that result in huge inequities The Oswaldo Cruz Foundation (Fiocruz)5 was then invited within and between countries. This situation is aggravated in to act as the privileged focal point for such cooperation, an increasingly interdependent and unequal world, where the confirming the national and international role it has played effects of poverty and ill-health are not confined within historically. country borders. A Fiocruz regional office was inaugurated in Africa in That critical situation once again called international October 2008, in Maputo, Mozambique, with President Lula development cooperation into question. Since it was and both countries’ health ministers present, reiterating the institutionalized in the 1950s, industrialized countries have institution’s international mission and the government’s sought to address and solve global issues of poverty and commitment32. social exclusion. Despite the numerous bilateral, regional and Closely attuned with Brazilian foreign policy, Fiocruz is multilateral international agencies and organizations devoted reaffirming its international calling by leading initiatives in to this cause, the record shows few initiatives having South-South cooperation in health in South America and contributed effectively to achieving that goal. Africa. And other initiatives also deserve attention: the setting More recently, South-South cooperation (or Technical up of two new federal universities and, in 2008, a new Cooperation Among Developing Countries), a foreign policy institute for the joint training of Brazilian and foreign and international development promotion tool introduced in students6; and the creation of regional research network7. the late 1970s by the “non-aligned countries”, has steadily This paper discusses the Brazilian conception of “structural gained importance. The political and economic situation of cooperation in health”, in the realm of South-South the 1990s, represented an important turning point for Brazil’s cooperation. After a brief theoretical review, it presents the foreign policy and its South-South cooperation. Brazilian proposal formulated over the past decade and how Brazil has endeavoured to consolidate its re-entry into the it has developed to date. international system, seeking to take advantage of both post- Cold War global geopolitics and its own political and A brief history of international development economic process (democratic and economic stability, civil cooperation: changing approaches society participation and more inclusive social policies). The Bilateral or multilateral allocation of international foreign policy of both Lula administrations since 2003 has development cooperation funding to countries and regions differed markedly from that of previous governments by anywhere in the world occurs on the basis of complex seeking more decisively what the authors term “diversified political processes permeated by national and international autonomy”1. strategic, economic and political considerations. In the 21st century, technical cooperation has gained a Conditionalities and priorities have changed over the decades. strategic place in Brazilian foreign policy2, at the same time In the 1950s and 1960s, influenced by the modernization as health is recognized as a predominant theme on the paradigm8, international technical cooperation was regarded national agenda for South-South cooperation, revealing an as a way to provide human and technological inputs in order unprecedented approximation between the Foreign Ministry to fill development gaps9. From the mid-1960s onwards, de- and the Ministry of Health3. colonization movements, dependency theorists, and the Globally, Brazil is also leading the way in forging closer movement of “non-aligned southern countries” articulated relations between health and foreign policy. In 2007, the strong international criticisms against the modernization initiative on Global Health and Foreign Policy, to which Brazil paradigm, which stimulated further rethinking of is a signatory, emphasized that “health is one of the most development cooperation10.

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The 1970s saw the first significant reorientation of were signed and international organizations set up to technical cooperation, with the Basic Human Needs (BHN) broaden and strengthen international cooperation in health. approach embodying greater concern for the human and This process culminated in a historical milestone: the World social aspects of development. A number of initiatives paved Health Organization (WHO) was set up in 1948, along with the way to pursue opportunities for alliance-building among the International Sanitary Regulations, an extraordinary set of countries of the South. rules for the control of infectious diseases. Together, these Technical Cooperation among Developing Countries initiatives produced the first “processes, rules and institutions (TCDC) – also called “horizontal cooperation” – became an for global health governance”20. important instrument for the strategy of South-South Since the 1950s, approaches to international cooperation cooperation and has evolved to gain new political, economic in health have varied, accompanying trends in development and strategic contours. The “horizontality” principle thinking. In the 1960s and early 1970s, influenced by non- represented an alternative to the “verticality” – unilateral aligned and alternative development movements, transfers of ready-made packages – of what was then known international health cooperation focused on building up as North-South international aid11. health systems based on strong primary health care In the 1980s, following the second (1979) oil shock and (PHC) services21. subsequent economic crisis, the neo-liberal principles From the mid-1970s onwards, fiscal crisis turned imposed by loans conditional on Structural Adjustment attentions to the high costs of medical care. In the 1980s, Programmes (SAPs) held centre-stage in the economic and economic crisis, debt repayment, implementation of SAPs political spheres and also in development cooperation. In this and deep political shifts22 exacerbated poverty and inequality context, TCDC suffered setbacks, and developing countries’ in the South. The worldwide HIV/AIDS epidemic, together political and administrative deficiencies were addressed with other fatal diseases, disproportionately burdened the through programmes to strengthen government institutions health systems in low- and middle-income countries. All this, (“institutional development”) by training national personnel together with unequal globalization, increased emigration to perform “essential roles”. (mainly to the North) by health workers from the countries At the beginning of the 1990s, widespread agreement on (mainly in the South) that had invested in their training. SAP failures led to the understanding that a new Nonetheless, during the 1980s, restrictive health sector development paradigm was needed. During that decade, a reform agendas prospered and were disseminated series of United Nations conferences12 emphasizing human, worldwide, backed by hegemonic neo-liberal ideology and social and environmental concerns stressed the need to criticism of the Welfare State. Health spending was bundled review the way development-related projects and activities with macroeconomic demands, incorporating the same had been implemented. principles of “less State”, privatization, flexibility and At the end of the decade, TCDC was also reviewed13, and deregulation23. Access to health services ceased to be the “capacity-building” approach to development has regarded as a public good, and privatization worsened this redirected many such endeavours14. This reorientation has situation, demanding greater private spending, even among brought significant changes to the role of international agents the neediest populations. This was accompanied by and foreign consultants in all fields of development disregard for epidemiological concerns and for public health cooperation15. activities, prevention and control of endemic, epidemic and By the early 2000s, some forward-thinking developing transmissible diseases24. nations themselves were incorporating this principle into These reforms of health systems did not help overcome their foreign policies, and TCDC took up the new challenge existing inequalities in either North or South; rather, of constituting an alternative means of neutralizing, or at particularly in the South, they further impaired health least reducing, the adverse forces resulting from economic systems’ already precarious problem-solving capacity, thus globalization processes16. worsening the inequities. Meanwhile, development The first decade of the 21st century poses new challenges. cooperation shifted towards technological interventions to On the one hand, the international donor community improve product research (new drugs and vaccines), while is coordinating more intensely and broadly to improve the support to systems for delivering interventions weakened effectiveness of international cooperation17, and capacity considerably. By the late 1990s the results of these decades building continues to be an international priority. On of (at best) under-investment were apparent. the other hand, the September 2001 terrorist attacks on By 2000, the scenario was more complex, and a number the USA brought the term “securitization” to international of recent international initiatives signal a new global attitude cooperation, underlining its potential role in global to tackling the critical state of global health: the Millennium threat containment18. Development Goals (MDGs, 2000), with three of eight objectives addressing health problems25; the Global Health International cooperation in health Initiatives (GHIs) (since the early 2000s)26; the Commission International cooperation in health emerged relatively early, on Macroeconomics and Health (2001)27; the Commission largely as a result of 19th-century advances in knowledge of on Social Determinants of Health (2005–2008)28; the Oslo infectious diseases and in transport technologies19. From Declaration (2007)29; and the worldwide celebration of 30 1851 onwards, international conferences were held, treaties years after Alma Ata Conference (2008).

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Box 1: Comunidade de Países de Língua Portuguesa (CPLP) idea of “horizontality” in international health cooperation, The community of countries where Portuguese is the official which interrelates South-South cooperation with partnering language was set up in 1996 in Lisbon, Portugal, by the heads directed to exchanging experience, learning jointly and of state of Angola, Brazil, Cape Verde, Guinea-Bissau, sharing results and responsibilities. Mozambique, Portugal, and São Tomé and Príncipe. With its independence in 2002, East Timor became the community’s The conception of “structural cooperation in health”: eighth member. The groundwork began to be laid in the late the Brazilian approach 1980s, when the first meetings of heads of state and The conception of “structural cooperation in health” government of Portuguese-speaking countries were held in Brazil (1989 and 1994). rests fundamentally on the approach of “capacity-building 31 The CPLP was set up in order to consolidate cultural for development” . This new paradigm innovates in conditions that endow Portuguese-speaking countries with two respects in comparison with previous ones, by their particular identity, promote political and diplomatic integrating human resource development with organizational coordination and to stimulate cooperation, so as to foster and institutional development. It also tries to break with concerted initiatives to promote the economic and social the traditional model of passive, unidirectional transfer development of the community’s peoples. Priority areas are the of knowledge and technology, proposing rather to Portuguese language, education and health. It is composed of the Conference of Heads of State and Box 2: Union of South-American Nations Government, the Council of Ministers, the Permanent Steering The Union of South-American Nations (USAN/UNASUL in Committee, the Executive Secretariat (in Lisbon), the Meeting of Portuguese) is an intergovernmental union integrating two Sectoral Ministers (such as the Health Ministers), the Meeting existing customs unions: Mercosur and the Andean of Cooperation Focal Points and the International Portuguese Community. It is part of an ongoing process of South American Language Institute. In 2007, the Parliamentary Assembly was integration. Its Constitutive Treaty was signed on 23 May 2008, established. The CPLP has 44 consultative observers, that is, in Brasilia, Brazil, by 12 heads of state. It is modelled on the member-country scientific, cultural and economic institutions European Union. that contribute to achieving the community’s objectives. Under the Treaty, the union’s headquarters will be in Quito, Equatorial Guinea, Mauritius Islands and Senegal are also Ecuador. The South American Parliament will sit in observers. Cochabamba, Bolivia, while the Bank of the South will be In the health field, the CPLP has passed several agreements housed in Caracas, Venezuela. on HIV/AIDS, malaria, illegal drug use, temporary medical The USAN’s provisional structure is as follows: visas, and others. The latest agreement established the 1. The Council of Heads of State and Government will be the Strategic Health Cooperation Plan for 2009–2013. In the lead political actor; international sphere, CPLP has also signed agreements with 2. The Council of Ministers of Foreign Affairs will formulate various United Nations units (such as UNAIDS) and is currently concrete proposals and make executive decisions; negotiating health agreements with WHO. A specific agreement 3. The Council of Delegates, composed of high-level on health documentation in Portuguese, the e-Portuguese, was government officials, will organize the work of the two reached with the WHO, where the platform is housed. councils and implement their decisions; There are major differences among the CPLP countries, not 4. A Secretary-General will be elected to set up a permanent only in population and income, but also culturally and in health secretariat in Quito, Ecuador. indicators and needs. CPLP country populations range from 189 million in Brazil to 155 000 in the islands of São Tomé and Presidents will call sectoral Ministerial Meetings, which will Príncipe, and income from US$ 21 500 per capita in Portugal to follow Mercosul and Andean Community procedures. The Pro only US$ 729 in Timor East, US$ 830 in Guinea Bissau and US$ Tempore Presidency will be held for a year and will rotate 1200 in Mozambique. There are also great disparities in health among Member States. indicators and life expectancy. Under-five mortality ranges from These 12 South American countries share thousands of miles 5 per thousand in Portugal to 260 per thousand in Angola; and of inland borders. Covering 10.99 million square miles of land, life expectancy, from around 70 years in Portugal and Brazil to they are home to some 385 million people (2008) and extend less than 50 years in Angola and Mozambique. to both the Atlantic and the Pacific Oceans. They span the South American continent from the Equator to Antarctica and contain the Amazon forest – the largest on the planet. Unfortunately, the proliferation of players, resources and In December 2008, the presidents convened in Bahia, Brazil, political support for global health has yet to deliver tangible to set up the South American Health Council, comprising the 12 change in health outcomes for all populations. In many parts Ministers of Health. of the world, even in countries credited as economic success There is great heterogeneity among and within South stories, health remains a conspicuous challenge. American countries. Populations range from 189 million in That realization led to major global debate on the Brazil and 40 million in Argentina and Colombia to less than effectiveness of international – and particularly North-South – one million in Suriname and Guyana. The per capita income health cooperation, traditionally structured in the form of range is from around US$ 15 000 in Argentina to around US$ vertical programmes connected with specific diseases, which 3000 in Bolivia. Under-five mortality ranges from 9 to 60 per apparently were having little effect on health systems and thousand and life expectancy is around 70 in all the countries. public health outcomes. Despite evidence mitigating these Bolivia and Guyana are clearly the poorest countries in the region and have the worst social and health situations. criticisms30, that debate resulted in a crucial shift towards the

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Cooperation projects Countries Ongoing Under negotiation At the exploratory stage Mozambique 1) Establishment of the public 1) Support for restructuring the FARMAC (CPLP) pharmaceutical company in Mozambique, enterprise and introducing the “Popular to produce antiretroviral and other drugs. Pharmacy” programme. 2) Strengthening the National Institute of 2) Support for distance learning. Health. 3) Capacity-building in programme and 3) Masters programme in Health Sciences. service monitoring and evaluation (part 4) Setting up the Polytechnic School of of the Brazil/USA/Mozambique Trilateral Health. Agreement on AIDS). 5) Technical capacity-building in equipment 4) Capacity-building in logistics (part of maintenance. the Brazil/USA/Mozambique Trilateral 5) Setting up the National Institute for Agreement on AIDS). Women and Children. 6) Service capacity-building in maternal and child health. 7) Elaboration and implementation of the Strategic Health Cooperation Plan (PECS).

Angola 1) Masters programme in Public Health. 1) Support for setting up the National (CPLP) 2) Elaboration and implementation of the School of Public Health. Strategic Health Cooperation Plan (PECS).

Cape Verde 1) Setting up the Technical School of Health. 1) Support for setting up the National (CPLP) 2) Support for strengthening the recently Institute of Health. created university to form health 2) Doctoral programme in Public Health. professionals. 3) Elaboration and implementation of the Strategic Health Cooperation Plan (PECS).

Guinea Bissau 1) Setting up the Technical School of Health. 1) Support for setting up the National (CPLP) 2) Elaboration and implementation of the Institute of Health. Strategic Health Cooperation Plan (PECS). 2) Support for strengthening the health system.

East Timor 1) Elaboration and implementation of the 1) Support for restructuring and strengthening the (CPLP) Strategic Health Cooperation Plan (PECS). health system.

São Tomé and 1) Elaboration and implementation of the 1) Advice and technical support for health system (CPLP) Príncipe Strategic Health Cooperation Plan (PECS). development (services, organizations and health programmes).

Nigeria 1) Support for strengthening the essential drug production.

Burkina Faso 1) Advice and technical support for health system development (services, organizations and health programmes).

Mali 1) Advice and technical support for health system development (services, organizations and health programmes).

Tanzania 1) Advice and technical support for strengthening the essential drug production.

Table 1: Health Cooperation Projects with Africa conducted by Fiocruz

exploit each country’s existing endogenous capacities in either research, teaching or services, and to strengthening and resources. or setting up health system “structuring institutions”, such as The purpose is to go beyond traditional forms of ministries of health, schools of public health, national health international aid and to redefine Brazilian cooperation in institutes, faculties for higher professional training (medicine, health as “structural”, i.e., centred on strengthening dentistry, nursing etc.), polytechnic health colleges, recipient-country health systems institutionally, combining technological development and production institutes and concrete interventions with local capacity building and factories. The proposal is for these institutions to work knowledge generation, and promoting dialogue among together in national and regional networks and support efforts actors, so that they can take the lead in health sector to structure and strengthen their respective health systems. processes and promote formulation of a future health Brazilian health cooperation with Africa prioritizes the development agenda of their own (Figure 1). In such a Community of Portuguese-Speaking Countries (Comunidade context the role of the international agent changes substantially. dos Países de Língua Portuguesa, CPLP) (Box 1 and Chart The main cooperation projects in Africa and South America 1), although cooperation projects and negotiations are are thus directed to human resource training/capacity-building ongoing with other African countries.

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Capacity building for devlopment

Structural cooperation in health

Integrates: Breaks: Human resources Traditional passive transfer of Development knowledge and technology Organization development resources Institutional development Role of International agent

Strengthening health systems Exploring country’s potential endogenous capacities and resources

Figure 1: The concept of “structural cooperation in health: conceptual and operational innovations”

The model of health cooperation adopted by CPLP comprises the ministers of health of the 12 Member States countries is based on a prior, joint strategic health cooperation and an executive structure36. The Council’s goals are to plan (Plano Estratégico de Cooperação em Saúde, PECS) consolidate South American integration in health through constructed with intensive participation by senior authorities consensual policies, and coordinated activities and from the eight countries’ Ministries of Health and resting cooperation efforts between countries37. on local “focal points” tasked with identifying interests and The health cooperation model adopted by UNASUL is quite needs by mobilizing ministry authorities and other actors. similar to the CPLP model, and the preliminary Work Plan, Funding is from government and other national and also called the South American Health Agenda, was approved international sources. in April 200938 (Box 3). Another important piece of this The CPLP structure for cooperation in health consists of the process involves engaging politicians, leading public health Council of Health Ministers, which decides the “focal points” figures and civil society. in each country and is coordinated by the CPLP Executive The main goals of UNASUL health cooperation are to Secretariat, with formal technical support from Fiocruz strengthen health systems and services and their structuring (Brazil) and the Institute of Hygiene and Tropical Medicine institutions and to further develop human resources for (Portugal). This model was discussed and approved at health. Unlike the CPLP proposals, however, they also successive meetings of the member countries’ health include establishing the South American epidemiological ministers32. shield and jointly negotiating with pharmaceutical companies The CPLP PECS has the distinguishing feature of clearly to secure fair prices for drugs, diagnostic kits, vaccines and taking into account MDG advances in each country, as well medical equipment. as the social determinants of health33. To begin with, the PECS spans seven priority areas and includes a number of Reflections on lessons learned so far specific diseases and thematic areas, but that array can be It is still early to evaluate impacts, but Brazil is attempting to revised periodically, according to each country’s needs34. apply the structural cooperation approach to South-South This form of health cooperation does not exclude any of the health cooperation, based primarily on five interrelated other bilateral or multilateral projects in place in each country, political, strategic and technical aspects: (a) horizontal South- including those involving the CPLP countries. However, the South cooperation, (b) focus on developing capacities in model does also seek articulation and coordination among them, health, (c) coordinated initiatives in the regional context, (d) with a view to reducing fragmentation and leveraging results. strong involvement of health ministers in constructing The countries have welcomed the PECS warmly, leading strategic and political consensuses, and (e), nationally, the the CPLP to apply a similar model to other areas of social close partnership between its Health and Foreign Ministries. cooperation, such as education, the environment and others. The horizontality of its South-South cooperation is evident Brazilian health cooperation with South America has been in the continuous emphasis on exchanging experience, driven by its foreign policy focus on the recently created learning jointly and sharing results and responsibilities with Union of South-American Nations (União de Nações national and international partners. This is a political and Sul-Americanas, UNASUL)35 (Box 2). strategic posture framed by the recent democratic experience The South American Health Council (UNASUL Saúde), set of grassroots social participation in making social policy – up in December 2008 at the UNASUL Presidential Summit, particularly health policy – in Brazil. Cooperation projects do

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Box 3: The South American Health Agenda frequent meetings among the countries at a variety of The South American Health Agenda includes the following locations and levels, in partnership with other international themes: organizations and prominent actors committed to promoting 1) The South American epidemiological shield: coordination South-South cooperation in health. These meetings have among Member States’ surveillance and response enabled provisional consensuses to be built, thus permitting networks according to international health regulations: these endeavours to advance. – early detection and response to outbreaks; Lastly, the close partnership between Brazil’s Ministry of – elimination of communicable diseases. Health and Foreign Ministry – called “health diplomacy”40 – 2) Universal health systems: development of health systems signals the national effort to associate expertise in health that assure peoples’ universal right to health and are with the strength of the foreign affairs sector, especially as based on the comprehensive primary health care approach. regards South-South cooperation.

3) Universal access to drugs and medications: To conclude – South American drug policy; In order to formulate a better notion of international health – health production complex. cooperation in developing countries, the following alternatives – which challenge traditional practices in one 4) Health promotion and social determinants of health: way or another – must be taken into consideration: – setting up the South American Commission on supporting comprehensive health system development, Determinants of Health; surmounting fragmentation and lack of coordination; – implementing intersectoral measures to address the social determinants of health. emphasizing long-term needs. By strengthening key institutions to acquire true leadership, promoting a 5) Human resource management and development: future-oriented agenda and balancing specific actions – assessment of progress by sub-regional groups in with knowledge generation; identifying the capacities and knowledge necessary for moving from programmes based on a single global training human resources; orientation to strategic planning centred on “recipient” – the UNASUL Health Scholarship Program; country realities, broadly incorporating the social – establishment of the South American Institute of Health determinants of health; Governance (Instituto Sulamericano de Governo em prioritizing population-based (health needs-oriented) Saúde, ISAGS), whose mission is to develop innovation programmes over activities focused strictly on individual for health governance and to prepare high-level care. personnel to lead health systems in the region. In the process of building a conception of structural cooperation in health, Brazil is continuously learning from involve a wide range of actors from both sides and, successes and errors. There are great challenges ahead, but consequently, decisions are taken at several levels and the prospects are also very promising. different loci of power, involving different organizational and institutional cultures in different countries. Celia Almeida MD, MPH, PhD is Senior Researcher and Meanwhile, the focus on health capacity-building is a Professor of the National School of Public Health, Oswaldo Cruz major challenge. Despite this important conceptual change, Foundation (Fiocruz), RJ, Brazil and Director of the Fiocruz little has been done to explore how to do it with a view to Regional Office for Africa based in Maputo, Mozambique. strengthening health systems. In addition, the role of “international agents” becomes less clear and more complex, Rodrigo Pires De Campos has a Masters and PhD in while partnering is crucial to identifying issues and tackling International Cooperation and is a researcher with the Fiocruz problems. Also, high expectations for effective results go Regional Directorate in Brasília and a member of the Global hand-in-hand with seriously limited administrative Health and Health Diplomacy research group, Health mechanisms on both sides. There is a need to define the Administration and Planning Department (DAPS) in Brazil. most appropriate institutional arrangements to respond to foreign policy decisions and to avoid the risk of Paulo Buss MD MPH is Professor of the National School of responsibilities being pulverized39. Public Health, Fiocruz, RJ, Brazil and Director of the Fiocruz The shift to region-wide coordination in Brazil’s Centre for Global Health. He is also the Brazilian representative on cooperation in health, both in Africa and in South America, the WHO Executive Board, on “CPLP Health” and on the stems from the understanding that in order to assure a “UNASUL Health”. foreign policy of “diversified autonomy”, and also greater effectiveness in its international cooperation in the present, José Roberto Ferreira MD is Doctor Honoris Causa of the Fiocruz Brazil must find a place in regional arrangements that enable National School of Public Health and Chief of the Fiocruz it to build political strength and gain greater strategic room for International Cooperation Division. He is also Senior Advisor to the manoeuvre than afforded by merely bilateral relations. Brazilian Ministry of Health Programme to Reorient Medical Training. The strong involvement of health ministers in building strategic and political consensuses has been secured by Luiz Eduardo Fonseca MD, MPH is adviser to the Fiocruz Global

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Health Centre and a PhD student on Comparative Health Policies International Cooperation Advisor to the National School of Public and Global Health and Health Diplomacy. He is also Health, Fiocruz.

