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IN THIS ISSUE DIA 2013 49th Annual Meeting Preview: “Advancing Alzheimer’s Innovation: A Call to Action”
Chaired by Meryl Comer President, Geoffrey Beene Foundation Alzheimer’s Initiative
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Process Cyan PMS 2935 PMS 296 ggff CONTENTSCONTENTSTOGETHER, wE CAN CHANGE THE wORLd * ART As ACTIVIsm * ORGs wE LOVE TO sUppORT LEARNLEARN FIGHT LOVE Your FDA submission documents FIGHT are serious. So are their translations. LOVE INFORM ADVISE REACH EDUCATE When translating documents for FDA submission such as dossiers, CRFs, 10 54 64 108
labeling, adverse event reports, and product information, Corporate peter staley UNLEAsHING THE pOwER OF p HOTO: © w illiam Lucas Acts Up HOw TO sURVIVE A pLAGUE
Translations understands the critical need for accuracy Our rigorous alker translation process includes multiple quality inspections, guaranteeing Open Forum 6 AIDS Advocacy 46 the most accurate translations quickly and cost-effectively. We stand by Andrzej Czarnecki Richard M. Klein the quality of our translations by providing a certification of accuracy President’s Message 8 with each document. Partnering with Corporate Translations allows you Ling Su Inaugural President’s Award Presented to Center for AIDS to prepare your submissions with confidence. That’s why Corporate inform 10 Program of Research in South Translations is the preferred supplier of ISO 9001 translation and Africa (CAPRISA) 50 Of DNA, HIV, Advocacy, Humanity, linguistic validation solutions to the world’s leading life science companies. Therapeutic Innovation and Regulatory Science 11 PROFILE Nikos Dedes 52 Stephen P. Spielberg ADVISE 54 3 www.corptransinc.com Exploring Impact of ‘US v. Caronia’ 55 1-855-727-6003 ACT UP Crashes the Gates 13 Jim Eigo Imaging Biomarkers: A Potential Tool for Cost Savings in Drug How Civil Society Helped Shape Development 57 the Response To Hiv/Aids: The Sheela Agarwal French Experience 22 Jean-François Delfraissy and Anna Laura Ross What Lies Ahead for 2013? 60
reach 64 Interaction Between the European Medicines Agency and HIV Advocates/ China 65 Patients Over the Years 25 5th DIA China Annual Meeting 65 Isabelle Moulon Understanding and Implementing Best Ethics Practices in Clinical Partnering with Community - Research 67 Translation | Back Translation | Desktop Publishing| Independent Review | Editing | Proofreading Could the Past Hold More Promise than the Future? 31 Europe 69 Lew Sibert Report on 25th Annual EuroMeeting, 4-6 March 2013, Amsterdam 69 How Cambodian Sex Workers Helped Change the Rules for Community 2013 EuroMeeting Student Engagement 41 Poster Winners 73 Meg Egan Auderset CORPORATE TRANSLATIONS Driven by Definition ®
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The Global Forum (ISSN: 1944-1991) is a publication of the Drug Information Association. Editorial Office: Drug Information Association (DIA), 800 Enterprise Road, Suite 200, Horsham, PA 19044-3595, USA; phone - 215.442.6100; PUBLISHING fax: 215.442.6199. INFORMATION Copyright © 2012, Drug Information Association.
The Global Forum (ISSN: 1944-1991) is published six times a year, in February, April, June, August, October, and December. Andrzej Czarnecki, MD, PhD, DSc, Periodical postage paid at Horsham, Editor-in-Chief Pennsylvania, and additional mailing offices. Global Forum Staff Thirteen dollars of each member’s annual Judy Connors, Associate Director, membership fee is for a year’s subscription. Editorial Services Prices include postage and are subject to Chris Slawecki, Senior Copywriter change without notice. Notify DIA eight weeks Jenny Kimbel, Senior Editorial Assistant in advance of address change with a copy Joe Krasowski, Sr. Digital Content Strategist of the mailing label. Back issues of most previously published issues are available from DIA. Mission The Global Forum provides a multidisciplinary, PUBLICATIONS MAIL neutral forum for communicating information AGREEMENT NO. 41103506 related to drug development and lifecycle 4 RETURN UNDELIVERABLE CANADIAN management on a global basis. The Global ADDRESSES TO CIRCULATION DEPARTMENT, Forum disseminates content that is relevant to PO BOX 1051, FORT ERIE, ONTARIO L2A 6C7 members’ professional experiences, including Postmaster: Send changes of address to international industry and regulatory updates Global Forum, 800 Enterprise Road, Suite 200,
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Publishing and Subscription: DIA is a neutral organization that does not Drug Information Association (DIA), advocate for or against any issue. The views 800 Enterprise Road expressed by the individual authors or Suite 200, Horsham, PA 19044-3595, USA. interviewees in the Global Forum are theirs and do not necessarily represent the views of the Contact Information Drug Information Association. for Advertising: Mike Boucher Influence Media Director, Client Publishing Services The DIA Global Forum 267-419-8735 CONTENTS
India 76 Gujarat FDCA Signs MOU with DIA 76 Kaushik Desai
The Core Competencies of a Medical Writer: Should a Medical Writer be Medically Qualified? 76 Dr. David Clemow Helle Gawrylewski Dr. Nimita Limaye
Latin America 81 Questions and Answers with Dr. Gustavo Kesselring 81
Japan 83 Clinical Data Management Workshop in Japan 83 Kenji Nagaya
7th Annual Asian New Drug Development Conference 85 Tetsuomi Takano EDUCATE 108 North America 87 EPSA Intern Reflects on DIA 2013 EuroMeeting 109 5 DIA 2013: Alzheimer’s Call to Action 87 Milos Stojkovic Meryl Comer Regulators Meeting the Regulated Engaging the Patient: Birth of the at DIA 2013 92 DIA Patient Engagement Community 111
Marketing Pharmaceuticals 2013 Philanthropy Grant Workshop 95 Recipients Report 114
FDASIA, PDUFA & DIA 96 DIA Celebrates National Volunteer Appreciation Week 116
Exploring Social Me-DIA 98 Association news Courtney Ingram Governance Corner 118 Board Approves Bylaws Amendments at March Meeting 118 Structured Approach to Benefit-Risk 101
Asia Pacific 105 DIA, IFPMA & HSA Singapore Present Asia Regulatory Conference 2013 105 gf GLOBAL FORUM
OPEN FORUM
Recognizing Patients’ Role and Needs and Financing of Innovation
It has been a year since we patients in all activities related published a first interview with a to drug development and patient representative Mary Baker, advice on new pharmaceuticals. the President of the European Regulatory bodies have over time Brain Council (Global Forum 2012, involved representatives from 4, 2, 104). She drew the attention several patients’ organisations in of everyone in the industry, discussions and their decision- 6 regulatory bodies and academia making process, which is to the importance of patients, presented in the Special Section their thinking, involvement and in more detail. Broader patient different perceptions that are not involvement has expanded our frequently, if at all thought about. knowledge and understanding VOL 5 ISSUE 2 of the differences in patients’ Following on the need to improve perceptions of acceptable understanding of patients, in this treatments, risk and benefits. It ANDRZEJ issue the Special Topic section has also provided with different has been edited by Nikos Dedes, directions in drug development CZARNECKI HIV advocate and a member and has enriched it with many of EATG and the Management views of patients, which frequently Board of EMA. Several articles in the past came as a surprise. cover a range of topics on HIV issues presented by patients Having gained different and by regulators on patients’ experiences from patients with involvement in improving research respect to drug development, and regulatory processes. I their needs and thoughts about would like to thank Nikos for this treatment (acceptable risks, important contribution to this convenience of drug use), it has publication. become even clearer that we need to strive to provide innovation for Ten years ago during the them overcoming all difficulties EuroMeeting that I was chairing in research and its financing, but we included a ‘patients’ theme”, also make them available through organised by Yann Le Cam, approval by the HTA assessment a recipient of this year’s ‘DIA in many parts of the world. President’s Award for Outstanding Achievements in World Health’. The cost of innovation limits Ever since, the DIA has had a their number, and the number of much broader involvement of enterprises that can financially support this activity. Few people to pay ‘royalties’ e.g. for 10 outside of the industry realize years to the designer of the that approximately only 30% of innovative product which would Global Forum phase III compounds get to the amount to for instance 5% of market and only approximately their sales of the generic version Editorial Board 20% of those are truly profitable, of a drug. From an objective i.e. provide sufficient income point of view such a decision Andrzej Czarnecki, MD, PhD, DSc to repay development costs, would be justified, as innovative Editor-in-Chief finance further research, and development is very costly and the existence of the originator not extremely successful (as per Richard Chamberlain, PhD company. Looking at these crude statistic above). This solution - ECS, Inc. statistics, targeting the innovative ‘royalties type’- would provide Ronald D. Fitzmartin, PhD, MBA industry to make cheaper drugs additional funds for research in the FDA does not seem to be the only innovative company. Therefore, appropriate solution. Despite investment into a new generation Alberto Grignolo, PhD this, recently GSK indicated that of medicines so crucial for PAREXEL the cost of development will be patients would not have to come falling and the achieved saving from future sales of only a few Justina A. Molzon, MS Pharm, JD can and will be passed on to the drugs but would be co-paid from CDER, FDA health services. In addition to ‘royalties’ coming from intellectual industry improvements, there is property of the past years. In other Sarah Powell certainly an important role of the words, the substantial losses from Thomson Reuters regulators across the world to failed clinical development to be 7 be considered and delivered to absorbed by the company would Nancy D. Smith, PhD facilitate new drug treatments. not have to be paid for by new Potomac, MD I am convinced that there are products only. Such a solution Jean H. Soul-Lawton, DPhil many options debated in various would help to lower the prices countries. To add to those, I of the final 6% of phase III truly GlaxoSmithKline have decided to share some of successful products as they would Veronica Todaro my personal thoughts on what not have to cover all costs of Parkinson’s Disease Foundation we could change to achieve the successful or failed development, access to innovative medicines in addition to future research. J. Rick Turner, PhD at an acceptable price to all who Quintiles need them. From the generic companies’ perspective, they should Imagine that a new medicine not complain if such legal is being treated similar to an arrangements were to come into innovative piece of music. Last force (I know they would) as their year’s modification of the law profit is based entirely on others’ special role for the regulators, extended ‘patent protection’ for investment in R&D - innovation to strive to facilitate new approaches a piece of music to 75 years, which the generic industry does to support innovation and the which means that royalties have not contribute. A payment of 5% requirements of HTA bodies to be paid for using it over that of ‘royalties’ to the innovator is not to make them available. Many period of time. Imagine, therefore, a huge price for companies that concepts could help including the that the current 20 years (since always seem to have sufficient view presented above, provided being granted) patent protection funding to challenge patents in the appropriate legal framework for a new chemical entity that very expensive legal suits once is created. There may be other may become a medicine, which the brand product becomes a solutions to support future public usually translates into 8-12 years success. health and all of them should be of drug sales, would be modified. considered. We need to find them, The current financial constrains Such modification, after the decide quickly and implement. patent has expired, would legally felt in many parts of the world bind any generic manufacturer require that everyone, with a gf GLOBAL FORUM
PRESIDENT’S MESSAGE
Reflections from Europe’s Horizons
I have just returned from I invite you to enjoy the reports participating in Board meetings from our EuroMeeting in this and all the education and issue, and to join me in thanking networking which surrounded our our volunteer network and staff in celebratory 25th EuroMeeting: Europe. Gratitude for organizing Amsterdam 2013 in March. While and presenting such an exemplary this year’s EuroMeeting was held event goes to our Program Chairs earlier than usual, the weather Beatriz Vicén Banzo (Head of allowed for lovely walks to and Regulatory Affairs, Bayer Hispania, 8 from the convention center and S.L., Spain) and Peter Bachman the charming city and its residents (Senior Expert, European Drug welcomed DIA meeting attendees and International Affairs, BfArM, with all the warmth for which Germany. Jytte Lyngvig, our new the Dutch are known. Looking European Director, insightfully VOL 5 ISSUE 2 forward, we will soon have our noted that our EuroMeeting was 5th China Annual Meeting in first presented in Amsterdam 25 Beijing in May; and I will soon years ago to share knowledge and Ling SU begin to plan my travel to our facilitate dialogue and that, while President, DIA DIA 2013 49th Annual Meeting: communication technology since Board of Directors Advancing Therapeutic Innovation then has greatly changed the way and Regulatory Science in Boston in which we do those things, our this June, where we will kick off communal imperative to do them the celebration around DIA’s 50th basically remains unchanged. anniversary in 2014 and our new journal, Therapeutic Innovation I also wish to thank Nikos & Regulatory Science, will be Dedes who served as Special showcased. Section Editor for this issue’s retrospective series of articles that looks back across thirty years of AIDS scientific advancement and the vital, profound role than a relentless patient community and its activism played in these developments and helped to frame and model the empowerment of many patient groups since then. DIA endeavors to include the patients’ voice in Horizon Three is even more every aspect of our initiatives, expansive and visionary – and and this issue also announces challenging. In this horizon’s the recent launch of our new DIA framework, DIA will pilot new Patient Engagement Community channels, based on strategic and whose articles and initiatives will business intelligence gathered remind us of the power of the through ongoing assessments, to patients’ voice. meet the long-term goals of an organization that is simultaneously I was honored to speak about strong in each region, and yet DIA during the EuroMeeting’s operates within one unified and welcoming plenary session and truly global vision. share, on behalf of the Board of Directors, DIA’s strategic All of DIA continues to work positioning for the future, which toward this shared global vision we finalized during our scenario as our Executive Committee and planning exercise at our 2012 other Board Committees, our Board of Directors meeting in Global Management Team and Beijing. This strategic planning other association leadership looks frames DIA’s future in Three toward identifying candidates with Horizons: the appropriate expertise and 9 wisdom to help lead DIA as our In Horizon One, DIA continues to Executive Director. develop and enhance successful activities to ensure their value We look forward to the challenges is optimized, while eliminating and ahead and invite you to join initiatives that have not added us as we refine, modify and grow value and shifting their resources DIA. Be assured, we will keep you to the successful ones, thus updated through this publication creating a cycle of continual and our website as we move refinement and improvement. forward in this quest. Thank you for all your continued support of Horizon Two raises our vision to our organization. look more forward: Identifying goals to be accomplished within a three to six year timeframe and the processes which must be established to accomplish them. In this Horizon, DIA prudently modifies current structures to ensure our business model is built for long-term sustainability, growth, and relevance both to our stakeholders and the marketplace. ggff INFORMINFORMTOGETHER, wE CAN CHANGE THE wORLd * ART As ACTIVIsm * ORGs wE LOVE TO sUppORT Aids Retrospective LEARNLEARN FIGHT LOVE from a Patient FIGHT Advocacy Perspective LOVE
INFORM now houses the Special
UNLEAsHING THE pOwER OF peter staley p HOTO: © w illiam Lucas Acts Up HOw TOSections: sURVIVE A pLAGUE Devised to educate alker
and update you on advances in a
specific area of research, drugs,
diagnostics or devices. Of DNA, HIV, Advocacy, Humanity, Therapeutic Innovation and Regulatory Science
February 2013 marks the 60th anniversary of the announcement of the structure of DNA by Watson and Crick. Our understanding of the basis of heredity and of biology as a whole would forever be changed. In 1981, only 28 years after that landmark, reports of a new type of
Stephen P. “acquired immune deficiency” emerged. The scientific and Spielberg social responses to the new epidemic continue to evolve, and the lessons learned in both spheres have impacted Editor-in-Chief, 11 TIRS the discovery, development, and evaluation of therapeutic interventions for all human disease.
The first lesson of the AIDS only possible in the context of the epidemic is the recognition science developed from 1953 to that advocacy for cures in the 1981 to figure out that we were absence of sufficient scientific facing a retrovirus. Yet with that understanding of a disease recognition and understanding process can be futile and even of the biology of these agents, counterproductive. Imagine defining the cause of the disease that the AIDS epidemic began in rapidly led to translation of that 1951. We lacked knowledge of knowledge into a potential drug molecular biology, DNA and RNA target- reverse transcriptase. function, retroviruses. Contrast While we look back as though the this to leprosy, clinically described rest was scientifically obvious, thousands of years ago, attributed both defining the organism and to a variety of causes based on target were unimaginable only superstition and prejudice until we 30 years prior. Thus, the basic began understanding infectious science of the mid-20th century disease. The organism was primed the pump to move from discovered barely a hundred years disease recognition to potential ago, and no useful intervention drug targets (including multiple was developed until much later. targets – including reverse Even in 1981, at the outset of the transcriptase, protease, integrase AIDS epidemic, the etiology and to address the emergence of pathogenesis were obscure; was resistance), to multiple effective the syndrome caused by a toxin therapies in less than a decade. or by an infectious agent? It was gf GLOBAL FORUM | INFORM
With crucial basic science and experience represents a human and ethically driven stance on technology in place, the process triumph beyond reckoning only a behalf of prevention, talking of translation and conversion very few years ago. The number forthrightly about sex education of knowledge into therapies of heroes in this story is too and condoms. Equally critical was driven pivotally by patient numerous to count, but we should was his stance on behalf of advocacy. The perspective of step back and celebrate just how the fundamental humanity of patients, organized advocacy remarkable an achievement this all afflicted by the disease, for science, and for the rapid is in our history. It also represents regardless of the origins of their development of medical products, a fundamental shift in our view of disease. He lived his view that set the stage for a change in how science can be translated, he was Surgeon General for all pharmaceutical and regulatory and how drug development and people in need. Contrast again science. Open discourse of regulatory science and practice the stigmatization and isolation benefit-risk for a fatal condition can be aligned in real time. As of those afflicted by leprosy for without therapy at the outset, of scientific insight in human biology so many centuries. So, too, with rapid validation of biomarkers that changes ever more rapidly, it AIDS, so many patients were (and could serve as early indications challenges us all to assure that continue to be) stigmatized and of efficacy, and accelerated, but therapeutic innovation is matched shunned internationally. We often scientifically rigorous, approaches by regulatory innovation. The lack the courage that Dr. Koop to approval of drugs all benefitted good news is that the better had in framing the discussion. from strong interaction with the the science, the more open There are so many throughout the advocacy community, physicians, and collaborative the scientific world still becoming infected, and drug companies, and the environment, the more confident still untreated for AIDS. One of 12 regulatory community. Recognition we can be in advancing regulatory the miracles of the HIV epidemic of rapid emergence of resistance science. The recent development has been prevention of “vertical drove increasing basic and of a drug targeted against transmission” of the disease from applied science to seek different one mutation responsible for mothers to infants by HIV drugs, targets and drug combinations. cystic fibrosis, the basic and nearly wiping out neonatal AIDS VOL 5 ISSUE 2 As compounds that prolonged life translational science driven by in the US. Yet in so much of the became available, the advocacy patient advocacy, the clinical world, despite knowing how to community wisely began trials optimized by detailed prevent the disease, the epidemic emphasizing the need for greater understanding the disease, continues, and babies continue consideration of the quality of its pathogenesis, and clinical to be born with a preventable life, number of medicines and outcomes owes so much to our disease. regimens, and decreased side experience with HIV. Reviewed effects. New drugs and regimens and approved in barely 3 months The AIDS epidemic has been were developed in time frames at FDA (following a discovery and crucial in driving a new era not before thought possible. development program of barely 6 of therapeutic innovation Strikingly, while some of those years), the primacy of outstanding and regulatory science. That medicines have been supplanted basic, translational, and regulatory innovation will yield therapeutic by newer, more effective and less science has been validated yet interventions beyond our current toxic drugs, none were withdrawn. again. imagination. The final translation of Biomarkers were validated for our science into maximum health patient relevant outcomes, A final thought – recently, Dr. and wellbeing for all requires a and new models for scientific C. Everett Koop died at the new level of commitment and translation were defined. age of 96. He became Surgeon courage; we struggle yet to align General of the US at the outset basic, translational, and regulatory None of this happened without of the AIDS epidemic. Based on science together with social false starts, without examples medical and epidemiologic data, systems recognizing, respecting, of scientific hubris, without it quickly became apparent that and celebrating the humanity in considered suffering and pain; the disease could be sexually us all. this was a complex human transmitted. Even before medical undertaking with all the foibles interventions were available, Dr. of the human condition. Yet, the Koop took a strong, scientifically ACT UP Crashes the Gates
Jim Eigo Author, Activist, Patient 13
By the time I attended my first human immunodeficiency virus, meeting of ACT UP New York the causative agent of AIDS, and in the fall of 1987, AIDS had the infections and cancers that been ravaging New York City’s preyed on people with wasted gay community for six years. At immune systems. first scores, then hundreds and now thousands of gay men were But that was a few years away. falling ill to a range of strange New York’s gay community had infections and disfiguring cancers. already built and staffed the basic Almost without exception these service organizations that were men died. The AIDS Coalition caring for our sick. But ACT UP to Unleash Power would be the insisted there was a political first AIDS group to muscle its dimension to the AIDS crisis. way into the clinical research America could ignore the dying, establishment’s halls of power. and the many more that were We would eventually take seats not yet sick but infected with on the committees making the HIV, because the worst of the basic decisions about testing destruction was occurring among and approving drugs to fight the gay men and intravenous drug users, groups that the mainstream barely tolerated. Until our community engaged the politics surrounding AIDS, today’s crisis would only worsen. We would gf GLOBAL FORUM | INFORM
have to, through non-violent direct action, force the powers-that-be to take us and our dying seriously.
