Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Department of Medicines Research Basel, 23rd June 2010 Comparison of Clinical Trials in the industrialized world and Africa Life Science Forum Basel PD Dr. Christian Burri Head of Department Swiss Tropical & Public Health Institute The Swiss TPH … … is an associated institute of the University of Basel … has the mandate to contribute to the improvement of the health of populations internationally and nationally through excellence in research, services, and teaching & training at the levels of innovation, validation & application … has over 500 staff from 40 nations thereof ~100 PhD students 1 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Swiss Tropical & Public Health Institute The Swiss TPH … … the Swiss Tropical Institute (STI) was founded in 1943 as a public organisation based on a local government act … became the “Swiss Tropical and Public Health Institute” (Swiss TPH) at the beginning of the year 2010 after the integration of the Institute of Social & Preventive Medicine (ISPM) of the University of Basel … is supported at ~20 % by the Swiss Federal Government & Canton of Basel- Stadt … earns the greater part of funding through competitively acquired project funds and the earnings of the Service Departments Agenda • Contribution by the Swiss Tropical & Public Health Institute • Background • Overview on trials conducted in Africa • Trials in resource limited settings in Africa • Access to medicines 2 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Swiss TPH contributions Research Development Implementation Clinical Testing Phase I Phase II Phase III Drug Preclinical Phase IV Systems Discovery Application Parasite Chemotherapy - Screening HAT - Orally available diamidines Malaria drug discovery Molecular Immunology P.f. malaria: Development of a subunit vaccine candidate Intervention optimization Cost and cost-effectiveness of large-scale insecticide treated nets and indoor residual spraying programmes Systems optimization Effects of scaling up antiretroviral therapy for HIV/AIDS on health systems in BF, Tz & Ug (ARVMAC) Intermittent preventive treatment for malaria in infants Innovation >> Validation >> Application Swiss TPH contributions Research Development Implementation Clinical Testing Phase I Phase II Phase III Drug Preclinical Phase IV Systems Discovery Application Clinical Trials – µCRO: Pharmaceutical Medicine Unit Pharmaceutical Sciences & Services Pharmaceutical Health Services Design Implementation Management Monitoring Auditing Teaching & Training Capacity Building Innovation >> Validation >> Application 3 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute STI Clinical Research Background Trials 1990 –2010 Clinical Trials with STI / ISPM / Swiss TPH participation • 10 Phase I Trials • Malaria, Shigella • 22 Phase II Trials • Malaria, HAT, Hookworms, Schistosomiasis, Buruli Ulcer • 19 Phase III Trials • Malaria, HAT, Hookworms, Schistosomiasis • 1 Phase IIIb / Effectiveness Trials • Malaria • 21 Phase IV Trials • Malaria, HAT, Hep A, Hep B, Schistosomiasis, Tb • 8 Intervention Studies • Malaria, vitamin A, zinc, rational drug use, environment, water purification, HIV, Cholera • 3 Research / descriptive / observational studies • HAT, cholera, surgical site infection Background Geographic overview on poverty Percent of national populations living on less than $1.25 per day UN Estimates 2000-2007 Source: http://en.wikipedia.org/wiki/File:Percentage_population_living_on_less_than_$1.25_per_day_2009.svg 4 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Background Worldwide life expectancy at birth 2008 Source: http://en.wikipedia.org/wiki/File:Life_Expectancy_2008_Estimates_CIA_World_Factbook.png Background Burden of disease Source: Equitable access: research challenges for health in developing countries - A report on Forum 11, People’s Rep. of China, 2007 5 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Background Burden of disease (2002 – 2030) Source: PLoS Medicine, 2006, Mathres & Loncarn Background Partition of World Pharmaceutical Market 2008 Africa Japan • US$ >900 billion Europe 1% 16% 29% Latin America 8% Middle