References

1. Vigevani T & Cepaluni G. A Política Externa de Lula da Silva: A Estratégia Development: Technical Advisory Paper No. 2. Management Development da Autonomia pela Diversificação. Revista Contexto Internacional, 2007, and Governance Division, Bureau for Policy Management, New York. 29:273–335. 1997, p.89. 2. Agência Brasileira de Cooperação-ABC. Cooperação bilateral com América 15. Morgan P. “Capacity Development: An Introduction”. In: Morgan P and Latina e Caribe. Via ABC Boletim eletrônico da Agência Brasileira de Carlan V, eds. Emerging Issues in Capacity Development: Proceedings of Cooperação (ABC/MRE), June 2006, p.16. Available at: a Workshop. Institute on Governance, Ottawa, Canada, 1994, pp.5–21. http://www.abc.gov.br/documentos/via-junho.pdf (accessed on 1 August 16. Amador EA. El nuevo rostro de la cooperación técnica entre paises en 2009). desarrollo (CTPD) y las nuevas tendencias internacionales. Ciências 3. Agência Brasileira de Cooperação-ABC. Cooperação técnica brasileira em Sociales, 2001, Vol. I, No. 94, pp.169–188. saúde. Via ABC Boletim eletrônico da Agência Brasileira de Cooperação 17. Paris Declaration. Paris Declaration on Aid Effectiveness: Ownership, (ABC/MRE), March 2007, p.24. Available at: Harmonisation, Alignment, Results and Mutual Accountability. High http://www.abc.gov.br/documentos/viaABC-baixa.pdf (accessed on 1 Level Forum on Joint Progress Toward Enhanced Aid Effectiveness: August 2009). Harmonisation, Alignment and Results. 2nd High level Forum on Aid 4. Oslo Ministerial Declaration. Global health: a pressing foreign policy issue Effectiveness, Paris, France, 28 February–2 March 2005. Available at: of our time. Lancet, 2 April 2007, Vol. 369, Issue 9570, 1373–1378. http://www.oecd.org/dataoecd/11/41/34428351.pdf (accessed on 3 Available at http://www.thelancet.com (accessed on 5 August 2009). August 2009). And the ACCRA Agenda For Action, 3rd High Level Forum 5. The Oswaldo Cruz Foundation (Fiocruz) is a public foundation connected on Aid Effectiveness. Accra, Ghana, 2–4 September. Available at: with the Brazilian Ministry of Health, and right arm of the Unified Health http://www.undp.org/mdtf/docs/Accra-Agenda-for-Action.pdf (accessed on System (SUS). Fiocruz has a diversified mission – teaching, research, 3 August 2009). production and technological development performed through different 18. This is quite evident in the 2003 World Bank report. World Bank. technical and scientific units, and also engages in global interchange with Breaking the Conflict Trap: Civil War and Development Policy. A World scientific and technological centres in developed and developing countries. Bank Policy Research Report. 26121. The World Bank Group and Oxford Its headquarters and 10 specialized units are in Rio de Janeiro, but University Press, May 2003, p.221. Fiocruz has units in seven provinces in Brazil, giving it national scope. 19. The 1st International Sanitary Conference, a historic landmark in The Fiocruz Centre for Global Health was set up in January 2009 in Rio international health cooperation, was held in Paris In 1851. At that time, de Janeiro. The centre provides advisory support to the Fiocruz Presidency European states were discussing for the first time coordinated cooperation and coordinates the Fiocruz International Cooperation Technical Group, initiatives to combat the threats from cholera, plague and yellow fever. which comprises representatives of the institution’s 17 technical and That event represented “one such dramatic transition in how health was scientific units. conceptualized and approached internationally”. Fidler DP. Germs, Norms 6. The International Portuguese-African-Brazilian Integration University and Power: Global Health's Political Revolution, Law, Social Justice & (Universidade Internacional da Integração Luso-Afro-Brasileira, UNILAB), Global Development (LGD, 2004, No. 1. An electronic journal available in Fortaleza, Ceará, Brazil; the International Latin-American Integration at: http://elj.warwick.ac.uk/global/issue/2004-1/fidler.html (accessed on 3 University (Universidade Internacional da Integração Latinoamericana, August 2009). UNILA), in Foz de Iguaçu, Brazil, at the triple border between Brazil 20. Fidler DP. The globalization of public health: the first 100 years of Argentina and Paraguay; and the South American Institute of Government international health diplomacy. Bulletin of the World Health in Health (Instituto Sul-americano de Governo em Saúde, ISAGS), set up Organization, Vol. 79, No. 9, 2001, pp.842–849. for the purpose of heading a network of schools of government in the 21. The trend was strengthened in the late 1970s by PHC programmes and countries of South America. All the initiatives will offer several courses, the “Health for All in 2000” strategy proclaimed in the Alma Ata including Public Health, to Brazilian, Portuguese-speaking and South Declaration (1978). American students, respectively. 22. Civil and political unrest, the spread of neoliberal hegemony, processes of 7. The Amazon Agreement on Health Research, which gave rise to the political re-democratization in South America and the building of new Pan-Amazonian Health Research Network, an articulation among scientific nations following post-colonial wars of liberation in Africa. institutions from the Amazon countries (Bolivia, Brazil, Colombia, 23. Almeida C. As reformas de saúde nos anos 80: crise ou transição. Um Ecuador, Guyana, Peru, Suriname and Venezuela) – Fiocruz among them estudo dos países centrais – EUA, Reino Unido, Alemanha, Suécia, Itália – with the objective of jointly carrying out relevant projects for the specific e Espanha (Health Sector Reforms in the 80’s: Crisis or Transition? A and defying situation of this vital region for the planet. Currently in the study of the central countries – USA, United Kingdom, Germany, health sector there are projects in malaria, haemorrhagic fevers (including Sweden, Italy and Spain). PhD Thesis, National School of Public dengue fever) and health systems. Health/Fiocruz, 5 July 1995. Almeida C. Reforma de sistemas de 8. Todaro MP. Economic Development, 6th ed. England, Longman, 1997. servicios de salud y equidad en América Latina y el Caribe: algunas 9. Stokke O. Foreign Aid Towards the Year 2000: Experiences and lecciones de los años 80 y 90 (Health services reform and equity in Latin Challenges. London, Frank Cass, 1996. America and the Caribbean: lessons from the 80s and 90s). Cadernos de 10. Jolly R. A Future for UN Aid and Technical Assistance? Society for Saúde Pública, 2002, Vol. 18, No.4, pp.905–925. International Development, 1989, No. 4, pp.21–6. 24. Almeida C. Health Sector Reform in Latin America and the Caribbean: the 11. The 1978 Buenos Aires Plan of Action (BAPA) proved a seminal role of International organizations in formulating agendas and document in establishing and advancing “horizontality” as the implementing policies. Wellbeing and Social Policy, 2006, Vol. 2, fundamental principle of TCDC. pp.123–160. 12. For a complete list and brief explanation on each conference held in the 25. Millennium Development Goals Report 2009. Available at: 1990s, visit the United Nations website: http://www.un.org/millenniumgoals/ (accessed on 3 August 2009). http://www.un.org/News/facts/confercs.htm (accessed on 30 July 2009). 26. The GHIs comprise increasing involvement by the private sector, 13. As indicated in the United Nations Economic and Social Council philanthropic bodies and civil society in health, as a result of the resolution (1993), and in the 10th Session of the United Nations High- proliferation of global initiatives in health at the start of the 21st century. Level Committee on TCDC (1997). WHO Maximizing Positive Synergies Collaborative Group, 2009. “An 14. UNITED NATIONS DEVELOPMENT PROGRAMME (UNDP). Capacity Assessment of interactions between global health initiatives and country

106 Global Forum Update on Research for Health Volume 6 100-107 almeida:gf6 23/10/09 14:23 Page 107

Social innovation incentives: from “push” to people

References continued

health systems”. Lancet, 2009, 373:2137-2169). Union of South American Nations community (União das Nações 27. The Commission Report and the Declaration on the Second Consultation Sulamericanas-UNASUL) crowns a movement to broaden the process and on Macroeconomics and Health (Geneva, October, 2003), "Increasing scope of regional integration in South America. This movement was Investments in Health Outcomes for the Poor" are available at: initiated in 1994 when Brazil, Argentina, Paraguay and Uruguay (the http://www.who.int/macrohealth/en/ (accessed on 3 August 2009). original Mercosur member countries) proposed to set up a South 28. The report is available at: http://www.who.int/social_determinants/en/ American Free Trade Area (ALCSA). Although the move was first tabled in (accessed on 2 August 2009). the mid-1990s, it was only in 2004, ten years later, that the movement 29. Oslo Ministerial Declaration. Global health: a pressing foreign policy issue regained political momentum. UNASUL was officially established on 23 of our time. Lancet, 2007, Issue 9570, 369:1373–1378. Available at: May 2008, in Brazil’s capital, Brasilia. http://www.thelancet.com (accessed on 5 August 2009). 36. The structure of the Council includes a Coordinating Committee composed 30. World Health Organization Maximizing Positive Synergies Collaborative of representatives from each country’s Ministries of Health; a Technical Group, 2009. “An Assessment of interactions between global health Secretariat under the responsibility of the country currently occupying the initiatives and country health systems”. Lancet, 2009, 373:2137–2169. UNASUL Pro Tempore Presidency, the last country that held it and the 31. “Capacity building for development” is defined as “the process by which country that will hold it next; workgroups on specific themes; and the individuals, organizations, institutions and societies develop abilities health-related focal points (UNASUL Steering Committee on Health). (individually and collectively) to perform functions, solve problems and set 37. The main objectives of UNASUL Saúde include strengthening Ministries and achieve objectives”. United Nations Development Programme of Health and other “structuring institutions” within health systems; (UNDP). Capacity Development. Technical Advisory Paper 2. Management developing policies and inter-sectoral actions to tackle social determinants Development and Governance Division, Bureau for Policy Development, of health; establishing sectoral institutional networks; providing a 1997, p.34. Available at: http://mirror.undp.org/magnet/Docs/cap/ coordinated response to emergencies and disasters; promoting scientific Capdeven.pdf (accessed on 15 March 2009). research and stimulating innovation in health; and harmonizing sanitation 32. The meetings were held in Praia, Cape Verde, April 2008, and in Rio de standards and health actions in border areas. Janeiro, Brazil, September 2008. The PECS for the coming four years 38. The South American Health Agenda was developed by Technical Groups (2009–2013) was given final approval in another meeting Lisbon, on specific priority themes, was reviewed by the UNASUL Steering Portugal, in May 2009. Committee on Health, and approved in April 2009 at the Council meeting 33. MDG Africa Steering Committee. Achieving the Millennium Development in Santiago, Chile. Goals in Africa. New York, 2008, p39. Available at: http://www.mdgafrica 39. França C, Sanchez MR. “Política Externa – A horizontalização da política .org/pdf/MDG%20Africa%20Steering%20Group%20Recommendations%2 externa brasileira”. Portal Global 21, 9 July 2009. Available at: 0-%20English%20-%20HighRes.pdf (accessed on 8 January 2009). http://www.global21.com.br/materias/materia.asp?cod=24489&tipo=noti 34. Initially, these areas are: health workforce development, epidemiological cia (accessed on 11 July 2009). surveillance, emergency and disaster preparedness, information and 40. The concept of “health diplomacy” has emerged to contemplate health communication, research & development for health, technological factors that transcend national boundaries and expose countries to global development and drug and vaccine production, health promotion and influences, and to enforce better and more cohesive coordination between protection including inter-sectoral actions (health determinants). The governments’ health and foreign affairs sectors. Kickbusch I, diseases are malaria, tuberculosis and HIV/AIDS, and the thematic areas Silberschmidt G & Buss PM. Global health diplomacy: The need for new are health and migration, and health diplomacy. perspectives, strategic approaches and skills in global health. Bulletin of 35. Mercosur and the Andean Community (CAN) have been for many years the World Health Organization, 2007, Vol. 85, No. 3, pp.230–232. the two main regional blocs of South-American countries. The creation of

Global Forum Update on Research for Health Volume 6 107 2 - MFF_Cover.ai 21/10/09 15:49:33

Edited by Erik Landriault and Stephen A Matlin

One of the key messages heard as part of the 2008 Global Ministerial Forum on Research for Health in Bamako, was that not only do low- and C middle-income countries need to develop capacity to conduct research, M but there needs to be a greater sense of accountability for health Y research systems globally.

CM This issue of Monitoring Financial Flows examines the importance of MY monitoring financial flows to health research, with a special focus on 7 CY selected Latin American countries: Argentina, Bolivia, Brazil, Chile, CMY Cuba, Paraguay and Uruguay. By describing how these countries

K established priorities for health research in recent years, the study makes the case that with limited resources, governments benefit from better alignment of national health research priorities with the populations’ health profile.

The failure to prevent and treat disease is devastating to communities, economies, individuals and nations. In this context, and despite the many challenges in measuring investments, the Global Forum Report Card (Chapter 10) has been developed to measure progress against agreed targets and – based on international efforts – track investments by region, disease category and funders. In undertaking the most recent issue of the Report Card, the Global Forum found that although policy-makers set ambitious targets to ramp up research and development for health, the majority of countries are ill-equipped to monitor these investments. Particularly in a time of a global economic crisis, the 2009 issue of Monitoring Financial Flows urges us to remember that health research is not a luxury.

Copies of this publication are available online and can be ordered (at no charge) via the website www.globalforumhealth.org 109 TP:gf6 26/10/09 15:01 Page 109

Technological innovation incentives: “push” and “pull”

110 Giving innovation a push: public and philanthropic R&D funding Mary Moran with Javier Guzman, Klara Henderson, Alina McDonald and Brenda Omune

116 Government and philanthropic funding for technological innovation to develop new and better tools for neglected diseases Catherine M Michaud

119 Between pull and pools, where’s the “push” for global health R&D? Anthony D So

123 PDPs as social technology innovators in global health: operating above and below the radar Joanna Chataway with Rebecca Hanlin, Lois Muraguri and Watu Wamae

127 Innovation in life sciences Where do technologies come from? Vijay K Vijayaraghavan

131 Financing social entrepreneurship: innovation awards to cross the “Valley of Death” Charles W Wessner

138 Global health partnerships: a “pull” mechanism for innovation and new products Michel D Kazatchkine with Rifat Atun and Mary Ann Lansang

142 The pneumococcal Advance Market Commitment (AMC): innovative finance to help the poor Tania Cernuschi

147 Comparative advantages of push and pull incentives for technology development: lessons for neglected disease technology development Cheri Grace and Margaret Kyle

153 Emerging innovation practices and policies for the health-care needs of resource-poor people Raghunath Anant Mashelkar, with Bhushan Patwardhan and Shiladitya Sengupta

Global Forum Update on Research for Health Volume 6  109 Technological innovation incentives: “push” and “pull”

Giving innovation a push: public and philanthropic R&D funding

Article by Mary Moran (pictured) Director of Health Policy Division, the George Institute for International Health, with Javier Guzman, Klara Henderson, Alina McDonald and Brenda Omune

eglected disease research and development (R&D) option – efficiencies to make product development cheaper – has traditionally been “neglected” because the size of is rarely discussed. This article examines the key funding Nthe end market is too small to offset the cost of mechanism that has driven these changes – push funding. developing products for that market. However, the landscape The vast majority of the products now in development or on of R&D of new products to diagnose, prevent and treat the market have been the direct result of push funding, neglected infectious diseases of the developing world has although we believe traditional public procurement changed substantially in the past decade. 1 New business mechanisms have also played a role. This assertion can be models of public and private collaboration have materialized confidently made since the majority of the ND products noted in the form of Product Development Partnerships (PDPs); above were already in development in 2007, yet no pull new industry institutes fully focused on neglected disease mechanisms existed at that time. The impact of push funding (ND) R&D have been set up; and new funders, including has been underwritten by the presence of publicly funded developed and developing country governments and mechanisms to purchase the resulting medicines (at least for philanthropic heavy-weights such as the Bill & Melinda Gates some diseases) for the developing world. For example, the Foundation, have come on the scene. In 2007, for instance, Global Alliance for Vaccine and Immunizations (GAVI) created US$2.5 billion was invested globally in R&D of new in 2000 (which provides vaccines for diseases including neglected disease products. Of this, 69.4% was from public yellow fever, pneumonia, Hepatitis B, rotavirus, Haemophilus sources, 21% from philanthropy and 9.1% from private influenzae type B); and the Global Fund to Fight AIDS, companies. 2 Tuberculosis and Malaria (GFATM) created in 2002 to These changes have dramatically increased the size of the improve access to drugs (and other products like bednets and product development pipeline for neglected diseases. At the condoms) for the three diseases. end of 2004, there were 63 projects in the ND pipeline 1, In 2007, the dynamic began to shift as pull incentives while others estimate that 106 ND products entered the R&D gained donor support. The most well-known pull mechanism pipeline between 2000 and 2007. 3 Presentations at the is the Advanced Market Commitment (AMC), with donors recent WHO Expert Working Group on Innovative Financing launching a pilot AMC for a pneumococcal vaccine in 2007 for R&D showed that the Gates Foundation alone is to the tune of US$1.5 billion. 6 Another pull device is the supporting 77 drugs and vaccines in late-stage preclinical or Priority Review Voucher (PRV), enacted in the United States clinical development, largely through product development in September 2007 to reward research and development for partnerships (PDPs) 4; while industry is involved in 67 a neglected disease product with reciprocal expedited projects, including 39 projects in the preclinical phase, 23 regulatory review of a commercial drug.. projects in the clinical phase, and 5 projects in the registration phase. 5 As a result, diseases such as tuberculosis Push funding (TB), malaria and sleeping sickness now have their largest Push funding usually flows through one of three key channels portfolios ever. 5 (see Table 1): The literature describes two types of funding to stimulate  self-funding for internal research; R&D of new products for neglected diseases – ‘push’ and  funding granted directly to external researchers and ‘pull’ funding. Push funding decreases the developer’s R&D product developers; costs by providing funding along the development pathway,  funding routed to external researchers and product thus allowing developers to break even or make a profit even developers through intermediary fund and research if the end-market is small. Pull mechanisms do not assist managers, such as PDPs. developers with their R&D costs, but instead increase the end return on investment to cover these costs retrospectively, also These channels offer funders a choice in how they allowing developers to break even or make a profit. A third participate in push funding. Each channel also has a different

110  Global Forum Update on Research for Health Volume 6 Technological innovation incentives: “push” and “pull”

Self-funding or “intramural” Funding granted directly to Funding directed through intermediary research researchers and product developers managers such as Product Development Partnerships (PDPs)

Type of group disbursing funds Scientific, health and technology Scientific, health and technology Official Development Assistance (ODA) agencies e.g. the US National agencies e.g. the US National agencies e.g. Irish Aid, UK Department for Institutes of Health Institutes of Health International Development (DFID)

Philanthropic funders with deep scientific knowledge e.g. the Wellcome Trust

Degree of control afforded and Very high High Low management input required

Scientific knowledge and High High Low or none decision-making capacity required

Type of organization receiving Scientific, health and technology Small-scale researchers in the PDPs e.g. Medicines for Malaria Venture funds departments e.g. the Malaria academic and the biotech sectors (MMV), Drugs for Neglected Disease Vaccine Development Branch of the e.g. University of Liverpool, Sanaria Initiative (DNDi) NIH

Recipient organization location Domestic Domestic for public funders International

Domestic and international for philanthropic funders

Stage of product development Basic research Basic research All stages of the product pipeline except targeted basic research Early clinical development Early clinical development

Table 1: Channels of push funding

profile in terms of the management effort required and risk, since funding is disbursed within large portfolios rather control afforded; the depth of scientific knowledge required; than into individual projects. Efficient PDPs have the the type of funder involved; and the recipient and product additional advantage of lower R&D costs due to their ability profile. Each of these influences the attractiveness of different to leverage in-kind contributions 1, foster partnerships and channels to funders. cooperation and use each actor in their area of maximum In general, push funding affords funders a far greater efficiency. degree of control over the features of the final product including price, allows them to target their funding to Case studies specific diseases, products or R&D players and, has a The case studies below explore the two external push substantially lower cost of capital compared to industry self- funding channels – funding granted directly to researchers funded product development. There are also benefits from and product developers, and funding directed through the recipient’s perspective, as push funding provides the intermediary managers such as PDPs. These two channels much needed cash injection for biotechnology companies, are chosen as the focus as together they represent 80% of small pharmaceutical companies and academics to conduct the total global investment in neglected disease R&D. 2 The the R&D activities, However, these benefits come at a price. four case studies examine public and philanthropic funders, Push mechanisms, since they require funders to review, with the aim of understanding how funder profiles differ, and select and monitor the projects they invest in, are more as an indicator of how future investments into ND R&D might resource intensive than market based

mechanisms, where little or no government 10 i intervention is required. As a direct 9 consequence, push funding also requires 8 funders to bear all the risks of decision 7 6 making. We note that these disadvantages 5 are offset in certain situations. PDPs allow 4 funders to participate in R&D without 3

2U n

having the otherwise necessary scientific G i t e

- 1 d F S i U n expertise, as PDPs take responsibility to t a

n 0 d t e i N t N S e s e S e G o d e o w r w N C u e t F f

select, monitor and manage a portfolio of / K D A i h R F i r t a B t o A S Z n J I G r i m h u e e z u a n s I n r a e e m w l e r s r n s w r a p a S A a g B l n a e l D r t a s g a e a e n d a n d r a p l l l f c r i e m a a a d i n r r a a d n a a e y y P u o a i i l projects. PDPs and large intramural n n n e l d z c c * * * * * * * * r i m m i d d d n n a a a i k s * * * * * * * * l ( 1 /

programmes also allow funders to diversify 1 0 0 , 0 ** G-FINDER 2007 funding data likely incomplete for these countries 0

i 0 In practice, some “pull” mechanisms Sourc)e: Neglected disease 2007 R&D investment data from G-FINDER 2008 report 2; GDP data 2007 8. require more extensive government 10.0% intervention than others e.g. AMC. Figure 1: Neglected disease R&D funding (G-FINDER) per $100,000 of GDP %

Global Forum Update on Research for Health Volume 6  111 Technological innovation incentives: “push” and “pull”

be affected by the changing economic climate. Data included Disease area US$ % split by disease 2007 in the case studies is sourced from the G-FINDER 2008 Malaria 7 805 463 43.0 survey and includes previously unpublished data (see full HIV/AIDS 2 375 195 13.1 Tuberculosis 1 269 898 7.0 description of the G-FINDER project in the G-FINDER 2008 Helminths (worms & flukes) 1 053 789 5.8 report). 2 Diarrhoeal diseases 764 645 4.2 Dengue 689 533 3.8 Bacterial pneumonia & meningitis 549 170 3.0 Ireland General diagnostic platforms 545 152 3.0 In 2000, Ireland committed, and re-committed in 2005, to Kinetoplastids 442 719 2.4 increasing its ODA to reach the United Nations target of 0.7% Rheumatic fever 385 170 2.1 Buruli ulcer 220 585 1.2 of national income. This has translated into significant Other R&D 2 065 461 11.4 investment in both overall development assistance for health (DAH), and specific funding for neglected disease R&D. As a Table 2: % of Australia’s total funding – spread across diseases result, Ireland ranked first in terms of dollars invested into neglected disease R&D relative to GDP in 2007, as reported among the highest rates of rheumatic fever and rheumatic in G-FINDER; and fourth on overall DAH as a percentage of heart disease in the world, with an average incidence of 2.5 GDP in 2007 behind Sweden, Luxembourg and Norway as per 1,000/year for rheumatic fever among children aged 5- reported by the Institute of Health Metrics. 7 14 years (2003-2006) and a prevalence of 20-23 per 1,000 The Irish government’s investments in R&D for ND were for rheumatic heart disease at the end of 2006. 15 channelled through its aid agency, Irish Aid. In 2007, Irish Eight-five percent of the US$18.2 million invested by Aid invested over US$24 million in R&D for ND in 2007, Australian governments in R&D for ND was channel through with 97% directed towards the ‘Big Three’ diseases: HIV, TB the National Health and Medical Research Council and malaria. All funds were channelled via PDPs, with seven (NHMRC). Most of the remaining funding came from the groups receiving and subsequently disbursing the Irish Aid Queensland government, one of the Australian states with investment. This core, un-earmarked funding was provided to high risk of re-emergence of mosquito-borne diseases. PDPs without specific conditions on how it was spent. A great Australian public investments not only have different deal of the burden and risk of project selection was removed drivers to those of Ireland, but have also followed a different from Irish Aid since the recipient PDPs, and their associated investment path. While Australian public funding also Expert Committees and Scientific Review Boards, provided predominantly goes to the big three diseases (63%), there is the scientific and management expertise to ensure Irish Aid’s a greater spread across the more neglected diseases, funding was efficiently invested. reflecting Australia’s own health and economic interests. However, because Ireland’s participation in the neglected Close to sixty percent of this funding was directed towards disease R&D arena has come under the aid umbrella and the basic research, and just under 20% to early stage aid budget has been cut, the size of their investments may development of drugs, vaccines and diagnostics. prove volatile. Since the global financial crisis, Ireland has Australian public funders channelled 100% of their reduced its aid budget, with the two last cuts representing a 2007 funding into a large network of small to medium 22% decrease of the 2009 ODA budget. 9 These cuts are Australian academic and government research institutions, likely to be felt by those neglected disease PDPs who have with no investment outside Australia and no funding to been funded to date by Irish Aid. PDPs. This nationally oriented investment approach Australia supports the local economy. Australia’s investments into R&D for ND differ from those of Since Australian public funding is partially motivated by its Ireland, since they are arguably influenced by domestic own interests, as well as the health interests of the region; health and economic interests. On the health front, Australia’s and since all funding returns directly to Australian near neighbours suffer from many neglected diseases. researchers, we would not expect to see a significant Malaria is endemic in the Solomon Islands (with an incidence decrease in Australia’s neglected disease R&D investment in of 311 per 1,000/year 11 ), Papua New Guinea (PNG) (295 the near-term future as a direct result of the global financial per 1,000/year 10 ), East Timor (134 per 1,000/year 11 ), crisis. Vanuatu (41 per 1,000/year 10 ) and Indonesia (27-68 per 1,000/year 11 ). Furthermore, PNG has the highest prevalence Brazil of HIV (1.28% among adults age 15-49 years) and incidence Domestic health and economic interests also appear to be a of TB (250 per 100,000/year) in the Pacific region. 12,13 key motivator for Brazilian government funding of R&D for Australia has close ties with these neighbours, ties that are ND. Brazil has a high neglected disease burden, with HIV bound through immigration, security, military, trade and aid. topping the list, followed by TB and the kinetoplastid diseases The health of its own citizens also plays a part. The (particularly Chagas’). (see table 3) proximity of Australia to its near neighbours, coupled with the While local disease burdens drive the need for investment effects of global warming, makes the re-emergence of in R&D, the local health biotech industry has also been mosquito-borne diseases within Australia’s borders a real supported and encouraged to capture and capitalise on this threat. For instance, Australia now averages over 300 cases public investment. This sector, traditionally dominated by of dengue per year.v Australia’s indigenous peoples also have public firms, now features a growing private sector. Since the

112  Global Forum Update on Research for Health Volume 6 Technological innovation incentives: “push” and “pull”

1970s, the Brazilian government has championed Disease % split by US$ DALYs (‘000) disease 2007 2004 pharmaceutical development to meet domestic public health Kinetoplastids (total) 22.3 4 906 145 215 needs, with a focus on developing affordable generic versions - Chagas disease 6.3 1 390 121 178 of existing products, which are directly procured and - Leishmaniasis 15.5 3 413 447 37 HIV 13.6 2 995 779 485 disbursed to the Brazilian public. The Ministry of Health’s Helminths 11.7 2 568 936 65 own research institute FIOCRUZ and its affiliated Malaria 9.9 2 175 502 44 manufacturing plants Bio-Manguinhos and Far-Manguinhos, Tuberculosis 8.1 1 781 186 261 16 Dengue 7.4 1 623 000 16 are key examples of this. Leprosy 6.6 1 455 070 9 Brazil’s private biotech sector is growing due to recent The remaining 20% went into platform technologies and other R&D. changes in national innovation policy, with human health Source: World Health Organization (2008). The global burden of disease: 2004 update. research currently the largest life science biotech sector at Table 3: Brazilian disease burden and R&D investments into ND 30%. 17 With the implementation of the Agreement on Trade- (G-FINDER) Related Aspects of Intellectual Property Rights (TRIPS) in 1996 the sector is shifting focus from generics to innovative close to US$60 million in neglected disease R&D in 2007. 2 products. While both patenting levels and technology It is a significant supporter of R&D for the big three diseases, revenue are up, there is room for improvement, with Brazil’s with 63% of its ND R&D investments directed to HIV, TB and overall R&D intensity lower than that of fellow BRIC malaria, with a particular interest in malaria. Kinetoplastids (Emerging Economies – Brazil, Russia, India, China) are the next biggest recipients of funds at 25%. (see Figure 2) countries China and Russia. 18 Key gaps in R&D know-how, The Wellcome Trust’s funding profile is similar to that of financial and human capital are still real hurdles. 19 public funders. The Trust predominantly funds small- to In 2007, the Brazilian government invested US$21.9 medium-size academic research organisations (87%) to million in ND R&D, with 88% originating from the Ministry conduct basic research (63%); while PDPs receive only of Health and 12% from the Brazilian Innovation Agency about ~6% of Trust funding. Where the Trust differs from (FINEP). Brazilian funding shows greater diversity than the public funders is in the spread of its funding recipients. In previous two case studies, with the largest share of funding 2007, the Wellcome Trust provided neglected disease R&D going to kinetoplastids R&D (22%). By contrast, AIDS, TB funding to over 40 organisations in 14 countries. (see table and malaria collectively received only 32% of total Brazilian 4 below) Indeed, of the four case studies, the Wellcome public funding for neglected disease R&D. (see Table 3) Trust exhibits by far the greatest geographic diversity of Ninety-seven percent of Brazilian funding is disbursed funding recipients, although the lion’s share of funding was domestically, being directed to over 50 Brazilian academic nevertheless invested in the Trust’s home country (UK, and government research institutions and public sector 78%). pharmaceutical companies. Although there is no investment into PDPs, Brazil’s public research institute, Fiocruz, has a Conclusion long standing collaboration with the Drugs for Neglected The last decade has brought significant change to the Disease Initiative (DNDi), a PDP that is developing drugs for development of neglected disease products. There are now malaria. Nearly one third of Brazil’s investments were directed to basic research, including creating a science base and conducting upstream work in diseases that are 1.8% 1.7% Diarrhoeal not fully understood (e.g. Chagas’ disease). As noted, this 2.4% Dengue 0.4% type of funding requires in-depth scientific knowledge from Trachoma diseases Other the funding provider. 4% R&D 0.3% Bacterial Pneumonia Given Brazil’s long history of public investment into ND Tuberculosis and Meningitis R&D, and the link to domestic health and economic 5.3% priorities, we would not expect to see decreases in Brazil’s Helminths R&D funding to ND. Like other members of BRIC, Brazil (worms and flukes) may also be more resilient to the global economic crisis due to trade surpluses, foreign exchange reserves, the government’s willingness to use those reserves to increase 11.6% spending, and consumer demand, 20 all of which support HIV/AIDS 47.1% Malaria the view that Brazilian public investment in ND R&D is unlikely to wane in the near-term.