For my first weekly ACT UP meeting about a hundred people had gathered at the Gay & Lesbian Community Services Center in New York’s West Village, the oldest gay- identified neighborhood in the US. (Membership would soon explode.) As soon as I walked through the doors, I knew I’d found my first true home since AIDS began to kill my kind. The air in the room crackled with the charge of unswervable purpose. One after another, rank-and- file community members—gay Author Jim Eigo questioning ACTG PI, Tom Merrigan, from the floor of a plenary session of the June 1989 guys and our allies—grabbed International AIDS Conference in Montreal. This photo was shot by a treatment activist, Kevin Smith, who the mike to report on what his later died of AIDS; the shot was exhibited in NYC at the Whitney Biennial in the early 1990s. 14 or her working group had done that week to fight the disease we would accomplish little more Committee and Latino Caucus and the companion epidemics of than burying our dead. If we rose would do life-saving work in ignorance and discrimination. together—so many of us men communities of color even as they who’d been told our whole lives alerted the mainstream to societal
VOL 5 ISSUE 2 I would experience that electric we were sissies—we just might inequities that were fueling the charge week after week over become a fist big enough to epidemic. The range of ages in the next five years that I was an demand attention. the room was startling for a gay- active ACT UP member. It’s what centered group. I was 36, several galvanized more and more people ACT UP was an unlikely collection years older than ACT UP’s median to come back week after week, of individuals. Nothing but AIDS age. Cute college-age guys stood even when their lovers were sick, could have drawn us together. I’m in a row against the back wall at even when they themselves were a gay guy, like most who attended Monday night meetings—we’d call sick, and it kept a lover coming my first meeting. Some had AIDS; them “the swim team.” ACT UP back even after his lover had some carried the HIV virus but drew on their youth and vigor, but died. We worked without pay or were not yet sick. Some of us drew as well on the expertise of guarantee that our best efforts were HIV-negative; many more older members, schooled in the would make the least dent in were unsure. A good quarter of Gay Liberation groups that sprung the enormity that was AIDS in the room were women; some but up in the wake of the Stonewall 1987. But we knew that as long not all were gay. The women of Riots of 1969 and helped forge as we let this beast of a plague ACT UP, in the work they did in modern Gay America. ACT UP keep us alone and frightened the organization and in a series of also harbored veterans of the campaigns that focused on AIDS civil rights, anti-war and women’s and women, would change the movements. Across the divides course of the epidemic. Most in of health, serostatus, sexual the room that night were white, preference, gender, race and but ACT UP’s Majority Action age, in the unpitying heat of the epidemic, the people in that room could forge uncommonly enduring bonds. That first meeting Iris Long spoke. AIDS treatment effort, including for pneumonia, threatened with Iris was a doctor of chemistry. data on local hospitals that were expulsion from the trial unless Before retiring in middle age conducting AIDS-related clinical he abandoned his painkiller, and to Queens, New York, with her trials under the National Institutes promised that, once the trial was husband, she’d worked for the of Health’s umbrella, the AIDS over, he’d receive AZT should it drug giant Burroughs-Wellcome. Clinical Trials Group—an effort prove effective. This promise was Iris’s message that night—that that had largely stalled because broken when the narrow post-trial ACT UP had to tackle the federal patients, despite the need, were treatment protocol deemed John drug bureaucracy if we wanted staying away in droves. But my too sick to take the drug! John’s effective AIDS treatments—wasn’t major teacher was Iris, a stubborn example taught us a lot of what very well heard. She was not a woman of boundless generosity. we needed to know about current cute young guy; the audience of The epidemic of death she saw AIDS clinical research. gay activists did not naturally snap on TV had driven her to find to attention when she opened people she could help. All that By the end of January 1988, Iris, her mouth. And the specifics of was important to Iris was the Garry Kleinman and I had written what she was saying—clinical work, important because it had a comprehensive critique of that trials, IRBs, placebos—seemed the potential to relieve misery research effort. After presenting it arcane, scientific, distant from the and save lives. Less loftily, Iris to AIDS researchers at New York epidemic we knew. Vito Russo had two types of knowledge University, we revised it and sent took the microphone from Iris. that the first generation of AIDS it in early spring to everyone in Few members of New York’s gay treatment activists needed in the AIDS research and regulatory community were more respected order to understand AIDS drug establishments for whom we than Vito, a veteran of the early development. She knew the could find an address. We asked 15 Gay Activists Alliance and author chemistry of drugs and she knew them why almost all of the ACTG of The Celluloid Closet, one of gay the regulatory maze a drug had to trials were tinkering with the toxic, history’s indispensible books. Vito negotiate to secure approval by already approved therapy, AZT. chided the general membership the Food & Drug Administration Why were the trials for AZT’s for not paying closer attention for therapeutic use. cousin drugs stalled? HIV was to Iris: he said the work she a complex virus that presented was trying to initiate had more AIDS activists already had the many potential vulnerable points. potential to change the epidemic third type of knowledge we’d Where was the new generation than anything else ACT UP was need to become experts in the of AIDS drugs that would target doing. That’s when it clicked in my world of AIDS clinical research. them? And where were the head. I’d known from the moment Being of the community, we trials to test treatments for the I walked into the meeting that I’d knew what drugs people with infections and cancers that were be working with ACT UP. I was a AIDS were taking, the medical killing people with AIDS? quick study, a writer with a knack conditions they were suffering A lot of the ACT UP critique took for making a case out of a lot of from, the reasons they were aim at drug regulation. It was loose facts. Iris Long, I flattered refusing to enroll in clinical trials taking seven years or more to myself, could use someone like even though the only approved approve a drug for use in the US; me. treatment, AZT, was too toxic or ineffective for fully half of people Use me she did. I approached with AIDS. In the original phase Iris after the meeting and within a 2 study of AZT, ACT UP’s John week we’d produced the first of a Bohne had been put on placebo, stream of papers we’d co-author taken off preventive treatment for ACT UP. I started as her guy Friday, editor, mouthpiece. To get up to speed, I read everything that David Kirschenbaum, ACT UP’s one-man data-gathering effort, had compiled on the government gf GLOBAL FORUM | INFORM
people with AIDS were living less require drug sponsors to continue Iris, Garry, David and I, along than two years after diagnosis. clinical research—into things like with David Barr, a lawyer from Because so many of them dosing, common drug interactions the Lambda Legal Defense Fund, had exhausted AZT or found it and how to use a drug in all presented ACT UP’s critique of intolerable, much of the treatment populations—even after a drug the AIDS treatment bureaucracy for AIDS and its related conditions secured FDA approval. in teach-ins in the spring and would be, for the foreseeable summer of 1988. ACT UP member future, experimental. (Standard- If the clinical trials establishment Mark Harrington volunteered to of-care therapy for AIDS-related wanted to protect the integrity write a detailed glossary of terms retinitis and prophylaxis for of AIDS drug trials, it would for us to pass out at these events; AIDS-related pneumonia were still have to come up with a way to soon he was making presentations officially “experimental.”) The two provide a study drug outside the himself. By the fall of 1988, ways to get a drug before FDA drug’s trials to people who had ACT UP was ready to make approval were to join a clinical trial no treatment options and whose these demands in person: more or obtain it through “extraordinary health put them beyond the trials’ than a thousand AIDS activists release.” The ACT UP critique criteria. “Extraordinary release” from around the country, after a called for speeding up trials by shouldn’t be so extraordinary. For weekend of activity in Washington, consolidating the more traditional every drug in safety trials, ACT DC, took over the FDA for a day three phases into two. Trials would UP suggested “a parallel trial for of dramatic direct action. All accrue more quickly if designed that segment of the population of ACT UP’s future success in to accommodate the lives of real eliminated from the trial,” that securing reform of the way AIDS people with AIDS—they’d also be could also collect supplementary drugs were tested and approved 16 likelier to produce usable, real- data on the study drug. We builds on that day’s bedrock. The world data. For trial participants, demanded the speedy publication federal healthcare bureaucracy trials were healthcare. They could of data from government-funded could see at close range how ACT no longer require patients to trials, even “failed” trials, and UP was a widespread grassroots abandon common prophylaxes opposed licensing a drug to movement of people with AIDS VOL 5 ISSUE 2 for AIDS-related infections, and a single company if its clinical and their allies: We were not a few they’d have to eliminate placebos research had been paid for by lone critical voices. ACT UP could wherever possible, measuring trial the government. A drug company without much trouble deliver a drugs instead against approved that had a license to a drug as thousand bodies several hundred therapy. The clinical research a result of government-funded miles from home. establishment would have to trials should have to open its do the real work of conducting books to defend its pricing. Finally, Though the FDA heard us that trials in populations that were we called for the involvement day, it didn’t listen so well. A startlingly underrepresented in of people with AIDS and their month after ACT UP’s siege, FDA AIDS clinical trials: people of color, advocates in all phases of drug announced a new set of protocols women, IV drug users, children. development, from ACTG planning for DHPG (gancyclovir). This Faster drug approval would committees to the Institutional drug had been in use for years to Review Boards at local research treat AIDS-related CMV retinitis facilities. And we asked FDA without yet gaining FDA approval. to recognize valid community- A new clinical trial, ACTG 071, generated research conducted would randomize participants to at a burgeoning network of immediate treatment or delayed community-based facilities. treatment, a time-limited placebo, despite defining the retinitis as “severe, progressive, sight- threatening.” This trial banned concomitant use of many drugs, including AZT, as did the other new “open label” and “treatment” protocols. For activists, these protocols forced patients to into the drug’s ongoing trials for who himself had CMV retinitis) choose between sight and life— treating CMV colitis. Denying challenged Dr. Anthony Fauci, unless randomized to delayed one group access to a drug head of the NIH AIDS Program, on treatment, in which case they because researchers want to the new DHPG protocols, Fauci might have to sacrifice both. test it in another group seemed said he disagreed with FDA’s inhumane, and an admission by requirement for further efficacy Activists were angry that DHPG the regulators that the research data: There was enough already had not secured approval for establishment had failed to create to grant full marketing approval. treating CMV retinitis the year a clinical trials program that even AIDS activists used this public before when FDA had looked at a fraction of people with AIDS declaration (not the last time we’d the existing data in support of would consider entering. play the federal research and the drug. That data came from a regulatory wings against each compassionate use protocol— The activist response to the other). On February 2, a busload doctors collecting it from patients new DHPG protocols provided of angry ACT UP members treated privately and in clinics— a successful template for future confronted Dr. Ellen Cooper, that had been in place since AIDS treatment campaigns. David Director of FDA’s Division of Anti- 1984. The drug sponsor, Syntex Kirschenbaum had the protocols Viral Products, as she delivered Corporation, provided the drug to before the ink was dry, so that I a speech in Bethesda, MD— about 6000 immunocompromised could write a paper (one sheet, then several activists marched people with severe CMV infection, two sides) for quick distribution cross-town to the campus of most of them people with AIDS, within ACT UP that skewered both NIH, met Dr. Fauci and secured most with retinitis. The two FDA and NIH and made concrete a promise from him to press members of FDA’s Anti-Infective demands of each. Activists met FDA to reconsider available data 17 Drugs Advisory Committee who with other community groups immediately. were ophthalmologists voted to to explain what was going approve the drug. But FDA sided on and why it mattered. We with the majority who voted to recruited frontline AIDS doctors reject the application, despite the and ophthalmologists, men and evidence showing that more than women with medical knowledge 80% of patients with CMV retinitis and practical savvy in treating had significant improvement or AIDS, to agitate in favor of ACT stabilization in their condition after UP’s position. Members of ACT two weeks of treatment. More UP argued the activist case than 90% of untreated patients against the new protocols in progressed to blindness— meetings with officials at FDA and who comprised in effect the NIH; we were told in return that compassionate use protocol’s the clinical trials establishment “historic” control group. considered the new protocols to be “state-of-the art.” These retrospective data were gathered from several hundred In January 1989, when San patients; many thousands more Francisco AIDS activists (among had been treated in the US and them the late Terry Sutton abroad. No committee member convincingly questioned DHPG’s efficacy; it had become standard- of-care. But several voiced concerns about voting to approve a drug without clinical trial data. One member speculated that the drug’s approval for retinitis Author, Jim Eigo, at a printing press would interfere with accrual gf GLOBAL FORUM | INFORM
In a few weeks, FDA AIDS clinical research to the same Conference in a couple of weeks. Commissioner Frank Young committee Ellen Cooper had been announced that in May an addressing when we zapped her In June 1989, ACT UP sent Advisory Committee would two months before, the National hundreds of AIDS activists up to reconvene to reconsider the Committee to Review Current Montreal by car, bus, train and DHPG data, and that people with Procedures for Approval of New plane. Many more fellow activists peripheral retinitis could begin to Drugs for Cancer and AIDS. Sam came from around the world. receive DHPG outside the clinical Broder, who’d discovered that Here ACT UP achieved the status trial. Both were unprecedented AZT and its cousin drugs had anti- of an international movement. concessions to activists’ HIV potential, was in attendance From opening to closing plenary demands. ACT UP secured a and let it be known (we were later session, activists dominated. promise from the New York Civil told) that he agreed with a lot of AIDS research could no longer Liberties Union: It would sue the what the AIDS activists said. Also be conducted in a bubble. ACT FDA should it fail to reverse its present, NCI’s chief biostatistician, UP presented its first Treatment stand at the May meeting—at Dave Byar, living with AIDS Agenda, a broad vision of how which ACT UP showed up again himself, resolved to seek out AIDS research in the US might in force. In prepared remarks the activists and coach them in look if community members Garry Kleinman delivered the ACT the basic statistics they’d need helped shape it. Our agenda won UP position. Several community as they pushed deeper into the over several scientists involved members spoke in support of clinical trials establishment. in the NIH research effort. Mark the drug’s approval. So did three Harrington’s proposals for poster community doctors, who reported Meanwhile, in his public papers had secured several 18 that their CMV patients on DHPG appearances Dr. Fauci was slots for ACT UP. One paper I were living longer than other CMV beginning to float a plan for a presented was retrospective, patients. A year-and-a-half after “parallel track” for experimental looking back on the activists’ role its last hearing, FDA had more AIDS drugs. To ACT UP’s in the recent approval of DHPG; of the same sort of data it had treatment activists this sounded the other was prospective, looking VOL 5 ISSUE 2 before. The general profile of the suspiciously like our old plan for ahead to how a parallel track for drug was much the same: Toxic, parallel trials. When Fauci and AIDS drugs could benefit people unwieldy but beneficial in treating his colleague Dan Hoth, head with no treatment options even the vast majority of patients. In of the ACTG, came to New as it advanced research. After a addition to “response to therapy,” York to address local healthcare raucous plenary session, Ellen FDA could now measure “time professionals, he again invoked Cooper, under questioning, to retinitis progression” as well. parallel track. I raised my hand, voiced tentative support for a All agreed that ACTG 071 was expressed interest in the notion, parallel track to supplement a brightly designed failure: No and then filled the empty name phase 2 efficacy trials. At another patients wanted to enroll. So with the specifics of ACT UP’s session I grilled ACTG researcher the Committee voted (with one formulation of parallel trials. Once Tom Merigan. Two years after abstention) to advise approval of an AIDS drug entered phase the discovery that the drug ddI, the application to market DHPG to 2 efficacy trials, it should be AZT’s less toxic cousin, showed treat CMV retinitis. available in studies with loose potential against HIV, it had yet to criteria so that any person with move beyond his tiny phase one On that very same day, cross- AIDS who had no viable treatment safety trial. “Why?” I wondered. I town in Bethesda at the National option could enroll. From such got no satisfactory answer, but I’d Cancer Institute, Iris Long, Mark studies researchers might capture fingered the obvious candidate to Harrington and I were delivering broad, real-world data about the initiate a parallel track. the broader ACT UP critique of drug in use in various populations. Fauci and Hoth nodded and That summer the notion of a grinned. Now I knew what I’d be parallel track for AIDS drugs doing at the International AIDS snowballed. ACT UP met with FDA and NIH officials, at their respective headquarters outside Washington, DC, and in New the drug works in people too the Committee voted to endorse York City at a conference on sick for the clinical trials. By a parallel track, it was ACT UP’s community-based AIDS research doing good—helping people in vision of it. It all had gone so organized by ACT UP members need with a drug that was now fast. Terry Beirn, of AmFAR and Debra Levine and Mark Harrington their best hope—Bristol-Myers Senator Ted Kennedy’s office, for the American Foundation for could do well, winning the AIDS claimed it was unprecedented. AIDS Research. At these meetings community’s good will, spreading I was named to a committee ACT UP pushed our ideas about word about the drug. I found of the National AIDS Program parallel track and the wider ACT the company’s representatives Office—along with representatives UP Treatment Agenda. Officials impossible to read as we made from FDA, NIH, the healthcare briefed us on the ongoing design our case. I left the meeting fearing bureaucracy, drug companies, a of phase 2 efficacy trials for ddI: we’d failed. But within a few days few community groups—to draw now more than ever ddI seemed the company informed officials at up regulations for parallel track, the right drug for a prototype of FDA that it would make its drug officially renamed expanded parallel track. available in an expanded access access. Our work was shaped by program, parallel to the drug’s real world experience: In October, In July a delegation of ACT UP’s phase 2 efficacy trials. Which of ddI went into phase 2 trials and treatment activists met with our arguments carried the day? expanded access. Before the representatives of Bristol-Myers Was the company concerned end of the year, the end of a very to talk about making its drug, ddI, about a direct action backlash rough decade, our committee had available on a compassionate unless it cooperated? Perhaps drafted the regulations. They’d sit use basis, a test run for a parallel the company had its own dark around for several months before track. This program would enroll purpose. I never learned. publication without significant 19 people with AIDS who were not change. eligible for ddI’s phase 2 trials At the end of July, I testified and for whom AZT was too toxic before a subcommittee of Before the end of the year we also or ineffective. We’d secured Congress about a parallel track had an agreement with Fauci and the support of FDA and NIH for for AIDS drugs, with west coast Hoth on another ACT UP demand: our version of a parallel track. AIDS activist Marty Delaney and That people with AIDS and their How could we win over the drug a panel of the biggest names in advocates sit on ACTG planning company that would be doling out federal AIDS policy, Jim Mason committees. The deal would free drugs to several hundreds of of the National AIDS Program fall through when some ACTG people for who knew how long? Office, Frank Young, Tony Fauci investigators opposed the move. We could always appeal to a and Sam Broder. All of our stars It would take another major ACT public official to act in the public aligned. Several days later in New UP demonstration, this time on good. What could we say to a York City, I joined community the suburban Maryland campus for-profit company? That morning AIDS doctors and representatives of NIH, to secure this particular in the law offices of Arthur Kramer, from Bristol-Myers, FDA, NIH and victory. But by June 1990, the brother of ACT UP’s godfather, community groups to hammer doors to the ACTG’s quarterly Larry Kramer, the ACT UP out criteria for the ddI expanded meetings were officially open to delegation said: a parallel track will access program. On August 17, AIDS activists—before that we’d be good for Bristol-Myers. It will before an Advisory Committee had to crash them. Individual take pressure off the clinical trials. of FDA, I presented the ACT UP activists assumed committee People desperate for the drug but version of a parallel track for posts. ddI would secure approval ill-suited to the trials’ selection AIDS drugs. ACT UP members criteria will have an approved filled the room. No other speaker source for the drug. Parallel track offered a detailed program, or could supply supplemental data spoke against ours, so that when about ddI’s potential interactions with the many drugs that people with AIDS take for their many medical conditions and how 20 VOL 5 ISSUE 2 who were sickanddying,was safe, effective treatment forthose smart, andourcause,providing on treatment issueswere pretty women ofACTUPwhoworked homosexual. Themenand establishment were identifiably the gatesofAIDSresearch a lotofuswhocrashedthrough full-blown fairytale—eventhough A happyending?Thisisnota somewhat manageableone. transfigure adeadlydiseaseinto AIDS drugsthatwouldbeginto would makeupthecocktailof analogs (AZTanditscousins) the muchmalignednucleoside quickly aswell.Thosedrugsplus trials, itwouldgetusthosedrugs AIDS drugwentintoclinical new generationofmore powerful but, inafewyearstime,when a lotofmediocre AIDSdrugsfast, new regulatory frameworkgotus were official regulatory policy. The “expanded access,”thesenow of “expeditedapproval” and Translated intothereforms had nobettertreatment options. ineligible fortheefficacy trialsand available topatientswhowere they’d finishedtheirsafetytrials, would makethosedrugs,once AIDS drugsandaprogram that for quicker, consolidatedtrialsof clinical research hadbeencalls ACT UP’s originalcritiqueofAIDS Two oftheprincipalplanks they hadto. patients couldjuggledrugsas toxicities sothatmore and more effective, theyallhaddifferent drugs soonfollowed.Onlymildly trials; severalofAZT’s cousin years afterthestartofphase2 the nextyear, lessthantwo g g f f GLOBAL FORUM|INFORM to theAIDScrisis. its beginning,toputatlastanend carry outthemissionitstatedat much smaller, goeson,workingto treatments. SoACTUPNewYork, worked tosecure donotgetthose the treatments thatAIDSactivists people thatcouldbenefitfrom delivery systems,halfofthe gaps intheworld’s healthcare BecauseofOf mostconcern: Europe are againontherise. rates intheUSandacross to useitthatHIVtransmission little lovedbythemenweexpect of thedisease,condom,isso have againstthesexualspread one fairlyeffective weaponwe no cure, stillnovaccine,andthe a fullgenerationlaterthere isstill realm oftreatments andinothers, of ACTUP’s successes,inthe the numbersittouches.Forall into existence,butfarwiderin ago whenACTUPfirstsprung less ferocious thanitwas26years That epidemiccontinuestoday, would decimateus. epidemic that,leftunchecked, on thelinetoputanend members ready toputtheir bodies through nonviolentdirect action, to fightingAIDSonseveralfronts organization thatwasdedicated various, grassroots community embedded withinalarge,vibrant, only advancebecauseitwas ACT UP’s treatment agendacould high ground onlygetyou sofar. just. Butbrainsandthemoral “United inAnger.” to SurviveaPlague”and recent documentaries,“How That workisprofiled intwo treatments tomanypeople. that havehelpedbringmany proval andexpandedaccess, regulation, expeditedap- two reforms ofAIDSdrug City. Heisanarchitect of activist livinginNewYork Jim EigoisawriterandAIDS TOGETHER, wE CAN CHANGE THE wORLd * ART As ACTIVIsm * ORGs wE LOVE TO sUppORT
HOW TO SURVIVE A PLAGUE HOW TO SURVIVE A PLAGUE is a 2012 LEARNLEARN FIGHT LOVE American documentary film about the early years of the AIDS epidemic and is the story of two FIGHT coalitions—ACT UP and TAG (Treatment Action Group)—whose activism and innovation turned AIDS from a death sentence into a manageable LOVE condition. Faced with their own mortality an improbable group of young people, many of them HIV-positive young men, broke the mold as radical warriors taking on Washington and the medical establishment. Despite having no scientific training, these self-made activists infiltrated the pharmaceutical industry and helped identify promising new drugs, moving them from experimental trials to patients in record time. With