East Australasia 2% 1% US Southeast Asia & 34% China 7% Canada 2007 2% • Per capita health expenditure • USA ~ US$ 6’100 • CH ~ US$ 4’000 • Tanzania ~ US$ 29 • Rep. Dem. Congo ~ US$ 15 Sources: PhRMA 2002, 2005; http://www.aegis.com/NEWS/BW/2007/BW070638.html & Human Development Report, 2007 6 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Background Costs of drug development $800 Million to develop a single drug Synthesis & Extraction 10% Biological Screening 14% Toxicological and Safety Testing 5% Formulation and Stability 7% Clinical Evaluation: Phase I, II, III 29% Clinical Evaluation: Phase IV 12% Process Development Mfg & QC 8% Regulatory: IND & NDA 4% Bioavailability 2% Other 9% 0 20 40 60 80 100 Percentage Source: Tufts Center for the Study of Drug Development, 2001; PhRMA Annual Survey, 2001 Trials in resource-limited settings Motivation • Lower costs of research • Mainly due to salary levels • Cost per case report at first-rate academic medical center in India approximately $1,500 to $2,000 • Ca. 10x higher in the United States • Large pool of potential research participants • (ICH)-GCP rules wide spread adopted • Increasing bureaucracy and regulatory environment in industrialized countries • Expected lower regulatory barriers • New interventions for local use Source: S. Glickman 2009, New England Journal of Medicine 7 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Tropical and poverty related diseases “The new landscape” PPP direct R&D spend (including projections to 160 2006) 140 120 100 In kind (estimated) US$ US$ 80 Total direct R&D spend Millionen 60 40 20 0 2000 2001 2002 2003 2004 2005 2006 MMV iOWH TB DNDi Alliance • Neglected disease and product funding in 2008: US$ 2.956 Bio • 31 diseases listed • Total R&D expenditure by pharmaceutical industry 2006: US$ 89 Mio Sources: Moran 2005, New Landscape of Neglected Disease Drug Development; Medicines Australia 2008 Clinical trials in Africa Clinical trial sites November 2007 Source: S. Glickman 2009, New England Journal of Medicine 8 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Clinical trials in Africa Clinical trials conducted November 2007 Source: S. Glickman 2009, New England Journal of Medicine Clinical trials in Africa Excellence centers in clinical research Source: Adapted and updated from AMANET 9 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Clinical trial in Africa Number of trials per country Country # South Africa 252 Uganda 43 Tanzania 34 Kenya 30 Mali 21 Zambia 17 Ghana 12 Malawi 12 Burkina Faso 10 Nigeria 9 Zimbabwe 8 Mozambique 7 Gambia 6 Senegal 6 Cameroon 5 Total 591 Source: International Clinical Trials Registry Platform, Status 20.04.2009 Clinical trial in Africa Ongoing trials in South Africa by indication Source: South African Clinical Trial Register, Status 22.06.2010 10 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Trials in resource-limited settings in Africa Variation in quality of trial sites Manhiça Health Research Centre, Mozambique ARCEAU at Kin SOPH, DRC Ifakara Health Institute, Tanzania CDTC Maluku, DRC Trials in resource-limited settings in Africa Benefits • Capacity building in less developed countries and areas • Fostering of relationship between physicians globally • Comprehensive insight into efficacy and safety of interventions 11 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss Tropical and Public Health Institute Trials in resource-limited settings in Africa Factors to be considered • Trial objectives • Type of design • Control group • Choosing trial’s blind • Bias and confounding factors • Sample size • Randomization procedure • Patient recruitment • Compliance • Staff qualification and training needs • Logistics Trials in resource-limited settings in Africa Specific problems encountered Specific and typical problems encountered • Lack of experience in the conduct of clinical trials • Insufficiently trained / inexperienced staff • Overworked physicians • Low level infrastructure • Cultural differences • Illiterate patients • No nursing care 12 Life Science Forum Basel 2010 Comparison of Clinical Trials in the industrialized world and Africa Christian Burri; Swiss