The Wellcome Trust 25.1% Kinetoplastids The Wellcome Trust is a dominant player in the biomedical non-government sector, it is UK’s largest charity and the largest non-government source of funds for biomedical research. The Wellcome Trust has deep scientific roots and Figure 2: Wellcome Trust – % invested in R&D by disease 2007 a long history focussed on biomedical research, investing

Global Forum Update on Research for Health Volume 6  113 Technological innovation incentives: “push” and “pull”

Country of recipient % of total funding Key messages UK 78.0 Switzerland 12.1  Push funding mechanisms have been instrumental Kenya 4.9 Australia 1.2 in increasing the size of the neglected disease Unspecified 0.7 product development portfolio we have seen in Brazil 0.7 recent years. US 0.5 India 0.5  Pushing funding usually flows through one of three South Africa 0.4 different channels: Malaysia 0.4 1. self-funding for internal research; Czech Republic 0.2 Ecuador 0.2 2. funding granted directly to external researchers Belgium 0.1 and product developers and; Peru 0.1 Mexico 0.04 3. funding routed to external researchers and product developers via intermediaries. Table 4: Wellcome Trust R&D investments into ND by country for  These channels appeal to different funders, offering 2007 (G-FINDER) a choice in how they participate in push funding. This availability of choice has brought new over one hundred neglected disease products in the R&D funders who do not have the scientific capacity to pipeline, the vast majority as a direct result of government otherwise participate in the funding of neglected and philanthropic push funding. Over 30 countries, including disease research. Innovative Developing countries such as Brazil, India and South Africa, are now contributing, driven by varied motivations including meeting development aid targets, the University of Sydney. Her thesis examined HIV/AIDS political protecting their own populations from regional threats, commitment and funding in East Timor. In her early career she developing R&D and industrial capacity, and finding solutions worked as a policy and strategic development consultant with to diseases that affect their own populations. numerous Australian government agencies. She subsequently Different channels of push funding, such as PDPs, can spent time in East Africa working on HIV/AIDS projects and was a reduce the need for donors to have in-depth scientific HIV/AIDS policy and financing consultant for AusAID and UNDP knowledge or to conduct intensive due diligence across the Asia Pacific. Klara is a senior policy analyst with HPD, joining the whole R&D landscape, thus allowing new donors to team in 2007 and is currently working on the G-FINDER project. contribute and existing donors to reduce their management requirements. Fostering these approaches will allow greater Alina McDonald joined the HDP as a policy analyst in June participation of both new and smaller donors in times of 2006, following a secondment to WHO in Geneva. She conducts financial crisis. J qualitative and quantitative analysis, for projects including G- FINDER. Previously she has contributed to a series of health policy Dr Mary Moran trained as a physician, working for 13 years in roundtables run by the George Institute and the Chinese Ministry Emergency Medicine in Australia but embarked upon a diplomatic of Health, where she managed international stakeholders and career following a degree in international relations and politics at prepared policy reports. Alina also worked on an EU-funded the University of New South Wales and Monash University, both in bioethics research project based in Berlin. She has degrees in Australia. She subsequently worked with Médecins Sans Frontières science and law from the University of Sydney and is undertaking on access to medicines. In 2004, she founded the Pharmaceutical postgraduate study in intellectual property and regulation. R&D Policy Project (PRPP) at the London School of Economics Brenda Omune trained as a physician, working for several years (LSE), later moving the unit to Sydney, now the Health Policy as a casualty officer in Kenya. She was also involved in the initial Division (HPD) of The George Institute for International Health. As stages of rolling out antiretroviral therapy (ART) in Kenya and Director, she oversees all the unit’s projects, including the multi- gained experience in clinical management of patients with year G-FINDER survey tracking global investment into neglected infectious diseases including malaria, tuberculosis and HIV/AIDS. disease R&D funded by the Bill & Melinda Gates Foundation. She completed a Masters of International Public Health (Honours) degree from the University of Sydney in 2009. Brenda joined HPD Dr Javier Guzman trained as a physician, working for several in June 2008 as a research associate and now works on the years in planning and implementation of primary health care G-FINDER project. projects in Colombia. He moved to the UK in 2002 working as a Postgraduate Fellow at the Royal London Hospital. He has an MSc in Health Policy, Planning and Financing from the LSE and the London School of Hygiene and Tropical Medicine. In 2000 Javier joined the HPD, and has since worked on key projects in the area of product development for neglected diseases, including the malaria product development pipeline and G-FINDER. Javier is the HPD’s Director of Research.

Klara Henderson has a PhD in international health policy from

114  Global Forum Update on Research for Health Volume 6 Technological innovation incentives: “push” and “pull”

References

1. Moran M, Ropars AL, Guzman J, Diaz J & Garrison C. The new landscape 7 April 2009 of neglected disease drug development. London School of Economics and (http://www.alertnet.org/thenews/fromthefield/218328/123912700376.ht The Wellcome Trust. September 2005. m, accessed 07 August 2009). 2. Moran M, Guzman J, Ropars AL, McDonald A, Sturm T, Jameson N, Wu 10. WHO/WPRO data, (http://www.wpro.who.int/, accessed 05 August 2009) L, Ryan S, Omune B. Neglected disease research and development: how 11. WHHO/SEARO data, (http://www.searo.who.int/, accessed 05 August much are we really spending? The George Institute for International 2009) Health. February 2009. 12. The United Nations Joint Programme on HIV/AIDS. New estimates: the 3. Meredith S. Health Partnerships Review: The new landscape of product face of the HIV epidemic in Papua New Guinea. UNAIDS, 2007 development partnerships (PDPs). The Global Forum for Health Research, 13. WHO Statistical Information System (WHOSIS), 2008:11-14 (http://www.who.int/whosis/en/index.html, accessed 05 August 2009). 4. Bill & Gates Foundation. R&D Financing by the Bill and Melinda Gates 14. Australia National Notifiable Disease Surveillance System, Foundation, presented by Neill McDonnell to WHO Expert Working Group (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-pubs- on R&D Financing, January 12, 2009, (http://www.who.int/phi annlrpt-nndssar.htm, accessed 05 August 2009). /1stmeeting/en/index.html, accessed 28 July 2009). 15. Australian Institute of Health and Welfare, 5. IFPMA. IFPMA Presentation to WHO Expert Working Group on Funding (http://www.aihw.gov.au/publications/ihw/aatsihpf08r-da/atsihpf08r-c01- R&D for Diseases of the Developing World (DDW), presented by Alicia 06.pdf, accessed 28 September 2009) Greenidge to WHO Expert Working Group on R&D Financing, January 12, 16. Ferrer M, Thorsteinsdóttir H, Quach U, et al. The scientific muscle of 2009, (http://www.who.int/phi/1stmeeting/en/index.html, accessed 28 Brazil’s health biotechnology. Nature Biotechnology, December 2004, 22 July 2009). (Suppl.):DC8-DC12. 6. GAVI Alliance, 2009. Preventing Pneumococcal Diseases: An innovative 17. Biominas Study of the Brazilian Biotechnology companies, October 2007. way to make vaccines available for children, 18. OECD 2008 Science and Technology and Industry Outlook by Country, (http://www.vaccineamc.org/files/AMC_FactSheet2009.pdf, accessed 07 p164. August 2009). 19. Rezaie R, Frew S, Sammut S, et al. Brazilian health biotech—fostering 7. Ravishankar N, Gubbins P, Cooley RJ, et al. 2009. Financing of global crosstalk between public and private sectors. Nature Biotechnology, June health: tracking development assistance for health from 1990 to 2007. 2008, 26(6):627-644. Lancet, 20 June 2009,73(9681):2113-24. 20. Egbhal M. BRIC economies withstand global financial crisis, Euromonitor 8. IMF World Economic Outlook data. International, 7 November 2008 (http://imf.org/external/pubs/ft/weo/2008/02/weodata/index.aspx, accessed (http://www.euromonitor.com/BRIC_economies_withstand_global_financial 10 August 2009) _crisis, accessed 07 August 2009). 9. Reuters, Ireland's fourth aid cut in 10 months to have devastating impact.

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Technological innovation incentives: “push” and “pull”

Government and philanthropic funding for technological innovation to develop new and better tools for neglected diseases

Article by Catherine M Michaud, independent consultant, previously senior research scientist, Harvard University

he world is ill equipped to reduce the burden of that are widely available and affordable in resource-poor neglected diseases because existing tools to do so – settings. They also lead pharmaceutical companies to Tdrugs, vaccines, diagnostics and vector-control agents – endorse greater social responsibility. often do not reach those most affected as they are too Public-private partnerships, such as the Global Fund and expensive, are not well suited to developing country contexts, GAVI, are the hallmark of the new global health architecture. or are simply not available. Drug and vaccine development They have successfully attracted large financial resources, has stalled in the latter part of the 20th century, in part engaged the active participation of developing country because pharmaceutical firms best equipped to do so lacked stakeholders and are achieving results. Similarly, product financial incentives to invest resources needed to develop development partnerships (PDPs), most of which were new products, and in part because government and established since 2000 to catalyse the development of new philanthropic institutions had other priorities. Hence, only 13 drugs and vaccines for neglected diseases and are still in drugs were developed for the WHO list of ten neglected infancy, have nonetheless already succeeded in vastly diseases between 1975 and 2000, and no new classes of expanding the number of compounds currently under tuberculois (TB) drugs were developed in the past 40 years. development. PDPs are non-profit organizations that build As a result, neglected diseases have become more prevalent partnerships between the public, private, academic and and drug resistance has developed. Rapidly spreading philanthropic sectors to drive the development of new multidrug-resistant TB, and emerging resistance to products for underserved markets. Through their unique artemisinin in Southeast Asia, are causing great concern but collaborative efforts, PDPs are able to access a variety of also provided a unique opportunity to develop push funding sources, and to apply a wide range of tools and incentives that could spark innovation and bridge the gap knowledge to their programmes. PDPs retain direct between market opportunities and people’s needs. management oversight of their projects, though much of the Government and philanthropic institutions have grappled work is done through external research facilities and with this fundamental problem and developed a range of contractors. In the public health arena, PDPs have been innovative mechanisms to spark technological innovation, established to accelerate the development of new which include “push” and “pull” incentives. Pull incentives technologies to fight TB, AIDS, malaria and a wide range have focused on financial incentives to create commercial of neglected diseases. PDPs are created for the public good; markets and stimulate research and development by their products are made affordable to all those who multinational drug companies, and on advance purchase need them. commitments. This paper focuses on government and philanthropic funding to “push” technological innovation. It Key findings emphasizes what innovation can do for health and its Twelve major PDPs have been established between relevance to resource-poor settings. 1995 and 2007 – six to develop new vaccines, five to Over the past decade, the institutional landscape of develop new drugs and one to develop new diagnostics technological innovation for neglected diseases has changed (see Table 1). in the context of renewed interest in global health and Public-private product development partnership is a unprecedented increase in public and private funding to misnomer when it comes to funding, particularly during the support global health programmes1. Effective advocacy has first few years as the lion share of initial funding was provided increased public pressure on governments to assist the by a few philanthropic donors – the Bill & Melinda Gates developing world in reducing the burden of major neglected Foundation (BMGF), the Rockefeller Foundation and diseases by investing in development of new and better tools Médecins Sans Frontières (MSF). For example, the BMGF

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Technological innovation incentives: “push” and “pull”

PDP Total income Year Location Disease Product 2005–2007 established focus focus US$, million

International Aids Vaccine Initiative 181.2 1996 New York, USA HIV/AIDS Vaccine International Vaccine Institute NA 1996 Seoul, Korea Cholera, shigellosis, Vaccine typhoid fever Medicines for Malaria Venture 147.1 1999 Geneva, Switzerland Malaria Drug PATH Malaria Vaccine Initiative NA 1999 Seattle, WA, USA Malaria Vaccine Global Alliance for TB Drug Development 69.2 2000 New York, USA Tuberculosis Drug Institute for One World Health 66.7 2000 California, USA Visceral leishmaniasis; Drug malaria; diarrhoeal disease; Chagas disease; soil- transmitted helminthes Human Hookworm Vaccine Initiative/ NA 2000 Washington, DC, USA Hookworm Vaccine Albert B Sabin Vaccine Institute Pediatric Dengue Vaccine Initiative NA 2001 Seoul, Korea Dengue Vaccine International Partnership for Microbicides 27.1 2002 Silver Spring, MD, USA HIV transmission Microbicide Drugs for Neglected Diseases Initiative NA 2003 Geneva, Switzerland Human African Drug trypanosmiasis; visceral leishmaniasis; Chagas disease; malaria Aeras Global TB Vaccine Foundation 111.3 2003 Rockville, MD, USA Tuberculosis Vaccine Foundation for Innovative New Diagnostics FIND 2003 Geneva, Switzerland Tuberculosis, malaria, Diagnostics African trypanosomiasis

Table 1: Public-private product development partnerships for global health

provided US$ 182 million to Medicines for Malaria Venture Grant commitment Amount years US$, million (MMV) between 2000 and 2007, or 64% of total International AIDS Vaccine Initiative 1999–2007 130.1 contributions to MMV during those years. All other donors PATH Malaria Vaccine Initiative 1999–2004 150 contributed 8% or less. The UK Department for International Medicines for Malaria Venture 2000–2007 202 Drugs for Neglected 2007 25 Development (DFID) was the second largest funder and Diseases Initiative contributed US$ 23.4 million. In contrast, governments TB Alliance 2000–2006 129.4 provided more than 85% of total funding between 2005 and Institute for One World Health 2002–2009 160.7 Aeras Global TB Vaccine Foundation 1999–2008 308.6 2007 to IAVI. International Vaccine Institute 1999–2009 80.1 PDPs and TDR received US$ 584.4 million from Total 1,185.9 governments and philanthropies, effectively channelling Source: Bill & Melinda Gates Foundation, Grants on line almost 25% of total R&D funding for neglected diseases in 2 2007 (US$ 2.56 billion) . Table 2: Bill & Melinda Gates Foundation – total grant Incomplete data does not allow us to fully capture overall commitments to PDPs trends in philanthropic and government funding for PDPs between 2000 and 2007, but it appears that philanthropic Discussion funding (mostly from the BMGF) remains the main driver of It is interesting to note that neither governments nor PDPs. The BMGF contributed US$ 1.2 billion to nine PDPs pharmaceutical companies have provided the largest share of between 1999 and 2008 (see Table 2). Most PDPs have funding. Rather it is the financial support provided by diversified their funding base to include a larger number of philanthropy, above all from the Gates Foundation, that has donors from governments but there is often no information enabled PDPs to develop an innovative business model regarding funding provided each year by each donor or the allowing them to create a new relationship with year when they first contributed. pharmaceutical companies. The large pharmaceutical Five new drugs have been launched: paromycin (Institute companies are best suited to discovery, using the techniques for One World Health, 2006) was approved for sale in India they employ for commercial drugs, but PDPs have added a for leishmaniasis treatment; two new malaria drug clear focus on the most suitable products for neglected combinations – artesunate-amodiaquine (ASAQ) (DNDi and disease patients, and provided money and links to others in Sanofi-Aventis, 2007) and artesunate-mefloquine (ASMQ) academia or business involved in the process of research. In (DNDi and Farmanguinhos, 2008); Coatem Dispersible particular, by acting as an honest broker, PDPs have been (MMV and Novartis, 2009) and a combination for sleeping able to foster cooperation between traditional competitors. As sickness (DNDi, 2009). Although PDPs have been quite a result, even drugs companies no longer directly involved in successful in expanding the portfolio of pipeline drugs and neglected disease work, including Roche, Merck and Abbott, several new drugs have been approved, future funding levels are willing to offer scientific advice or access to their libraries remain uncertain. This is particularly worrisome as the of compounds. By design, PDPs also ensure equitable access number of products entering the most expansive Phase III to new and better tools that are essential to reach clinical trials increases (see Table 3). There is no doubt that MDG targets. a large gap in funding to develop drugs, vaccines and PDPs have undoubtedly provided fresh impetus to the diagnostics needed to meet Millennium Development Goals development of drugs and vaccines to prevent, diagnose and (MDGs) targets remains. treat neglected diseases and sparked technological

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PDP Disease Phase I Phase II Phase III Phase IV Total

Global Alliance for TB Drug Development TB Alliance Tuberculosis 2 1 4 Drugs for Neglected Diseases Initiative DNDi Human African trypanosmiasis; visceral leishmaniasis; Chagas disease; malaria 6 6 Institute for One World Health IOWH Visceral leishmaniasis; malaria; diarrhoeal disease; Chagas disease; soil transmitted helminthes International Partnership for Microbicides HIV 6 6 5 17 Medicines for Malaria Venture MMV Malaria 4 4 8 16 Aeras Global TB Vaccine Foundation AERAS Tuberculosis 1 1 International AIDS Vaccine Initiative IAVI HIV 5 3 8 International Vaccine Institute IVI Cholera, shigellosis, typhoid fever 7 1 5 13 PATH Malaria Vaccine Initiative MVI Malaria 2 7 9 Pediatric Dengue Vaccine Initiative (PDVI) PDVI Dengue Human Hookworm Vaccine Initiative/ Albert B Sabin Vaccine Institute HHVI Hookworm 2 2

Note: ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the United States and around the world. Source: Clinical Trials Database

Table 3: Studies sponsored by PDPs registered in the US Clinical Trials Database, 2000–2008

innovation as evidenced by the rapid expansion of the nevertheless too soon to know how many pipeline drugs will portfolio of new drugs and vaccines since 2000. Medicines yield new tools tailored to the particular needs of developing for Malaria Venture (MMV) has built a robust pipeline of countries, and will ultimately be affordable and widely almost 50 antimalarial drug projects over nine years, and has available to poor populations who need them most. three new combination therapies in late stage development, In addition to offering a flexible and innovative business with one, Coartem Dispersible, approved and ready for model, PDPs were also able to provide money. It is launch. It is the first artemisinin-based combination therapy noteworthy that MMV and the TB Alliance jointly funded half (ACT) developed by Novartis and MMV especially for children of the 100 scientists of Tres Cantos – the research centre with malaria. Glaxo established in Spain to develop drugs for neglected The TB Alliance has made great strides towards meeting its diseases. Glaxo covers the other half of the costs. goal to accelerate the discovery and development of new TB Finally, commitment by developing countries themselves to drugs that will shorten treatment; be effective against address global health problems has also increased, as susceptible and resistant strains; be compatible with evidenced for instance by the meeting of health ministers of antiretroviral therapies for those HIV-TB patients currently on 27 countries held in Beijing on 31 March 2009 to address such therapies; and improve treatment of latent infection. the problem of multidrug-resistant TB. Researchers from the Phase III clinical trials enrolled 2400 patients to test whether Institute of Microbiology of the Chinese Academy of Sciences it is possible to cut standard TB treatment from six months to will work with the TB Alliance in a bid to discover and four months, sharply reducing the cost, inconvenience and develop new TB drugs from natural sources, including likelihood that patients will fail to properly take all their microbial metabolites and ingredients used in traditional medicines. The Phase III trial being run in six sites in Africa Chinese medicine. marks a pioneering collaboration with Bayer Schering, the These few examples are by no means exhaustive but German-based drug company that developed the antibiotic nevertheless highlight the richness and diversity of innovative moxifloxacin, which will be added to existing drug strategies sparked by PDPs. Cautious optimism leads us to combinations to speed up treatment. The company has concur with the Institute of Medicine (IOM) that PDPs “are agreed to make its drug available at low cost in the developing one of the most promising approaches to bridge the world if the results prove successful, while retaining the rights enormous and widening gap in the availability of drugs, to sell it at a commercial rate in richer countries. It is vaccines and diagnostics”3. J

References

1. Moran M. The new landscape of neglected disease drug development. 3. Committee on the US Commitment to Global Health, Board on Global London, Wellcome Trust, 2005. Health. The US commitment to global health: recommendations for the 2. Moran M. Neglected diseases research and development: how much are public and private sectors. Washington, DC, The National Academies we really spending? PLOS Medicine, 2009, 0137–0416. Press, 2009.

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Technological innovation incentives: “push” and “pull”

Between pull and pools, where’s the “push” for global health R&D?