unfettered access to a treasure trove of never- UNLEAsHING THE pOwER OF peter staley p HOTO: © w illiam Lucas Acts Up before-seen archival footage from the 1980s and HOw TO sURVIVE A pLAGUE ‘90s, filmmaker David France puts the viewer alker smack in the middle of the controversial actions, 21 the heated meetings, the heartbreaking failures, and the exultant breakthroughs of heroes in the making. “Served powerfully, with minimal Winner of Sundance film festival and an Academy Award nominee for Best Documentary Feature. adornment... A moving and Available in DVD at Amazon, iTunes, Google Play, meticulous documentary about and NETFLIX. AIDS activism in the late ‘80s and Information found at surviveaplague.com/ and en.wikipedia.org/wiki/How_to_Survive_a_Plague early ‘90s” -A.O. Scott, The New York Times
“…An epic celebration of heroism and tenacity, and less directly, a useful template for any fledgling activist movement, demonstrating the effectiveness of inside/outside strategy.” -David Rooney, The Hollywood Reporter
This photo is a shot of activist Jim Eigo that director David France took during the editing of the film. gf GLOBAL FORUM | INFORM
How Civil Society Helped Shape the Response To Hiv/Aids: The French Experience
Jean- François Delfraissy 22
Virus cells in blood VOL 5 ISSUE 2
The initial years of the HIV/AIDS In parallel, and with a rapid epidemic were dark and difficult reaction, knowledgeable and Anna Laura years for all. Following the first educated activists organised Ross reports in 1981 in the United themselves to create one of States, very rapidly in France, the most important civil society clinicians were also reporting responses to any given disease. cases of AIDS and by the end In the mid-eighties in France, of 1981, more than 10 patients communities of gay men rapidly had been diagnosed with AIDS. followed in the footsteps of their Scientists and physicians were American peers to form one of the struggling to gain insight into the strongest civil society responses terrible disease which had such to HIV/AIDS in Europe. a shockingly dramatic health impact. The dialogue between HIV activists, civil society organisations and health care professionals was initially stilted. The medical community was confronted with a devastating unknown disease and it was ill-prepared for the shocking emergence of HIV/AIDS. In parallel, clinicians were confronted for the first time with a group of educated activists demanding those permitting pre-market ties between the ANRS and the to be informed and to actively approval for compassionate civil society and community- participate in the response to the use for some HIV drugs (also based associations became overwhelming disease. At the known as expanded access stronger over time, leading to time, diagnosis of HIV infection programmes). At the time, a close present collaboration. was often only confirmed at a late the FDA (Food and Drug As one of the first steps in the stage of the disease, but many Administration) in the United interactions, ANRS led specific infected men still had sufficient States had granted expanded training sessions on HIV/AIDS strength and determination to fight access to make promising research open to members of for themselves and their friends. experimental antiretroviral drugs the community and civil society. However, many clinicians felt that available to patients who were Secondly, it was essential to their medical authority was being severely sick and with no other include patient association challenged and openly questioned viable treatment option. The first representatives in the various the right of activists to interfere antiretroviral drug to show efficacy committees of the ANRS: The with the purely scientific and in the treatment of HIV infected board of administration, the medical issues. Conversely, the patients, AZT, benefited in the scientific advisory board and infected community felt patronized US from this programme as early the ANRS working groups. by the medical sphere and as 1986-87. Other drugs used Consequently, the Agency demanded to have an active role in the treatment of opportunistic suggested that the associations in their health care and treatment. infections in AIDS patients were name their own representatives for also granted pre-market approval the working group on therapeutic The unprecedented mobilisation, for compassionate use. trials and urged them to federate. the sheer motivation and charisma As a result, TRT-5 (a multi- 23 of this group of highly informed As the French civil society association group) became the and organised members of the was highly informed about the privileged partner of the Agency. civil society fighting for human response to the epidemic in other The associations continue to rights led to the most significant countries, and in particular in the provide advice on study protocols, community responses to a United States, it was successful in in particular on trial information, disease. The determination of playing a key role in transposing the communication of study civil society members and some the pre-market approval for results to the patients and the of the key activist groups soon compassionate use programme informed patient consent sheets. managed to forge a significant to the French regulatory and meaningful relationship with authorities. The process, known The historical relationship between the clinicians treating the disease. as ATU (Autorisation Temporaire the ANRS and the civil society d’Utilisation in French) was unique continues to grow over time and In an era of unknowns and in Europe for the provision of remains a distinctive element of uncertainty, the civil society played drugs to those who desperately the Agency. Currently, the civil a significant role in encouraging needed them. society representatives meet with the medical community to seek the director of the ANRS every answers and further insight The ANRS (the French National three months to discuss clinical into the disesase outside the Agency for Research on AIDS and French borders, by forming new Viral Hepatitis), created in 1988, international collaborations. For rapidly realised the importance many young clinicians at the time, of interacting with members the HIV/AIDS epidemic was the of the civil society involved in reason behind several of their first the fight against HIV/AIDS. The professional interactions abroad.
In particular, it is important to remember the critical role of the civil society in introducing novel regulatory authorizations, namely 24 VOL 5 ISSUE 2 HIV research. involvement andcollaboration in rights tothemore recent informed early daysoffightingforhuman response toHIV/AIDS,from the in Franceshapingtheglobal crucial role ofthecivilsociety This briefoverviewoutlinesthe perspective. from acommunityandpatient advice andopiniononthetrial aim ofproviding continuous based organisations,withthe of memberscommunity- community committee,composed follow thetrial:anindependent to formanewtypeofgroup to In addition,theANRSdecided meetings todiscusstheprogress. of thetrialandparticipatein since theoutsetofdesign have beeninvolvedintheproject this trial,communityorganisations men-who-have-sex-with-men. For exposure prophylaxis ofHIVin the ANRSIpergaytrialforpre- organisations isprovided by the ANRSandcommunity the closecollaborationbetween A secondrecent exampleof members innon-medicalsettings. testing bytrainedcommunity in particulartheuseofrapid testing andprevention research, civil societyorganisationsin involves theimplicationofthese One ofthemore recent projects community-based research. organisations isbeingsetup: relationship withcommunity A newstageinthestrong plan oftheAgency. generally thescientificstrategic trials, cohortstudiesandmore g g f f GLOBAL FORUM|INFORM in 1972andhisPhD1977. obtained hismedicaldegree diseases. Professor Delfraissy auto immunityandinfectious well asclinicalresearch in fundamental immunologyas reviewed publications on has authored over398 peer- 1996. Professor Delfraissy medicine departmentsince where hehasledthe internal career attheBicêtre hospital he continuedhisclinical by HIVasearly1983and assisting patientsinfected against AIDSandstarted of thepioneersinfight Medicine. Hehasbeenone the Paris-SudFacultyof Medicineatand Internal of ClinicalImmunology Delfraissy isProfessor (Inserm Aviesan). Prof Diseases andMicrobiology of theInstituteInfectious Prof DelfraissyistheDirector In addition,asofMay2008, Hepatitis sinceJune2005. Research onAIDSandViral French NationalAgencyfor is theDirector ofthe Prof. Jean-FrançoisDelfraissy Delfraissy Jean-Frnçois Cambridge, UK. PhD from theUniversity of to HIV-1. DrRossholdsa mechanisms ofrestriction out research oninnate France) where shecarried the InstitutPasteur(Paris, LMB (Cambridge,UK)and Medical Research Council postdoctoral trainingatthe Dr Rosscompletedher Prior tojoiningtheANRS, Vaccine 2009conference. coordinator fortheAIDS of theANRSandasscientific the Vaccine Research Office served inthepastasHeadof hepatitis). DrRosshasalso Research onAIDSandviral (French NationalAgencyfor Relations attheANRS Affairs andScientific the HeadofInternational Anna LauraRossiscurrently Anna LaurRoss Interaction Between the European Medicines Agency and HIV Advocates/Patients Over the Years
Isabelle Moulon is a medical 25 doctor spe- cialising in endocrinology and metabolic diseases,with In October 2012, The European Those who were working in Medicines Agency (EMA) national authorities in the late post-gradu- published its fifth report on the eighties/early nineties will ate studies interaction with Patients’ and remember hundreds of HIV in nutrition, Consumers’ Organisations. activists lying in the street in front statistics and of official buildings, representing methodology. Although this document may be the bodies of patients dying Since 2005, seen as just another record of of AIDS, urging the authorities she has served activities, it shows that patients to take action. This produced as Head of are now routinely involved in discomfort, shock and fear but Medical Infor- the Agency’s work and that the for some regulators it was also real life experience of patients is mation, and a wake-up call. The seed was now embedded in the regulatory co-chair of the planted for a collaborative future. output. But involving patients has PCWP (EMA not always been the norm for There was always a risk that Working Party regulators. inviting patients to contribute with Patients could be seen as an attempt by and Consum- the public bodies to fulfill their ers’ Organ- obligation for public consultation isation) since without ever really listening 2007. and taking on board patients’ views. Conscious of this risk, the EMA has made constant 26 VOL 5 ISSUE 2 watch onthesepartnershipsand Board willtherefore keep acareful system wouldbethreatened. The any way, theeffectiveness ofthe were weakenedorfractured in regulatory system.Ifanyofthem partnerships are attheheartof pharmaceutical industry. These the healthprofessions andthe the customersbeingpublic, and thecustomersonother, the regulators ontheonehand “There isapartnershipbetween Management Board declared: Strachan Heppel,chairofthe In the1996annualreport, patients between regulators and concept ofinteraction foundations ofanew 1995-2000: buildingthe the ManagementBoard. EATG, wasappointedmemberof advocate andmemberofthe In early2013,NikosDedes,HIV suggestions. and takeonboard useful necessary structures ofinteraction organisations putinplacethe of engagementwithpatients the EMAtodevelopitspolicies as itwasinstrumentalinhelping has beenbeneficialtoallparties advocates/patients inthisway cooperation. Working with HIV progressed through anevercloser board theirneedsandhas its stakeholdersbytakingon term commitmenttowards effort todemonstratea long- g g f f GLOBAL FORUM|INFORM
the tri-therapy, andthere were a inhibitors. Itwasthebeginning of HIV, includingthefirstprotease evaluation forthetreatment of five newmedicineswere under anti-HIV medicinalproducts and to considerintheassessmentof had justpublishedsomepoints The CPMP(laterknownasCHMP) year forpatientsaffected byHIV. in early1996.1996wasaspecial European AIDSTreatment Group Progress wasprompted bythe the EMAisunique. and howthemodelputinplaceat embedded inthescientificwork patients’ contributionsare now was sought,whichexplainswhy in theAgencycore business In parallel,involvementofpatients the Agency. transparency intheoperationsof further initiativestowards greater and mediagroups toexplore patients, pharmaceuticalindustry a widerangeofconsumers, institutions, representatives of competent authorities,European for anumberofnational represented afirstopportunity and accesstodocuments workshop ontransparency with civilsociety. In1997the transparency required adialogue that theneedforopennessand The agencyearlyunderstood exchange ofviewsandconcerns. scientific committeesallowingfor industry) andmembersofthe physicians andpharmaceutical interested parties(consumers, meetings were organised between Management Board, regular Under theleadershipof shaping itspolicies.” take themfullyintoaccountin opinions. the exchange ofknowledgeand advocates inorder topromote to developfurtherlinkswith access totreatment anddecided Agency recognised theurgencyof the evaluationprocess. The beyond theircomfortzonein treatment” pushingtheregulators for “betterandfasteraccessto not alwayseasy:theywere asking HIV advocates.Thedialoguewas fromlearnt ourinteractionwiththe the mostimportantlessonswe new medicines.Thatwasoneof parameter intotheevaluationof its treatment andtointegratethis to-day lifewiththeirdiseaseand into accountthepatients’day- There wasalsoaneedtotake was necessarybutnotsufficient. civil societyinpolicydiscussion It becameclearthatinvolving way ofinteractingwithpatients. and setthefoundationsofanew This meetingwasamilestone debate.” and patientsbutasharpscientific discussion betweenregulators outnottobeameeting turned and regulatory knowledge.The impressed bytheirscientific patients’ advocates.Iwas “It wasmyfirstencounterwith present atthismeeting: then aCPMPmember, was Professor F. DeAndres-Trelles, with theCPMPon16April1996. andreflectionstheir concerns delegation wasinvitedtoshare the ChairofCPMP, anEATG In response toalettersent to approval intheUSandEurope. regardingconcerns accelerated therapies aswellhopesand and howtousecombination when tostartthetreatment, when viral load)asprimaryendpoints, surrogate markers (CD4 count and lot ofunknownsaboutthevalue
The CPMP and the EATG determine and support rigorous agreed that such exchange methods for investigating should happen regularly as new safety questions common to all knowledge was gathered in order antiretroviral products. to facilitate the regulatory process. Today the HAART oversight Following this first contact, committee still operates and HIV advocates were invited receives status reports and to participate in the ad-hoc evaluates the progress of the expert group on anti-retrovirals studies, e.g. the Data Collection on a regular basis, as further on Adverse Events of Anti-HIV biomedical advances brought Drugs (DAD) study. new knowledge in this field. They had the opportunity to share During this period, EMEA their experience with regulators, experts were invited by the academia and learned societies EATG to present and explain and discuss the evolving the new European regulatory requirements for registration of framework created in 1995 new anti-retroviral medicines. and discuss opportunities for This led to the early approval of improvement such as issues new antiretrovirals on the basis of linked to compassionate use surrogate markers. and conditional approval. These proposals were later on 27 The introduction of HAART in introduced in the revision of 1995/1996 represented a major the pharmaceutical legislation turning point in the treatment of following the first audit of the HIV, as a fatal disease became a European regulatory system. This chronic manageable disease. In fruitful cross-fertilisation further light of this and after listening to reinforced the mutual trust and patients, the CPMP’s attention confidence between the European turned towards the management regulators and the HIV advocates. of the side effects of long-term treatment. A specific expert 2000-2005: widening the group was convened with concept to a broader patients, academia, the US range of patients’ FDA and the pharmaceutical and consumers’ industry in 1999. The objective organisations was to discuss the strategy for In 2000, the creation of the research on the long-term medical Committee for Orphan Medicinal consequences of treatment Products represented another with protease inhibitors and the milestone in the Agency’s associated body composition relationship with its stakeholders. and metabolic changes. As a Not only was the legislation the response to this request from the EMEA, the Oversight Committee for the evaluation of metabolic complications of HAART was created in 1999. It was a unique collaboration between academic institutions, industry, EMEA, US FDA and the patient community which was established to 28 VOL 5 ISSUE 2 years ofintensivework,the “pharmacovigilance.” After two advocate wastopicleader for as topicleadersandanHIV Patient representatives acted representatives oftheCPMP. and beganabrainstormingwith were represented inthis group organisations includingtheEATG Eight patientsandconsumers’ • • • • workshop identifiedascritical: for actioninfourfieldsthe recommendations andproposals created andmandatedtoprepare patients andconsumerswas EMEA workinggroup with organised inMay2002,aCPMP/ consumers’ organisations workshop withpatients’and As aresponse toageneral collaboration withtheEATG. building onitssuccessful consumers’ representatives, its interactionwithpatients’and to betterdefineandstructure decade, theAgencyfeltneed and thebeginningoffollowing created attheendof nineties patients’ organisationswere Furthermore, asnewEuropean scientific committee. appointed membersofanEMEA time patientsrepresentatives were patients groups, butfor the first pharmaceutical industryand the regulatory authorities, result ofcooperationbetween CPMP andtheorganisations Interaction betweenEMEA/ Pharmacovigilance Information onmedicines of information Transparency anddissemination g g f f GLOBAL FORUM|INFORM EMEA working group andprovide recommendations from theCPMP/ framework wastoimplement the in 2006.Theobjectiveofthis was endorsedbytheboard consumers’ organisations which interaction withpatientsand developed aframeworkof The agencyconsequently activities. its missionandoneofcore stakeholders anintegralpartof the Agency’s interactionwith Management Board declared In September2005,the consumers’ organisations. interactions withpatientsand formalise andfurtherdevelopits the righttimeforAgencyto patients andconsumers.Itwas with stakeholdersincluding committees todevelopcontacts Management Board andvarious responsibilities totheAgency, its came intoforce, givingnew (Regulation (EC)No726/04) the newfoundingregulation pharmaceutical legislation, review oftheEuropean Union In thesameperiod,following the group atthetime. all proposals whichwere madeby to allproduct-related information, safety studiesandpublicaccess collaborative post-authorisation reporting, riskmanagementplan, and integratesdirect patient new legislationtakesintoaccount pharmacovigilance where the particularly inthefieldof them havebeenimplemented striking torealise thatmost of legislation. Retrospectively, itis called forachangeinthe looked quiteunattainableand Some oftherecommendations EMEA websiteinMarch 2005. for actionwere published onthe recommendations andproposals and European PatientForum. Alliance ofPatients’Organisations, Health Alliance,International Organisations), European Public (the European Consumers’ were invited,includingBEUC consumers’ organisations several generalpatientsand Immunodeficiencies). Inaddition, Patient OrganisationforPrimary dysfunctions (International Federation) andimmune Diabetesdiabetes (International of Neurological Associations), disease (European Federation Patient Coalition),neurological Group), cancer(European Cancer (European AIDSTreatment medicines (EURORDIS),AIDS by theAgency, suchasorphan medicines havetobeevaluated therapeutic areas where chosen onthebasisofthose organisations involvedwere and transparency. The10 legitimacy, representativeness work onthebasisoftheir to becloselyinvolvedinits to selectthoseorganisations The criteriaallowedtheAgency organisations (PCWP). with patientsandconsumers’ the Agencyworkingparty activities andthecreation of to beinvolvedintheAgency’s consumers’ organisationsinorder must befulfilledbypatients’and development ofcriteriathat the frameworkrelies onthe The structure described in organisations the agencyand interaction between and consolidating the 2005-2012: developing Agency activities. of patientsandconsumersinthe tools tomonitortheinvolvement
The PCWP replaced the working question-and-answer documents In addition to paving the way for group. It was officially created in on the safety of the products. the involvement of patients in the December 2006. Its chairmanship Although there is currently no legal pharmacovigilance working party was shared between the EMA and basis for their membership in the and later the Pharmacovigilance an elected member of the working CHMP, patients are consulted on and Risk Assessment Committee party. specific topics. Experts from the (PRAC), the recognised expertise EATG participate in the scientific of HIV advocates allowed them to Recognising the leadership advisory groups on HIV products participate in scientific projects at of the HIV advocates in the to answer questions from the European level: development of the interaction, CHMP on the benefit/risk balance the group elected Nikos Dedes, of products under evaluation. • They have a member representative of EATG as a representing the PCWP in co-chair of the PCWP. The They also contributed to the the steering group of the first action was to define clear preparation and revision of the ENCePP (the European rules to prevent criticism about HIV drug development guideline Network of Centres for potential risks linked to patient’s and more particularly in 2011 they Pharmacoepidemiology and involvement in the work of the contributed to a reflection on the Pharmacovigilance) established Agency committees. These rules development of medicines for HIV to oversee the mid to long term especially addressed the balance prevention at the EMA together implementation of the project; between confidentiality and the with WHO, African Institutional need to share information with the body and academia. • In the Innovative patients’ groups concerned and Medicines Initiative, in how to provide clear boundaries HIV advocates play an important particular the PROTECT 29 between their role as experts on role in the progress made in the (Pharmacoepidemiological one hand and as representatives field of pharmacovigilance and Research on Outcomes of of their organisations on the clinical trials. Therapeutics by a European other. These rules are now fully Consortium) project led by In 2009 two observers, one operational and systematically the Agency where they have a from EATG and one from IAPO, applied. Like any other experts, member in the External Advisory participated in a pilot phase in patients abide by the policy on Board. the pharmacovigilance working conflict of interests and sign a party to analyse the pros and They remain extremely vigilant in confidentiality undertaking. cons of having patients involved in the field of clinical trials particularly In the meantime, patients had discussions relating to the safety regarding their transparency been appointed members of the of medicines. This pilot phase advocating the public availability of Agency Management Board in provided evidence of the potential the results of all trials irrespective 2005, members of the Paediatric benefit for both the regulatory of the positive or negative Committee (PDCO) in 2008 and outcome and communications. outcome. Ethical considerations members of the Committee for It showed that the patients’ are also high on their agenda and Advance Therapies (CAT) in 2009. views can enrich the debate they played a prominent role in and improve the information on the international workshop on the Nowadays the representatives the safe and appropriate use of ethical and good-clinical-practice of the EATG are involved in medicines. aspects of clinical trials conducted the Agency’s activities like in third countries which was held representatives of other patients’ in September 2010, where they and consumers’ organisations. focused their attention on the They are systematically invited practical application of ethical to review all information and standards. communication materials related to products for HIV and other co-infections, such as package leaflets, EPAR summaries, and 30 VOL 5 ISSUE 2 regulatory process. provided reassurance aboutthe with thepatientcommunityand recall, healsofacilitateddialogue by thecontaminationand of thepatientpopulationaffected this incidentandanunderstanding on thepotentialconsequencesof only didheprovide information representative oftheEATG. Not knowledgeable andreliable Agency rapidlyinvolvedavery impurities intheproduct, the of theidentificationgenotoxic medicine) wasrecalled because (ananti-retroviralwhen Viracept patient community. In2007, between theAgencyand they haveactedasaninterface been extremely valuable when the supportofEATG has From adifferent perspective, g g f f GLOBAL FORUM|INFORM the interests ofthepatients.” benefits theevaluationprocess, in no more, noless.Eventually, it level asthoseofotherexperts, puts ourcontributionatthesame will hasdevelopedsincethen.It creation oftheAgency, andthis the regulatory process sincethe strong willtoinvolvethepatientin measured. There hasbeena it isreal, constant,andcanbe our viewsisnotpurely formal, the patients.Considerationof and informationprovided by into accounttheviews,opinions “The Agencylistensandtakes EMA andthepatients’groups: which hasdevelopedbetweenthe confirmed thetruecollaboration since the16April1996meeting, interaction withtheAgency EURORDIS andinvolvedin Francois Houyez,representing (scientific) expertscannotfill. thereby fillingagapwhich other and itstherapeuticenvironment life experienceofthedisease critical inputbasedontheirreal- process bringsaunique and Involving patientsintheregulatory to thefuture 2013: lookingforward
and rationaluseofmedicines. objective bypromoting thesafe reach acommonpublichealth European regulatory systemand confidence ofcivilsocietyinthe to furtherdeveloptrustand challenge asanopportunity the Agencylooksatthisnew and consumers’organisations, collaboration withpatients’ Building uponitssound future plans? integrate thisnewdimensioninits the patients?HowwillEMA society concurwiththoseof theinterests ofthecivilWill meetings. agendas andminutesofthe decision, thepublicationof to betterinformtheregulatory the request forindependentdata introduction ofpublichearings, operation tocivilsocietywiththe the EMAisfurtheropeningits pharmacovigilance legislation, the implementationofnew transparency ofitsactivitiesand theincrease intheWith the Agency. routinely involvedinthe work of and respect. Patientsare now Agency basedonmutualtrust patients’ organisationsandthe a closecollaborationbetweenthe and allowedthedevelopmentof as apositivestimulusfortheEMA their constructivecriticismsacted expertise, theirindependenceand regulators andpatients. Their in thecollaborationbetween HIV advocateswere pioneers PROTECT: http://www.imi-protect.eu ENCePP: http://www.encepp.eu ec.europa.eu European Commission:http:// EMA: http://www.ema.europa.eu following websites: Information wasretrieved from the
Partnering with Community - Could the Past Hold More Promise than the Future?
Lew Sibert
31
GRID, GAY, Silence = Death, It’s worth noting that one of Compound S, 1984....It’s been the key presenting features over 30 years (1981) since of GRID/AIDS in 1981 was the first report of Gay-related Kaposi’s Sarcoma which was Immune Deficiency was first a rare cancer classically found noted in clusters of men in Los among men of Mediterranean Angeles and New York City. The and Jewish descent. It was this disease was more neutrally, and clinical presentation, coupled formally, named AIDS - Acquired with a scientific hunch and deep Immunodeficiency Disease nucleoside chemistry experience, Syndrome - in mid-1982. It would that led Burroughs Wellcome be almost another two years until and principal scientist Dr. Janet the causative agent was identified. Rideout to begin screening a In April 1984, a retrovirus was library of existing compounds identified to be that cause, the for activity against the virus. Dr. human immunodeficiency David Barry, working closely with virus (HIV). Rideout and Drs. Phillip Furman, Sandra Lehrman and Marty St. Clair went on to be named on six patents issued for AZT, its preparation and methods of use in AIDS. 32 VOL 5 ISSUE 2 array of‘in-house’scientific was historicallylimitedto a broad multidisciplinary approach that regulatory approval. It’s atrue, to pivotalphaseIIItrialsand idea from preclinical development perspectives, movingaconceptor takes manypeoplewithdiffering Drug discoveryanddevelopment So whystartwiththishistory? months bytheFDA. in arecord timetoapproval of3.5 approval cominginMarch 1987 screening andclinicaltestingwith was rapidlymovedthrough further Samuel Broder. Thecompound activity intheNIHlabsofDr. was confirmedtohaveanti-HIV later in1984,CompoundS(AZT) in compoundscreening andthen, Duke collaboratedwithWellcome inhibitor. Dr. Dani Bolognesiat acting asareverse transcriptase against theAIDScausativevirus, analogue mighthaveactivity posited thatthisnucleoside anticancer compound.Dr. Rideout Jerome Horwitzasapotential AZT wasfirstsynthesizedbyDr. not patented. library ofcompoundsthatwere Rideout tohoneinonanexisting acyclovir amongothers)ledDr. development (trifluridineand a fresh perspectiveonantiviral with nucleosidesynthesisand extensive chemistryexperience retroviruses. TheWellcome team’s transcriptase inresearch onavian for theidentificationofreverse were awarded aNobelPrize Drs. DavidBaltimore and Temin with HIV/AIDSandAZT. In1975, upon oneanotherandsoitwas contributions andideasthatbuild and progress, there are many As inmostscientificdiscovery g g f f GLOBAL FORUM|INFORM number ofpatients accessing available from theseclubs.The opportunistic infections,were well asotherdrugsuseful for and, toalesserextentddI, as them intheUnitedStates. ddC manufactured expressly for and eventuallyhadsomedrugs in drugsfrom othercountries hands. Initially, theysmuggled process, tookthingsintotheirown lengthy Federaldrugapproval with AIDS,frustratedbythe They beganformingwhenpeople in thelate1980s-buyersclubs. Yet another phenomenonbegan here tostay. development. TheCommunitywas positioned tochangedrug unique tosocietyanduniquely followed duringthattimewere organizations andtheothersthat Coalition To UnleashPower. These ACT UPwasfounded-theAIDS and treatment. Then,in1987, involve patientsintheirowncare was toempower, educateand life inSanFrancisco;itspurpose In 1985,Project Informcameto for AIDSResearch (amfAR). become theAmericanFoundation merged inSeptember1985to formed. Thetwoorganizations AIDS Research Foundationwere the LosAngeles-basedNational AIDS MedicalFoundationand 1983, boththeNewYork-based became knownasAIDS.In to investigatetheconditionthat formed aninformalstudygroup of researchers andscientists Also, intheearly1980s,agroup Gay Men’s HealthCrisisin1982. disease camethefoundingof Parallel withthenamingof AIDS changedallofthat! and, from theoutside,‘subjects.’ disciplines, researchers, clinicians case-by-case basis.Expanded investigational compoundsona access potentiallylife-saving first provision forindividualsto was alsodebutedin1987; the New Drug(TIND)application The Treatment Investigational priority inthereview process. they wouldreceive thehighest AIDS therapiestoensure that all applicationsforpotential “AA” prioritycategorytoclassify Administration (FDA)created an Also in1987,theFoodandDrug Adult ACTGRetreat. the firstCABforumwasheldatan organized and,finallyinlate1998, years formonthlyCABcallstobe formed in1991.Ittookanothersix Guideline Subcommitteewas ACTG siteandaProtocol (CABs) beestablishedateach Community AdvisoryBoards (PCG). Soonitwasagreed that a PatientConstituencyGroup at meetingsandthencreate few communityrepresentatives move toreluctantly includea years, theACTGswouldgradually December 1987.Overtheensuing Trail Group (ACTG)meetingin convened itsfirstAIDSClinical Diseases (founded1948) Institute ofAllergyandInfectious and approval. TheNational approaches todrugdevelopment existence so,too,were novelnew While ACTUPwascominginto voice oftheCommunity. profound magnifyingaffect onthe undoubtedly hadadirect and products instead.These concerns being siphonedtotheseillegal participate inclinicaltrialswere patients whootherwisewould thatindustry wasveryconcerned well-being. Thepharmaceutical to worryaboutpatientsafetyand sufficiently largetocause theFDA drugs through theseclubs was Access also grew out of the government and industry toward discuss access to an early CMV TIND discussion and provided a more collaborative and inclusive treatment and with Bristol Myers yet another option for patients approach to drug development Squibb (BMS), demanding broader to receive therapies that were in and community/consumer availability of investigational ddl. clinical trials but not yet vetted involvement. Much of what took through the required Phase place and is described in the Other “actions” and “visits” III pivotal trial process or FDA preceding discussion is directly followed both with industry and reviewed and approved. attributable initially to ACT UP and with various arms of the US subsequently to TAG and other government, including the NIH, Progress continued at the FDA, community activists who were FDA and the Executive Branch, with Subpart E Regulations both strategic and relentless. as previously summarized. The following the first AA priority impact on the government side of response in 1988. These In Europe, the founding of the drug development was significant; regulations provided for early European AIDS Treatment Group really a game-changer. Industry phase I meetings with sponsors (EATG) in 1992 and the European took a bit longer to come around. and placed careful emphasis on Community Advisory Board disease severity and treatment (ECAB) in 1997 mirrored the early It was not until April 1992 when options; shifting the risk:benefit work in the US and, subsequently, Wellcome reached out to various ratio for drug development forever. they moved to take the lead in members of the community and many areas of pharmaceutical invited them to the first, structured It took until 1992 for Accelerated company dialogue and drug meetings with Community Approval to be implemented - for development in the 2000s. representatives. It was called the first time drug approval was a “Day of Dialogue” and it 33 permissible based upon surrogate What was different? The founding would set the example for other markers and not necessarily members of these organizations companies who were nearing on tidy clinical endpoints. In were people (not ‘subjects’) product approval or ramping up late 1992, Stavudine (d4T) was scared of dying from an unknown, development of new potential submitted for consideration under untreatable disease. They were anti-HIV candidate therapies and the new Parallel Track Policy. a suppressed minority with a treatments. Approximately 12,000 patients big twist. This minority arguably received Stavudine through the consisted largely of people with BMS and Roche, along with parallel track mechanism. An a well above average, inquiring Astra Zeneca, Boehringer accelerated new drug application intellect, education and a Ingelheim, Pharmacia & Upjohn for stavudine was approved more favorable socioeconomic and DuPont followed suit in the June 17, 1994. The application background and/or level of early to mid-1990s. Generally, received full marketing approval personal achievement. The the tone of these early meetings on December 21, 1995. This was “Community” was motivated not was paternalistic and, by some the only instance of use of the only to seek change but to make it accounts, patronizing. The Parallel Track and it may be largely happen. And they did. companies appeared to be more attributed to direct Community interested in recruiting allies action and engagement. One of the first and most for greater marketing success notable drug company (pharma) and to better understand their The Treatment Action Group (TAG) interactions with the Community consumers. There was, initially, splintered away from ACT UP in took place in April 1989, when an under-appreciation of the January 1992 to move the focus four activists occupied an talent and tenacity of members away from targeted ‘actions’ executive office of Burroughs of the Community and the range (or ‘zaps’ as they called them) Wellcome in North Carolina and of experience and thinking they and toward expanded scientific demanded a reduction of the price could offer in terms of drug research, drug development of AZT. Shortly thereafter, they development. and pathogenesis. As they met with Syntex (now Roche) to changed their focus and modus operandi, TAG began moving both 34 VOL 5 ISSUE 2 g g f f GLOBAL FORUM|INFORM treatment because ofbothclinical Many patients begantoeschew complicate treatment decisions. resistance begantoemergeand continued toevolve,drug became availableandtreatment Unfortunately, asmore products these compounds. integral tothedevelopmentof became more valuedandmore steadily, Communityinvolvement inhibitor, tenofovir. Slowlyand nucleotide reverse transcriptase T20 (enfuvirtide)andthefirst class ofdrugsrepresented by Also, inthewingswere afourth triple combinationtreatment. protease inhibitorandthefirst in eachclass;thefirstboosted with multipleapproved treatments the approval of3classesdrugs ensuing halfdecadewouldsee developed andapproved. The inhibitor combinationwasbeing the firstreverse transcriptase trials. Itwasalsoatatimethat moving intoandthrough clinical and protease inhibitors(PIs)were transcriptase inhibitors(NNRTIs) of non-nucleosidereverse was timelyasthefirstgeneration This Communityinvolvement they were listening. inviting more substantiveinput; convening theirownCABsand Soon, multiplecompanieswere and thoughtsabouttrialdesigns. combinations ofdrugclasses) burden, fastingvsfed,possible product benefits(ie.pill and invitedinputastopriorities, pipeline ofanti-HIVmedications asked Communitytoreview their Board and,forthefirsttime, routine CommunityAdvisory Wellcome convenedanow- timeframe, itwas1994when that occurred inthesame been other, similarmeetings While there maywellhave and Virco’s Antivirogram offered genotypictestingin1997 testing -followed.Stanford of resistance -andresistance mass around theimportance for clinicaldevelopment.Acritical andPIsnext generationofNNRTIs resistance informationtoidentifya techniques alongsidethisnew using traditionaldrugscreening wasresistance testing,Tibotec Virco wasdevelopingandrefining the previous three decades.As been donewithantibioticsover that resistance -muchashad way tomeasure andunderstand thought itimportanttodevelopa resistance developmentand Virco becausetheyanticipated buildings) cametogethertoform the companies(andinsame worked closelytogetheracross in 1994.Thescientists,who companies, Virco andTibotec, Enter twosmallBelgian far from ideal. many patientsthechoiceswere were manytreatment options,for lipodsytrophy. Now, althoughthere from intolerabletoxicities to and biomorphicchallenges, Annual Interscience Conference be held,inChicago atthe41 were formedandscheduledto first ScientificAdvisoryBoards at thesamemeetingas convene aCommunitymeeting timing seemedappropriate to follow thereafter. Itwas2001and toa PI-andsecondNNRTI andsimultaneously -anNNRTI undergo developmentalmost compounds; twowere setto of three new, next generation resulted intheidentification Tibotec’s screening efforts followed thatsameyear. discussions andguidelines first resistance testingpublished commercialized in1998.The (R) was st
on Antimicrobial Agents and “A European Community Advisory the community of patients Chemotherapy (ICAAC) meeting Board would be independent participating in the trials.” during September. 9/11 (2001) from individual pharmaceutical resulted in the meeting being companies, its composition was The timing for this approach postponed until December, to be decided upon by the EATG, could not have been more when all 3 Advisory Boards were and it is accountable to EATG and prescient. There were, potentially, held. There was tremendous the community. competing protease inhibitors, enthusiasm about the new new NNRTIs, new integrase Company and its compounds. “It took additional years of work candidates on the horizon and Everyone was intrigued by the and experience to establish new combinations moving into challenges of bringing two new the model of the ECAB which and through development. For the compounds from two classes is still the basis of today’s first time the number of options for through development. The design work. A fundamental point patients, even those with resistant of the clinical program was, was the implementation of a virus, were clearly on the rise. however, daunting. working structure of 10-20 (and There were a number of potential nowadays even more) members trials, trial designs and a limited Between the first resistance who would meet several times number of potential investigators testing in 1997 and the first a year to discuss clinical trials and participants. (This dynamic, Tibotec CAB meetings, seminal with pharmaceutical companies, particularly limited participants, events were unfolding, defining a organize trainings for new continues to be a major challenge clearer role of Community in the members and provide information in new drug development today.) drug development story. ECAB about ongoing research to the convened their first industry EATG As always, rapidity of program and 35 meeting - and it was a pivotal trial development, trial recruitment, meeting. For the first time, rather “Objectives, structure and working data analysis and time to filing than the host/sponsor inviting procedures were described early were critical. Sponsors and their Community representatives to in 1998 as follows: employees were measured on participate in their agenda-driven speed to completion of essential • review the design of clinical meeting, ECAB was the convener. tasks and meeting or exceeding trials during the process of They established the date, time, milestones along the development protocol development details, participants, agenda and path. Any issue, process or procedure that could negatively intended outcomes. To put this in • promote best practice impact this forward progress perspective, here is one member’s procedures views, Dr. Stephan Dressler, who was viewed as unacceptable shared his historical recollections • suggest / initiate trials according until proven otherwise. This in 2006. to community needs imperative created an internal challenge when Community “...These early models of • review informed consent urged companies to permit them CABs were unsatisfactory for procedure to review and comment on the various reasons: In many CABs, development program, including pharmaceutical companies • monitor ongoing trials as far as informed consent, trial design, trial (and not the EATG or another adverse events, compliance and monitoring, DSMBs and sharing community-based organization) community needs of interim results - most of which would decide on the structure had previously only been the realm • be informed of interim results of the CAB, including number of the sponsor and a handful of and choice of invited attendees. • interact with other involved investigators. Especially ad hoc CABs did entities such as investigators, While ECAB prospectively moved not provide a satisfactory way Data and Safety Monitoring to duplicate its early success of communication, as there Boards (DSMBs) etc. was not always a commitment and expand it more broadly by companies for continuous • be visible to all involved across industry, Communities cooperation. parties and in particular to in the US were paying attention 36 VOL 5 ISSUE 2 development programs forboth Over thenexttwoyearsas TMC125. Thestagewasset. timelines forTMC114and down ofthedrugdevelopment that there wouldbenoslowing than everbefore -withtheproviso agreed toworkfarmore closely the Community’s interests and acknowledged thelegitimacyof senior managementofTibotec new anti-HIVcompounds.The development worldofcritical as weknewitbutintheclinical of change-notonlyintheworld understanding thatthiswasatime gainedaclearTibotec From the2001ICAACmeetings, entities aswell. course, industryandgovernmental between theorganizationsand,of continuous flowofinformation technology greatly aidedthe The evolutionofcommunication for theirownindividualmeetings. have individualcompaniespay on anannualbasisratherthan general organizationalsupport approached industryforgrantor maintained; bothorganizations independence andintegritywere funding wouldpermit.Financial at asmanymeetingsthat of oneanother’s organizations began hostingarepresentative same time,thetwoorganizations pharma companies,too.Atthe reaching outtotheUSoffices of and theybegantheprocess of by theECABstatedobjectives members were heavilyinfluenced (ATAC) wasformed.Thefirst AIDS Treatment ActivistCoalition to theirprogress. In2001,the g g f f GLOBAL FORUM|INFORM