Article by Anthony D So, Professor of Practice of Public Policy, Terry Sanford School of Public Policy, Duke University

en years ago, a policy cascade began with the call for fourfold between 1990 and 2007, from US$ 5.6 billion to lower-priced AIDS drugs. In that time, the price of triple US$ 21.8 billion, doubling over the last six years3. By 2003, Tdrug therapy for AIDS has fallen from US$ 10 000– 45% of the estimated US$ 125.8 billion spent on health 15 000 to treat a patient for a year to less than US$ 100, R&D globally came from direct public funding. High-income and the ranks of those treated have swelled to several million or transition countries provided 96% of this funding. Another in developing countries. Still short of the mark, these efforts 7%, or an estimated US$ 9 billion, was provided by private, downstream to the research and development (R&D) pipeline not-for-profit funders. In sum, government and nonprofit have invited greater scrutiny of the innovation upstream. sectors financed over half of the health R&D globally4. The The process leading from the WHO Commission on private, for-profit sector contributed the balance. Intellectual Property, Innovation and Public Health to the In global health, it is not just the traditional push Intergovernmental Working Group process and finally to the mechanisms of grants or R&D tax credits that are helping to Global Strategy and Plan of Action, adopted by the 2008 turn the tide. Reflecting the broader mix of funding for R&D, World Health Assembly, opened a window for considering public sector and philanthropic funding have fuelled the alternative models of innovation that might better meet public emergence of product development partnerships (PDPs). health needs. Proposals from prize funds to pools have arisen PDPs have sought to address these failures in marketplace from these discussions. In this new context, the role of push mechanisms to meet public health priorities for developing mechanisms – those that pay for inputs of R&D such as countries. These PDPs have created a virtual pharmaceutical grants or R&D tax credits – deserves strategic rethinking. company model, mobilizing financial and technical inputs There is good reason to re-examine how financing from both public and private sectors. mechanisms might better work to advance innovation and By the end of 2004, one study documented 63 neglected- access to health technologies. Further progress in global disease drug R&D projects underway5. Of note, multinational health depends on narrowing the affordability gap for corporations conducted nearly half of these projects, either treatments, faltering research productivity in the alone or with PDPs. In all of these cases, such work was done pharmaceutical industry has raised concerns on several on a noncommercial basis, a “no profit, no loss” model. fronts, and turning the corner on finding cures for neglected Importantly though, the other half were largely conducted by diseases will require a sustained commitment. smaller-scale commercial firms working with PDPs, and this That older triple drug therapy regimen for AIDS now costs was done on a commercial basis. For these firms, the US$ 87, but the gulf between innovation and access opportunity costs for entering the pipeline might be different. threatens again to widen with the growing need for new fixed- A recent survey by the same group showed US$ 2.5 billion dose combinations of drugs for AIDS. Using WHO’s current of R&D funding in 2007 for new neglected disease products, recommendation for first-line AIDS treatment, the most mostly for drugs and vaccines6. This is a rather modest slice affordable regimen costs between US$ 613 and US$ 1033 of the estimated US$ 21.8 billion in overall development when priced with originator products, at least eight times assistance for health. Three-quarters of this neglected disease more than the older regimen1. product funding went to the “big three” diseases of HIV/AIDS, From 1993 to 2004, pharmaceutical company R&D malaria and tuberculosis (TB). By far, the largest funder was expenditures climbed 147% while the number of new drug the US National Institutes of Health (US$ 1.1 billion, applications to the FDA rose only 38%, and the number of 41.75%), followed by the Bill & Melinda Gates Foundation new chemical entities, a disappointing 7%2. Concerns over (US$ 452 million, 17.72%) and the European Commission the number of new candidate drugs in the R&D pipeline have (US$ 121 million, 4.76%). surfaced over not only neglected tropical diseases and rare However, push mechanisms remain a key part of proposals diseases, but also classes of drugs such as antibiotics. for innovative financing of R&D. For example, the Overall development assistance for health multiplied International Federation of Pharmaceutical Manufacturers &

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Associations and Novartis have commissioned a feasibility study for a Fund for R&D in Neglected Diseases (FRIND) and A target product profile could lay out the key features estimate that US$ 6–10 billion would be needed over the and attributes of the intended product. By defining coming decade to bring promising neglected disease upfront the contours of a technology appropriate and products in the pipeline to market7. FRIND would be open to affordable for resource-limited settings, clearer applications from for-profit companies as well as from PDPs expectations are set or academic institutions. As proposed, these public investments would result in intellectual property, retained by the inventing institution or company, but exclusively licensed features and attributes of the intended product. By defining to the fund for the particular neglected disease. Dual market upfront the contours of a technology appropriate and opportunities, such as a secondary indication with affordable for resource-limited settings, clearer expectations commercial potential, would remain with the funded are set. institution or company. Push mechanisms can also redress the failings of market Of course, proposals such as FRIND raise important policy priorities that fall short of meeting public health needs. questions. Keeping the scope to neglected diseases, might Without targeting push mechanisms, fixed-dose this fail to address critical needs of adapting health combinations or paediatric formulations for AIDS might be technologies that might respond to significant sources of the left unfinished, HPV vaccines beyond affordable reach of burden of disease in developing countries, such as vaccines those in developing countries, or drugs like Ivermectin or for huma papillomavirus (HPV) or meningitis? Will such eflornithine sustainably produced only when donated from a funding just substitute the “no profit, no loss” efforts of dual market, veterinary or human. multinational companies with “for profit” undertakings? Would PDPs and companies be equal to the responsibility of Providing value-added funding ensuring affordable end-products for those in need? How Public funding should bring value-added contribution to should the funding be conditioned to ensure that resulting existing efforts. Such funding can change the risk calculus for inventions are not just licensed back to FRIND, but registered firms and lower their barrier to entry into these areas of R&D. and delivered for the intended markets in the developing However, to sustain production of a health technology in world? Would PDPs and drug companies competing for the resource-limited markets, the firm’s return on investment same pool of public and philanthropic monies for these must justify these efforts. The firm’s revenues are a function projects accelerate innovation or result in less sharing and of unit price, volume produced and production costs. scientific exchange by companies with PDPs? How can such Price and volume might vary inversely to achieve the same funding be conditioned, so that it is not business as usual, revenue target. Developing business models for high-volume, but with the objective of delivering an appropriate and close-to-marginal cost pricing is key. Generic competition is affordable product for those in developing countries? How one proven way of achieving this. Absent that, and dual might such efforts also build capacity and engagement of market arrangements offer potential. Markets segmented by scientists and firms in developing countries? use (human versus veterinary), clinical indication (neglected These questions suggest the need for a framework for disease versus non-neglected disease), or geography (low- rethinking the public sector’s strategy behind push and middle-income countries versus high-income countries) mechanisms of funding. Some starter considerations for this offer opportunities to piggyback or cross-subsidize production framework might address: of a drug for a market receiving preferential pricing or access. targeting push mechanisms; Alternatively, push mechanisms might strategically lower providing value-added funding; the costs of production. Securing royalty-free access through ensuring fair returns to the public; and humanitarian licensing, making compound libraries freely re-engineering the value chain of R&D. available, pooling essential building blocks of knowledge, facilitating technology transfer, or capitalizing the production Targeting push mechanisms facility costs – these are all steps that might help firms meet Limiting the scope of push mechanisms to neglected the target product profile specifications, including an diseases, as narrowly defined, may miss key infectious affordable price point. diseases, such as HIV/AIDS or even Chagas disease that If the opportunity costs are lower for small firms or afflicts those in Latin America; ignore the need to adapt developing-country firms, how can this part of the industry health technologies for developing country needs, as be engaged to bring a drug, device, vaccine or diagnostic to suggested by the recent advance market commitment for developing-country markets? An instructive example comes pneumococcal vaccine; or gloss over novel approaches from the University of California, Berkeley. Funded initially by required to treat the growing burden from noncommunicable the US National Institutes of Health, a university research diseases in developing countries. team found a way of synthesizing artemisinin in microbes. The public sector might engage with PDPs, academic The Gates Foundation provided a US$ 42.5 million grant in institutions and pharmaceutical firms from both support of a three-way partnership among the university, its industrialized and developing countries to generate target spinoff company (Amyris Biotechnologies), and the Institute product profiles. A target product profile could lay out the key for One World Health. UC Berkeley provided a royalty-free,

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co-exclusive licence to One World Health and Amyris Key messages Biotechnologies, limited by field to malaria treatment in the developing world. In return, Amyris has committed not to take The role of push mechanisms – those that pay for profit from sales of the product to the developing world. inputs of R&D – deserves strategic rethinking. Under the Gates grant, Amyris will receive milestone A starting framework for rethinking push payments up to US$ 12 million for its work. This funding, mechanisms might address how to better target described as bootstrap philanthropy, does not give up equity these mechanisms, add value through such funding, in the early biotechnology start-up company, yet provides ensure fair returns to the public, and re-engineer the resources to develop the technology further before seeking value chain of R&D. later rounds of venture capital when company shares In this world of pull and pools, push mechanisms for would be more valuable. The technology itself also has dual financing offer strategic opportunities for the public market uses, such as synthesizing biofuels. Together with and philanthropic sectors to create a more enabling Sanofi Aventis, the Institute for One World Health will conduct environment for enhanced innovation and more the clinical trials, file for drug registration and bring this drug affordable access to health technologies, to market. particularly for those in developing countries. Another example of innovative push financing involves the sale of bonds, backed by guarantees from donor governments. It is one mechanism used by the International transaction costs for cross-licensing patented inventions, Financing Facility for Immunization to raise monies now for thereby facilitating innovation such as of fixed-dose repayment later. This may help smooth out the uncertainty of combination drugs or paediatric formulations for AIDS. Open year-to-year appropriation cycles among donor country access repositories for journal articles, public compound governments as the government-backed bonds could be libraries and reagent repositories constitute other pooling repaid with grants or PDP product revenues in the future. efforts to diminish the transaction costs of accessing building blocks of knowledge. Ensuring fair returns to the public Push financing might require a non-exclusive licence to be From push financing, the public may seek returns in various extended for resulting research tools, data, journal articles or ways. Having reduced the risk of R&D, the public sector end products to a pool. The licence could be royalty-free for might expect lower prices for the resulting products. noncommercial applications, but royalty-bearing at Constructed well, push mechanisms might also contribute to reasonable rates for commercial use depending on the target capacity building by involving scientists and firms in market. Building on such pooling efforts, push financing developing countries in substantive ways. Push mechanisms could support the development of a technology trust that might also condition funding, so that resulting study findings, leverages the collective management of intellectual property, research tools and reagents, clinical trial data, and journal so that the public and philanthropic sectors use their strategic articles are widely accessible and freely exchanged. Such position to encourage greater scientific exchange and conditions on grants, set by funders, can importantly innovation not only of inventions, but also of underlying data, influence norms within the scientific community. Greater reagents and research tools, and journal articles9. public funding of clinical trials would strengthen calls for Re-engineering the value chain of R&D, the Open Source disclosing clinical trial findings and treating the results as a Drug Discovery (OSDD) project, led by India’s Council of public good8. Scientific and Industrial Research, serves as a platform for Push and pull mechanisms can also work in tandem. Pull scientific exchange, from gene sequencing to drug mechanisms, such as prizes or advance market development, about Mycobacterium tuberculosis. Backed by commitments, pay for the outputs of R&D, and in so doing, the Indian government with US$ 38 million of funding, OSDD advantage those who have the upfront resources to run requires participants to sign a click-wrap licence to grant the race for the prize. Push financing can help level the back additions or modifications to the on-site information. playing field by building capacity, particularly among OSDD also plans to license drug companies to develop those where the disease is endemic, to participate in the resulting new products without royalties and to cover part of process of innovation. their clinical trial costs. In return, the firms would not claim intellectual property on their products and would offer the Re-engineering the value chain of R&D lowest possible price to patients. Though still at an early Some financing mechanisms bring needed funding, but pay stage, OSDD has already enlisted over 70 projects and over less attention to the process of how the R&D is done. 1100 registered participants from 26 countries in its initiative Lowering the costs of production though may require re- in the first nine months. engineering the R&D process rather than emulating the In this world of pull and pools, push mechanisms for traditional pharmaceutical value chain. financing offer strategic opportunities for the public and For example, pooling key building blocks can help re- philanthropic sectors to create a more enabling environment engineer the value chain of R&D and eliminate the need for for enhanced innovation and more affordable access to workarounds. Patent pools such as UNITAID’s proposed health technologies, particularly for those in developing Medicine Patent Pool initiative for AIDS drugs lower countries.

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Acknowledgements Anthony D So MD, MPA, is Professor of the Practice of Public The author gratefully acknowledges the capable research Policy at Duke University’s Terry Sanford School of Public Policy, assistance of Dan Mueller in preparing this contribution and where he directs the Program on Global Health and Technology useful feedback from Shaoyu Chang, Cecilia Oh and Chris Access in the Center for Strategic Philanthropy and Civil Society, Manz. The Programme’s work on conceptualizing a and is also a member of the Duke Global Health Institute. technology trust is supported, in part, under a grant from Previously, Dr So served as Associate Director of the Rockefeller the National Human Genome Research Institute (Grant Foundation’s Health Equity Program, Senior Adviser to the 5R01HG003763). Administrator at the US Department of Health and Human Services’ Agency for Health Care Policy and Research, and as a White House Fellow.

References

1. UNITAID. The Medicines Patent Pool Initiative, March 2009. Available 2005. from: http://www.unitaid.eu/images/projects/ 6. Moran M et al. Neglected disease research and development: how much PATENT_POOL_ENGLISH_15_may_REVISED.pdf. are we really spending? PLoS Medicine, 2009; 6(2):e1000030. doi: 2. US Government Accountability Office. New drug development: science, 10.1371/journal.pmed.100030. business, regulatory, and intellectual property issues cited as Hampering 7. Herrling PL. Making drugs accessible to poor populations: a funding drug development efforts. GAO-07-49, November 2006. model. Global Forum Update on Research for Health, Volume 5. Geneva, 3. Ravishankar N et al. Financing of global health: tracking development Switzerland, 2008, pp.152–155. assistance for health from 1990 to 2007. Lancet, 2009; 373:2113–24. 8. Lewis TR, Reichman JH, So AD. The Case for Public Funding and Public 4. Global Forum for Health Research. Monitoring financial flows for health Oversight of Clinical Trials. Economists’ Voice January 2007. research 2006: the changing landscape of health research for 9. So A, Stewart E. Appendix F: Sharing knowledge for global health. In: The development. Geneva, Switzerland: Global Forum for Health Research, US commitment to global health: recommendations for the public and 2006, p.39. private sectors. Institute of Medicine, Washington, DC: The National 5. Moran M et al. The new landscape of neglected disease drug Academies Press, 2009. development. London, UK, LSE Health and Social Care, September

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PDPs as social technology innovators in global health: operating above and below the radar

Article by Joanna Chataway (pictured), Professor of Biotechnology and Development at the Open University, with Rebecca Hanlin, Lois Muraguri and Watu Wamae

roduct Development Partnership (PDP) success rests addressing. Moreover, for technologies and products to be on an ability to create new science and technology but successful they must be appropriate to local conditions and Pit also depends on the creation of new organizational need to be demanded locally. Local demand involves not only structures and cultures which can successfully develop appreciation for the product but also for the means of appropriate technology and products and get them to those distribution. Thus, PDPs need to engage with and contribute who need them. One of the main reasons PDPs are supported to local organizations, institutions and individuals which have and funded is that they constitute a “social technology” and are building political voice. It is PDPs’ ability to combine innovation. As such they work both with “above the radar” product development with this targeted and efficient established and formal mechanisms for developing new approach to working locally in developing countries with products and with “below the radar” networks, organizations health, community and development organizations which and physical technologies in developing countries so that makes them distinctive. products are appropriate, understood and accepted and can be made accessible to those who need them. We argue that PDPs as social technologies thinking about PDPs in this light provides a useful framework Richard Nelson defines social technologies by using an analogy for evaluation. to the limitations of written recipes for food preparation: “… a recipe characterization of what needs to be done Introduction represses the fact that many economic activities involve Global PDPs are often characterized as “technology push” multiple actors, and require some kind of a coordinating initiatives aimed at providing new science and technology mechanism to assure that the various aspects of the recipe based products for neglected diseases, applying the best are performed in the relationships to each other needed to science and technology to meet global health needs. Yet this make the recipe work. The standard notion of a recipe is mute characterization is only a partial description of many PDPs. It about how this is to be done…. [We] propose that it might be is also possible to view PDPs themselves as innovators useful to call the recipe aspect of an activity its ‘physical’ developing novel networks, new ways of dividing labour and technology, and the way work is divided and coordinated its relevant management and organizational skills to serve global ‘social’ technology”1. health objectives. Looking at PDPs in this light, we can see During the 1990s it was widely perceived that neither the them as social technology innovations designed to develop public, nor private nor nongovernmental organization (NGO) and distribute physical technologies in the shape of new sectors alone could develop new technologies and make products and drugs. them accessible to the world’s poor who needed them. The PDPs develop new medicines or medical equipment for hope was that the imbalance in spending on health research people in developing countries who lack the economic and development (R&D), in favour of the world’s wealthy, resources and political clout to demand and access effective could be partially rectified via the creation of new products. Yet it is now well established that new technologies organizations which would bring a range of actors together to and products alone are not enough. Highly complex work effectively around specific disease and health agendas. manufacturing and access problems need also to be resolved. While the recipes for doing this may have been understood This set of issues is difficult in large part because the answers (bringing together the power of public and private sectors in are not standard. Whereas an AIDS vaccine may have in technological innovation and the private and NGO sectors in theory widespread global or regional applications, distributional distribution) creating and managing the organizations that and access issues involve numerous local factors which need could divide and manage the work was an entirely different

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matter. We are only now beginning to see analysis of the In some respects IAVI and MVI seem to be moving in different organizational forms operating under the PDP opposite directions with IAVI moving in a more “integrator” umbrella and the various modes of working that resulted in fashion – increasingly becoming identified with particular the effort to create social technologies for neglected disease. scientific approaches (rather than a very broad umbrella) and Using the concept of social technologies highlights a increasing commitments to basic science in the US and number of shortcomings in other ways of looking at the Europe. In MVI on the other hand, we see a move towards intractable issues involved in addressing neglected diseases. addressing delivery issues and health systems strengthening One powerful strand of argument for instance views the (development and broker issues) and working more closely problem as one of incentives and investment. According to with a variety of UN, multilateral and bilateral agencies. In this argument if enough money is pumped into the area of some senses IAVI maintains its virtual pharma company neglected diseases and if the right incentives are created, the identity and MVI is moving away from thati. problem will be solved. In a previous Global Forum Update The reasons for this divergence include the stage of for Health Research Review, Orsenigo et al make clear the scientific progress. First, the scientific challenges effecting limitations of this approach2. Using the example of IAVI, both AIDS and malaria vaccine research are immense but at Orsenigo et al argue that PDPs are both innovation present malaria vaccine researchers have been able to make integrators, providing a hub for science and technology more headway than AIDS vaccine researchers. Second, each development and brokers among the plethora of health and organization has evolved a different history or “institutional development stakeholders needed to put potential product logic”6 whereby different norms, values and cultures vie for candidates through clinical trials and to ensure widespread attention and come to dominate. The implication is that there access should a safe and efficient product be the outcome. are different ways IAVI and MVI could take to approach the Thus PDPs go well beyond classic measures for addressing problems affecting the science and reaching its intended “market failure”. They are necessary attempts to address goal; there is not one way of successfully engaging in vaccine “social technology failure”. This argument is developed in development for infectious diseases such as AIDS and further articles which provide more detail about the way in malaria and outcomes in decisions about how to tackle which IAVI fashions itself in both roles3, 4. problems are influenced by technical factors but also by a It is the combination of these two sets of activities around organization’s history, structure and culture. concrete product development agendas which is, in part at least, why PDPs have attracted widespread support and have Using PDP social technology for better outcomes and secured financial resources; PDPs bring together a range of below the radar innovation actors in public, private and NGO sectors with a targeted An analogous and useful way of looking at the roles of mission of introducing, developing and making accessible PDPs can be taken from work by Gardner et al who argue new technologies and treatments to those who need them that improving access to essential products and services in poor countries. Their efforts have had to include requires three forms of innovation: technological, social and support for new science, technology and product adaptiveii. Adaptive means “involving both providers and development and a range of brokering and capacity building communities to contextualize the adoption of goods and activities around defined product development activities services to local settings”7. including clinical trials. It is now well established that successful innovation is in This is PDP’s social technology innovation and this is why most cases “non-linear”, that it often involves numerous PDPs are widely considered appropriate vehicles for the interactions between consumers and users (and of course development of new physical technologies. Other public, patients). Adaptation then is not a passive phenomenon but private and charity organizations can undertake activities in often requires active interaction and communication between discrete bits of the value chain and have specific capabilities those who produce and those who use products and but PDPs introduced a coherent organizational, management technologiesiii. This adaptation can be around modification of and cultural approach to bringing together innovation and physical technology (feedback and knowledge from local development under one organizational banner in a targeted consumers which help improve the recipe) or in social way that moved things forwards more rapidly than technology (new ways of dividing and conducting work the alternatives5. which can facilitate the development and the distribution of PDPs may share characteristics but they are not of course technologies). identical. For example IAVI and the Malaria Vaccine Initiative Many PDPs, including MVI and IAVI are in a good position (MVI) are similar in overall goal and mission: both are PDPs to learn about local contexts and innovate in the area of aiming to develop and make accessible to poor people in social technologies on the basis of local knowledge. This developing countries vaccines for major neglected diseases. i. While there is truth in these broad characterizations there is also a good deal Both have been based around clinical trials. However, their more subtlety in a more detailed account of the strategies that both social technology histories differ and IAVI and MVI behave organizations are pursuing. differently in their integrator and broker roles. These social ii. Technological and social innovation are used in the sense of creating new technology differences are becoming more accentuated as products and processes on the one hand and ensuring access on the other. their respective success in developing new physical iii. A recent article in The Economist about “frugal innovators” provides excellent technologies becomes more apparent. examples of adaptive innovation in the Indian health service11.

i

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social technology will be invaluable in devising plans for the be found in a range of sectors but is of particular production, distribution, acceptance and use of new relevance in health, agriculture and energy as these are key treatments and drugs. It is clear from many studies that have sectors for poor people. been carried out that vaccines and other drugs are rejected Feedback and adaptation requires competence and because not enough resources are devoted to understanding capability building. PDPs themselves have to acquire the local contexts8. Moreover, the structure of local distribution capabilities which will let them absorb local knowledge. channels impacts significantly on the way drugs and When working in poorer developing countries they will often treatments are consumed9. Thus, by using their connections also need to contribute to local capacities and capabilities. A and networks which span local contexts and global product number of PDPs have impressive records in building new development, PDPs can hopefully give rise to social scientific, technological and management capacity in technology innovations which will contribute to making new developing countries3, 12. products and technologies more accessible. By using their existing social technology innovation (existing networks and Conclusion: evaluating PDPs as social technology new working partnerships) to generate further useful social innovators technologies. Clearly the mission of most PDPs is to develop appropriate PDPs can also use their distinctive networks, ethos and new technologies and products for global health. All activities orientation to input into physical technology development. need to be judged in relation to this mission. Yet narrow As mentioned previously it is now widely accepted that metrics looking at outputs may miss some of the real most innovation is relatively non-linear with many feedback contributions that PDPs make. They may also provide loops between different stages of product development. Most perverse incentives for autonomous styles of operation when companies now innovate on the basis of this analysis and collaborative approaches may be far more suitable have ongoing communication with their users and particularly in light of recent concerns about health systems consumers. They know their customer base and innovate strengthening. accordingly. If PDPs are viewed as social technology innovators and if, Although the feedback loops are perhaps less in some as we have argued, this is their raison d’etre, they should be areas of drug development, it is certainly true that most large evaluated on the basis of their contributions to a variety of companies orient their new product development activities activities involved in developing new products and making towards the world’s wealthier customers in high- or middle- them accessible to poor people in developing countries. income companies. Drugs and treatment regimes are oriented Outcomes rather than strictly output based assessments of towards those markets. They are less likely to know about or overall contribution might evaluate whether PDPs have be interested in the range of treatments or medical practices positively changed the behaviour of a range of groups, used in poorer countries and by poorer people. This of course individuals, organizations and institutions involved in was one of the factors behind the creation of PDPs. There is complex interactions around getting better medicines to poor scope for PDPs to use their different connections, networks people in developing countries. For example, assessment of and social technologies to generate new science, technology how activities such as capacity building or advocacy activities and products. Although this may sound to some to be naïve has contributed or is likely to contribute to better outcomes wishful thinking, the artemisinin story or the science around for target groups’ access to medicines needs to be evaluated. sex workers and others who have high level resistance to HIV In turn this type of evaluation may contribute to health are examples of the potential of this approach. systems strengthening objectives by encouraging parties We have labelled this more user-led innovation process involved in global health to view their activities as part of a involving poorer consumers in developing countries, below complex whole. the radar innovation (BRI). Below the radar because the potential for productive innovation for poor users and Key messages consumers is not generally of interest to large companies in developed countriesiv and is therefore not a major focus for PDPs constitute social technology innovations which product development activity. Large companies in developed promote, develop and aim to distribute physical countries are unlikely to be interested in working to adapt technologies to those who need them, and they products on the basis of feedback from poor consumers and need to be evaluated on this basis. areas of product and service activity related to poor people’s More attention needs to be paid to PDP’s needs remain below the radar. PDPs and companies from organisation and management. Incorporating this other developing countries may be able to progress this type of analysis into evaluation may reinforce type of innovation in much more direct ways. BRI can engagement in types of collaboration important to health systems development and strengthening. PDPs can use their distinctiveness to capture and iv. However, as Christenson10 has pointed out highly successful and disruptive (in the sense that it disrupts existing supply and value chains) innovation use below the radar networks and knowledge to often has its roots in low-income markets. In some sense the rise of the Indian further develop social and physical technologies in pharmaceutical industry can be seen as an example of this as Indian the interests of global health. companies have their roots in developing generic drugs for poor users.

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Joanna Chataway is Professor of Biotechnology and December 2007. Lois’s academic background is in law. Her Development at the Open University. She is also Co-Director of the research interests include intellectual property rights and their UK Economic and Social Research Council INNOGEN research interface with health and agricultural innovation, public-private centre investigating innovation in the life sciences. She has led partnerships in innovation, the innovation process, technology and participated in international and national research projects on transfer, biodiversity and access to plant genetic resources, the the dynamics of health and agricultural innovation, risk regulation relationship between plant variety protection and patent law, and and socio-economic development. She has published extensively. the international politics of intellectual property rights. Her webpage can be found at: http://dpp.open.ac.uk/people/ chataway.htm Watu Wamea obtained a PhD in Economics (summa cum laude) as well as a Masters in Economic Policies, Macroeconomics and Rebecca Hanlin is Lecturer in Development Policy and Practice at Development and a BA in International Economics from the the Open University and a researcher with the ESRC Innogen Centre. Université de la Méditerranée Aix-Marseille II (France). Having She has worked with and researched health product development held a post-doctoral position at the United Nations University partnerships for 10 years. Her work is in the area of innovation and UNU-MERIT in Maastricht and carried out various research development with a specific focus on health innovation and its consultancies for international, regional and national bodies, Watu implications for the provision of equitable health care. joined Development Policy and Practice as a Research Fellow in September 2008. Lois Muraguri joined INNOGEN as a Research Fellow in

References

1. Nelson RR. What enables rapid economic progress: what are the needed 6. Dimaggio P. Culture and cognition. Annual Review of Sociology, 1997, institutions? Research Policy, 2008, pp.1–11. Vol. 23, pp.263–287. 2. Orsenigo L. Beyond market failures: IAVI and the orgnizational challenges 7. Gardner C, Acharya T, Yach D. Technological and social innovation: of vaccine development. Health Partnerships Review: Focusing a unifying paradigm for global health. Health Affairs, 2007, Vol. 26, collaborative efforts on research and innovation for the health of the No. 4 pp.1052–1061. poor, 2008. 8. Leach M, Fairhead J. Vaccine anxieties: global science, child health and 3. Chataway J et al. The International AIDS Vaccine Initiative (IAVI) in a society. Earthscan, London, (2007). changing landscape of vaccine development: a public-private partnership 9. Mackintosh M, Mujinja PGM. Pricing and competition in essential as knowledge broker and integrator. European Journal of Development medicines markets: the supply chain to Tanzania and the role of NGOs. Research, 2007, 19, 1, pp.100–117. IKD Working Paper No. 30, 2008. 4. Chataway J et al. Below the radar: what does innovation in Asian Driver 10. Christenson C. The innovator’s dilemma. Cambridge, Mass. Harvard economies have to offer other low income countries? INNOGEN Working Business School Press, Boston, 1997. Paper No. 69, 2009. 11. Lessons from a frugal innovator. The Economist. 16 April 2009. 5. Moran M et al. The new landscapes of neglected disease drug 12. Chataway J et al. Global health social technologies: reflections on development. Wellcome Trust, London School of Economics and Political evolving theories and landscapes. INNOGEN Working Paper No. 76, Science, London, 2005. 2009.