and ATAC) providing guidance from bothorganizations(ECAB meeting withrepresentatives pivotal eventswasatwoday andoneof themostTibotec development progress at fully integratedintheclinical Ultimately, Communitywas analysis meetings/callinclusion. meetings, andinterimdata participation atinvestigator design consultation,delegate broadened toincludeprotocol TMC114 POWERtrials involvement withtheregistrational ECAB andATAC. Community the communityselectedby data review bymembersof participation andadvanced comment; thefirstDSMB consent reviews; trialdesign trials incorporatedinformed The ArtemisandTITAN TMC114 strategies. development programs and fully supportedTibotec’s drug the commitmentsbutthey Johnson notonlymaintained To theircredit, Johnson& to Communityremained intact. forward andthecommitments ThetransitionmovedTibotec. and Johnsonhadacquired it wasannouncedthatJohnson was takingplace.InMarch 2002, Meanwhile, anotherintegration views. continued toexpress their minority to themajority, evenasthey members whoultimatelydemurred cooperate withafewdissenting both ECABandATAC agreed to began totakeplace.Membersof the integrationofCommunity compounds were conceived, exploring improved approaches to questions while, atthesametime, answer someoftheseimportant to jointlydevelopatrialthat would Scientific AdvisorsandCommunity brought together bothTibotec compared tomen. including Prezista inwomen and tolerabilityofaregimen assess differences intheefficacy studies. Thestudysoughtto represented inUS.HIVclinical have historicallybeenunder- in womenandthat over 25%ofHIVcasesoccur study. It waswidelyknownthat from 2005to2006-theGRACE vetted through theUScommunity imagined, designedandfully One othernotablestudywas January 2008. 2006 andTMC125(Intelence)in TMC114 (Prezista) inJune compounds becameavailable; and completedboth the Company. Thetrialsregistered for patients,theCommunityand The endresult wasatruesuccess and approval. in thefinalstagesofregistration would beusedinthetrialasitwas balancing actwasthatTMC114 compounds. Anotherpieceofthe registration andlicensingofboth endpoints thatwouldfacilitatethe and leadtostatistically-significant as possible,facilitaterecruitment access toactivedrugsasquickly balance placebocontrol with would minimizepatientrisk, different classesinawaythat candidate compoundsfrom two of howtodesigntrialswithtwo Belgium totackletheproblem Advisors, theCommunitymetin convening oftheScientific to earlier. Simultaneoustothe trials -thedauntingtaskreferred on developmentoftheDUET patient recruitment AND retention of the trial sites and to help design An independent view of industry in a trial. The result was the and organize the investigator’s and Community interactions GRACE trial - Gender, Race And trial launch meeting in New York. was published in TheBody.com Clinical Experience. The designers Working together investigators, in September, 2009. This is an agreed that to be a ‘women’s community trial consultants and excerpt from TheBody.com that study’, a high percentage of community site representatives Bonnie Goldman conducted with participants should, in fact, be developed an armamentarium activist Bob Huff in September women. The benchmark was set of potential approaches 2009. He is talking about ATAC’s at 70% across the 3 participating and solutions to anticipated just-released - and first - industry countries. Total enrollment was challenges. report card. The report card was over 400 participants; 67% were widely distributed and garnered female and, of those, 88% were Funding was included in the national news media attention, women of color. into the study budget to enable including reporting from The New the sites to offer support with York Times. A quote from Dr. Kathleen Squires child care, transportation and best characterizes the importance food vouchers. By addressing “...Let me start with I think that of the GRACE study which key challenges that prevent the highest grade was a B overall. launched in September of 2006. women from enrolling in studies, Tibotec, for example, got its recruitment was completed on high marks because they have “GRACE not only showed us that schedule, making it the largest really embraced the principles of PREZISTA/r had similar efficacy women’s study of its kind to be community member engagement and tolerability in treatment- conducted in the US Additionally, at all levels and all stages of the experienced men and women, the clinical development team and drug development process. That’s 37 but it also taught us that through advisors prospectively identified kind of built into their thinking unique recruitment and retention important substudy analyses that now. I think they recognize the strategies, a large number of could be done in parallel with the value of it. women and people of color can conduct of GRACE. Several of enroll and stay in HIV clinical these have also been published. trials,” said Kathleen Squires, MD, Director, Division of Infectious Thus, during these two decades Diseases, Thomas Jefferson from 1987-2007, we have University and primary investigator seen how the evolution of the in the GRACE study. “GRACE has role of Community and clinical the potential to shape how future development occurred. It HIV studies should be conducted completely redefined, at least in because it addressed head-on one company’s approach, the the social and economic barriers, clinical development program such as lack of support, stigma, mentality, design and it added availability of child care and lack of important new milestones for both transportation, which often have patients and their Community. prevented women and people of color from participating in HIV Tibotec were not the only ones clinical studies and remaining in to embrace these changes but care.” (GRACE press release, July they clearly were the leaders in 20, 2009.) making this approach a healthy, scientifically and socially sound This trial further expanded the one. role of Community in clinical development while simultaneously being much more attentive to the needs of trial participants. Tibotec engaged Community representatives to work with each 38 VOL 5 ISSUE 2 true aboutotherdiseasestates? “When yousayunique,isthisnot HIV research structure. between thecommunityand historical anduniquerelationship knocked down.There’s adeep works whenthosebarrierswere the AIDSClinicalTrials Group of Health]works.Itchangedhow the NIH[U.S.NationalInstitutes Administration]. Itchangedhow the FDA[U.S.FoodandDrug change. Anditworked.Itchanged offices togetattentionandmake themselves invariouscompany into thestreets. Theyhandcuffed the olddays,activistswent “Well, there’s alotofinertia...In Bob Huff offered thisperspective. At theconclusionofhisinterview, reserved.) Resources Corporation.Allrights (Copyright ©2009BodyHealth recognize thevalue...” long time,ifyoutalktothem,they side who’vebeendoingthisa think mostpeopleontheindustry role andtheadviceare builtin.I is builtin,butalsotheconsultation “The watchdogrole ofcommunity doctors doandmonitorthat. look atthesameinformationthat clinical trialsfornewdrugsthat on safetymonitoringboards for a clinicaltrial.Membershavesat meetings whenthey’re launching public, suchasinvestigator’s that were neverseenby the who attendtheseinnersanctums “They havecommunitymembers g g f f GLOBAL FORUM|INFORM
data showingthatthedrug has serious diseasebasedon clinical to approve adrugtotreat a program, whichallowstheagency the FDA’s acceleratedapproval “Sirturo isbeingapproved under and Research... FDA’s CenterforDrugEvaluation of Antimicrobial Products inthe M.D., M.P.H, director oftheOffice available,” saidEdward Cox, have othertherapeuticoptions for patientswhohavedon’t provides much-neededtreatment throughout theworld,andSirturo poses aserioushealththreat “Multi-drug resistant tuberculosis 31, 2012. press release issuedonDecember follows isanexcerptfrom anFDA the waningdaysof2012.What treatment inover40years the FDAapproved thefirstnew a significantproblem intheU.S., tuberculosis. Althoughthisisnot areas ismultidrugresistant development toothertherapeutic experience from AIDSdrug transference ofknowledgeand The mostrecent exampleof thing...” threatening thing.It’s agood that,“Wow,learned it’s nota in theirbusiness.TheHIVdoctors don’t wantthepatients meddling resistance, frankly. Doctorsoften those lessons.There’s alotof into thosefieldsandare bringing HIV activistshavemovedover now. Basically, it’s becausethe happening withtuberculosis is nowstartingtohaveone.It’s have donesomestuff. Hepatitis cancer. Somegreat activists “There’s beensomeinbreast something else atplay? commercial perspective?Oris a ‘satisfiedmarket’from the progression andareflection of AIDS drugdevelopmenta natural particular, istheslowinginHIV/ doing? And,ifnot,whynot? In follow thisleadandhoware they is, whoelseissteppingupto andquestion todayA keyconcern emulate. clearly, amodelforothersto for Johnsonandand, of thedevelopmentparadigm Community involvementisapart Sirturo developmentprogram. fromof thelearnings HIVto has successfullyappliedsome and keenbusinessmanwho is obviouslyanastutescientist development process. Dr. Stoffels integration ofCommunityintothe as thekeysupporterof Pharmaceuticals becredited Worldwide Chairman,Janssen Johnson &Johnson,and now ChiefScientificOfficer, andVirco, andof Tibotec Stoffels, oneofthefounders It isonlyfittingthatDr. Paul rare disease,respectively...” exists, andisintendedtotreat a therapyno satisfactoryalternative safe andeffective treatment where need, hasthepotentialtoprovide potential tofillanunmetmedical The drugdemonstratedthe and orphan-product designation. track designation,priorityreview “The FDAalsograntedSirturo fast use. drug’s clinicalbenefitandsafe additional studiestoconfirmthe while thecompanyconducts access topromising new drugs program provides patientsearlier a clinicalbenefittopatients.This that isreasonably likelyto predict an effect onasurrogate endpoint There is no question that the Clearly, any drug development The I-Base report by Simon Collins industry has had to go through program has to satisfy both a also states that “...On 24 July serious financial constraints. risk/reward balance as well as 2012, a press release from Merck These constraints have resulted in an investment/return ratio. In announced that the company reductions in staff and reductions drug development, both hurdles had signed licensing agreements in budgets, including the critical remain high. In order for candidate for the development of two new drug development budgets. Tough compounds to be advanced, nucleoside analogues and is decisions are continuously being they must demonstrate low risk about to launch a phase 2 study made today. There has been and a high rate of return - or for its in house NNRTI...” One of a shift from the ‘blockbuster’ they will be shelved. A review of the NRTIs is being in cooperation mentality (think Lipitor) to premium the pipelines of historical AIDS- with a Japanese company. Finally, pricing for smaller, niche-type or focused companies suggests that Collins notes that “...Although orphan drugs. the favorable conditions continue less well publicised, Merck is also to be met. It also suggests that one of the companies investing A recent posting (January 15, all of the legacy companies are in cure research...” This is a 2013) on the Rare Diseases hedging their bets by expanding promising report as a review of Legislative Advocates web page their profiles broadly across the company’s website and mid- provides one perspective on other therapeutic categories. 2012 pipeline did not list any HIV current orphan drug development. The following briefly reviews compounds in development. While there are fewer patients the progress of four legacy eligible for treatment with these companies and an interesting new The unique approach of compounds, the per patient/per development in China. GlaxoSmithKline and Pfizer in year cost of compounds approved the formation of ViiV Healthcare, 39 in the last few years clearly Merck clearly deserves recognition in collaboration with Shinogi, presents some ‘sticker shock.’ for their historical development is potentially yielding two new programs. They garnered the candidate integrase inhibitors “..The pace of designations, next best grade on the ATAC (like Isentress) as well as a approvals, and orphan drug report card in 2009 and have combination product containing investment has accelerated over successfully developed Isentress the lead integrase inhibitor. A the last few years. Along with as an invaluable, first-in-class recent decision to cancel a continued strong Congressional HIV treatment. This development development program for a support for orphan drugs, some however, occurred largely in an new NNRTI is a disappointment very large drug companies have otherwise vacuum of HIV drug for all. It is hoped that ViiV will suddenly discovered the orphan development. Today, Merck’s continue to actively pursue other market. main focus seems heavily focused opportunities as it remains the on other therapeutic areas with only company whose sole focus is “At the same time, orphans 15 compounds listed in Phase II on HIV/AIDS. With the formation have seen more than their development and 20 in Phase III, of ViiV, both Pfizer and GSK are share of controversy and public none of which are for HIV. able to separate their therapeutic questioning. At least one company bets in HIV, while each pursuing a took an inexpensive compounded However, according to the I-Base broad range of research in other drug and set a market price for website, “...It is promising news therapeutic areas. It remains their approved orphan version at that Merck is developing an to be seen how successful this $1500, more than 50 times its active programme of research approach will be. prior cost. Recently, there have for new HIV drugs in parallel been projections that orphan to development of integrase drugs in development may cost inhibitors...” more than $400,000 per patient per year and that “million dollar orphans” are on the horizon...” 40 VOL 5 ISSUE 2 Chinese. involvement willoccurwiththe to seeifandhowCommunity meeting. Itwillbeinteresting at theSeptember2012ICAAC presented onthecompound Biotechnologies. Aposterwas company, ChongqingFrontier formulation bytheChinese fusion inhibitorinalong-acting is theresurrection oftheT20 in HIVcompounddevelopment Finally, aninteresting newfrontier inphaseII.nucleotide RTI of asinglenewcompound, indicates current development The current websiteinformation multiple othertherapeuticareas. have expandedtheirfocusinto is remarkably thinandthey however,ViiV theirHIVpipeline new integraseinhibitor. Like (like Abbott’s ritonavir)anda new pharmacokineticinhibitor as standalonecompounds-a had notyetbeenFDA-approved four components,twoofwhich combination product containing the firstcompanytomarketa August, 2012,Gileadbecomes Stribild’sWith approval in and combinationproducts. full portfolioofbothindividual HIV therapeuticmarketwitha Gilead dominatesthecurrent through PhaseIIcandidates. compounds and7post-discovery lists twophaseIIIcandidateHIV Myers Squibb,whosewebsite development maywellbeBristol- A quiet,brightspotinHIV g g f f GLOBAL FORUM|INFORM and whenwillitbegin? Who willwritethenextchapter Community inChina? been takentocreate andactivate progress? Andwhatstepshave Europe fared inthisevolutionof integration? Howhaseastern out aroadmap forbestpractice constituentstolaygovernment a broad group ofindustryand for Communitytobringtogether in thisreview? Mightitbetime been passedover(unintentionally) best practicesexistthathave of Communityintegrationand gridlocked? Whatotherexamples and developmentbecome beginning? HasHIVresearch perhaps weare backtothe over 30yearsago.Inconclusion, This review startedwith“GRID” financial attraction. development haslostmuchofits may wellsuggestthatHIVdrug candidate integraseinhibitor. This Stribild. TheotherisViiV’s new in Gilead’s approved quadpill alone compoundscontained are listed.Two oftheseare stand three HIVcandidatecompounds listed byTheStreet.com , only fifty calendared regulatory events other therapeuticcategories?Of for HIVcompoundapprovals vs. How doesthe2013calendarlook in Tampa, Florida. AIDS Instituteandresides part-time ConsultanttoThe Currently, heservesasa Global Professional Affairs. where helastserved as VP, and Johnson Burroughs Wellcome (GSK) increasing responsibility at dustry. Heheldpositionsof for thepharmaceuticalin- 39 yearsinandconsulting Francis. Sibertretired after from theUniversityofSt. MS inHealthAdministration Dickinson Collegeandan Biology andChemistryfrom Lew Sibertreceived aBSin How Cambodian Sex Workers Helped Change the Rules for Community Engagement
Meg Egan Auderset a writer and 41 editor of 20 years who has worked in a variety of set- tings in both Engaging the local community is uninfected female sex workers the US and a given when researchers design who would be randomized to Western Eu- and execute clinical trials in receive either 300 mg of tenofovir rope. Currently HIV, but the process has grown or a placebo daily for one year. a Medical/Reg- increasingly systematic over Three research entities were ulatory Writer the last 10 years, thanks in part collaborating – the University of for Thomson to a group of tenacious female California, San Francisco (UCSF), Reuters, her sex workers in Phnom Penh, Australia’s University of New primary as- Cambodia. South Wales (UNSW), and the signments in- Ministry of Health of Cambodia Members of the Women Network (NCHADS) – and funding came clude reporting for Unity (the WNU, established from the US National Institutes of on FDA advi- in 2000 “by a group of sex Health (NIH) and the Bill & Melinda sory committee workers for sex workers”) were Gates Foundation. Tenofovir was meetings and part of the intended participant already in wide use to treat HIV drug approv- pool in 2004 for a clinical trial to infection in combination with other als for IDRAC’s evaluate oral tenofovir for pre- antiretrovirals. Could the drug help AdComm Bul- exposure prophylaxis (PREP). The prevent infection, too? The HIV letin. phase 3 trial was to enroll 960 community looked on with hope.