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Innovation in life sciences Where do technologies come from?

Article by Vijay K Vijayaraghavan, Chairman, Sathguru Management Consultants, Cornell-Sathguru Foundation for Development

ife sciences innovations have surpassed every other institutions of repute generate several upstream technologies, discipline to unearth the nature of plants, animals they may not have the resources and/or the ability to validate Land humans. This has been due to the rapid these technologies through the translational phase and apply generation of new knowledge resulting from a convergence of them in a wide range of market relevant products. The interdisciplinary sciences. translational phase is resource intensive, time-consuming, Initially, North America and parts of Northern Europe took has a potential risk of failure and requires investments the lead in interdisciplinary research for life science equaling millions of US dollars. innovations. The human and plant genome research projects In many instances, the patents generated by national have brought billions of US dollars of public research funding research organizations are also licensed to large to research labs in the USA for engaging in up-stream multinationals with exclusive technology access, thereby research in genomics and proteomics, applying some of the preventing technology access to part II countries. The advanced bio informatics tools. The advances in bio- exclusive licensing arises many times due to the fact that engineering with high throughput sequencing, screening and several of these technologies require millions of US dollars’ synthesizing have considerably shrunk the time for identifying worth of research for their translational validation prior to and synthesizing potential genes and compounds. successful marketing. Since time is of the essence for However, most of the advanced research efforts have been commercializing these technologies, the urge to license to confined to only a few countries. In the parlance of the large corporations in advanced markets results from a lack of International Finance Corporation (W)-World Bank, these are alternative avenues for the academic institutions to take these Part I countries that are currently investing a high percentage technologies through the translational phase. The advanced of their GDP in cutting-edge frontier research. The public and technologies generated by global research systems are also private enterprises in these countries generate a significant constrained due to an, at times, all too real fear of volume of new knowledge and protects it through patents, irresponsible use of technology without proper stewardship. trade secrets and copyrights. Currently over 70% of platform Many countries do not have adequate protective mechanisms technologies in life sciences are protected by just five for technologies within a sound eco system. All these countries that invest over 80% of the global research constraints limit the global access of vital technologies. investment in life sciences through patents, trade secrets and other forms of intellectual assets protection. So, will the technologies remain confined to only a The whole world is in need of contemporary technologies few countries? to ensure the health of not just humans, but also plants and Not really. The economic growth in countries such as Brazil, animals. As humans and animals move across the world, the Russia, India and China (BRIC) and other middle-income disease vectors also mirror this movement, resulting in a economies such as Israel, the ASEAN region, South Africa convergence of global agriculture and health-care issues. and some of the CIS nations provide attractive market Critical issues in global health and agriculture cannot be opportunities for the entry of global corporations with addressed unless there is a broader flow of technologies innovative products. The attraction of Foreign Direct cutting across economic and social disparities. Investment (FDI) has triggered some of the global corporations in the private system to engage in “enterprise-to- Why are we not in a position to access vital enterprise level technology transfer”. Some of them have technologies? necessitated unlocking prior commitments of exclusivity in The vital technologies that are needed for application research licensing in order to encourage local enterprises to engage in are generally protected by large national research institutions product commercialization. Such opportunities have arisen in and universities based in Part I countries and multinational agriculture (vital traits for new seed development such as Bt companies in the private sector. While global research cotton), animal health and human health (preventive,

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therapeutic and diagnostic products). While these co-invest in economically and socially relevant research technologies have appreciably changed the landscape of areas. The members of the consortium develop a common innovation within the private sector, they have not provided a research hypothesis, pool their intellectual assets and agree sustainable capacity for research within the emerging to engage in responsible translation and application of economies. These countries have been able to introduce research results for their own country’s needs. However, current generation products but have not attained the ability such an effort is not an easy process and requires foresight to develop next generation products. on the part of science planners, professionally skilled technology managers, to structure the technology transfer How do we then introduce next generation products agreements with skilled researchers abiding by best practices to emerging economies? in research and product validation. Engagement in next generation research would require The BRIC countries and South Africa are some of the creation of a comprehensive eco system that would address: countries that have begun to realize this potential for intellectual assets pooling within a responsible and collaborative global partnerships. China has taken an legally enforceable mechanism of IP protection; aggressive approach to license frontier technologies from investment in frontier research capacity across the global research organizations in order to further advance national research organizations; those technologies into application products. China has also investment in translational platforms that can help to contributed to global consortiums with significant co- validate products and their efficacy; investment commitment in order to partake in research enterprise development support for private sector to results emanating from such multicountry research engage in generation and application of novel solutions partnerships. China aims to double its agriculture output in for products. the next 20 years and this is achievable due to extensive Chinese engagement in global research platforms to address These mechanisms help to create the vibrant eco system plant yield improvement solutions with reduced application that would help to generate new inventions and apply them of natural resources. The Chinese Government has for developing innovative products that would address the announced its intention to commit annually over US$ 300 need for next generation solutions. million for the generation of intellectual assets and their protection in agriculture biotechnology with focus on the What is the role of public and private investment in identification of plant genes of potential value in conferring this process? desired traits in economically important crops. The Chinese While in most emerging economies there has been a spurt in Premier has on more than one occasion stressed the desire research investment within the public sector, such of the nation to match the power of the Western world in investments have predominantly focused on creating basic development, introduction and commercialization of research infrastructure and broadening the research agenda genetically engineered crops. Similar efforts are triggered by to cover wider areas of research needs that are nationally or the Chinese government to engage in health-care research regionally relevant. Generally, the private sector has lagged in that would address the health-care needs of the country. this endeavour because of their inability to raise requisite capital and to foresee returns on such capital in a shorter Investment in translational research platforms? time frame. Investments in isolation in public institutions Fundamental research results have potential for wide have resulted in the creation of islands of excellence with applications in several products. The platform technologies complete disconnection from the translational platforms that generated from public research consortiums need rapid can convert results of basic research to innovative products. translation to products that are relevant and cost effective in The research investment in public institutions has also a competitive market environment. Translational research suffered from a lack of access to vital technologies and also would require a larger number of private enterprises protected biological materials, without which the research engaged in a competitive spirit of innovation and results could take several years to accomplish. Most public commercialization. The translational research platforms are a institutions do not have the process or the capacity to acquire vital link to validate great science into great products that are protected technologies that are generated in Part I countries. relevant, competitive and consumer worthy. South-East The negotiation capacity is limited and several of such public Asian countries have established research platforms in semi- research institutions might approach the same source for in- conductor based technologies several years ago and have licensing, without a central agency effectively negotiating gained supremacy in penetrating global markets in broad spectrum licensing. electronics and communication products. India, China, Israel, Cuba and Thailand have realized the potential for How do we then, effectively pool IP for public creating translational research platforms in health for research investments? advancing biomedical research results. Such efforts would The research planners in some of the countries have begun require extensive public investment support in providing to overcome this hiatus through bilateral and multilateral access to common research infrastructure to the public and consortium-based approaches wherein countries pool their private entities. Apart from providing vital funding during the resources and bring in global developmental investors to pre-seed, seed and commercialization phases of product

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development, these efforts should also provide mentor access to enterprises that require expert guidance and technology management hand- holding support in the form of IP protection and technology licensing advice. The holistic intervention also helps to provide vital recognition and goodwill to start-up enterprises which otherwise suffer from an identity crisis. Translational research platforms in the USA have spurned around the knowledge generation networks. Large research-focused universities such as MIT, Stanford, Cornell, Harvard et al have created highly successful translational research networks around their regional presence. This has helped them all to Figure 1: Where would technology come from? accomplish high levels of commercialization success for their inventions, and immense gains from private sector access. China has taken the lead in acquiring royalties result from such commercialization. platform technologies that are passed on to national institutions for further application in downstream research. Is it essential to provide research funding and India has a strong potential to acquire protected technologies enterprise development support for the private for a nationwide application. Creating bio banks with sector? biological materials and funding bio networks for consortium Emerging enterprises and homegrown large corporations research in a public-private partnership model would be would essentially require their capacity to be enhanced necessary for accelerating research results in critical areas of significantly in order to engage in global collaborative crop yield improvement (agriculture) and preventive and research. This calls for national level public investment in curative drug development (health care). Some of the core building private sector research capacity. Over several technologies would require significant levels of basic research decades of investment by the USA, the private sector in the for further application in regionally relevant product country has gained global leadership in innovation generation development. The public-private partnership research would and commercialization. Over the years, the investments have require grant support for advancing such basic technologies triggered capacity building within the private sector through for development of specific products. The products developed funding mechanisms such as Small Business Innovation would require validation and regulatory assessment and such Research (SBIR) and the creation of world-class incubators advances are feasible through conditional grants and soft for access by the private sector with investment from federal funding options. and state sources. The private sector has returned the Technologies ready to be applied for commercially relevant contribution through State and Federal taxes, royalty returns products would require commercial licensing with returns for technologies sourced and regional economic growth. A that would accrue to the licensor through up-front payments Google would not have existed today if they were not the and royalties. There are a number of global platforms to recipients of such support during their incubation. To bring facilitate access to technologies. Private enterprises with Indian private enterprises that are homegrown on a par with research foresight have acquired invaluable technologies global innovation networks, technology incubation and through the licensing option for further advancement. translational research funding support will be necessary. The Figure 1 indicates a complex web of inter-related modules SBIR and BIPP initiatives of DBT are an effort in this in the overall matrix that would be necessary to engage in direction. There is a necessity to trigger specific funding holistic technology development and commercialization. The platforms for various research priority areas so as to attract diagram also indicates how a synergic engagement of public more and more small- and medium-size enterprises. and private research can be effective in accelerating the pace In the recent past, India has created a significant number of commercialization. of research parks and incubators within and outside the The diagram indicates two streams of technology academic environment. However, the key element to augment development and dissemination. In the first instance, the economic growth would be the facilitation of technology upstream technologies are validated through a longer access, combined with all other support such as the creation translational phase (indicated by (D) in the diagram) while in of research parks and pre-seed and seed stage funding. the second instance, relatively “ready-to-go” technologies are provided to enterprises (generally small- and medium-sized How do we ensure flow-through of technologies enterprises) for commercialization with complimentary through the national innovation systems? funding and enterprise incubation support. Core technologies that are hard to secure due to global All the elements of this eco system are essential for protection would require national policy planners to acquire countries to excel in attaining the capacity to develop and such technologies for application in public research and for commercialize next generation products. The window that

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blocks the fructification of this eco system is the constrained research initiatives carried out by Cornell University in association access to platform or core technologies. It is important to with Sathguru in the South Asian and South-East Asian region. He strategically access such technologies, applying prudent is also is an adviser to the Government of India in areas relating to technology management tactics in order to gain access to collaborative public-private research in life sciences and is vital basic technologies that are globally protected. Market engaged in strategic capacity-building initiatives for enhancing the access and pooling of research capacity are vital tools in regulatory capacity within the country and the region. His negotiating access to vital technologies. India and China are organization is engaged in collaborative partnership with the certainly on the global radar to attract fruitful engagement in world’s leading research organizations, public donor agencies and codevelopment of vital technologies and their translation into the private sector in addressing disease prevention and next generation products. therapeutic product developments. Sathguru is the leading repository of technologies that are developed with public and Vijay K Vijayaraghavan is a senior technology management private research investment in the health care arena. Vijay is professional engaged for over two decades in accelerating globally known for his longstanding contribution to intellectual collaborative research and intellectual property licensing for assets protection and technology transfer. He is a member of the globally relevant public health related technologies. He is the International Advisory Committee of the Association of University Chairman of Sathguru Management Consultants, a global Technology Managers in the USA and Honorary President of the consulting body engaged in health-care advice and public policy Society for Technology Management (STEM) in India. advancement. Vijay is the Regional in-charge of the life science

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Financing social entrepreneurship: innovation awards to cross the “Valley of Death”

Article by Charles W Wessner, Director, US National Academies’ Program on Technology, Innovation and Entrepreneurship

ddressing today’s global health challenges calls for the Flight of skilled workers: The fragmentation of health-care initiative of entrepreneurs to create new technologies in markets, in turn, leads to a relative dearth of Amedicine and public health and apply them in real opportunities for scientific research in many developing world contexts. In the United States, a public-private countries5. This has prompted the migration of skilled partnership called the Small Business Innovation Research workers to jobs in the developed world. As a result, Program (SBIR) draws on the ingenuity of small business trained personnel needed for the research and entrepreneurs to create new technologies. The programme’s deployment of effective solutions are very hard to find in concept and effectiveness have been recently validated in a many developing countries. Low literacy levels compound major study by the National Academy of Sciences. This this problem. flexible innovation award programme can be successfully Capital scarcity: fostering new technological solutions to adapted around the world to help spur new innovations in improve health requires large amounts of capital. This is global health. especially the case for new medical technologies where regulatory requirements are often steep, imposing Local innovation and global health substantial additional expenses for their development6. In Improving health for people in all nations by promoting economies with underdeveloped capital markets, it is wellness and eliminating avoidable disease, disabilities and especially hard for entrepreneurs to find the funding deaths is an internationally recognized objective1. Global necessary to explore innovative approaches and health encompasses a broad set of challenges from eventually create new solutions. combating communicable diseases to the provision of potable Poor governance: an additional challenge, in some water and adequate nutrition to improving infant and countries, is that officially sanctioned markets for health maternal health2. This challenge involves generating care do not exist, with care provided, at least nominally, technologies and know-how that is relevant to the needs of by government agencies and the informal sector. In the low- and middle-income countries and, moreover, effectively absence of functioning market-based institutions, delivering health-care solutions in ways that the intended governments of poor countries and aid organizations beneficiaries can apply them in local contexts3. have sought to implement non-market mechanisms to While the private sector can play a vital role in the financing provide health care and sanitation, although these non- and delivery of innovative health-care solutions in the market efforts themselves are frequently subject to developing world, traditional models of health-care research, failure. Regulatory hurdles and poor public governance development and delivery in poor countries have not focused remain a fact of life in many developing countries, on the role of private entrepreneurs. Some reasons inhibiting inhibiting the development of entrepreneurial solutions to the growth of indigenous innovative capacity in developing local health-care challenges7. countries are identified below. Market asymmetries: the production and provision of Fragmented health care markets: the market for health- health-care technologies and services in the rich care in many poor countries is fragmented. In some countries of the world can skew efforts to develop cases, markets are physically inaccessible, or accessible innovative approaches to health care in poor countries8. only at cost of substantial effort and resources4. Priorities for funding health research often reflect a focus Consumers in poor countries also often possess few on diseases prevalent in wealthier societies, and on the resources and face limited access to information. The interests of major health-care institutions and resulting disaggregation of demand makes it more pharmaceutical companies9. As a result, areas such as difficult to develop market-based solutions to fund women’s health and infant mortality that are of greater the research and development relevant to local importance for developing societies often receive less health problems. funding and policy attention.

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Social The challenges of global health call for solutions and Private sector that are innovative, locally relevant, low cost, flexible Government needs investment

and sustainable. Competitive innovation awards that PHASE III PHASE II Product draw on the ingenuity of local entrepreneurs and PHASE I Research development Feasibility towards for Gov’t or small companies around the world can help spur research prototype commercial innovation needed to address these challenges. market

$100K $750K Government The innovation “Valley of Death” investment Although innovative businesses are increasingly recognized as a major driver of high-technology Tax revenue innovation and economic growth, they often face a Federal investment variety of challenges in bringing their ideas to market. Figure 1: The multi-gated structure of the SBIR Program One major challenge concerns the availability of capital, especially at the early stages of a technology’s Program (SBIR) was initiated in 1982 in the US. SBIR development. Because new ideas are by definition unproven, provides competitively awarded innovation grants and the knowledge that an entrepreneur has about his or her contracts to small businesses with technologies that show innovation and its commercial potential may not be fully promise and commercial potential, thus helping them grow appreciated by prospective investors10. The term “Valley of and develop new products that help government agencies to Death” has come to describe the period of transition when a address a variety of national missions. developing technology is deemed promising, but too new to validate its commercial potential and thereby attract the An open, bottom-up innovation programme capital necessary for its continued development11. SBIR is funded by a set aside of 2.5% of the extramural This means that inherent technological value does not lead research and development budgets of US government inevitably to commercialization; many good ideas perish on agencies, including the Department of Defense, the National the way to the market. Even capital markets in the United Institutes of Health and the National Science Foundation States, widely believed to be broad and deep, often fail to (NSF). Each year these agencies identify various research identify promising entrepreneurial ideas and finance their and development (R&D) topics, representing scientific and transition to market. In 2008, venture capitalists in the technical problems requiring innovative solutions, for pursuit United States invested US$ 28 billion over the course of by small businesses under the SBIR Program. These topics 3808 deals. However, over two thirds of venture capital in are bundled together into individual agency “solicitations” – the United States was directed to firms in the later stages of publicly announced requests for SBIR proposals from development and only 5% of venture funding was directed to interested small businesses – that are placed on the Internet. the earliest or “seed” stage of funding12. Any small business can identify an appropriate topic that Typically, venture capitalists are also interested in larger it is capable of pursuing from these solicitations and, in investments that are easier to manage than is appropriate for response, propose a project for an SBIR grant. The required many small innovative technology firms13. In the US, venture format for submitting a proposal is different for each agency. capital deal size has risen over the past decade, prompted in Proposal selection also varies, though peer review of the part, by the high costs of meeting due diligence proposals on a competitive basis by experts in the field is requirements12. In 2008, the size of the average venture typical. Each agency then selects through a competitive capital deal was US$ 7.4 million, whereas funding needed process the proposals that are found to best meet the at the seed and early stages of a firm’s development are Program selection criteria, and awards contracts or grants to much smaller, ranging from US$ 60 000 to conduct initial the proposing small businesses. feasibility research to US$ 1 million to develop a prototype. The current financial crisis has further widened the “Valley A multi-gated programme of Death”. Reflecting the sharp drop in liquidity in the As conceived in the 1982 Act, the SBIR grant-making economy, venture capital funds are conserving capital to process is structured in three phases: preserve the existing portfolio investments. Few new Phase I grants essentially fund a feasibility study in investments are being undertaken as these venture funds which award winners undertake a limited amount of retrench15. The liquidity shortage also affects the graduation research aimed at establishing an idea’s scientific and of firms, sharply reducing the number of acquisitions and commercial promise. Legislation reauthorizing the SBIR initial public offerings. Silicon Valley produced just one initial Program in 1992 standardized Phase I grants at US$ public stock offering in 2008, down from an average of 28 100 000. Approximately 15% of all small businesses IPOs a year since 198516. that apply receive a Phase I award. Phase II grants are larger – typically about US$ 500 000 The role of Competitive Innovation Awards: the SBIR to US$ 850 000 – and fund more extensive R&D to Program develop the scientific and technical merit and the To help address this “Valley of Death” for new firms, a PPP feasibility of research ideas. Approximately 40% of programme called the Small Business Innovation Research Phase I award winners go on to this next step.

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Phase III is the period during which Phase II innovation proven to be remarkably successful in selecting very early moves from the laboratory into the marketplace. During stage projects that reach the market, although after some this phase, companies normally do not receive additional time lag. The National Academies’ research found that funding from the SBIR Program. To commercialize their more than 30% of funded projects reach the market at a product, small businesses are expected to garner given point in time and that about 60% of projects additional funds from private investors, the capital eventually reach the market18. markets or from the agency that made the initial award. Leveraging additional investment: NIH firms that win SBIR awards have in many cases been able to attract A highly competitive programme additional investment funding from private capital The SBIR Program is a merit-based, highly competitive markets. Some firms interviewed in the course of the programme. In 2006, for example, only about 18% of National Academies study claimed that venture funders proposals submitted to the NIH succeeded in initial see SBIR awards as a form of quality assurance, given competition for Phase I funding. Further, only about 40% of that winners must have successfully traversed the proposals that had already been validated by a successful rigorous NIH peer review selection process for technical Phase I award subsequently merited a Phase II award. value and potential utility. The Academies’ survey The fact that more than 80% of the initial proposals are indicated that about 50% of respondents had received rejected indicates that the programme is highly competitive. additional investments that were related to the surveyed The fact that the application rates to the programme remain SBIR award. high indicates, moreover, that it is a very attractive New firm formation: SBIR awards offer significant, often programme. The credibility of the selection process is decisive, support that encourages entrepreneurs to found important to the effectiveness of SBIR, allowing a selection a company. About 20% of companies responding to the among the most promising proposals. Academies’ survey indicated that they were founded wholly or in part because of the SBIR funding they A flexible programme received. This high rate of firm formation may be of Although the SBIR programmes at all participating US particular importance in the context of supporting local government agencies share the common three-phase entrepreneurs in developing countries, given that these structure, they have each evolved separate administrative individuals often have a unique understanding of local structures that are adapted to their particular mission, and cultures and opportunities. working cultures. For example, the NSF’s operation of its Addressing niche markets: importantly, the SBIR Program SBIR differs considerably from that of the Department of is highly effective in addressing niche markets and niche Defense, reflecting in large part differences in size of the needs. This capacity of the SBIR model to solicit agencies as well as the extent to which “research” is coupled innovative approaches to help solve idiosyncratic societal with procurement of goods and services. challenges is especially important in the context of global This flexible approach is also reflected in the NIH SBIR health, where the focus of major donors is often on large, Program. SBIR grants awarded by NIH substantially exceed more well publicized challenges such as malaria and the standard limits, reflecting the substantial inflation in the HIV/AIDS. Even in these large programmes, the bio-research sector17. Currently, the average size of NIH innovative research of small firms can make important Phase I awards is just over US$ 150 000 per project, which contributions. is a 50% increase over the standard grant size. Small numbers of grants can be quite large, totalling several million SBIR and global health dollars in both phases. While no single programme, however well designed, can In these respects, SBIR is a unique government funded solve every problem, or even most of the problems, in global innovation award programme. When implemented effectively, health, our analysis suggests that an SBIR-type programme these programme features provide government agencies with that is highly competitive, multi-gated, transparent and a unique tool for drawing on the innovative potential of focused on specific technological needs and social objectives entrepreneurs around the country to meet a wide range of can make important contributions to improving global health. government missions and social objectives. If one accepts the twin premise that more low-cost innovation is needed and that small firms (and the researchers who Does the model work? found them) innovate more creatively than major The short answer is yes. incumbents, then the SBIR innovation awards offer a In a recent comprehensive assessment of the programme, promising avenue of advance. Such an innovation award the US National Academies found that SBIR encourages new programme would engage the substantial creative potential of entrepreneurship needed to bring innovative ideas from the innovators around the world, in both the developed and laboratory to the market by providing scarce pre-venture developing world, to focus on problems that are not capital funding on a competitive basis17. In the case of the adequately addressed, while connecting entrepreneurs to NIH, SBIR helps bring innovative solutions to the challenges local markets and local needs. SBIR provides an efficient of health care, as we see below. funding mechanism to help innovative start-up and existing Reaching the market: the SBIR Program at NIH has firms cross the early stage funding “Valley of Death” in order

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to bring new techniques and new products to the market. Key messages Some additional advantages of applying the SBIR concept to local conditions include its ability to: Advancing global health requires a higher rate of Motivate poor country entrepreneurs: an SBIR-type innovation across a wide variety of needs. mechanism can provide seed capital to entrepreneurs to Small businesses in France, Germany and the US are develop new technologies through the early stages of a proven source of effective, low-cost innovation. innovation. It does so without requiring entrepreneurs to Many promising innovations suffer from a lack of repay the grant or relinquish ownership shares, and it initial capital, often called the “Valley of Death”. can do so quickly and across a large geography. Innovation awards bridge this funding gap and Use local knowledge: SBIR brings in new entrepreneurs encourage innovative solutions to health problems, and firms, and provides existing firms incentives to both in the industrial world and at the bottom of address current social challenges. Local entrepreneurs the pyramid. have the potential to make significant contributions to global health by using their detailed understanding of local conditions, needs and opportunities. But until now, Dr Charles Wessner is a National Academy Scholar and directs these entrepreneurs have been largely excluded from a programme on Technology, Innovation and Entrepreneurship. As participating in this innovation ecology on the a policy advisor, he is recognized nationally and internationally for widespread assumption that innovation is to be found his expertise on innovation policy, including public-private elsewhere, primarily in large firms in rich countries. partnerships, entrepreneurship, early-stage financing for new Draw on worldwide innovation: small businesses in more firms, and the special needs and benefits of high-technology advanced innovation ecosystems can also participate in industry. He testifies to the US Congress and major national developing innovative solutions in global health. They commissions, advises agencies of the US government and already provide much of the innovation in the more international organizations and lectures at major universities in advanced economies, many of which are later adapted the United States and abroad. Reflecting the strong global interest and enhanced by larger firms. in innovation, he is frequently asked to address issues of shared Connect local, regional and national markets: though policy interest with foreign governments, universities and research often undeveloped, the potential for large-scale public institutes, often briefing government ministers and senior officials. and private sector markets for health services and Dr Wessner’s work addresses the linkages between science- products exists in many poor countries. Traditionally, based economic growth, entrepreneurship, new technology this demand has been difficult for small firms to access. development, university-industry clusters, regional development, The innovation award process can itself help build up small firm finance and public-private partnerships. His an innovation ecosystem while providing market programme at the National Academies also addresses policy guidance for entrepreneurs about demand for products issues associated with international technology cooperation, and services. investment and trade in high-technology industries. The National Academies’ Technology, Innovation and While not a panacea, SBIR-type programmes can help Entrepreneurship programme has ongoing relationships with build both indigenous and external capacities for innovation senior officials in countries as diverse as India, China, Taiwan, in global health. This approach has a proven track record in Vietnam, Mexico, France, Sweden, Finland, the Czech Republic the United States for over a quarter of a century across a and Hungary. Dr Wessner provides policy advice on questions of variety of mission cultures, needs and objectives. The innovation policy, including support for basic science, applied programme has the unique potential to draw on the research, the role of the 21st century university, and principles of innovative capacity of entrepreneurs in both the wealthy and cooperation between universities and industry. developing countries and regions of the world to address the unique challenges of global health.