Researchers hadn’t yet begun recruiting for the trial in mid- August 2004 when Cambodian Prime Minister Hun Sen ordered 42 VOL 5 ISSUE 2 prevention trial.” really couldhavebeenaboutany related tothePrEPstudies,they controversies atthatmoment “We realized thatwhilethe influential inHIVresearch. Foundation, andotherplayers HIV/AIDS (UNAIDS),theGates United NationsProgramme on meetings convenedbytheJoint represented AVAC atseveral devoted toHIVprevention. Warren AVAC, non-profit aninternational Warren, executivedirector of communities,” saysMitchell as wellhigh-HIV-incident in bothlow-resource communities complex HIVprevention studies related totheconductofvery prophylaxis. Attheirheartthey tenofovir andpre-exposure issues were notuniqueto “It becameveryclearthatthe PrEP trials. and interruptionstoothertenofovir meetings, yearsofsoul-searching, off-guard, sparkingscores of the HIVresearch community terminate trialpreparations caught The primeminister’s decisionto pressto international reports. Cambodians,” hesaid,according it onanimals,anddon’t use “If atrialisneeded,pleasedo sex workers’protests seriously. suggested hehadtakenthe hospital opening10daysbefore research ataPhnomPenh words hespokeaboutHIV offered apublicexplanation, While theprimeministernever preparations tobeshut down. g g f f GLOBAL FORUM|INFORM • • • • also receive: toxicity. Trial participants would for tenofovirsideeffects and changes, andtheywouldmonitor drug regimen, andforbehavioral infection, foradherence to the participants forratesofHIV researchers wouldevaluate July. March 2003andapproved itin a preliminary trialprotocol in Ethical ReviewBoard received on thetrial.TheCambodian previously hadsignedoff The Cambodiangovernment the trial Cambodia hadbacked the trial’s conclusion. illnesses developedfollowing treatment forsideeffects or Participants wouldnotreceive experienced duringthetrial. Treatment forsideeffects Health clinic. treatment attheMinistryof comprehensive care and free, preferential access to during thetrialwouldreceive who becameHIV-positive guidelines. Enrolled participants in accordance withnational where theywouldbetreated Ministry ofHealthHIVclinic, be referred totheCambodian at theinitialscreening would Women testingpositiveforHIV enroll onlyHIV-negative women. HIV screenings. Thetrialwould behaviors. counseling aboutrisky transmitted infections,and and treatment forsexually- Free condoms,free screening USD for12months. Monthly compensationof$3
According totheprotocol,
met inJanuaryandJuneof2004. Health Organization(WHO);they from UNAIDS,andfrom theWorld representatives from government, board inJanuary2004,including advisoryformed anexternal and Mayof2004.TheNCHADS group (CAG),whichmetinMarch a 13-membercommunityadvisory sex workers.Researchers formed community members,including focus groups andinterviewing researchers were holding about thetrial.BySeptember, community informationsession same monththeyheldtheirfirst Cambodian Ministryof Health; that of understandingwiththe signed aformalmemorandum October. InJuly2003,researchers an IRBatUNSWapproved itin trial protocol inFebruary 2003; board (IRB)atUCSFapproved the the WNU.Aninstitutionalreview provided technicalsupport to Change, theorganizationthat Cambodian Womyn’s Agendafor 2003, includingNGOslikethe with stakeholdersbyearly They hadalready begun meeting when preparing forthetrial. to havedoneathorough job The research teamappeared humans.” (In preclinical trials monkeys –never onhealthy only beentestedonhealthy especially whenthedrughas like Cambodiaforexperimentation of sexworkersin[a]poor country stating theiroppositionto “the use 29, 2004,issuingapress release ever press conference onMarch The WNUorganizedtheirfirst- and exploitation. sex workersallegedpartialtruths tenofovir, andrequested feedback, extolled thepotentialbenefitsof where theydescribedtheirplans, meetings withalltherightpeople But whileresearchers convened tenofovir had reduced the risk of chanting and carrying signs that UNAIDS and AVAC approached simian immunodeficiency virus read “Sex Workers Infected by the task collaboratively. In infection in newborn macaques.) Gilead,” “Gilead Prefers Us HIV+,” September 2006, an international The women demanded 30-plus and “$3 Can’t Buy Sex Workers’ working group developed the years of insurance to protect Lives.” They spilled fake blood first draft of what would become against potential side effects – on Gilead displays and draped the Good Participatory Practice and they questioned why they the company’s booth with a large Guidelines for Biomedical HIV hadn’t already been promised black banner reading, “Closed Prevention Trials. The agencies such insurance if tenofovir was Due to Death.” The drama published the first edition of the as safe as researchers said. “If attracted international media GPP guidelines a year later. our members agree to take the attention. risk, which may one day benefit “I often say that, as challenging people in richer countries and the One month later, Cambodian as those days were … as bad drug company, then we deserve Prime Minister Hun Sen ordered as some of the things were that adequate protection for our future trial preparations closed down. happened, the one positive lives and our families,” the release outgrowth was the development Good Participatory read. of the Good Participatory Practice Practice (GPP): A Guidelines,” AVAC’s Warren says. Trial preparations continued, systematic approach to While the 2007 edition was “far including focus groups and community engagement from perfect,” UNAIDS and AVAC meetings attended by WNU agreed they should present the The events in Cambodia shocked representatives. The CAG held guidelines to the research world HIV researchers and mobilized its second meeting in May 2004, for a test drive, he says. 43 protesters. In February 2005, and the second external review the Cameroonian government board meeting took place in June. “This sounds perhaps somewhat suspended a tenofovir PrEP On June 15, the WNU held a obvious and maybe simplistic, trial in that country; once again, second press conference. They but if we were going to do ethical violations were alleged. accused researchers of “unethical guidelines for participation, they HIV advocates worldwide met recruiting practices,” such as needed to be developed in a very to discuss events, evaluate withholding the name of the drug participatory fashion,” Warren the damage, and plan the way and asserting that tenofovir use says. AVAC issued a series of forward. The International AIDS carried no side effects. “WNU small grants in June 2008 to Society (IAS) convened a 2-day wants recruitment processes to 12 “GPP partners”: Community meeting at the request of the be better and more honest, with groups, trial sites, and nonprofits Gates Foundation, the US sex workers not pressured or engaged in HIV prevention. In May Centers for Disease Control and given wrong information about the 2009, AVAC and the 12 partners Prevention (CDC), and NIH. An drug,” the accompanying WNU met in South Africa to exchange international meeting on “creating press release read. reactions and recommendations. effective partnerships,” convened A revision process followed; In July 2004, sex workers from in June by UNAIDS, was preceded AVAC and UNAIDS published the WNU travelled to Bangkok, by several regional consultations. the second edition of the GPP Thailand, for the fifteenth As ethicists, researchers, and guidelines in 2011. International AIDS Conference. advocates unraveled and reviewed There they met up with members events, one gap surfaced of Act Up-Paris and the Asia again and again: The need for Pacific Network of Sex Workers systematic guidelines for engaging (APNSW). Together, the 3 external stakeholders at every organizations staged a protest of step of the clinical research the tenofovir trials that focused process. on tenofovir manufacturer, Gilead. Protesters interrupted a symposium on antiretrovirals, 44 VOL 5 ISSUE 2 assistance. sites regularly contactAVAC for who saythatresearchers andtrial according toWarren andHannah, researchers tofollowthem, funders increasingly are requiring body enforces GPP. Evenso, (GLP) standards, noregulatory and goodlaboratorypractice Unlike goodclinicalpractice(GCP) Putting GPPintoaction we’re thinkingaboutallofthis?’” for ‘howdowemakesure that up. GPPisreally justaguideline different issuesthatmightcome have different considerationsand different. Everytrialisgoingto is different. Everycommunityis thing aboutGPPisthateverytrial says. “And,youknow, thehard “It’s anongoingprocess,” Hannah change overtime. as a“livingdocument”thatwill AVAC refers totheGPPguidelines trial products orprocedures.” through to“post-trialaccess from “formativeresearch activities” step oftheclinicaltrialprocess: engagement activities”foreach identifies “stakeholder The documentsystematically autonomy” as“guidingprinciples.” and communitystakeholder transparency, accountability, mutual understanding,integrity, Hannah. GPPespouses“respect, Program ManagerStacey development, saysAVAC Senior aspect ofclinicalresearch for thecommunity-engagement need for“normativeguidance” The GPPguidelinesanswerthe g g f f GLOBAL FORUM|INFORM trial personnelevery4weeks. weeks; participantswillmeet with Each treatment periodwilllast8 after receptive analintercourse. gel, appliedrectally before and and tenofovirreduced glycerin1% glycerin 1%gel,appliedrectally; Truvada; dailytenofovirreduced in different orders: Daily oral same 3treatment periods,but Each group willexperiencethe randomize eachto1of6groups. to enroll 186participantsand Center. Researchers expect University ofPittsburghMedical of InfectiousDiseasesatthe Research Program intheDivision of theAnalDysplasiaClinicand chair forthetrialanddirector Cranston, MD,FRCP, protocol engagement, according toRoss has includedextensivecommunity prevent HIVinfection,MTN-017, 2b trialofarectal microbicide to Development ofthefirstphase for TBDrugTrials. Participatory PracticeGuidelines drug trials,publishingGood GPP guidelinesfortuberculosis Regimens initiativeadaptedthe 2012, theCriticalPathtoTBDrug beyond theHIVarena. Andin 14 advocatedapplyingGPP human volunteers,oneofthe sponsored research involving recommendations forfederally Bioethical Issuespublished14 Commission fortheStudyof In 2011,whenthePresidential developing theirstudyprotocol. use oftheGPPguidelineswhen for PrEPspecificallymention of Truvada (emtricitabine/tenofovir) researchers from theiPrEXstudy ofMedicine, New EnglandJournal In a2010articlepublishedinthe touted theGPPguidelinesaswell. Groups outsideofAVAC have not ahard line inourculture, in make sensebecause there’s well, essentially, thatdoesn’t community folksthere were saying “When wewere inThailand,the them otherwise. meetings inThailandconvinced complicated trial.Stakeholder would overcomplicate analready- enrolling transgenderwomen researchers concludedthat around atableinPittsburgh, with thetrialmedications.Sitting treatments thatcouldinteract In addition,manytakehormonal have different sexualidentities. needs, researchers reasoned; they Transgender womenhavedifferent transgender womenaswell. have sexwithmen–toinclude trial population–menwho wisdom ofextendingtheproposed researchers questionedthe discussions inPittsburgh, significantly. Duringplanning the MTN-017trialprotocol Stakeholder inputaltered aura ofdistrust.” before you’re goingtocreate an but ifyouhaven’t talkedtothem may becompletelyfinewithit, them knowwhat’s coming.They something onthemwithoutletting You can’t justcomeintofoist its input,askedquestions… engaged andgivenitsopinions, community thathasnotbeenfully want tolaunchsomethingona 017 protocol team.“You donot (IRMA) andamemberoftheMTN- Rectal Microbicide Advocates Jim Pickett,chairofInternational “This isacomplicatedtrial,”says engagement beganearlyon. this spring,butcommunity plan tobeginenrollment at 4sitesintheUS.Researchers South Africa,Peru,Thailand,and The trialwilltakeplaceatsitesin our communities, between gay of unused pills and gel at study men and transgender women,” visits, researchers estimated an Pickett recalls. “It’s more fluid. overall adherence rate of 90%. Gender identity is not this bound Blood tests of study participants thing.” Similarly, after community told them otherwise: On average, meetings in Pittsburgh, the tenofovir was present in the research team decided against blood of just 23% of participants enrolling partners as trial randomized to 1% tenofovir gel, participants. It was stakeholders 28% of participants randomized who pointed out that the to oral tenofovir, and 29% of those exchange of body fluids could randomized to oral Truvada. The alter PK measurements. rate of new HIV infections among VOICE participants were shocking. “[Stakeholder meetings] took up Overall, 5.7 of participants an awful lot of time, and they were contracted HIV during the trial, absolutely essential to moving with no statistically significant this [protocol] forward,” Cranston difference in the rate of new says. In each of the communities infections between participants “they were engaged. They were taking the study drugs and those vocal. They were absolutely taking placebo. invested in this study. It was very affirming.” As the clinical research field broadens its focus to include anal 45 Even the most thorough microbicides and, potentially, an engagement process can’t HIV cure, challenges associated guarantee the desired clinical trial with participant recruitment, outcome, however, as researchers enrollment, and participation for the phase 2b VOICE (“Vaginal are changing as well. There and Oral Interventions to Control is a question about how the Epidemic”) trial learned “generalizable” the GPP guidelines recently. The VOICE team followed are, Warren says. GPP continues the GPP protocol closely, Warren to evolve, and AVAC is focused on says, but even with all the vetting developing tools to help research and conversations, informed teams and trial sites adapt them consent forms and face-to-face to their own needs. meetings, researchers could not ensure that participants would “If we for one minute think this is actually take their assigned drugs. simple, that any one thing is the answer, that’s when we lose,” VOICE enrolled more than 5,000 Warren says. “There is no ‘one’ women in South Africa, Uganda, in AIDS. There is no ‘one’ cure. and Zimbabwe, randomizing There is no ‘one’ prevention. them to one of five trial arms. There is no ‘one’ treatment. When The study intended to evaluate we begin to think that there is the safety and effectiveness of one magical shiny new thing daily oral tenofovir, daily oral that’s going to magically end the Truvada, and daily 1% vaginal epidemic, then we have just given tenofovir gel, versus placebo, to the virus a gift.” determine whether the treatments offered protection against HIV References available upon infection. Based on participant request. self-reports and the collection 46 VOL 5 ISSUE 2 g g f f GLOBAL FORUM|INFORM Klein Richard M. activists stillreverberates today. AIDS. Thecryofthoseearly AIDS shape thefederalresponse to one –thatfueledandhelped conversation –anoftenheated role. Itwasthebeginningofa of theagency’s regulatory fully understandingthelimitations totheFDAforhelp, notturned AIDS patientsandtheirallies shadow oftheemergingepidemic, Beginning inthe1980s, unthinkable 30yearsago. treatments inawaythatwas the developmentofHIV/AIDS with activistsnowpartneringin and DrugAdministration(FDA), profound changeintheFood AIDS activismhasledtoa AIDS Advocacy was centered around thatcore that evolvedwithintheagency never knownbefore. Theculture that Americanconsumers had basic elementsofprotection food anddrugs-providing adulterated andmisbranded was toprotect thepublicfrom Food andDrugsAct.Theintent reaching backtothe1906Pure The FDAhasalonghistory, The Emergingpidemic but theyweren’t easilywon. There havebeenmanyvictories, come. reverberate forgenerationsto diseases. Theirimpactwill continue torippleoutother in improving drugdevelopment they did,andtherole theyplayed The pathstheyforged,thework mission, with a particular focus on was bad. By the time symptoms At the time, people at FDA were a protecting the public from dangers became apparent and a diagnosis little baffled, because they thought associated with medical products. made, patients didn’t have long they were doing something good. to live. Doctors were daunted by Something valuable for society. Over the years, drug-related injury a disease they knew little about, Yet they were being accused of and deaths were the historic and could provide no meaningful murder, of wasting time while tragedies that led Congress therapies to treat. People living people simply died, waiting. to give FDA greater regulatory with AIDS continued to die. oversight and authority. It was evident that not everyone The recent film, How to Survive a knew, or understood, FDA’s role Until the 1980s, when the AIDS Plague, relays the story of how an in drug development. A regulatory epidemic emerged, society did not advocacy movement developed. agency, FDA does not conduct seem to question the status quo. AIDS patients and their allies the research to develop new Drug development moved along began meeting to figure out a drugs and bring them to market. at its own pace in the United way to survive. They wanted and Nor does FDA fund or direct States. Regulations developed needed a way to focus resources research. The agency oversees to protect study subjects against and attention on finding out what drug development by ensuring the unreasonable risks during drug caused AIDS, how it spread, science behind that development trials. Other regulations evolved and how to treat it. Clearly, the is sound, that people are not to control the process, and government didn’t seem to be put in harm’s way by the drug protect particularly vulnerable taking the leadership role, or development process, and that populations, such as children or providing meaningful funding to the risks associated with the drug women of childbearing age, from get to the bottom of what was are acceptable in relation to the 47 possible harm from research or happening, and finding ways to risks posed by the underlying potential toxicities from approved stop the disease. disease. But because the activists therapeutics. didn’t see anything meaningful A community of activists came coming out of FDA, they believed Randy Shilts’ 1987 book, And together. Regular people, the agency wasn’t doing anything the Band Played On, chronicles with varied backgrounds and to respond to the AIDS crisis. the spread of AIDS, the discovery experience, armed with little more Individually, and as a community, of the Human Immunodeficiency than whistles and protest signs, they didn’t have time to sit back Virus (HIV) that causes AIDS, set out to wage war until someone and wait patiently for the glacial and follows the early years of paid attention. Clearly, Silence = pace of development, study, the infection. The story deftly Death. It was time to start making review and consideration of data portrays a systematic neglect of noise. from early clinical trials. Activists the growing AIDS epidemic in the called the FDA every day to United States by the press, the Looking to the FDA “encourage,” or more accurately, public, and the government. In October of 1988 the activists demand faster action. At first, With the unrelenting spread knocked on the FDA’s door in they focused on Ellen Cooper, the of the disease, sickness and Rockville, MD. Maybe “knocked director of the newly established death, those in the most affected at the door” isn’t exactly the right Division of Antiviral Drug Products. communities, especially young phrase. They surrounded the gay men in New York and San building, blocking entry or exit, Francisco, became increasingly and functionally closed the agency frustrated, and desperate to down for the day. see both political and scientific attention focused on AIDS.
In the terrifying early days of the epidemic, no one understood what caused AIDS. The diagnosis was devastating. The prognosis 48 VOL 5 ISSUE 2 contact. I becameaprimarypointof Affairs cameintobeing.And Office ofAIDSandSpecialHealth problems. ThisishowtheFDA of theagencytoaddress the scientific andpolicycomponents andworkwiththeto theconcerns point ofcontactwhocouldlisten was evidentthatFDAneededa in campaignsandFAX-zaps. It heard through coordinated phone- resources tomakethemselves community triedtotieupFDA to dotheirwork.TheAIDS stressed reviewers oftimeneeded activists wasrobbing already complaints andpleasofAIDS The timespentlisteningtothe insistent andmore threatening. died, theircallsbecamemore desperation asmore and more growing frustrationandWith a wideningcircle ofFDA officials. they begantocallandharangue officials andotherphone numbers, But astheydiscovered other g g f f GLOBAL FORUM|INFORM the air. were allspinninglikeplatesin politics, andthedrugdevelopment the sametime.Thescience, many thingswere happeningat Today, it’s easytoforgethow use them. AIDS, anddeterminehowbestto value ofdrugsinthefightagainst clinical trialstoestablishthereal empirical datafrom controlled realized theimportanceof didn’t havetimetowait,others products becausepatientsjust to simplyapprove therapeutic While someactivistswantedFDA howFDAworks.learning ideas. Andthepatientswere andfirst-hand theirconcerns face towithpatients,hearing people insideFDAwere meeting the agency. Forthefirsttime, for allofus–insideandoutside Those wereexperiences learning their situation. andwassympathetictoCalifornia, had workedwithAIDSpatientsin Antiviral DrugsDivision.Dr. Feigal Berkley totakethehelmin from theUniversityofCalifornia, her role atFDA.DavidFeigalcame Frustrated, EllenCooperresigned how theprocess wasmoving. happening insidetheFDA,and help themunderstandwhatwas consider theirpoints,andto arguments andsuggestions, often withactivists,listentotheir time. Hewaswillingtomeet Food andDrugsatthispivotal Kessler astheCommissionerof We were luckytohaveDavid W aves ofChange advance intreatment. patients tohold onforthenextbig literally tensof thousandsof scale treatment INDspermitted promise forextendinglives.Large once datastudiesshowed real access topromising therapies use ofthesemechanisms to give pressed forincreased, largescale clinical trials.ButAIDSactivists investigational drugsoutsideof in placetopermitaccess FDA longhadmechanisms the scienceprogressed. forward together, asresearch and each other, findingwaystomove fromoften, andcontinuedtolearn But FDAandAIDSactivistsmet the bestwaytomoveforward. controversies inthosedaysabout There were considerable Together Moving Forward, study arm. a treatment effect intheactive have tosacrificetheirlifeshow In otherwords, nooneshould benefit oftherapy. to activedrugandreap thehealth benefits couldswitchstudyarms way, thosenotseeingtreatment and usedtopredict failures. This should betakenduringthestudy, Cox arguedthatmeasurements Mark HarringtonandSpencer reliably measured, activistslike virus itselfinthebodycouldbe CD4 cells,andthenlevelsof As thescienceadvanced,and measurement ofsuccess. on, survivalwastheprimary living anylonger?Andearly getting activetreatments were be determinedwhetherpatients compare themto,howcould it somethingtostudies. Without to placebocontrol arms of the some patientsberandomized Early clinicaltrialsdemandedthat Meanwhile, FDA devoted more – and survival. It wasn’t an easy with infectious disease physicians, resources to reviewing AIDS path, but once at the table, they and government agencies to drugs. There were several effective had a lot to say. And people create national guidelines that drugs on the market. Most were began to realize just how informed would establish standards of approved in less than six months and astute they were about the treatment based on clinical from submission of the application issues that so affected their lives. trial data, and clinical practice to marketing approval. outcomes. The scientific advances that AIDS activists became more and unfolded allowed them to point to Today, there are nearly 200 more involved in the development regulatory innovations that could patients who have been recruited and study, not only at FDA, but at get useful drugs to patients even by FDA to represent people with the National Institutes of Health faster. Once markers such as viral more than 100 different diseases (NIH), at academic research load could be reliably measured, on FDA advisory committees. centers, and with established it was a short step to using Patient involvement has become pharmaceutical companies. They this strong predictor of disease the norm as more and more attended scientific conferences, progression as a surrogate people follow in the footsteps of met the people doing the endpoint – instead of waiting for those early pioneers who used to development work, learned the patients to progress beyond the file into Commissioner Kessler’s challenges, and that the science therapeutic point of no return. office, or meet with officials at was not always predictable. Accelerated approvals, based on FDA to find better ways to do this validated surrogate marker, what FDA does best: Protecting As they became familiar with rather than waiting for clinical patients. the scientific underpinnings endpoint of survival (comparing it 49 of drug development, they to non-survival) changed the way leveraged the process to find trials were conducted, and helped better designs that were flexible thousands of patients survive to Richard Klein is the director and innovative. Being patients go on to live reasonably healthy of the FDA’s Patient Liai- themselves, they recommended lives with new classes of drugs. son Program in the Office designs that provided quality data of Health and Constituent faster because of advances in With more new therapeutics Affairs, the primary interface recruitment and retention of study emerging from the pipeline, and between the agency and participants. the realization that the virus would patient and advocate com- develop resistance to the drugs, FDA relies on outside experts for it became clear that combination munities, ensuring patient advice in situations where data is therapies were becoming the voices are heard at FDA. Im- not adequate to make a clear cut norm, ushering in greater survival. mediately prior to becoming decision. AIDS activists came to the Patient Liaison Program advisory committees meetings, Activists worked closely with Director, he managed the and articulated their needs at the scientists and statisticians to try to agency’s HIV/AIDS Program, open public hearing portion of find the best ways to leverage the working with, and serving as each AIDS-related meeting. But various classes of drugs coming the primary FDA contact for the dicussion among committee to market. They became, in short, HIV advocates, for nearly 20 members at the table during the close partners in the development day would profoundly affect the of treatments for HIV/AIDS. years. fate of patients, and activists felt that their perspectives were not As the medical community sought being reflected in the on-going better ways to use the panoply discussion. of drugs, and learn from best practices, AIDS activists joined They advocated for a seat at the table, and engaged in the deliberations that had so much future significance to their health 50 VOL 5 ISSUE 2 g g f f Inaugural President’s Award Presented to Inaugural President’sAwardPresentedto Program of Research in Center forAIDSProgramofResearchin GLOBAL FORUM|INFORM organization to theimprovement individual, group ofindividuals,or and innovativecontributions ofan Health recognizes thesignificant Outstanding Achievement inWorld The DIAPresident’s Award for June 20inChicago,IL. DIA’s 47thAnnualMeeting,on of Science,MedicineandHealth, session atDIA2011:Convergence was presented duringtheplenary infection inwomen.Thisaward Tenofovir fortheprevention ofHIV gel formoftheantiretroviral drug groundbreaking research onthe in SouthAfrica(CAPRISA)forits the AIDSProgram ofResearch World HealthtotheCenterfor for OutstandingAchievementin inaugural DIAPresident’s Award In June2011,DIApresented its South Africa(CAPRIA) continue our commitment to announcing this Award. “Aswe Director PaulPomerantzwhile past DIAWorldwide Executive research studiesof2010,” said recognized asoneofthetop “CAPRISA 004hasbeen (USAID), respectively. Developmentfor International Agency (TIA)andtheUS through theTechnology Innovation Africa andtheUnitedStates, ofSouthby theGovernments This studywasjointlyfunded transmission ofHIVinwomen. drugs canprevent thesexual first evidencethatantiretroviral CAPRISA 004)whichprovided the team ofthestudy(knownas DIA recognized theleadership thisaward,of worldhealth.With providing patients with access the brunt of the HIV epidemic breakthrough would not have to quality medicines, DIA is in Africa. When implemented, it been possible without the close proud to present the inaugural could have a profound impact on collaboration between the three President’s Award for Outstanding the course of this epidemic,” said South African and the three US Achievement in World Health to Study Co-principal Investigator Dr. partners who led this study; I am the CAPRISA Leadership Team.” Salim S. Abdool Karim, Director of proud and honored to receive this CAPRISA and Pro Vice-Chancellor award on behalf of this remarkable “The CAPRISA 004 trial provides (Research) of the University of team.” new hope for women who bear KwaZulu-Natal, South Africa. “This
ART Effective, Study Shows
People with well-controlled HIV through antiretroviral therapy have no higher risk of dying than people without HIV, according to a new study in the journal AIDS. The study included 3,300 people with HIV with an average age of 43, who were on antiretroviral therapy and had undetectable HIV levels and high levels of CD4+ immune cells. Most of the participants were men.