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References

1. These priorities are reflected in the United Nations Millennium Issue 11. Development goals. 10. Lerner J. Public venture capital. In: National Research Council, The Small 2. Assessments from the World Health Organization and other sources Business Innovation Program: Challenges and Opportunities. op. cit. address a wide set of challenges in global health. See, for example, WHO 11. See Branscomb L, Auerswald P. Valleys of death and Darwinian seas: Fact sheet on Tuberculosis and Malaria, accessible at Financing the invention to innovation transition in the United States. www.who.int/mediacentre/factsheets/fs104/en/index.html and Journal of Technology Transfer, August 2003, 28(3–4). www.who.int/mediacentre/factsheets/fs094/en/index.html 12. PriceWaterhouseCoopers/Venture Economics/National Venture Capital 3. Institute of Medicine. The US commitment to global health. Washington Association Money Tree Survey, 2009. DC: National Academies Press, 2009. 13. As Joshua Lerner notes, “Because each firm in his portfolio must be 4. “John Roller, of African Transportation and Logistics, notes that closely scrutinized, the typical venture capitalist is typically responsible for transportation costs to, from and among African nations are 2.5 times no more than a dozen investments. Venture organizations are higher than anywhere else on the globe, with transit times running two to consequently unwilling to invest in very young firms that require only four times higher than anywhere else”. Charles W Corey. Africa needs small capital infusions.” See Joshua Lerner, Public Venture Capital: transportation capacity now, experts say. America.gov, 2 July 2008. Rationales and Evaluation. in National Research Council, The Small 5. Connella J et al. Sub-Saharan Africa: Beyond the health worker migration Business Innovation Research Program: Challenges and Opportunities, op. crisis? Social Science & Medicine, Volume 64, Issue 9, May 2007, cit. pp.1876–1891. 14. “Venture investments fell back in 2008”. Washington Post, 1 February 6. O’Sullivan M. Finance and Innovation. In: Fagerberg J, Mowery Nelson R, 2009; “Angels Flee from Tech Start-ups”. New York Times, 3 February (eds). The Oxford handbook of innovation, Oxford: Oxford University 2009. Press, 2005. 15. “Silicon Valley produced just one IPO in 2008”. Mercury News, 26 7. A 2006 World Bank report indicates that “about half of all funds donated December 2008. for health efforts in sub-Saharan Africa never reach the clinics and 16. The Biomedical Research and Development Price Index is a composite hospitals at the end of the line.” Cited by Garrett L. The challenge of index developed by the BEA that measures changes in the weighted- global health. Foreign Affairs, Jan–Feb 2007. average of the prices of all the R&D inputs for NIH research. To make the 8. Garrett L. The challenge of global health. Foreign Affairs, Jan–Feb 2007. awards equivalent in value to those made in 1992, based on this index, 9. The current “blockbuster” economic model that dominates biomedical the nominal value of 2008 awards should be increased by 88.8%. research and commercialization may exacerbate this problem. According 17. The Academies report concluded that “the SBIR program is sound in to some estimates, as much as 90% of biomedical R&D funding is going concept and effective in practice”. See National Research Council. An to solve only 10% of medical problems because the cost of developing assessment of the SBIR Program. Wessner CW, ed., Washington DC: and launching new medicines is so huge that only medicines that serve National Academies Press, 2008. major markets can be economically justified by pharmaceutical firms for 18. Lag effects explain the difference. Projects that received awards in 2002, investment and focus. See Cuatrecasas P. Drug discovery in jeopardy. which ended in 2004, may well not have generated revenues by 2006. Journal of Clinical Investigation, 1 November 2006, Volume 116,

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Global health partnerships: a “pull” mechanism for innovation and new products

Article by Michel D Kazatchkine (pictured), Executive Director, Global Fund to Fight AIDS, Tuberculosis and Malaria, with Rifat Atun and Mary Ann Lansang

nnovation is the lifeblood of development. Societies which mechanism has successfully created a thriving R&D sector have encouraged innovation have enjoyed fruits of aimed at developing more affordable drugs and commodities Idevelopment, including good health and longevity. for the poor3,4,5 with over 20 drugs in clinical trials or The 20th century marked a remarkable period of registration, and by 2010 eight to nine new drugs anticipated innovation in health sciences, leading to a better to market2. understanding of the determinates of health and the discovery Push mechanisms need to be coupled with pull of novel diagnostic and treatment methods to intensify the mechanisms to commercialize successful R&D and bring new fight against the major pandemics, with the eradication of innovations to market4. In addition, an enabling context is smallpox and near elimination of polio. Building on these needed to ensure newly commercialized innovative health successes, the 21st century began with newfound optimism technologies are adopted into health systems5. and global effort to improve health, with the world committing This paper describes how the Global Fund to Fight AIDS, to the Millennium Development Goals (MDGs) to tackle the Tuberculosis and Malaria (the Global Fund) has emerged as a global burden of disease and poverty. However, in spite of pull mechanism for innovation. We discuss innovation in a these achievements and newfound momentum to tackle broad context, using a unifying paradigm proposed by diseases, challenges to deliver global health abound, with Gardner et al that covers three forms: technological around 5 million people each year still dying from AIDS, innovation to provide cost-effective products; social tuberculosis and malaria. Sustained innovation to develop innovation to ensure equitable distribution; and adaptive new diagnostics, drugs and service delivery models is critical innovation to enable appropriate use of products within the if the health-related MDGs are to be achieved. local context6. Indeed, the eighth MDG encourages global development partnerships to “in co-operation with pharmaceutical The Global Fund and global public goods companies, provide access to affordable essential drugs in The Global Fund is a public-private partnership established in developing countries”1. Such a cooperation is essential to 2002 to intensify the fight against AIDS, tuberculosis (TB) drive innovation in areas such as neglected diseases for and malaria (http://www.theglobalfund.org) and in doing so which there is not a large enough market to attract private help achieve health-related MDGs. The global nature of these sector investment in research and development (R&D). To three diseases – involving around 33 million people living encourage investment and innovation in these areas, a with HIV (2007 UNAIDS estimate), 14.4 million prevalent number of “push” and “pull” mechanisms have been cases with TB (2006 WHO estimate) and 247 million developed by national governments and internationally. Push malaria cases (2006 WHO estimate) – demands the mechanisms provide investment to encourage research sustainable financing of global public goods to fight these institutions and private enterprises to invest in R&D aimed at three diseases7. Operating primarily as a financial instrument, generating new drugs for neglected diseases in developing the Global Fund invests in cost-effective, large-scale countries. Pull mechanisms either provide funds to purchase intervention programmes led by developing country partners these drugs or vaccines once they come to market, or signal through a country coordinating mechanism, with technical in advance a price or the presence of a “market” for drugs assistance from development and other partners developed for neglected diseases that are in R&D pipelines2. where needed. Public-private product development partnerships, such as the As of 2009, the Global Fund had mobilized US$ 21 billion, Medicines for Malaria Venture, the Global Alliance for TB approved investments of US$ 16 billion in prevention, Drug Development, the International AIDS Vaccine Initiative, treatment and care programmes, even as it stepped up efforts and the Malaria Vaccine Initiative, have emerged as the to strengthen national and sub-national health systems preferred route for push mechanisms, mobilizing over US$ (http://www.theglobalfund.org/en/resources/?lang=en). It is 250 million of philanthropic and public funding2. The push estimated that the Global Fund provides around 60%,

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cost-effectiveness analyses9,10 the large scale translation of 5% this knowledge to policy, programme and action in endemic 11% Other countries was driven by Global Fund support – as suggested Infra & equipment by the high correlation between ITN distribution and Global Fund investments in malaria control11. Contributing to the 12% impetus for developing long-lasting insecticidal nets (LLINs) Training 27% Drugs was the demand by implementing countries and the Roll Back Malaria Partnership, WHO and UNICEF for less 13% cumbersome net treatments, coupled with the large and Human resources secure market for this new type of bednet through public 12 17% programmes supported by the Global Fund . Today two LLIN products have a full recommendation from the WHO 14% Commodities and products Planning Pesticides Evaluation Scheme while six others have a time- and admin limited interim recommendation for use13. Another product relatively close to the end of the development pipeline is the promising RTS,S malaria vaccine Source: Survey of principal recipients, the Global Fund, 20088 under development by GSK Biologicals and the MVI, which Figure 1: Distribution of 2007 grant budgets according to grant was shown to be efficacious in Phase 2 trials in Mozambican cost category adults and children14,15 and now undergoing Phase 3 trials in 57% and 23% of all international funding for malaria, up to 16 000 African children. Given the public health TB and HIV, respectively8. Close to 140 low- and middle- importance of a cost-effective malaria vaccine for children, income countries (LMICs) have benefitted from substantial early discussions between MVI and the Global Fund would and predictable support from the Global Fund. As a result, in facilitate further product development and eventual policy Global Fund supported programmes, more than 2 million and financial support for roll-out of the vaccine in three to people living with HIV in LMICs have access to antiretroviral five years. treatment, while a cumulative total of 4.6 million people have availed of TB treatment under Directly Observed Social and adaptive innovations Treatment, Short-course (DOTS) and 70 million insecticide- Access to affordable medicines, commodities and products treated bednets (ITNs) have been distributed to families by those most in need also require social and adaptive at risk8. innovations. Although sizeable procurement funds can attract The scale of the interventions implemented by LMICs innovators, the price of new products may not always be through Global Fund grants entails huge investments in reduced or may not necessarily reach the poor. A review of drugs, commodities and other products for HIV/AIDS, TB and procurement transactions from the World Health malaria prevention, diagnosis, treatment and care. A 2007 Organization and the Global Fund records for 2002–2007 survey of a sample of grant recipients showed that around showed that high-volume purchases reduced prices in 5 out 27% of grant funds were budgeted for drugs and 17% to of 24 antiretroviral drugs (ARVs), while third-party other commodities and products such as condoms, ITNs and negotiations through the Clinton Foundation HIV/AIDS diagnostic tests (Figure 1). The magnitude and secure nature Initiative reduced prices for many generic and branded of these investments, for as many as 5–10 years, can offer a ARVs16. The Global Fund is actively working to improve market-pull lever for innovation as described below. pricing transparency and reduce the variability in pricing schemes in programmes it supports in LMICs, as well as Technological innovation and the Global Fund strengthening supply chain management systems to improve In contrast to push mechanisms that are able to fund basic efficient delivery and reduce stock-outs of drugs and research and drug discovery and are not risk averse to failed commodities – areas identified by the Global Fund as barriers projects, pull mechanisms reward successful innovators that to access to medicines. The Global Fund embarked on a manage to bring products to market. Although, by its very system of voluntary pooled procurement (VPP) in April 2009 nature, the Global Fund relies on its technical partners to as a concerted strategy to influence market outcomes such advise on effective drugs and products that can be rolled out as programme components of grants to LMICs, it can be an efficient driver of technological innovation because of the A review of procurement transactions from the World potential market size created through its investments as well Health Organization and the Global Fund records for as its knowledge of demand from LMICs and the country 2002–2007 showed that high-volume purchases context for product applications. reduced prices in 5 out of 24 antiretroviral drugs Furthermore, the Global Fund, in collaboration with its (ARVs), while third-party negotiations through the technical partners, is able to shape the market demand by Clinton Foundation HIV/AIDS Initiative reduced prices encouraging adoption of cost-effective technologies. For for many generic and branded ARVs example, while the cost-effectiveness of insecticide treated nets (ITNs) was demonstrated through randomized trials and

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as price, quality, supply and sustainability. Based on impact Key messages on global financing and market benefit, the initial focus of the VPP is on four product categories: first- and second-line The Global Fund to Fight AIDS, Tuberculosis and ARVs, artemisinin-based combination therapies (ACTs) and Malaria has emerged as a pull mechanism for LLINs17. Eighteen countries have registered for the initial roll- innovation largely through the scale of its out while discussions are ongoing with another 12 countries. investments on cost-effective intervention In addition, the Capacity Building and Supply Chain programmes led by low- and middle-income Management Assistance was established to strengthen their countries. national procurement and supply chain management Market demand is shaped by encouraging the wide systems, focusing on the areas of forecasting, procurement adoption of cost-effective technologies, such as planning and inventory control, and distribution, among combined drug regimens, long-lasting insecticidal others. It is expected that in the short term, procurement nets and, in the future, successful vaccines. bottlenecks will ease up, eventually leading to improved grant Innovative mechanisms launched by the Global performance. Over the long term, pricing, cost-savings and Fund, such as voluntary pooled procurement and the market share will be monitored, while national systems Affordable Medicines Facility – malaria (AMFm) are for procurement and supply chain management will opportunities to learn how to improve access to new be strengthened. products by those most in need. The Affordable Medicines Facility – malaria (AMFm) is an innovative financing mechanism to expand access to affordable ACTs for malaria, thereby saving lives and reducing Acknowledgements the use of inappropriate treatments. The AMFm aims to We thank our colleagues in the Global Fund: Olusoji Adeyi, enable countries to increase the provision of affordable ACTs Director of AMFm, and Tala Jallow, Manager of the through the public, private and nongovernmental organization Procurement Support Services Team, for their updates on the sectors. By increasing access to ACTs and displacing AMFm and VPP, respectively, and their review and artemisinin monotherapies from the market, the AMFm also comments on these sections. seeks to delay resistance to the active pharmaceutical ingredient, artemisinin. Launched in April 2009, the AMFm Michel D Kazatchkine is the Executive Director of the Global is hosted by the Global Fund, brokered by the Roll Back Fund to Fight AIDS, Tuberculosis and Malaria. He has spent the Malaria Partnership, and funded by UNITAID, the UK past 25 years fighting AIDS as a leading physician, researcher, Department for International Development and potentially administrator, advocate, policy-maker and diplomat. other donors. It involves price negotiations with drug Before joining the Fund, besides being Professor of Immunology manufacturers of quality ACTs and co-payments by the at Université René Descartes, Paris, and Head of the Immunology AMFm on behalf of buyers (public, private and non-profit Unit of the Georges Pompidou Hospital in Paris, he played key sectors) from participating countries. This is expected to roles in various organizations, serving as Director of the National reduce retail prices of ACTs from US$ 6–10 to as low as US$ Agency for Research on AIDS (ANRS) in France (1998–2005), 0.20–0.5018,19. Eleven countries were invited to apply to Chair of WHO’s Strategic and Technical Advisory Committee participate in Phase 1 of the AMFm, and implementation is (STAC) on HIV/AIDS (2004–2007), member of WHO’s STAC on TB expected to start in the first quarter of 2010. The AMFm is (2004–2007), and French Ambassador on HIV/AIDS and an example of innovation and pragmatism to achieve results communicable diseases (2005–2007). in public health. As reported by WHO Director-General, Margaret Chan, to the WHO Executive Board, “[The AMFm] Rifat Atun is the Director of the Strategy, Performance and looks at the reality of conditions in the developing world, Evaluation Cluster at the Global Fund. He is on extended leave identifies the forces that shape the reality, and then works to from Imperial College London, where he is Professor of outsmart them”20. It is an opportunity to learn new ways of International Health Management, and was the founding director achieving long-sought goals of universal access and delayed of the Centre for Health Management. He has worked with WHO, drug resistance21. the World Bank and the UK Department for International Development, serving as chair/member of various WHO expert Conclusion committees and as project leader/consultant on health policy and The global problems of AIDS, TB and malaria require a systems development. combination of technological, social and adaptive innovations by the global community to enable cost-effective interventions Mary Ann Lansang is the Director of the Knowledge Management to reach the millions of affected people in LMICs. Global Unit in the Strategy, Performance and Evaluation Cluster at the procurement funds from the Global Fund can act as a pull Global Fund. She is on leave from the University of the Philippines mechanism to catalyse innovations. To learn from these Manila, where she is Professor of Medicine (Infectious Diseases) innovations and continuously improve financing models for and Clinical Epidemiology. She has served various international improved health and equity, policy and systems research and organizations in leadership and advisory roles, such as the evaluation of these innovations will be critical. International Clinical Epidemiology Network, WHO, the Global Forum on Health Research and COHRED.

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References

1. United Nations General Assembly. United Nations Millennium Declaration. 2009). A/RES/55/2. 2000. Available: http://www.un.org/ 13. WHO Pesticides Evaluation Scheme. WHO recommended long-lasting millennium/declaration/ares552e.htm (accessed on 1 August 2009). insecticidal mosquito nets. Available at: http://www.who.int/whopes/ 2. Fisk NM, Atun R. Market failure and the poverty of new drugs in maternal Long_lasting_insecticidal_nets_Jan09.pdf (accessed on 27 July 2009). health. PLoS Medicine, 2008, 5(1):0022–0028. 14. Kester KE et al. Randomized, double-blind, Phase 2a trial of falciparum 3. Ravvin M. Incentivizing access and innovation for essential medicines: A malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naïve adults: survey of the problem and proposed solutions. Public Health Ethics, safety, efficacy and immunologic associates of protection. Journal of 2008, 1:110–23. Infectious Diseases, 2009, 337–46. 4. Atun RA, Sheridan D. Innovation in the biopharmaceutical sector. 15. Sacarlal J et al. Long-term safety and efficacy of the RTS,S/AS02 malaria Singapore, World Scientific Publishing, 2007. vaccine in Mozambican children. Journal of Infectious Diseases, 2009, 5. Atun R, Gurol-Urganci I, Sheridan D. Uptake and diffusion of 200:209-36. pharmaceutical innovations in health systems. International Journal of 16. Waning B et al. Global strategies to reduce the price of antiretroviral Innovation Management, 2007, 11:299–321. medicines: evidence from transactional databases. Bulletin of the World 6. Gardner CA, Acharya T, Yach D. Technological and social innovation: A Health Organization, 2009, 87:520–8. unifying new paradigm for global health. Health Affairs, 2007, 17. The Global Fund to Fight AIDS, Tuberculosis and Malaria. Voluntary 26:1052–61. pooled procurement (February 2009). Available at: 7. Deneulin S, Townsend N. Public goods, global public goods and the http://www.theglobalfund.org/en/procurement/vpp/ and common good. International Journal of Social Economics, 2007, http://www.theglobalfund.org/documents/psm/VPP_Products.pdf 34:19–36. (accessed on 27 July 2009). 8. The Global Fund to Fight AIDS, Tuberculosis and Malaria. Scaling up for 18. The Global Fund to Fight AIDS, Tuberculosis and Malaria. Affordable impact: results report. March 2009, Geneva, Switzerland, The Global Medicines Facility – malaria. Available at: Fund. http://www.theglobalfund.org/content/pressreleases/pr_090417_Factsheet. 9. Lengeler C. Insecticide-treated bed nets and curtains for preventing pdf (accessed 27 July 2009). malaria. Cochrane Database of Systematic Reviews, 2004, Issue 1. Art. 19. The Global Fund to Fight AIDS, Tuberculosis and Malaria. Affordable No.: CD000363. DOI: 10.1002/14651858.CD000363.pub2. Medicines Facility – malaria. Frequently Asked Questions. Available at: 10. Breman JG et al. Conquering malaria. In: Jamison DT et al. Disease http://www.theglobalfund.org/documents/amfm/AMFmFAQs_en.pdf control priorities in developing countries, 2nd ed. New York, Oxford (accessed on 27 July 2009). University Press, 2006, pp.413–32. 20. Chan M. World Health Organization. Report to the WHO Executive Board, 11. Macro International, Inc. The impact of collective efforts on the 122nd session. Geneva, Switzerland, 21 January 2008. Available at: reduction in disease burden. Global Fund 5-year evaluation: Study area http://www.who.int/dg/speeches/2008/20080121_eb/en/index.html 3. March 2009, Geneva, Switzerland, The Global Fund. (accessed on 31 July 2009). 12. UNICEF. Call for increased production of long lasting insecticidal nets for 21. Laxminarayan R, Gelband H. A global subsidy: key to affordable drugs for malaria control (press release), 23 September 2004. Available at: malaria? Health Affairs, 2009, 28:949–61. http://www.unicef.org/media/media_23447.html (accessed on 27 July

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Technological innovation incentives: “push” and “pull”

The pneumococcal Advance Market Commitment (AMC): innovative finance to help the poor

Article by Tania Cernuschi, Senior Manager, AMC, GAVI Alliance1

accines currently included in routine immunization to developing countries only after competition from other programmes save globally between 2 and 3 million market entrants leads to a reduction in prices. These factors Vlives every year and introducing new vaccines against have heavily contributed to the historical lag of 10–15 years pneumococcal diseases and rotavirus diarrhoea would help between the introduction of new vaccines in affluent and in prevent many of the more than 1 million deaths among poor countries5. children under five2. Also, many new vaccines could be One of the main reasons for limited commercial investment developed to prevent additional childhood deaths, but there aimed at introducing vaccines in developing countries is that are obstacles that impede progress. companies often perceive the market opportunity as too small This article reviews one of the major challenges to the to cover the risk-adjusted costs of R&D or of production introduction of useful vaccines in developing countries – lack capacity scale up. This is despite the long term revenue of commercial investment – and one potential solution – the opportunities from a high-volume low-margin market. Advance Market Commitment (AMC). The article outlines the An Advance Market Commitment (AMC) offers a potential design and potential benefits of a pilot AMC for solution. An AMC is a legally binding financial commitment pneumococcal vaccines and raises questions to help inform by donors to support purchase of target vaccines for poor work on potential future AMCs. countries if and when they are developed. The expected value of the financial commitment must be large enough to cover Why do we need an AMC? risk-adjusted costs of private investment and thus attract the Development of new vaccines depends on public and latter to serve developing countries. Meanwhile, the cost of philanthropic funding as well as commercial investment. the initiative must be less than the value accrued by society Commercial investment is particularly important for clinical and better value for money than alternative uses of the same trials, registration activities and manufacturing processes, resources. One way to structure an AMC is to guarantee a representing about two thirds of the total cost of vaccine relatively high price for the first doses of vaccines to allow development3. For vaccines developed for populations in companies to recoup investment costs, while contracting affluent countries, commercial investment is indeed the single suppliers to provide the vaccines close to manufacturing costs largest source of funding. On the contrary, for diseases for the long term6. This is the model which has been adopted affecting primarily poor countries, funding for research and in the design of the recently launched pneumoccal AMC, development (R&D) for vaccines is primarily from public and described below. philanthropic sources, despite increased investment by pharmaceutical industry in the past decade4. Lack of The pneumococcal AMC commercial investment is one of the causes underlying The pneumococcal AMC (pneumo AMC) was launched by limited development of vaccines for diseases primarily the GAVI Alliance, the World Bank, UNICEF and six donors affecting the poor. (Italy, UK, Canada, Russian Federation, Norway, and the Bill Even in the case of diseases that affect both rich and poor & Melinda Gates Foundation) in June 2009. The secretariat countries, commercial investment is focused on affluent for this initiative is housed at GAVI, a public private markets. Firstly, vaccines are primarily developed for use in partnership which aims to save children’s lives and protect rich countries and often require adaptation for use in people’s health by increasing access to immunization in 72 developing countries (as needs in terms of vaccine of the world’s poorest countries (GAVI eligible countries)7. formulation, presentation, storage and packaging differ). The pneumo AMC aims to accelerate introduction of certain Secondly, first to market biopharmaceutical companies pneumococcal vaccines deemed appropriate for use in GAVI generally have an incentive to exploit their advantage eligible countries through predictable vaccine pricing for both producing low volumes to be sold at high prices in affluent manufacturers and countries8. In particular, this AMC intends markets; they tend to increase the production scale and look to motivate suppliers with nearly licensed target vaccines9 to

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Firm $7 AUS$ 375M

AMC subsidy

Tail price cap $3.50

GAVI Country C-poay ( $0.1-0$ 0.30 per dose initially) funding

$0 2 4 6 8 10 years 1st eligible Supplier’s share vaccine available of AMC funds Supply commitment depleted fulfilled AMC period Tail period

10 years

* Co-financing levels will be in line with the appl icab-lfien GaAnVciIn cgo pol.i c y

Figure 1: Pneumococcal AMC, sources of funding

increase manufacturing capacity and to spur the the estimated marginal cost of production to ensure an development of second generation vaccines10. efficient production level and long-term access to the vaccine. The pneumo AMC offers a legally binding commitment to Each manufacturer’s share of AMC funds is disbursed as a support the market of pneumococcal vaccines with US$ 1.5 subsidy per dose (additional to the amount paid by GAVI and billion, the “AMC subsidy”, for which vaccine manufacturers countries) – bringing the total price up to the AMC price (US$ can compete. In practice, interested manufacturers compete 7) for the initial doses of vaccine (see Figure 1). This “AMC to supply a share of the annual forecasted demand of price” is set at such a level that it should enable companies vaccines (which is expected to increase over time and reach to quickly recoup a reasonable amount of development costs around 200 million doses at peak). The AMC provides in as well as cover manufacturing costs. Only a limited exchange a share of the US$ 1.5 billion directly proportional purchase guarantee is offered, equivalent to 45% of one to each manufacturer’s supply. For instance, if a year’s committed supply. Final purchase of AMC vaccines is manufacturer enters into an agreement to supply 50 million for the most part dependent on demand. In other words, doses of vaccines annually (i.e. 25% of the target dose countries must desire vaccines and must be able, jointly with amount), it could receive up to US$ 375 million of the AMC GAVI, to pay their share of the final price13. funds (i.e. 25% of the AMC funds). There is a limit to the The pneumo AMC has the potential to reduce the historical supply share each manufacturer can bid for: offers by lag in introduction of vaccines between affluent and poor manufacturers cannot be higher than the forecasted demand markets. It is estimated that GAVI eligible countries could five years into the future – the so called “sequential access the target pneumococcal vaccines in 2010, if recently tendering”11. Competing bids are assessed against four main licensed and forthcoming pneumococcal vaccines pass the criteria: ensuring supply to meet demand; country test of AMC eligibility (i.e. meet the target product profile preference; price offered by the supplier; continued vaccine which includes targets related to serotype, safety and supply and multiple manufacturer participation. presentation criteria) and suppliers participate in the deal. All manufacturers are required to enter into a standard Faster introduction should also be favoured by the “tail supply agreement: terms – such as duration of contract, price price cap” which stipulates a reduction of about 95% of the conditions, demand guarantee, penalties, opt out options – price per dose in the US public market14. It is expected that are set up front and are identical for all participants. Each prices will further decrease as more firms enter the market manufacturer must commit to supply its share of doses for with lower tail prices and production processes become 10 years. The doses supplied must be priced at a maximum more efficient. of US$ 3.50 per dose (“tail price cap”) to be paid by GAVI Indeed, this AMC encourages multiple firms’ participation and GAVI eligible countries12. The tail price cap is set close to and competition to ensure vaccine security (i.e. procuring

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from multiple suppliers to reduce manufacturing risk) and to should be noted, nevertheless, that earmarking part of the drive prices down. In this AMC, multiple firms’ participation available funds could nevertheless result in insufficient is enhanced through sequential tendering. As demand five manufacturing capacity to serve imminent demand. A clear years in the future represents the upper limit of suppliers’ bids prioritization of objectives should thus be done before a and as demand ramps up over time, it is likely that multiple choice on this issue is made. manufacturers will be able to enter the market. The offer of a Another design feature is the rigidity of contractual terms. guaranteed AMC price ($7) rather than a minimal total In the attempt to create early supply for imminent demand, revenue, in turn, ensures competition is not limited to time to this AMC has recognized that there are few first-generation market. With a guaranteed price only, just like in affluent suppliers and has aimed at encouraging their participation in markets, suppliers are pressured to satisfy customers for the programme. To achieve this objective, a contractual offer quality and tail price to receive a higher share of the AMC with equal terms to all satisfies the hypothetical requirements market and to keep it over time. of the early supplier supposedly facing highest production Using the World Bank US$ 100/DALY benchmark for costs (for the tail price cap) and supposedly more demanding developing countries15, with an average price per dose of US$ (for the AMC price, demand guarantee, opt out options, 4.2516, pneumo vaccines procured under the AMC represent inflation provisions etc.). However, firms already in a specific a highly cost effective health intervention with a cost of US$ vaccine business have different production technologies and 33–36 per DALY17. different concerns and objectives and may consequently be willing to accept different terms to participate in an AMC. Discussion Issuing one AMC offer for which manufacturers can compete, The pneumococcal vaccine AMC is an innovative financing while allowing some flexibility in negotiation of contractual mechanism, and as with all innovation, it entails risks. This obligations with single firms, may lead to efficiency gains for section discusses some of the design and operational all. Tailored contractual terms would probably not be required challenges that might be addressed in future if the funding in case of multiple potential suppliers or in case of an early and political will exists to launch a second AMC. stage AMC18.

Design Sustainable funding One important design aspect of this AMC is linked to its An AMC subsidy is meant to be additional to regular funding double objective: 1) motivating suppliers – with licensed (or for vaccine purchase: the AMC subsidy covers investment nearly licensed) vaccines – to increase manufacturing costs acting as stimulus for vaccine development and capacity and 2) spurring development of new vaccines. In capacity scale up, recognizing that the purchasers (usually light of these goals, the pneumo AMC targets two categories governments and development agencies) will need to of suppliers at different stages of product development, facing continue their functions as buyers of the final product at very different timelines to market: 1) first-generation suppliers manufacturing cost. The need for additionality of AMC funds with immediate or almost immediate ability to enter into a is very visible in the set up of the pneumo AMC: the pneumo supply agreement and thus with instant access to the AMC AMC funds are disbursed to manufacturers as a subsidy per funds; 2) second-generation suppliers requiring more time for dose topping up the lower manufacturing cost to be paid by development and able to participate only at a later stage. GAVI and its eligible countries. This design raises two key Despite these differences, both categories compete on equal points. First, to be encouraged to invest, interested firms need terms in the deal. As consumption of AMC funds by first- to have confidence in the buyer’s financial ability to pay its generation suppliers is only limited by speed of demand and per dose contribution, so to be able to access the AMC funds. vaccine security considerations, it seems that second- Secondly, the buyer must be in a position to purchase the generation suppliers may perceive their probability of vaccines for the life of the AMC contract, once large scale accessing the funds as too low. As a result, they may have capacity has been built to serve poor countries. Should this little incentive to participate. One option to address this issue not be the case, countries would not be able to continue would be to target early and second-generation suppliers with vaccination programmes and firms may be left with separately, perhaps with two simultaneous AMCs. This might unused production capacity19: what we could call a Pareto increase the chance of participation of second-generation worst outcome. suppliers by guaranteeing availability of earmarked funds. It Attribution As the pneumo AMC is meant to test the effectiveness and efficiency of an AMC, it will be very important to measure its As consumption of AMC funds by first-generation ability to achieve the objectives it was designed to address. suppliers is only limited by speed of demand and However, the R&D environment for diseases primarily vaccine security considerations, it seems that second- affecting poor countries is complex, with multiple funding generation suppliers may perceive their probability of actors and incentives. Push initiatives are likely to be present accessing the funds as too low prior to development of pull programmes and also to be introduced after the creation of pull initiatives. In the case of pneumococcal vaccines, for instance, a partnership was

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recently announced between the China National Biotec Key messages Group (CNBG) and PATH to accelerate the development of a pneumococcal vaccine. As part of a global access Commercial investment for developing appropriate commitment, PATH and CNBG will design their vaccines for developing countries’ needs is limited. pneumococcal vaccine candidate to meet the pneumo One of the main reasons is that commercial AMC20. If this vaccine participates in the AMC, it will be investors perceive the market opportunity as too difficult to assess the incentive effects of the push versus the small to cover the risk-adjusted costs of R&D or the pull funding. More generally, in such an intricate and costs of production capacity scale up. An Advance constantly changing setting, it may be difficult to attribute Market Commitment attempts to tackle this problem impact to an AMC as opposed to other interventions by offering a legally binding financial commitment or stimuli. by donors to support purchase of target vaccines for poor countries if and when they are developed, so Conclusion that the risk-adjusted costs of private investment Advance Market Commitments have been designed to can be covered. A first AMC, of the value of US$ 1.5 address the asymmetries between rich and poor vaccine billion, became operative in June 2009 and has the markets. A first AMC has become operative in June 2009 potential to accelerate access for poor countries to and has the potential to accelerate access for poor countries appropriate quantities of appropriate pneumococcal to appropriate quantities of appropriate vaccines at more vaccines at more affordable prices. affordable prices. It is critical to carefully monitor and The pneumo AMC presents some design and evaluate this experience, in terms of design, processes and operational challenges. Firstly, there may be a trade- impact, and to document learnt lessons for potential future off between the objectives of 1) building applications of this mechanism. manufacturing capacity to serve imminent demand and 2) encouraging development of new vaccines. Tania Cernuschi is currently managing the pneumococcal AMC It is important to prioritize among objectives to programme at the GAVI Alliance. Prior to this, Ms Cernuschi determine the appropriate structure of the deal. worked in policy-making on innovative finance for development at Secondly, in case of AMCs targeted at specific the United Nations Department for Economic and Social Affairs in potential suppliers, it may be useful to evaluate the New York (UNDESA). She also conducted field work in Eritrea option of contractual flexibility, whereby different where she designed and managed various projects in the areas of firms participate in the same deal at different terms. income-generating activities, food security, human rights, water Thirdly, it should be highlighted that, despite an and sanitation and public health for nongovernmental AMC subsidy, a challenge remains to fund the organizations and the Italian Ministry of Foreign Affairs. Other marginal cost of production of AMC vaccines – to experiences include assignments with UNICEF, the Council of effectively encourage investment in development Europe and the European Parliament working mainly on analysis of and manufacturing capacity scale up as well as to aid in social sectors. Ms Cernuschi holds an MSc from the London ensure sustainable introduction. School of Economics in Development Management. It is critical to carefully monitor and evaluate the first AMC, in terms of design and processes. It will also be very important to measure its ability to accelerate access for poor countries to appropriate quantities of appropriate vaccines at more affordable prices. As the R&D environment for diseases primarily affecting poor countries is intricate and constantly changing, it will be challenging to attribute impact to an AMC as opposed to other interventions or stimuli.

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References

1. I am particularly grateful to Gian Gandhi, Shanelle Hall, Peter Hansen, 9. At the time pneumococcus was chosen, there was a rich pipeline of Michael Kremer and Nina Schwalbe for constructive suggestions, potential candidate vaccines, two of which were already in advanced comments and support. I also thank Marina Krawczyk, Rohit Malpani, stages of development (a 10-valent formulation by GlaxoSmithKline Mary Moran, as well as participants to the Pneumococcal AMC Seminar [GSK], recently recommended for human use by the European Medicines in IAVI (July 2009) for information and constructive discussions. Agency [EMEA] and a 13-valent pneumococcal conjugate vaccine 2. WHO immunization work: 2006–2007 highlights. World Health [PCV13] which was submitted to EMEA in 2008). Organization, 2008. 10. Disease Expert Committee Report, available online: 3. Center for Global Development. Report of the Center for Global http://www.vaccineamc.org/files/iec_rec_pilot.pdf. Development Advance Market Commitment Working Group – Making 11. Economic Expert Group Report (EEG), April 2008. Available online: Markets for Vaccines. Ideas to Action, 2005. Available online: http://www.vaccineamc.org/timeline_media/Expert_Group_Report.pdf & http://www.cgdev.org/section/initiatives/_archive/vaccinedevelopment/chapt Implementation Working Group Report (IWG), July 2008. Available ers. online: http://www.vaccineamc.org/files/AMC_IWG10JULY08_2_.pdf 4. Firms are presently responding to the presence in selected disease areas 12. GAVI eligible countries will contribute accordingly with GAVI’s co- of development partners they can work with, corporate social financing policy. Please see: responsibility, strategic considerations such as positioning in emerging http://www.gavialliance.org/vision/policies/new_vaccines/cofinancing/index. markets. The George Institute for International Health, 2008. G-FINDER: php Neglected diseases research and development: how much are we really 13. Detailed information on the terms of the pneumo AMC can be found in spending? Available online: the AMC legal documents on the AMC website: www.vaccineamc.org. http://www.thegeorgeinstitute.org/shadomx/apps/fms/fmsdownload.cfm?file 14. Centers for Disease Control, CDC website, Vaccine Price List last updated _uuid=409D1EFD-BF15-8C94-E71C-288DE35DD0B2&siteName=iih on 8 July 2009 http://www.cdc.gov/vaccines/programs/vfc/cdc-vac-price- 5. Selected vaccine introduction status into routine immunization. WHO, list.htm. 2003. Available online: 15. World Bank. Disease control priorities in developing countries. Oxford http://www.who.int/immunization_monitoring/routine/schedule_analysis_2 Medical Publications, Oxford University Press for the World Bank, New 003.pdf. York, NY. 6. For early analysis of AMCs’ potential and possible structures, see for 16. Averaging doses sold at the AMC price and at the tail price – instance Kremer M, Glennerster R. Creating incentives for conservatively assuming all firms will sell at a tail price at US$ 3.50. pharmaceutical research on neglected diseases. Princeton, Princeton 17. IWG Report, please see reference 7. University Press, 2004. 18. Similar considerations to this regard were made in the Center for Global 7. These are countries with a Gross National Income (GNI) per capita below Development Report and the Economic Expert Group Report. Please see US$ 1000 in 2003. references above. 8. A pneumococcus vaccine is already widely introduced in developed 19. Although it is important to note that the pneumo AMC contract includes countries, a 7-valent by Wyeth. The pneumo AMC, however, rewards risk mitigation provisions for firms when demand does not materialize supply of an enhanced vaccine that would include also serotypes (fast AMC subsidy payout for early cash flow, partial demand guarantee, prevalent mostly in GAVI eligible countries. Please see the Pneumococcal opt-out provision in the absence of demand). Target Product Profile at 20. http://www.path.org/news/pr090622-cdibp.php http://www.vaccineamc.org/files/TTP_Master_Table.pdf.

146 Global Forum Update on Research for Health Volume 6 Technological innovation incentives: “push” and “pull”

Comparative advantages of push and pull incentives for technology development: lessons for neglected disease technology development

Article by Cheri Grace (pictured), health economist, and the Lead Specialist, Access to Medicines within HLSP’s global health practice, and Margaret Kyle, Toulouse School of Economics

An earlier version of this paper was written with funding from the UK Department for International Development 1

nly 10% of the total R&D spend worldwide is devoted even stronger pull signal was sent when donors committed to to developing country needs, where 90% of the the first Advanced Market Commitment (AMC), in which Oworld’s population lives 2. Not surprisingly then, only legally binding financial commitments to support a market of 16 of the 1400 (or 1%) of new medicines developed a pre-agreed total market value were made. Firms who between 1975 and 1999 were for these neglected diseases 3. develop a product meeting the pre-defined specification can However, this picture has begun to change during the past tap into the AMC “market” as soon as the product is ordered decade. Incentives for the development of neglected disease by developing countries. technologies have emerged, which can be categorized into With the emergence of new push and pull mechanisms for “push” and “pull” categories. “Push” funding policies aim to neglected disease technology development during the past incentivize industry via reducing industry’s costs during the decade, stakeholders have been concerned about how pull research and development stages, whereas “pull” and push relate – what evidence is there about how they mechanisms create incentives for private sector engagement might work together? Which is a more cost-effective way to by creating viable market demand. Push mechanisms incentivize research and development (R&D) on neglected essentially pay for “effort” on the part of researchers, by disease technologies? underwriting the cost of that effort, while pull mechanisms pay for “results”. The respective roles of push and pull in bringing In the “push” category, donors have begun supporting technologies to market product development partnerships (PDPs) with direct The evidence base for answering these questions is in fact research grants aimed at developing neglected disease limited and the “science” on the study of the entire spectrum technologies. And on the “pull” side, there have been large of such incentive mechanisms is embryonic. Nonetheless, a increases in development assistance for health, from US$ 5.6 few trends emerge upon review of push and pull incentives billion in 1990 to US$ 21.8 billion in 2007 4. Much of this across sectors. has been routed through global health institutions such as the The use of prizes and grants as pull mechanisms was Global Alliance for Vaccines and Immunisation (GAVI), the widespread in science historically 5. For example, during the Global Fund for AIDS, TB and Malaria, and UNITAID. It is 19th century, prizes were offered for the study of yellow fever, estimated that about 40% of Global Fund grants are used for improving the supply of quinine, and a cure for Asiatic health commodity purchase and a much higher percentage of cholera. Tuberculosis was the subject of prizes in France, the GAVI and UNITAID funds are directed towards commodity UK and the US. More recently, the XPrize Foundation and purchase. These funds send “pull” signals to industry that a Innocentive are examples of organizations that offer rewards credible market exists, though the strength of these signals is for inventions or solutions to specific problems in a number limited because the financial amount is not pre-defined well of scientific areas. in advance, donors are not legally obligated to honour their A key advantage of pull mechanisms is that the funder can funding commitments, and the products, volumes and draw on the expertise of a large and diffuse set of researchers, purchase price are not committed in advance. Despite these rather than identifying and funding a handful with the shortcomings as a pull mechanism, the sheer size of these greatest potential. This advantage is especially important in funds lends credibility to these markets for neglected disease cases where knowledge is spread throughout the world or and consequently, the number and diversity of suppliers experts are hard to identify. Brunt et al found that prizes targeting the corresponding product sectors has increased. An offered by the Royal Agricultural Society of England increased

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the number of inventors (competition) and the quality of their desired outcome, when agents are not capital constrained, inventions 6. Pull mechanisms of this sort may also induce and when the principal is risk-averse. In contrast, push competitive racing, with multiple parties vying for a prize. In mechanisms are expected to be superior when effort is easy theory, this may speed the rate of innovation, though it to monitor and measure, and when the principle has a higher comes at a cost: racing may involve wasteful duplication of tolerance for risk. The problem is that PDP effort is not easily resources and effort, and racing does not promote the monitored; large information asymmetries exist between sharing of ideas, which may be vital in some areas of donors – usually not disease or drug development experts – science. Finkelstein tested this theory empirically 7. and the PDPs. This makes the choice of which PDP to Examining the effect of policies that had the effect of pull fund, and monitoring that PDP’s use of the funds, mechanisms on vaccine markets in the US, she found that more challenging and transaction-intensive. Information the expansion in market size and reduced liability induced asymmetries can also exist between the PDP management innovation in the diseases affected by these policies, but and the firms, academics and laboratories with which they noted that much of the innovation was socially wasteful contract for expertise and drug development inputs, resulting business stealing and had little effect in early stages of in similar monitoring challenges. Further, donors who are vaccine development. less comfortable with risk, due to taxpayer accountability for In many of the historical examples of push and pull across instance, may be less comfortable with funding PDP push. sectors, we find both push and pull working together But there are potential problems with relying solely on synergistically. For example, about half of pharmaceutical “pull” mechanisms as well. Many of the organizations and R&D funding is provided by governments (push) through firms from whom innovation might be expected in the institutions such as the US National Institutes of Health and neglected disease field – such as biotechs – may need push the UK Medical Research Council. The other half is provided funding in order to access eventual pull funding. Being more by the pharmaceutical companies, with the expectation to capital-constrained than big pharmaceutical companies, recoup this investment through eventual sale (pull) in biotechs do not typically take candidates to market; more wealthy markets. The Orphan Drug Act in the United States often, they sell their candidates to big pharmaceutical also included both types of mechanisms (using R&D tax companies before expensive clinical trials, in order to credits to push and extended market exclusivity to pull) in an monetise their investment earlier in the process. We would effort to spur development of treatments for diseases that expect this “normal pharmaceutical market” dynamic to be affect a small number of patients. Lichtenberg and Waldfogel accentuated in the neglected disease field, where the eventual showed that the Act appears to have induced a significant market is all the more insecure. Research from Bioventures number of new drugs for orphan diseases, but it is for Global Health 10 , which relied on consultations with impossible to identify the separate effects of the push and industry, indeed concluded that the main respondents to pull components 8. AMCs would be large pharmaceutical companies. The development of the meningitis C vaccine in UK However, we know that small organizations, including provides another example of push and pull working together. biotechs, do respond well to push incentives in neglected When officials in the UK Department of Health recognized a disease markets 11 . Certainly some small biotech firms with growing public health problem of meningococcal disease, good financial connections and the right expertise might they announced that a tender would be issued for a respond to pull incentives alone, but participation would be meningitis conjugate vaccine. Push support was offered via more assured if pull were accompanied by push incentives. clinical trial support, and fast-track regulatory support was Within the R&D pipeline, the effect of push and pull will offered as well. Although a vaccine for meningitis C was only depend to some degree on the stage of the technology’s in the early stages of development at the time of the 1996 development. Theoretically, we would expect PDPs to have announcement of these initiatives, three companies were greatest impact at earlier stages, where the variety of actors able to respond to the tender by 1999. The combination of involved may not have ready access to finance and the clinical trial support, accelerated approval (push) and scientific risk outweighs thinking about market potential. guaranteed purchase (pull) brought forward the development Conversely, the strongest response to an AMC would be of the vaccine 9. expected once companies can see their way clear through the science to a plausible product, i.e. as one is about to Within the neglected disease sector enter animal or especially human tests, as this is the point As experience with push and pull in the neglected disease where market calculations start to weigh in more heavily sector is relatively new, there is little empirical evidence to than scientific risk. However, in reality push is proving to be demonstrate the impact of each mechanism. We can draw effective and efficient throughout the development pipeline on theory when anticipating differences in response within the neglected disease sector, not just in the earliest according to technology type, stage within the development stages 12 . In the later development stages, push has been pipeline, and firm type. However, there will still be micro- useful for facilitating technology uptake and links with other level differences in response according to each individual public institutions, as illustrated by product introduction of firm’s strategic positioning, goals and portfolio opportunities. the Drugs for Neglected Disease Initiative PDP and the work The principal-agent model of economics suggests that pull of the pneumococcal “accelerated development and mechanisms are superior when it is easy to specify the introduction plan”.