Researchers followed up three years later with the study participants, and found that 62 of them had died. However, nearly all of the deaths were from non-HIV related causes: 31% were from sudden death or heart disease, and 19 per- cent were from cancers not related to HIV. Only 3% of the deaths (two deaths, to be exact) were actually from AIDS.
Researchers found that those whose CD4+ cell counts were lower than the general population had an increased risk of death. But people with HIV whose CD4+ counts were normal (a “normal” level is considered 500 to 1,000 cells/ 51 mm3), there was no significantly increased death risk.
“Our data support the importance of early diagnosis and treatment to improve clinical outcomes and it is likely that much of the excess mortality associated with HIV would be preventable with timely diagnosis of HIV and initiation of ART,” study researcher Dr. Alison Rodger, of the University College London, said in a statement.
According to a study published late last year in the journal Archives of Internal Medicine, deaths from HIV have gone down for most people between 1993 and 2007. However, the study also showed that poor people and black women did not experience such significant declines in HIV-related deaths, HealthDay reported. * Standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to maxi- mally suppress the HIV virus and stop the progression of HIV disease. Huge reductions have been seen in rates of death and suffering when use is made of a potent ARV regimen, particularly in early stages of the disease. Furthermore, expanded access to ART can also reduce the HIV transmission at population level, impact orphanhood and preserve families.
In 2011, an estimated 34 million people were living with HIV.
WHO and UNAIDS estimate that at least 15 million people were in need of antiretroviral therapy in 2011. As of the end of 2011, over 8 million people had access to ART in low- and middle-income countries. WHO is providing countries with ongoing guidance, tools and support in delivering and scaling up ART within a public health approach. In 2010, WHO and UNAIDS launched the Treatment 2.0 strategy, which promotes radical simplification of ART, with accelerated treatment scale-up and full integration with prevention, in order to reach Universal Access. WHO is work- ing to release a revised guidelines on the use of anti-retrovirals in 2013, which will include recommendations on ART for adults and adolescents.
Currently, WHO is working to develop revised guidelines on the use of ARVs to be launched in 2013 and these guide- lines will include recommendations on ART for adults and adolescents.+
* Reported by the Huffington Post, Healthy Living. Accessed March 12, 2013, http://www.huffingtonpost.com/images/ lightbox/loading.gif + Reported by the WHO HIV/AIDS, antiretrovirals. Accessed March 26, 2012 http://www.who.int/hiv/topics/treatment/art/en/index.html 52
Q VOL 5 ISSUE 2 & g g f f GLOBAL FORUM|INFORM A Nikos Dede have worktodo! industry andthemedia.Allsides European Citizens,theagency, the and buildingoftrustbetween push forincreased transparency cycle ofregulatory oversightand of patientexpertsinthefull pursue evenfurtherintegration with diabetes),weshallhaveto (representing thosepatients Wientjens my colleagueWim is for3yearsandtogetherwith for thoseappointed.Theterm great challengeandresponsibility legislators call“civilsociety”isa the EMArepresenting whatthe The inclusionoftwopatientson role there is? voice. Whatdoyoufeelyour representing thepatients’ management board appointed ontheEMA Y European AIDS Treatment Group (EATG) with HIV, Positive Voice andpastchairofthe Chair oftheGreek Association ofPeople Living Nikos D ou haverecently been edes, S pecial S ection Editor, marketing authorization.As you compounds received final program before investigational processes and3.)anearlyaccess markers, 2.)acceleratedapproval clinical endpointswithsurrogate were 1.)thesubstitutionof processes. Themainobjectives medicines andfasterreview agenda formore effective importantly, pushtheresearch to existingtreatment but,more could contributetowards access as industryandpoliticianswho regulatory authorities,aswell research agencies,governments, exert extreme pressure towards together peopledeterminedto instituted in1992andbrought in 1991.Theorganizationwas World AIDSconference inBerlin and doctors)attendingtheHIV group ofHIVactivists(patients The EATG wascreated bya regulatory authorities? (EA AIDS T What wastheEuropean Nikos Dedes TG) engagementwiththe reatment Group PROFILE
can read in the excellent articles information and had a perfect included in this section, those balance between evidence based Nikos is a member of the DIA demands mirrored what took advocacy and political activism. It Advisory Council of Europe, place in the US. managed to prepare experts that the TIRS Editorial Board, the successfully interacted with the European Guidelines of Clini- There is no denial that HIV WHO, the ECDC the Commission, cal Management of HIV and patients led the way to EMA, scientific societies and local the Steering Committee of involvement in the agency and governments and policy makers. paved the way to the creation the European Clinical Trials of the ‘Patients and Consumers What do you feel is the most Network. He also acts as an Working Party’ and patients’ important challenge we face in advisor on HIV issues to the inclusion on Committees and the the coming years? ECDC, WHO and the Interna- Management Board. They also tional AIDS Society. led to more patient involvement Without a doubt, we are in research review at early stages witnessing a slowdown in that vastly improved trial design, innovation of new drugs and I recruitment and retention. believe we have not yet found the optimal mechanisms to When did you get involved with reward innovation. Even before the European AIDS Treatment the economic crisis it was clear Group and what prompted that the triptych of equitable you? and fair access to medicines, health system sustainability and 53 I was diagnosed with HIV in 1995- innovation had not managed to surely no comparison with the satisfy all three sides. Now, it has gruesome 14 years that preceded become an imperative to find this, but it was still an infection ways to reward what gives the with inevitable progression to greatest value back to society. AIDS and death. It still was a terminal diagnosis. Thankfully, a lot of progress had already been Impact of the New made and we were only two Pharmacovigilance Legislation years away from the treatment breakthrough that turned HIV in to on Regulatory A airs a manageable chronic condition. 4-5 June 2013 Hotel NH Harrington Hall, London, UK The majority of people back then dealt with such a diagnosis with denial. They preferred to pretend it Register by 23 April 2013! Early-bird rates available for members was not happening to them. Some of us though chose to fight back Group Discounts Available and decided to educate ourselves Send 3 participants and the 4th is free! on topics that were very foreign to the areas of our original academic Go to www.diahome.org > Meetings & Training studies. The EATG was a group for more information and to register online. that provided peer education and training, translated for lay people and disseminated all existing ADVISEADVISE ggff
ADVISE includes the “how
to” articles you have become
accustomed to reading in the
former Best Practices section:
Time management, skill
development, technology, software
topics and more are examined for
day-to-day implementation in your
own jobs and offices. Exploring Impact of ‘US v. Caronia’
On December 3, 2012, the 2nd The Court further ruled that US Circuit Court of Appeals it interprets “the misbranding vacated the conviction of former provisions of the FDCA as not pharmaceutical company sales prohibiting and criminalizing rep Alfred Caronia for promoting a the truthful off-label promotion drug for a use that had not been of FDA-approved prescription approved by the FDA. This is drugs” and “that the government John F. Kamp called off-label use. cannot prosecute pharmaceutical manufacturers and their JD, PhD In 2010, Caronia was convicted representatives under the FDCA Wiley Rein LLP of conspiracy to introduce a for speech promoting the lawful, 55 misbranded drug into interstate off-label use of an FDA-approved commerce, in violation of the drug.” Federal Drug & Cosmetic Act (FDAC). His appeal successfully On January 23, the DIA webinar contended that he was convicted Off-label Marketing Regulation for his speech – speech that in the Wake of the US v. Caronia promoted the off-label, but legal, Decision (#13209) reviewed use of an approved prescription highlights of the legal facts drug – which violates his First and history and some of the Amendment right to free speech. implications for regulatory and In its ruling, the Court concluded industry professionals, that are that Mr. Caronia had been sure to follow one of the most prosecuted and convicted for significant, recent commercial “mere off-label promotion,” and free speech decisions by a federal that “we construe the FDCA appeals court. This webinar as not criminalizing the simple explored the dimensions of promotion of a drug’s off-label conversations and decisions that use because such a construction will arise from the aftermath of would raise First Amendment this decision. “This decision is concerns.” far from over,” cautioned webinar moderator John F. Kamp, JD, PhD (Wiley Rein LLP).
Bert W. Rein (Wiley Rein LLP) summarized the history of this decision, the great divide between its majority and dissenting opinions (2-1), and what he called gf GLOBAL FORUM | ADVISE
“the eternal disconnect in the Mr. Bennett suggested that But the only voice subject to regulation of drugs and devices.” the government will most likely regulation through all these On the one hand, he explained, move forward by structuring conversations is the voice that FDAC gives FDA the authority new investigative strategies to works for or otherwise represents to approve pharmaceuticals develop evidence that goes the pharmaceutical company, for market use which have beyond promotional speech such as Mr. Caronia’s. All other demonstrably proven, through (such as internal marketing parties can freely speak. “I don’t rigorous testing and review, to be plans or directions to sales understand how you can decide adequately safe and effective for a representatives), and will attempt what is promotional,” Mr. Spears specific therapeutic purpose. On to further “Caronia proof” their said. “Any piece of information the other hand, the FDAC does investigations by more clearly that I share about my product can not give FDA authority to regulate stating that promotional speech is be seen as promotional.” the practice of medicine, and it is only offered as evidence of intent not illegal for a physician or other of intended off-label use. Mr. Spears further pointed out that authorized caregiver to prescribe off-label use is a common and a pharmaceutical product if the FDA will also have to focus on widely accepted medical practice. prescriber deems it helpful for that “false or misleading” promotion, Not only is it legal, but 50% of patient. which may not only force the all oncology prescriptions are for agency to prove the speech in off-label use; off-label use may “What do you do with a lawfully question is “false or misleading” constitute the standard of care distributed product when but may open debate over the in certain therapeutic areas, he additional information changes definition of “false or misleading” continued, and is recognized as 56 use patterns?” asked Mr. Rein. and perhaps even who gets to such by Medicare/Medicaid and Questions abound: Does the define it. “There is nothing in other reimbursement plans. FDAC authorize FDA to regulate the First Amendment that bars the pharmaceutical product or to false or misleading speech,” Mr. Caronia highlights the disconnect regulate the speech through which Bennett explained. “That is the between legal and acceptable
VOL 5 ISSUE 2 that product is distributed and key question: What is the ultimate off-label use and speech that administered? Does FDA regulate scope of the First Amendment promotes off-label use, for which the manufacturer, who tests and here?” Mr. Caronia was convicted gets a product approved for a and whose conviction was specific therapeutic indication, In his presentation “US v. Caronia: subsequently overturned, Mr. or the prescriber, who can legally A Victory for Patients,” James Spears said in summary. It can prescribe the product outside that “Mit” Spears, JD (Pharmaceutical help us move toward a new approved indication? Research & Manufacturers of regulatory paradigm based America [PhRMA]) proposed that on truthful, non-deceptive Alan R. Bennett JD (Ropes & Caronia is nothing less than a communications (including Grey) examined the evidentiary reaffirmation of the constitutional promotional speech) that will yield implications of Caronia. “There principle of free speech. FDA better outcomes for patients. are four things that the case can and Justice Department policies “Speech without intent is actually be said to stand for,” he around promotional speech are meaningless,” he concluded. began: rooted in the past, he suggested, when such discussions were • Off-label use is a legal activity primarily between industry, regulators and prescribers. • Pure speech about a legal Patients, and more recently activity cannot be prohibited payers, have now emerged as • False or misleading speech can discussants, too. be regulated
• These leave open the question of whether speech can be evidence Imaging Biomarkers: A Potential Tool for Cost Savings in Drug Development
Sheela Agarwal, MD Associate 57 Director, Imaging Clinical Trials, Massachusetts General The cost of drug development has substitute for clinical efficacy Hospital steadily increased over the years endpoint is considered a and it now costs an average of surrogate endpoint. If a surrogate $1.3 billion and ten years to bring is established as reasonably likely a new drug to market. Shortening to predict clinical benefit superior the drug-development timeline is to that of available therapies one potential way to stem rising for serious or life-threatening costs; it is estimated that potential diseases, it can be accepted for cost-saving would be about accelerated approval. $500,000 for a one year decrease in the time to market. The Under these criteria, imaging has increased use and development enabled accelerated approval of novel imaging biomarkers have by the FDA for at least 35 new the potential to contribute to such oncology drugs and 47 new time-savings through a number of indications. The biomarker used different mechanisms, particularly in all of these trials was tumor in the field of oncology. shrinkage, as measured by the Response Evaluation Criteria The US FDA recognizes in Solid Tumors (RECIST)4. The biomarkers as characteristics median time between accelerated that are objectively measured and approval and regular approval evaluated as indicators of normal of oncology products was 3.9 biologic processes, pathological years (range = 0.8-12.6 years) processes, or biological responses and the mean time was 4.7 years, to a therapeutic intervention3. representing a substantial benefit A biomarker that is intended to in terms of earlier availability gf GLOBAL FORUM | ADVISE
of drugs to cancer patients. tyrosine kinase inhibitor designed Moreover, the potential for greater to block an overactive enzyme in use of imaging biomarkers gastrointestinal stromal tumors beyond physical measurements (GIST). In these trials, a change is considerable. Molecular, in metabolic activity, measured functional, and phamacokinetic by PET, was detected 8 days imaging can provide important after initiation of treatment, biomarker data relevant to drug whereas it was 2-3 months development, especially for before tumor shrinkage was those that are directed towards observed. Furthermore, the PET a specific molecular targets response correlated with a longer that are arrived at through a progression free survival at one greater understanding of the year10. molecular mechanisms of disease. Biomarker imaging is especially Perfusion imaging may also valuable in the preclinical and provide useful prognostic early clinical phases of drug information. Both CT and MRI can development, when it can provide be used to estimate parameters data useful for internal decision such as blood flow, blood volume making, either to drop agents that and blood vessel permeability. In do not live up to expectations or several studies perfusion imaging to accelerate development of the has demonstrated changes 58 most promising agents. within a few days of initiation of treatment that may be indicative of Imaging as Prognostic response. For example, Willett et Indicator al. demonstrated that twelve days after a single infusion of the VEGF
VOL 5 ISSUE 2 Although measurements of specific antibody bevacizumab, tumor dimensions, typically using there was decreased tumor computed tomography (CT) perfusion and vascular volume in and RECIST, have been widely colorecatal cancer tumors and used to predict response to that a larger drop in blood flow treatment by oncological drugs, was associated with better patient this method has its limitations. outcome12. The measurements are somewhat subjective and it can be many Perfusion imaging also weeks before a response is demonstrated normalization of observed. Moreover, it can tumor vessels in patients with be impossible to differentiate recurrent glioblastoma in a Phase between tumor necrosis and II trial, in which patients were viable tumor on CT using size given AZD2171, an oral tyrosine criteria alone. kinase inhibitor of VEGF receptors. MRI measurements showed Other imaging methods may decreased vascular permeability provide an answer. For example, within one day of initiation a decrease in metabolic activity, of treatment. These findings as measured by a decrease in the corresponded with reduction uptake of 18F-fluorodeoxyglucose in tumor-associated vasogenic (FDG), visualized with PET, often edema and clinical benefit precedes a tumor response as as measured by reduced or measured by RECIST. This was eliminated need for corticosteroid first demonstrated in the drug treatments13. trials for imatinib mesylate, a Other Opportunities for Moreover, differences in focus on oncology and is co- Biomarker Imaging sensitivities between biomarker sponsored by DIA this year. It responses and clinical endpoints is to be held at Massachusetts The list of other imaging methods may also lead to biomarker General Hospital in Boston, MA for detecting therapeutic failure19. It is, therefore, essential on April 26-27th. More information response is considerable. There that the relationship between the and registration details for the are growing opportunities for biomarker, the pathophysiology conference can be found at using PET imaging utilizing novel of the disease, and a clinical www.massgeneralimaging.org/ 8 radiotracers . Agents are available meaningful end-point be clinicaltrials. that can measure DNA synthesis, thoroughly understood. hypoxia, and apoptosis, all of References/citations for this article which have the potential be used Despite these cautions, it is are available upon request. as a marker of response to cancer clear that there is potential therapy. for much greater use of well- selected imaging biomarkers in Novel modalities, such as drug development. A number of PET/MR, which combines the novel techniques touched morphological and molecular upon above as well as numerous imaging, could provide new others will be discussed in tools for biomarker imaging. MR greater detail at Harvard’s annual spectroscopy (MRS) can be used course on Imaging Biomarkers to measure several metabolites in Clinical Trials, which will and could also provide useful 59 early data on response to therapy. Choline phospholipid metabolism, which is associated with changes in the cell membrane, is profoundly altered in cancer and results in elevated choline peaks on MRS. Several studies have demonstrated that early changes in the choline peak are linked to subsequent tumor response in cancers such as brain, breast and prostate16. In some cases, unusual metabolites have been associated Mark Your Calendar with disease and enzymes The Development of Live Biotherapeutics associated with their metabolism Rockville, MD I September 24 could be potential drug targets. For example, some gliomas are DIA/FDA Oligonucleotide-based Therapeutics Conference Washington DC I September 25-27 associated with high levels of 2-hydroxyketoglutarate, which is Optimizing Expectations and Success in Support of First detectable by MRS17,18. in Human Trials (FIH) with Stem Cell Therapies September 26-27
Although the potential for US Conference on Rare Diseases and Orphan Products increased use of biomarker North Bethesda, MD I October 7-9 imaging is clear, there is a need Developing Global Animal Health Products to Support for caution. It is possible that Food Security and Sustainability a biomarker is not, in fact, on October 17-18 the pathophysiological pathway Visit diahome.org for more of disease or is not on the only offerings in the Fall pathophysiological pathway. gf GLOBAL FORUM | ADVISE
What Lies Ahead for 2013?
DIA has compiled its first What Lies Ahead? report, which provides expert insight into the year ahead for pharmaceuticals, biotechnology, and the product development of medical devices.