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although the total social cost of producing the product remains the same whether funded by private or public sector. Higher development costs and longer investment lead times, combined with a concentrated purchasing base, exaggerates the Cost of capital Approximately half of the US$ 802 million estimate cited unattractiveness of investment in vaccines, and above arises from private industry’s opportunity cost of especially for neglected disease vaccines capital, thus this cost parameter is a key one in the overall cost picture. An important distinction between push and pull as incentives for technology development is who bears the risk. The type of technology under development will also affect In push, donors fund R&D through grants and bear the the incentives required to have an impact on firms’ development risk, whereas with pull, industry funds and investment decisions. Differences between vaccines and bears the risk during development, with donors compensating drugs are illustrative. Higher development costs and longer industry upon successful development of the technology. investment lead times, combined with a concentrated Some have concluded that, when public sector carries the purchasing base, exaggerates the unattractiveness of risk in “push”, overall costs are lower, reasoning that the investment in vaccines, and especially for neglected disease public sector’s cost of capital, or rate of return is lower 21 . This vaccines 13 . Consequently, the incentives required to motivate assumption arises from a simplistic observation that when neglected disease vaccine developers are likely to be larger, governments borrow, the cost of government borrowing is and so it is not surprising that a vaccine has been chosen to usually low in comparison with the cost of private borrowing. serve as the technology pilot for the first AMC 14 . But the government borrowing rate is low only because the national taxpayer provides the government with an implicit Comparing cost-effectiveness of push versus pull guarantee of its debt obligations. In addition, the opportunity Another angle from which to consider the question of optimal cost of capital for public sector needs to reflect a social return positioning of push and pull incentives is to ask the question in investment in schools, police etc, which elevates the from a cost-effectiveness perspective, i.e. given a finite required rate of return above solely the rate on borrowing 22 . amount of donor funds, how should these be allocated In fact, the correct economic approach to calculating the among push and pull incentives in order to achieve the opportunity cost of capital is to derive it from the project risk, greatest effect for the least cost? and this comes from a comparison with investment in assets with similar risk profiles. Using this method, government and Three types of costs private industry should be applying the same discount rate, There are three types of relevant costs incurred in or opportunity cost of capital, to calculate the net present pharmaceutical R&D: out-of-pocket costs, costs of failure 15 value of investment in neglected disease technology and opportunity costs of capital 16 . In pharmaceutical R&D, development, and consequently, there should be no these three different costs take on different levels of difference between the cost of capital for public versus private importance depending on the stage in the pipeline. sector when it comes to funding a specific project with a Investments incurred earlier in the R&D pipeline are costlier specific risk profile. from both a time-value-of-money and risk perspective, whereas out-of-pocket costs escalate as one advances into Failure rates/managing risk animal tests, then Phase I, then Phase II, and finally Phase Cost estimates are also affected by failure rates. With a III and the development of mass production methods. portfolio management approach, candidates from multiple sources are compared to each other for their comparative Out-of-pocket costs advantage including cost, efficacy and potential for Kettler found that the cost of an NCE launched today can resistance. The role of the PDP’s Expert Scientific Advisory approach US$ 600 million 17 , while a detailed review from Committee (ESAC) is to cull the weaker candidates, relative to DiMasi, Hansen and Grabowski estimates the cost of bringing other technologies intended for the same disease area 23 . The a compound to market at US$ 802 million, including out-of- way this candidate “culling” is managed may differ between pocket costs, costs of failure and costs of capital 18 . private pharmaceutical companies and PDPs. Private Mahmoud et al hypothesize that neglected disease pharmaceutical companies usually manage a portfolio of technology development costs might be lower than the US$ 802 million; this view has been cited elsewhere 19 . And recent studies by two drug PDPs provide evidence that the costs of their neglected disease drug development are much less than The role of the PDP’s Expert Scientific Advisory the DiMasi figures 20 . However, the cost savings for neglected Committee (ESAC) is to cull the weaker candidates, disease research versus R&D for products aimed at wealthy relative to other technologies intended for the same markets would be realized whether the research were funded disease area by push or pull. Out-of-pocket costs may be also be reduced when funded by push due to in-kind inputs from industry,

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products aimed at many different diseases, making choices Key messages based on potential profitability across a range of diseases 24 , whereas PDPs have a more focused portfolio and may follow  In many of the historical examples of “push” and more leads in a particular field. Although theoretically the “pull” incentives for technology development across disease-niche portfolio approach of PDPs should reduce sectors, we find both push and pull working failure risk, PDPs are showing overall project failure rates together synergistically, whereby push is used to similar to those of DiMasi 25 . attract partners to engage in the work during Thus, there would appear to be no out-of-pocket, risk development, and pull is used to add credibility reduction or cost of capital cost advantage to either push or to the eventual market incentive for the pull within the neglected disease sector. The key comparative successful candidate. issue consequently becomes whether one mechanism or the  Pull mechanisms may be a superior incentive other, or some combination, is more effective at neglected mechanism when it is easy to specify the desired disease technology development. outcome, when agents are not capital constrained, and when the principal is risk-averse. Push Which is more effective – paying for R&D through mechanisms are expected to be superior when effort “push” grants or through “pull” payments? is easy to monitor and measure and when the We are just starting to see empirical data on how push principle has a higher tolerance for risk. funding channelled via PDPs performs, at least for drugs 26 .  There would appear to be no cost advantage to First, we know that there is increased drug R&D activity as a either push or pull within the neglected disease result of PDPs. Research also suggests that PDPs are proving sector, so the choice between the two incentives, or superior in terms of time to market, cost-efficiency, health how to combine them, should instead be based on value and innovative level of the products, when compared their comparative R&D effectiveness for with industry-alone neglected disease development in the development of the technology in question. absence of a pull incentive. Further research is needed in this area, although experience so far suggests that development of some technologies would be facilitated by the presence of push incentives, regardless of whether a pull incentive exists Margaret Kyle studies several aspects of innovation and for the technology. J productivity at the Toulouse School of Economics. She has written a number of papers examining R&D productivity in the Cheri Grace is a health economist and the Lead Specialist, pharmaceutical industry, specifically the role of geographic and Access to Medicines within HLSP’s global health practice. Cheri academic spillovers; the firm-specific and policy determinants of has provided support to DFID’s Access to Medicines work since the diffusion of new products; and the use of markets for 2001, working within DFID’s Central Research Department in technology. Recent work examines the effect of trade and IP 2005 –2006 to lead on Product Development Partnerships. policies on the level, location and direction of R&D investment and Selected consulting assignments include: leading a multi- competition, as well as strategic disclosure of information by firms disciplinary research study series examining the effect of changes engaged in R&D races. Her papers have been published in various in intellectual property rights on access to medicines; analysing journals of economics and health policy, including the RAND the effect of Global Health Initiatives on medicines’ pricing and Journal of Economics, Review of Economics and Statistics, Journal supply security; evaluating options for improving ACT supply of Law and Economics, Health Services Research, and Health security; analysing options for the G8’s investment into Advanced Affairs . Market Commitments (AMCs); supporting DFID on their new £50 Margaret holds a bachelor’s degree with honours from Cornell million neglected tropical disease commitment; advising the University and a PhD in economics from the Massachusetts Global Fund Board on the potential market impact if the Fund Institute of Technology. were to accept in-kind pharmaceutical donations; and review of She previously held positions at Carnegie Mellon University, country capacity needs for new technology introduction for the Bill Duke University and the London Business School. She has also & Melinda Gates Foundation. Earlier research and consultancy was been a visiting scholar at the Center for the Study of Innovation focused on drug distribution systems within developing countries and Productivity at the Federal Reserve Bank of San Francisco. such as Malawi, Vietnam, Nigeria, Ghana, Pakistan, Kenya. Prior She is a Faculty Research Fellow at the National Bureau of to becoming involved in global health research and consultancy, Economic Research (US) and Research Associate at the Centre for Cheri had careers in the pharmaceutical industry, in corporate Economic Policy Research (EU). finance, research and teaching with the London Business School, and two years of community-level maternal and child health work in the Moroccan mountains.

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References

1. Grace C. Developing new technologies to address neglected diseases: human clinical trials. The costs incurred for the four failed candidates the role of product development partnerships (PDPs) and advance market must be included in the costs of bringing the fifth, successful candidate to commitments (AMCs). DFID Health Resource Centre, 2006, market. These costs are calculated into the NPV model as a failure rate http://www.dfidhealthrc.org/publications/Issues_papers/push_pull_06.pdf discount on the numerator. (accessed 10 August 2009). 16. The opportunity cost, i.e. time value of money, of not employing the cash 2. The 10/90 report on health research. Global Forum for Health Research, in alternative uses, calculated into the NPV model as a decreasing (over 2000, http://www.globalforumhealth.org (accessed 10 August 2009). time) rate in the denominator. 3. Drugs for Neglected Diseases Working Group and the Campaign for Access 17. Kettler HE. Updating the cost of a new chemical entity . London, Office of to Essential Medicines. Fatal imbalance: the crisis in research and Health Economics, 1999. development for drugs for neglected diseases . Geneva, Médecins sans 18. DiMasi JA et al. Assessing claims about the cost of new drug Frontières, 2001. development: a critique of the public citizen and TB Alliance reports, 4. Ravishankar N et al. Financing of global health: tracking development 2004, http://csdd.tufts.edu/_documents/www/Doc_231_45_735.pdf assistance for health from 1990 to 2007. Lancet, 20 June 2009, (accessed 18 August 2009). 373:2113 –2124. 19. Mahmoud A et al. Product development priorities, disease control 5. For discussion, see Hanson R. Patterns of patronage: why grants won over priorities project. The World Bank, 2004. prizes in science , GMU Working Paper, 1998. 20. Mahmoud, et al. Product development priorities, disease control priorities 6. Brunt L, Lerner J, Nicholas T. Inducement prizes and innovation , CEPR project. The World Bank, 2006:4. Working Paper, 2008, 6917. 21. See pages 35, 56, 57 and 79 of PRPP and page 141 Mahmoud et al. 7. Finkelstein A. Static and dynamic effects of health policy: evidence from Product development priorities, disease control priorities project. The the vaccine industry. Quarterly Journal of Economics , 2004, World Bank. 119(2):527 –564. 22. As explained by a principal architect of the AMC concept, “The financial 8. Lichtenberg F, Waldfogel J. Does misery love company? Evidence from cost of capital to the public sector understates the social cost of capital to pharmaceutical markets before and after the Orphan Drug Act . NBER the public sector, because it ignores the implicit cost to taxpayers of Working Paper 9750, (2003). . underwriting those investments. Taxpayers face a non-zero expected cost 9. Kremer M, Barder O, Levine R. Making markets for vaccines, ideas to of having to bail out the government by paying higher taxes; and that action (chapter 2). Centre for Global Development, 2005. expected cost is broadly equal to the difference between the market cost 10. Advanced Market Commitment to Stimulate Industry Investment in Global of capital for the public and private sectors. When appraising expenditure Health Product Development: A Report on the Biotech Industry’s options, governments should (and do) take account of the overall social Perspective, Bio Ventures for Global Health , 2006, costs and benefits, including the social time preference rate, and not http://www.bvgh.org/documents/BVGH_AMCReportFINAL.pdf (accessed merely the financial costs reflected in market interest rates.” Owen Barder, 10 August 2009). Centre for Global Development, Public funding, private funding and the 11. Mehta P. Global Health Innovators: A Collection of Case Studies. Bio cost of capital for R&D , unpublished mimeo. Ventures for Global Health, 2009. 23. Moran et al. The new landscape of neglected disease drug development. 12. Moran et al. The new landscape of neglected disease drug development . Pharmaceutical R&D Policy Project (PRPP), September 2005, p.59. Pharmaceutical R&D Policy Project (PRPP), September 2005, p.13. 24. Research has shown difficulties in averting risk through portfolio 13. The vaccine market is smaller than the drug market and the primary strategies in the pharmaceutical industry. Essay contributed by Scherer vaccine customer is the public sector. On the cost and risk side, vaccines and Harhoff. In: Branscomb L, Auerswald P. Taking technical risks: how often require larger and more complex clinical trials and carry greater innovators, executives and investors manage high-tech risks . The MIT concern over liability. This is true of many preventative as well as “first in Press, 2001:125 –138. class” technologies, such as microbicides. Unlike drugs, vaccines also 25. Mahmoud A et al. Product development priorities, disease control require a proprietary manufacturing facility to be built in order to make priorities project. The World Bank, 2006:4. the product for Phase III trials. 26. As discussed elsewhere in this paper, drug R&D differs in several respects 14. Advance Market Commitments for Vaccines, http://www.vaccineamc.org/ from vaccine R&D and therapeutic products also may differ from (accessed 10 August 2009). preventive. 15. In the US, the FDA approves only one in five compounds that enter

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Emerging innovation practices and policies for the health-care needs of resource-poor people

Article by Raghunath Anant Mashelkar (pictured), President, Global Research Alliance; Bhatnagar Fellow, National Chemical Laboratory and Bhushan Patwardhan, Director, Interdisciplinary School of Health Sciences, University of Pune and Shiladitya Sengupta, Assistant Professor of Medicine and Health Sciences and Technology, Harvard Medical School

he emerging innovation practices and policies for Reverse pharmacology is a rigorous scientific approach to affordable global health solutions for resource-poor use the documented clinical experiences as well as qualitative Tpeople are demonstrated with suitable examples, both experiences and observations for developing target candidates illustrative and inspirational. It is concluded that innovation or formulations through robust preclinical and clinical can indeed impact the entire chain of diagnosis, drug research. In this process “safety” remains the most important discovery, development and health-care delivery. starting point and “efficacy” becomes a matter of validation7. The Council of Scientific and Industrial Research of India, Introduction under the programme known as the New Millennium Indian Making better health-care accessible, affordable and available Technology Leadership Initiative (NMITLI) invested in the to resource-poor people is an urgent challenge1. Innovation reverse pharmacology approach through a partnership with will be the key in attaining these goals. industry and academia. The approach will be illustrated with Innovation is required in the entire chain of diagnosis, a typical example of the development of a drug for psoriasis, discovery, development, health care delivery and even in which is presently in phase III clinical trials. financing2,3,4. The innovation challenge will be to get, as we A leading Indian pharma company used an indigenous shall show, “more from less for more”. knowledge base of a practitioner in a village. It did rigorous scientific and clinical work to validate the claims. Thus Discovery and development extensive studies comprising fingerprinting, activity-guided Just a decade ago, the journey from the discovery of a new fractionation, efficacy studies, toxicology, safety pharmacology, molecule to the marketplace used to take around 10 years pharmacokinetics and toxicokinetics helped the company in and cost around US$ 250 million. Today, the same journey filing an Investigational New Drug (IND) application. A single takes anywhere between 10 to 15 years and costs around plant-based oral herbal formulation was developed, which US$ 1–1.5 billion. On the other hand, the Food and Drug has a novel mechanism of action with effective modulation, Administration (FDA) approved only 21 new molecular the cellular function leading to marked psoriatic lesion entities as against around 30–40 a decade or so ago. In other improvement without any toxic effects. The guidelines laid words, we are getting “less for more for less” i.e. “fewer” down by the US FDA for botanicals as well as Drugs Control molecules approved by the FDA, which are developed with General of India (DCGI) norms on new drug development were much “higher” costs and taking a much “longer” time. This followed. The work is in phase III clinical trials and, if makes them less affordable, which means access of these successful, will be introduced in the market by the end of 2010. therapeutics to a lesser number of patients. The challenge is In this specific case, the contrast in terms of potential to reverse the current trend of “less from more for less” to lowering of cost of treatment (about US$ 100 as against, “more from less for more”, which means more (performance say US$ 20 000 for antibody treatment), the time for in terms of safety and efficacy) for less (cost of development) development (six years as against the conventional 10–15 for more (resource-poor people). years) and cost of development (about US$ 10 million as against upwards of US$ 500 million) is evident7. Traditional or alternative medicine Patwardhan and Mashelkar7 have given other examples of Traditional or alternative medicine can offer accessible and reverse pharmacology. Several drugs for other diseases such affordable health care, especially for preventive medicine and as cancer, diabetes, osteoarthritis, hepatitis, etc. are at various chronic pathophysiological states. It can also serve as a rich stages of development through the reverse pharmacology route. knowledge resource for new drugs5–8. One promising approach is traditional knowledge-inspired reverse Open source discovery pharmacology7, which reverses the routine “laboratory-to- The WHO Commission on Intellectual Property Rights, clinic” process to “clinics-to-laboratories”. Innovation and Public Health, of which one of the authors

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(RAM) was a Vice-Chair, made a recommendation in its also surviving the harsh conditions of dust, humidity and 2006 report: extreme temperatures. “Practical initiatives that would motivate more scientists to On the other end, advanced technologies can reduce the contribute to this field through “open source” methods should costs too. The possibility of resolving the sensitivity of be supported.”1 detection using nanostructures, such as carbon nanotubes It was India’s Council of Scientific and Industrial Research and nanocantilevers means that detecting a disease at an (CSIR) that made it into reality. It launched the first ever early stage is now a realistic goal. This can dramatically Open Source Drug Discovery (OSDD) consortium with global impact on the clinical outcome and reduce the burden on the partnership with a vision to provide affordable health care to health-care system14. the developing world by providing a global platform9. Similarly, disposable “lab-on-a-chip” devices can enable OSDD is a concept to collaboratively aggregate the rapid diagnostics at remote sites, which can enable effective biological and genetic information available to scientists in disease management15. This can especially revolutionize the order to use it to hasten the discovery of drugs. It management of HIV, where delayed diagnostics can mean incorporates a web-based platform for scientists and students loss of contact with the patient, who in most cases, will not all over the world to share research and collaborate on drug be able to afford a prolonged stay at the site of the health- discovery projects for malaria, TB and other neglected care facility. diseases (www.osdd.net). One such project leveraged the world’s largest Mycobacterium tuberculosis (MTB) database Innovations in delivery to bring together 13 researchers across India to decode 400 Innovations in delivery are as critical. Recently, at the 6th of the 4000 genes of MTB in less than six months9. Annual World Health Care Congress some interesting themes The Government of India’s commitment of US$ 38 million (http://www.worldcongress.com/events/HR09000/) were towards this project is being now followed with equivalent showcased as “Extremely Affordable Health Innovations”16 funding being raised from international agencies and with “extreme affordability” being demonstrated by the two philanthropists10. examples listed below.

“Out of patent” based innovative drugs Incubator for US$ 25 Most of the “out of patent” existing therapeutics have not yet Embrace is a nonprofit organization that aims to help the been fully optimized, which can be done by using innovative millions of vulnerable babies born every year in developing engineering approaches. This approach can offer potentially countries through a low-cost infant incubator. Unlike superior drugs at far cheaper prices. traditional incubators that cost up to US$ 20 000, the In a recent study, bioengineers at MIT engineered a novel Embrace infant warmer costs US$ 25. The device requires nanoparticle that could enable a rational combination of two no electricity, has no moving parts, is portable and is safe. drugs, where the sum of the effects was greater than the Twenty million vulnerable babies born across the globe each individual11. These could treat tumours more effectively than year can be helped. existing regimes and also reduce the side-effects. Because researchers designed them using polymers and Cataract surgery for US$ 25 drugs that are already approved for human use, one can Aravind Eye Care System (AECS) has successfully developed quickly move into clinical trials. Now at Harvard Medical and implemented a high-volume, high-quality, cost-effective School and Brigham and Women’s Hospital, scientists are eye care model and taken it to the doorstep of rural India17. working on extending these concepts to treat other diseases. With less than 1% of the country’s ophthalmic manpower, In addition, these scientists are using cost-effective AECS performs about 5% of all cataract surgeries in India. As biocompatible nanomaterials such as carbon-derived a result of the unique work flows and fee system, AECS has fullerenols to change the pharmacokinetic and become self-sustaining, treating over 1.4 million patients pharmacodynamice properties of existing therapeutic agents each year, two thirds of them for free. It works with more to increase the therapeutic index12. This has the potential to than 200 hospitals located all over India as well as in the improve upon the efficacy and safety of “out of patent” drugs. developing world, helping them to replicate the Aravind Nanotechnology holds the potential to deliver the active model in these countries. agents specifically to the desired site of action, thus reducing the total drug requirement, and therefore reducing the cost. Innovations to reduce patent monopolies When the market has very limited purchasing power, as is Affordable diagnostics the case in developing countries, patents are not necessarily Low-cost diagnostics for priority global health conditions is effective in stimulating research and development (R&D) and an initiative launched by the Bill & Melinda Gates Foundation bringing new products to the market18. Many innovations (www.grandchallenges.org). Out-of-the-box thinking will be have been suggested to address this challenge. increasingly needed. For instance, Whitesides and his group13 have developed Patent Pools “paper based diagnostics”, which can be used in villages. A patent pool is a mechanism, whereby a number of patents They have the advantage of not using any electronics and held by different entities are made available to others for

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production or further development. The patent holders receive Key messages royalties from the users. Patent pools are part of World Health Organization’s Innovation directed towards the goal of getting recently adopted Global Strategy on Public Health, Innovation “more (performance) from less (cost) for more and Intellectual Property to help increase access to medicines. (people)” is needed. Several such initiatives are underway. For instance, Innovation should be across the entire chain of Knowledge Ecology International (http://www.keionline.org/) diagnosis and discovery, development and delivery is trying to create a patent pool for medicines in low- and of therapeutics, diagnostics and vaccines. middle-income countries. In February 2009, Glaxo Smith Innovative Developing Countries (IDCs) should play Kline (GSK) has announced a patent pool initiative, with the a greater role in developing innovative practices intention of putting many drug patents for tropical diseases and policies for the health-care needs of resource- into a free pool. poor people. In July 2009, Alnylam Pharmaceuticals announced that it will contribute its RNAi technology patent estate and know- how to the GSK patent pool. GSK granted South Africa’s Conclusion Aspen the right to make its HIV drug abacavir in a royalty-free The emerging innovation practices and policies for health licensing deal, although HIV drugs have not so far been care needs of resource-poor people must hinge around included in the patent pool. The year 2009 has thus seen innovations that can get “more from less for more”. The entire progress19. chain beginning with diagnosis of a disease, to discovery and development of a new therapeutic, to its delivery needs Global Responsibility Licence radical innovations. Some illustrative, but also highly The proposed Global Responsibility Licence (GRL) is an inspirational examples, have been given to show how this approach with great potential20. GRL is envisaged to be a can be achieved. standard, global licence for patents, which allows public and Finally, the growing ability of some developing countries not-for-profit research organizations to undertake research for like India, China, Brazil, etc. (also referred to as Innovative “non-market uses”. This licence would be used to help Developing Countries (IDCs)) to undertake health innovation nonprofit organizations and research agencies improve the is an increasingly important means to improve health state of the world in very meaningful and practical ways. equity21. Health innovation networks from such as IDCs GRL is different to a “patent-pool” approach in that it does should increasingly be used to help achieve the goal of not give ownership of the original IP away. Any firm retains “health for all and not a privileged few”. control of its IP portfolio, but the transaction cost of licensing for philanthropic purposes is greatly reduced. Dr Raghunath Anant Mashelkar is President of the Global Research Alliance, a network of publicly funded R&D institutes Other emerging innovations in practices and policies from Asia-Pacific, Europe and USA with over 60 000 scientists. Current health financing includes international health funds He served as the Director-General of the Council of Scientific (e.g. the Global Alliance for Vaccines and Immunisation – and Industrial Research (CSIR) with its 38 laboratories and about GAVI), product development partnerships (e.g. IAVI, PATH), 20 000 employees for over 11 years. He was also the President of International Finance Facility for Immunization (IFFIm), the Indian National Science Academy. Advance Purchase Commitment (Pneumococal Advance Dr Mashelkar is a Fellow of the Royal Society (FRS), London, the Purchase Commitment), UNITAID, etc22. We need to move Foreign Associate of National Academy of Science (USA) and the beyond these. National Academy of Engineering (USA). Just as “outsourcing” has brought down the costs, so can He has been awarded honorary doctorates by 27 universities, innovative “crowdsourcing”. In “crowdsourcing” an undefined which include the universities of London, Salford, Pretoria, large group of people takes on tasks usually performed by Wisconsin and Delhi. employees in response to an open call23. Innocentive, Ninesigma, Foldit, etc. are brilliant examples of crowdsourcing. Dr Bhushan Patwardhan is a professor at the Interdisciplinary The current “push” and “pull” mechanisms work within the School of Health Sciences, University of Pune, India. existing regimes of IP protection. However, rewarding He has successfully integrated biomedical sciences and innovation by offering prizes or compensation based on the traditional knowledge to innovate on the current practices of extent of disease averted in developing countries is an pharmaceutical and natural product drug discovery. interesting innovation24,25. He has published over 80 research publications in peer review Finally, the “grand challenges initiative” posed by the Bill & journals and over 200 popular science articles. He also has a Melinda Gates Foundation (www.grandchallenges.org) is one number of international patents. Dr Patwardhan is one of the top of the most innovative ones in recent times. It is a five-year ten most popular authors of Elsevier’s SciTopics. He has worked as US$ 100 million initiative to encourage bold and a consultant to WHO Geneva and SEARO, and is a member of the unconventional research on novel global health solutions. It scientific advisory bodies of several academic institutions. challenges the best minds around the world with a chance to win US$ 1 000 000 grants to further their research. Dr Shiladitya Sengupta is an assistant professor of Medicine and

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Health Sciences and Technology at Brigham and Women’s (2009) from the US Department of Defense. He was a Nehru Hospital, Harvard Medical School. Scholar at Trinity College, University of Cambridge, and a fellow He is the cofounder of Cerulean Pharmaceuticals. Chosen as at the Massachusetts Institute of Technology (MIT). one of the top 35 innovators of the world under 35 years of age With the Department of Biotechnology, Government of India, he by Technology Review Magazine (2005), Dr Sengupta received the is establishing the Translation Health Sciences and Technology Era of Hope Award (2007) and Innovator Collaborative Award Institute in India.

References

1. Dreifuss R, Mashelkar RA et al. Public health, innovation and intellectual volume, portable bioassays. Angewandte Chemie International Edition, property rights. Report of the Commission on Intellectual Property Rights. 2007, 46, 1318–1320. World Health Organization, Geneva, 2006. 14.Wang C, Madou M. From MEMS to NEMS with carbon. Biosens 2. Widdus R, White K. Combating diseases associated with poverty: Bioelectron, 2005, Apr 15;20(10):2181–7. financing strategies for product development and the potential role of 15.Myers FB, Lee LP. Innovations in optical microfluidic technologies for public-private partnerships, point-of-care diagnostics. Lab on a Chip, 2008, Dec;8(12):2015-31. (www.mmv.org/IMG/pdf/Combatingpoverty/PPH.pdf), 2004. 16.Golden P. World Health Care Congress focuses on extremely affordable 3. Burke MA, Martin SA, eds. Global Forum For Health Research: health innovations. Medical News Today, 16 March 2009, Monitoring financial flows for health research, 2006. http://www.medicalnewstoday.com/articles/142318.php. 4. Editorial, Lancet, 2004, 364:1555–1556. 17.Tabin G. The Cataract Blindness Challenge Innovations Case Discussion: 5. Wonderling D et al. Cost effectiveness analysis of a randomized trial of Aravind Eye Care System. Innovations, 2(4), 53–57 acupuncture for chronic headache in primary care. British Medical (doi:10.1162/itgg.2007.2.4.53). Journal, 2004, 328:747–52. 18.Kaiser J. NIH to limit scope of foreign patents. Science, 2002, 296, 6. Oz M. Emerging role of integrative medicine in cardiovascular disease. 2316. Cardiovascular Reviews, 2004, 12(2):120–123. 19.Bioventures for Global Health, 2009. www.bvgh.org, [email protected] 7. Patwardhan B, Mashelkar RA. Traditional medicine-inspired approaches to 20.http://www.weforum.org/pdf/YGL/editorials/moody.pdf. drug discovery: can Ayurveda show a way forward? Drug Discovery Today, 21.Morel CM, Acharya T, Broun D et al. Health innovation networks to help 2009, 14(15/16), 811. developing countries address neglected diseases. Science, 2005, 309, 8. Padma TV. Ayurveda. Nature, 2005, 436, 486. 401–404. 9. http://www.osdd.net 22.IAVI insights. Innovative financing mechanisms to advance global health. 10. Kniaz S. The best thing to come out of India since “Slumdog Millionaire”. Policy Brief 21, 2009. Global Health Policy, 11 March 2009. 23.IAVI Report. Crowdsourcing vaccine challenges, 2009, 11.Sengupta S et al. Novel cancer therapy through temporal targeting of both www.iavireport.org. tumour cells and neovasculature using a unique nanoscale delivery 24.Nathan C. Aligning pharmaceutical innovation with medical need, Nature system. Nature, 2005, 436:568–72. Medicine, 2007, 13, 3004–3008. 12.Chaudhuri P et al., Fullerenol-cytotoxic conjugates for cancer 25.Love J. World cash prizes promote cheap drugs, 2007, chemotherapy. ACS Nano, 2009 (in press). http://www.newscientist.com/article/mg19626296. 13.Andres W et al. Patterned paper as a platform for inexpensive, low-

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