60
With thought leaders from to reduce the time to market for industry and academia asked to urgently needed medicines and to choose the trends they foresee avoid needlessly exposing patients VOL 5 ISSUE 2 shaping the world of medical to previously failed approaches product development in 2013, were highlighted as strong most agreed that the number motivators as well. one trend for this year will be “new models of innovation.” Susan Cantrell, Director, DIA Based on the report, it is highly North America said, “We are anticipated that industry will focus excited to provide insights into on collaboration and partnerships where the industry is heading which are becoming the new each year and what may continue norm for therapeutic research to grow in importance over the and development as companies next few years. These projections look to capitalize on innovations of the future landscape can be outside their own walls. The report valuable to companies as they points to shrinking industry R&D strategize to successfully meet budgets as being a motivator for the ever-changing needs of the such partnerships. The desire marketplace.” The study shows expectations of 2013 are that of the continued strengthening of consumer/ patient empowerment (2nd most expected trend), a focus on unmet medical needs as the driver for innovations, and growing regulatory cooperation 2. The Continued Rise will reimburse healthcare and convergence across multiple of Patient/Consumer providers based on quality regions. Empowerment: The outcomes and measures. All Importance of Patient/ of these applications of big “While this study is specific to Consumer Engagement. data will require collaboration, North America, and the United The goal of therapies is to new ways of thinking, and States in particular, as the global improve patient health and new skill development for forum for therapeutic innovation healthcare outcomes, and the industry professionals. and regulatory science we patient/consumer has been anticipate it being useful on a recognized and accepted 4. Achieving Market Access worldwide scale,” said Cantrell. as an important stakeholder is the New Goal, and Value in the development of Is a Key Driver. Companies Therapeutic Innovation & therapeutic products. Patient must now demonstrate Regulatory Science input has a growing influence the value of their products in 2013 on the design of clinical trials, in meeting medical needs the endpoints/outcomes effectively, safely and 1. New Models of Innovation. affordably. Connecting with Collaboration and sought, the weighing of regulatory agencies and partnerships are becoming benefit vs risk, the products patients/consumers is only the new norm for therapeutic that will be developed, and part of the task; companies research and development as whether they will stay on must develop early dialogs companies look to capitalize the market. Industry and with payers to understand on innovations outside their regulatory agencies continue their expectations as well. 61 own walls. Collaboration in to look for the best ways to Biopharmaceutical and precompetitive spaces, once engage patients in meaningful device companies can no taboo, is now sought after dialog and optimize their longer function solely as with the formation of such input. manufacturers of products; groups as TransCelerate and they must integrate into public-private partnerships 3. Learning How to Utilize The vast amount the healthcare ecosystem, like the Target Validation Big Data. of data available is spurring and partner with providers Consortium between NIH and innovations in medical and payers as a provider of industry. Industry-academic research, such as uncovering therapeutic options. They partnerships are increasingly the genetic basis for disease will do this by investing in important as industry and response to treatment. It comparative effectiveness leverages the innovations is now possible to combine research and by designing created in universities and multiple data sets to conduct trials to meet the needs of academic medical centers meta-analyses to gain insight both regulators and payers. while contributing its into complex medical issues expertise in development and in days rather than years. commercialization. Shrinking It is becoming possible to industry R&D budgets utilize a variety of different are a motivator for such data sets to understand partnerships, but the desire how therapeutic products to reduce the time to market are performing in the real for urgently needed medicines world. And under healthcare and to avoid exposing patients reform, accountable care needlessly to previously organizations (ACOs) failed approaches are strong motivators as well. gf GLOBAL FORUM | ADVISE
5. Regulatory Cooperation 6. Personalized Medicine/ are looking for ways to and Convergence. The Tailored Therapies and leverage the technology to alignment of regulatory Companion Diagnostics. communicate risk information requirements across countries Scientific advances have to patients and consumers. or regions is not new but is begun to improve our Patient recruitment can be becoming more common understanding of disease facilitated through mobile for multiple reasons. With a states, mechanisms of communications, and growing global market and action of new and existing one company has even the need to use resources treatments, and some reasons experimented with a virtual efficiently at both industry and for variable responses to clinical trial, enabled by regulatory levels, regulatory therapies among individuals. multiple mobile applications. agencies may share their Industry has recognized that Mobile applications have also workloads through consortia there is potential for success proven valuable in linking of agencies, such as the of therapies in smaller, more remote workers and multiple International Regulators appropriately identified patient worksites to central data and Consortium (TGA of Australia, groups. Increasing flexibility support services to maximize Health Canada, Swissmedic of regulatory agencies in the efficiency of professional of Switzerland, and the trial designs is helping teams. This is just the Health Sciences Authority sponsors to identify sensitive beginning of the innovations of Singapore). Cooperative sub-populations for whom that mobile health technology efforts among regulatory therapies at appropriate doses will support, but advances in agencies may include anything will be successful. Companies, data security will be essential 62 from supply chain inspections with the cooperation of to sustaining growth, and to clinical site monitoring to regulatory agencies, are regulatory agencies will be review of submissions. The optimizing processes for challenged to establish rules most compelling reason for developing companion and guidelines to protect convergence, however, is to diagnostics for new and patients and their privacy. VOL 5 ISSUE 2 share expertise to improve existing therapeutic products. the quality of reviews and Successful patient outcomes 8. Continued Importance of to promote consistent on first prescribed therapies Global Markets.* Due to approaches to the protection will benefit overall costs of changing demographics and of patient health in a care, making this an important the influence of emerging scientifically complex and trend for payers, as well. markets, companies must global healthcare market. work within a global market Other examples of strong 7. An Explosion of Mobile to achieve the greatest convergence initiatives include Health Applications. success. There are significant the Asia-Pacific Economic The possibilities are benefits to expanding globally, Cooperation (APEC); almost endless as mobile such as increased revenues the China/Korea/Japan technologies become more and lower costs, but also Tripartite Cooperation; the reliable, sophisticated, and new risks. Growth can be International Serious Adverse interoperable. Companies sporadic in different regions, Events Consortium (iSAE); are utilizing the technology and health needs, healthcare the increasing cooperation for patient reported data, systems, health payment between the US FDA and the monitoring, and simple structures, business concerns EMA; and even cooperation communication. Context- and cultural concerns are through parallel review of based applications can unique within each country. products by regulatory and collect data about the Successful companies medical coverage agencies. patient’s environment and conduct early stage analysis prompt reminders or medical and planning to account team alerts. Regulators for varying global factors when selecting countries for expansion. They also create partnerships to address publicly. TransCelerate and in some developing markets, these varying needs and to similar groups are planning there is a huge chronic build infrastructure, including to share data within their disease burden and unmet training of the workforce. BRIC own boundaries for now, and medical need in diseases countries are still important further developments can be such as Alzheimer’s Disease, as emerging markets, and expected in 2013. cancers, and diabetes. companies are looking at Emerging trends such as a “pharmerging” countries 10. Growing Ability to Make focus on wellness, health, and in Indonesia, Asia, Africa, Meaningful Benefit–Risk prevention of chronic disease and Latin America. Higher Assessments.* Many are driving research on obesity growth rates for therapeutic different approaches to therapies. Rare diseases also product sales in regions like assessing the balance of represent a large collective Latin America, India, and benefit versus the risk of disease burden and will China are having an impact in using a therapeutic product continue to be a focus of the US and Europe, too, by are beginning to converge therapeutic development. prompting a shift in sponsors’ around a set of common development efforts away elements that are accepted *Trends 8-11 each received from the mature and toward as integral to a meaningful the same number of votes the growing regions. This analysis. The industry and for inclusion in the “Top 10” affects not only the product regulatory agencies are also trends. pipeline but also marketing, growing in their understanding sales, reimbursement, and of the variable importance The next trend received medical affairs efforts, which of different elements at almost as many votes as the 63 must be culturally compatible different stages of the product four-way tie for the last spots and meet local needs. The development. The use of in the top “10” and deserves development of appropriate a common framework for an honorable mention – it will teams abroad is expected to decision-making will enable certainly be important in the continue to accelerate. the process to be more next few years: transparent, but methods 9. Clinical Trial Data and best practices for 12. The Era of Data Transparency.* Though successful communication of Standardization Is Here. clinical trial data may be the assessment to the patient Driven by regulatory agencies’ viewed as proprietary by (or caregiver) will continue to needs to meet the new review some, there is a growing evolve. timelines in PDUFA and other movement to share clinical user fee agreements and to trial data, within the bounds 11. Laser Focus on Unmet do the best, most thorough of protection of individual Medical Needs.* In both reviews, data standardization patient privacy. In November mature and developing is being given high priority 2012, the EMA expressed markets, the search for this year. Industry and its intention to create an innovations is focusing regulators alike need better implementation plan for on unmet medical needs. tools and readily available the release of clinical trial Products that duplicate data to make better informed data, and that effort is set available treatments are no decisions more quickly. Data to begin in April 2013. FDA longer valued unless they are standardization efforts in has discussed in various meaningfully superior or lower therapeutic disease areas will forums the benefits of the in cost. In developing markets, enable sharing of data across prudent release of clinical needs may be country- platforms to leverage multiple trial data, and though there is specific, and products must fill data sets for real world no specific plan to do so, at a need at a competitive price assessment of therapeutic least one US-based company in order to be successful. In efficacy and safety. (GSK) has announced that it mature markets, as well as will share its clinical trial data REACHREACH ggff
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5th DIA China Annual Meeting
The 5th DIA China Annual Meeting and local pharmaceutical will be held on May 12-15, companies, CROs, academic 2013 at the Beijing International institutes, clinical sites and Convention Center, Beijing. This regulatory agencies. year’s theme of “Patient Safety: A Sustained Focus from Scientific The meeting will provide a neutral Ideas to Innovative Medicines” will platform for information exchange, reinforce patient safety as a core and will feature the preconference element of therapeutic innovation workshops, the plenary and a key philosophy throughout and parallel sessions, panel the life cycle of pharmaceutical discussions, scientific posters, and biopharmaceutical exhibitions, and networking management. The meeting is receptions. Representatives from expected to attract over 1000 many global pharmaceutical professionals from international companies, research institutions and government regulators will participate as speakers and panelists. Patrizia A. Cavazzoni, gf GLOBAL FORUM | REACH
MD, (Senior Vice President of As the national capitol, Beijing carved ivory, jade, and lacquer, Worldwide Safety and Established offers a wealth of things to see all of which make excellent Products Regulatory, Pfizer) will and do. Some of the “must-see” souvenirs. There are popular deliver the keynote address on tourist sites include ancient sites pedestrian centers on Wangfujing May 13. like the Great Wall, the Forbidden Street, Qianmen Street, and Xidan City, Tiananmen Square, and the Street, as well as the well-known Session topics will focus on Imperial Gardens at the Summer Hongqiao Pearl Market and Silk 14 different themes, including: Palace, as well as modern sites Market. All are excellent places to Clinical Research and Operations; such as the National Stadium and shop for trinkets to take home. Regulatory Science; Drug Safety National Aquatics Center from the and Pharmacovigilance; Statistics; 2008 Olympics. Some excellent resources Vaccines and Biologics; CMC/ for those looking for tourist cGMP; Traditional Chinese Beijing offers dining options for information include http://english. Medicine; Target-based Oncology every taste. Those looking to visitbeijing.com.cn/ and http://www. Drug Development; Pharm/Tox; experience typical Beijing cuisine travelchinaguide.com/cityguides/ Clinical Data Management/e- should be sure to sample roast beijing.htm. Clinical; Innovation on Medical duck during their trip. Beijing is Devices and Combination also known for Imperial Cuisine, a For general inquiries and Products; Contracted Service style of food with its roots in the registration for DIA China’s Annual Organization Roles and Values; Imperial Palace that features raw Meeting, contact DIA China Office Pharmacoepidemiology Best materials and carefully selected Phone +86.10.6260.2240; dia@ Practices and Drug Safety; Post- ingredients. There are several diachina.org approval and Real World Studies. restaurants offering Imperial Cuisine in the city. For less formal For exhibiting, hosting, and Program Co-chair Dr. Lingshi Tan, fare, try traditional Beijing snacks advertising inquiries, contact Ms. Vice President, Pfizer Worldwide such as ShaoMai (steamed Jean Xu, Phone: +86.10.5923.1096 66 Development Operations, said, dumplings), Zha Gao (fried cake), or [email protected] “The China Annual Meeting helps and Bao Zi (steamed stuffed to enhance communication and buns). You can see more or register collaboration between China and online at www.diahome.org. the world. This year’s sessions will Beijing is known for its traditional highlight the latest developments handicrafts, especially cloisonné,
VOL 5 ISSUE 2 within the pharmaceutical industry in China, explore ideas that will impact global health, and feature open debates among senior professionals, top academics and high-level officials from various fields in medicine development. Patient safety will be reinforced as a core element of therapeutic innovation and a key philosophy throughout the life cycle of pharmaceutical and biopharmaceutical Management.”
Program Co-chair Yajun Zhao, th Director-General, China Center 5 Annual Meeting for Pharmaceutical International Exchange, SFDA said, “Patient DIA CHINA 2013 care and drug safety will be the theme of the Annual Meeting; in the meantime, drug safety is May 12-15, 2013 also the pivot mission of China’s Beijing, China drug regulatory agencies. DIA China Annual Meeting will be an extraordinary platform for Register Today! sufficient exchange between drug regulatory agencies, industry and www.diachina.org academic institutes, exploring ideas and thoughts to ensure drug safety and protect people’s health.” Understanding and Implementing Best Ethics Practices in Clinical Research April 9-10 | Nanjing Hotel, China
With successful ethics trainings guidelines, global and regional in Beijing for the past two years, requirements, and practicalities DIA China is pleased to announce on performing research studies that the 3rd Best Ethics Training including risk assessment and will be held in Nanjing, China management. There will be more on April 9-10, 2013. The 2-day case studies and interactive comprehensive agenda on ethics discussions, which will facilitate practices in clinical research will learning and knowledge and focus on overview of international experience sharing. ethical standards, regulations and
In December, two delegations 67 from the Stae Food & Drug Administration, China – the SFDA Good Manufacturing Processes (GMP) team and the SFDA Information Center team – spent several days at DIA worldwide headquarters in Horsham, PA, for training and an overview of DIA. gf GLOBAL FORUM | REACH
EUROPE
68 The State Food & Drug Administration, China (SFDA) Drug GMP Inspectors’ Training Program continued at DIA worldwide headquarters in March 2013, as representatives received instruction in GMP law and enforcement, cold chain management, toxicology and cleaning limits, and related considerations. VOL 5 ISSUE 2 Be Smart – Sign Up for SmartBrief
Kathleen Doyle
Subject: FW: January 31, 2013 - Glaxo refuses settlement in U.K. Avandia diabetes cases
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Glaxo refuses settlement in U.K. Avandia diabetes cases Despite settling U.S. lawsuits over claims that the diabetes drug Avandia causes heart attacks email publication that gives quick, and strokes, GlaxoSmithKline has decided to fight similar claims in the U.K. It has become “increasingly difficult in the U.K. to challenge large corporations such as pharmaceutical companies," said Liz Thomas, policy manager at the patient-safety charity Action against Medical Accidents. Pharmalot.com (1/30) easy-to-read summaries of articles Europe
EMA to consider blood clot risks of newer contraceptives The European Medicines Agency will review third- and fourth-generation combined oral contraceptives' safety to decide if restricting their use is necessary. The move was requested by France, which wants to limit the newer contraceptives' use due to blood clots. "There is no relevant to you. Get the latest news reason for any woman to stop taking her contraceptive," the EMA said. "If a woman has concerns, she can discuss this with her doctor." Reuters (1/28) , PharmaTimes (U.K.) (1/29)
U.K. drugmakers and physicians call for transparency in financial ties in drug development innovations A coalition of British physicians and pharmaceutical companies have created a template for disclosing payments and other financial ties between drugmakers and doctors as the U.K. works toward greater transparency. Similar efforts are under way in the U.S. and France. The effort is to find "whether there is, in principle, support for a publicly available, single, searchable system for disclosure of payments," said Richard Thompson, president of the Royal College of Physicians. Pharmalot.com (1/29) worldwide wherever you are on Drug industry group disputes lowering cost-effectiveness thresholds Lowering the current threshold of quality-adjusted life years, or QALYs, for assessing the cost effectiveness of new drugs and medicines would deny such medications to thousands and lead to a decline in U.K. health standards, according to the Association of the British Pharmaceutical Industry. The group was responding to a study by University of York health economists who your laptop or smart phone with said the current standard "is not based on evidence" and should be reduced. PharmaTimes (U.K.) (1/30)
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Report on 25th Annual EuroMeeting, 4-6 March 2013, Amsterdam Delegates at DIA’s 25th tutorials were led by an expert Anniversary of the EuroMeeting, faculty and 120 students, young held on 4-6 March in Amsterdam professionals and patients all were offered the mouth-watering attended sessions created prospect of more than 100 especially for them. DIA’s 25th sessions across 17 themes, Anniversary EuroMeeting was co- addressed by 300+ speakers chaired by Beatiriz Vicén Banzo from the EMA, the European (Head of Regulatory Affairs Bayer Commission, the FDA and other Hispania) and Peter Bachman national regulatory agencies. The (Senior Expert, European Drug most popular sessions included and International Affairs, BfArM). Implementation of the New Pharmacovigilance Legislation, the Addressing a full auditorium at Regulatory Town Hall Meeting and the opening plenary session, the sell-out European Landscape Jytte Lyngvig, Director DIA on HTA – the EUnetHTA Joint Europe, compared the 2013 Action. Eighteen pre-conference EuroMeeting with the first one gf GLOBAL FORUM | REACH
map to develop to three years. He explained that DIA’s strategic the framework focuses on existing positioning into issues that can be developed and the future. Ling enhanced to ensure their value revealed that is optimised. The idea being to Horizon One leverage the value of current, looks at DIA successful DIA activities while today and what eliminating non value added can and should initiatives - thus freeing up vital be developed resources that were previously in the next one underutilised.
held in Amsterdam 25 years ago. “The EuroMeeting was created to support dialogue and share knowledge. In this day and age this is just as much on the top of the agenda as it was back in 1989 – communication technology or not. People need to meet to really take major steps forward. And major steps forward are necessary 70 if we are to have a chance of making available much needed health products and treatments in an economic and demographic societal environment that is not VOL 5 ISSUE 2 too friendly. The EuroMeeting is the unique opportunity for all participants to get updates, exchange views, meet colleagues and make new friends from all scientific areas, in one place, in a Horizon Two is slightly more few intensive days,” she said. forward thinking - identifying goals to be obtained within a three to six year timeframe and what processes need to be put in place to achieve these goals. In this horizon DIA takes note of its current structure, determines its long-term sustainability and modifies it to ensure DIA’s business model is built for growth.
Finally, Horizon Three, which is where DIA as a global organisation will pilot new channels to meet long-term goals. Those channels are based on intelligence gathered Dr. Ling Su, President of DIA, through ongoing assessments. updated EuroMeeting participants Ling stressed that as DIA moves on DIA’s strategic framework forward and as this strategic plan called Three Horizons - a road is implemented the organisation from the panel, comprised of Pharmacy, University of Coimbra, is well-aware and highly sensitive Jan Geissler, (Director, EUPATI, Portugal for her work on DNA to the fact that each region has its Belgium); Kemal Malik, (Head of microencapsulation through own needs and focuses, and that Global Development, Member of external gelation. The second there is no one-size-fits-all. To that the Bayer HealthCare Executive prize was won by Aditi Shah of end, DIA is intent on strengthening Committee and Chief Medical Topiwala National Medical College, DIA’s global imprint by ensuring Officer, Bayer HealthCare India for Assessment of Disease each region is given additional and Pharmaceuticals, Germany); Activity in Patients of Rheumatoid ongoing support to carry out its Arthritis on Disease Modifying mission. In other words, while DIA Anti-Rheumatic Drugs (DMARDs). is a worldwide organisation, it is The third prize went to Jaroslaw also one that succeeds when its Jarzebowski, Wroclaw Medical regions succeed. DIA has and will University, Poland for his work on, continue to truly think globally and Socio-economic costs of heroin act locally. dependence and evaluation of methadone maintenance therapy Annual Awards (MMT) from the social perspective.
Annual Outstanding Service Other student programme Awards were presented by Jytte Aginus Kalis, (Executive Director highlights included the sessions, Lyngvig and Beat Widler, ACE of the Medicines Evaluation Board Making the most of the DIA Chair, to Angelika Joos (Head, Agency, The Netherlands); Luca Euromeeting in order to enter Regulatory Policy, EU and Most Pani, (Director General, Italian the industry, Enhancing your soft 71 of World, Sharp & Dohme Inc., Medicines Agency); Andrzej Rys skills by improving your emotional Belgium) and Julianne Hull (CEO, (Director of Health Systems and intelligence and Perspectives WenStar Enterprises, UK). The Products, European Commission); and Collaboration between Founders’ Service Award went and Thomas Kühler, (Vice Patients and Students. A Student to Francoise Augier de Cremiers, President, Regulatory Policies & Feedback session gave students (FDC Consulting, France), and Intelligence at Novo Nordisk A/S). the opportunity to provide the Distinguished Career Award feedback on their EuroMeeting Winner to Odette Morin (Director, Students and Young experience to key DIA staff. Regulatory & Scientific Affairs, Professionals Many of the recommendations IFPMA (NGO), Switzerland). The President’s Award for Outstanding Nearly 80 students and young Achievement in World Health professionals took part in was made to Yann Le Cam, the programmes specially (EURORDIS, France). tailored for them at the 25th Annual EuroMeeting. Activities Plenary Panel commenced with a student and Discussion young professional networking reception, an evening reception Spurred on by the success of held at the beginning of the the panel discussion at last meeting that allowed students year’s EuroMeeting, this year’s and young professionals to meet panel, led by Steffen Thirstrup, each other and senior DIA staff, Director of the Licensing including members of the ACE Division of the Danish Medicines made will be used to enhance (Advisory Council Europe). Agency, addressed the highly the programmes for students and young professionals at the topical issue of Public/Private At the students‘ poster session EuroMeeting 2014 in Vienna. Partnerships: Working together three worthy winners were given in the interest of patients. The awards. First prize went to Claudia packed auditorium heard many Oliveira from the Faculty of thought provoking responses gf GLOBAL FORUM | REACH
Patients and during the Community Meet and Eat lunch. This took place Forty patients and patient in the RAI Auditorium Lounge representatives attended their on Tuesday, 5 March, when 50 own Patient Networking Lunch, people attended; both old and giving them the chance to get new Community members. A to know each other before their Speakers Corner with open sessions started. The patient microphone was set up in programme included patient- the middle of the area where centric sessions, including Public short welcomes were made by Private Partnership for BioMedical commenced. Finally, a Patient Community Leadership Council Research under Horizon 2020: Feedback Lunch gave patients Co-Chairs Deb Dolan and Gesine Patients Perspective on Scientific and Patient representatives the Bejeuhr, who officially launched Priorities, Perspectives and opportunity to give feedback to the new era of DIA Communities. Collaboration between Patients key DIA staff on their EuroMeeting and Students, and EUPATI, The experience. In addition, Barbara Leishman European Patients Academy launched the new Anti-Doping on Therapeutic Innovation – An DIA Communities Community and invited people unprecedented public private The DIA Communities, formerly to the kick-off meeting on partnership to empower patients known as SIACs (Special Interest the following day and several to engage as real partners in Area Community) were very other Community Chairs made the drug development process. active during the conference. announcements about ongoing 72 A dedicated Patient Booth in The Get Involved Booth was activities, introducing themselves the exhibition area served as incorporated into the main DIA and inviting people for discussion. a meeting point. Its informal Booth in the exhibition area, with nature allowed patients to get in Speed Networking was, as usual, very positive outcome, providing great fun and a huge success. touch with each other and share extremely useful synergies both VOL 5 ISSUE 2 So much so that the organisers information. Organisations brought for marketing and for volunteer flyers, pictures and posters to had to double up at the tables services staff. DIA staff gave provided. Immediate repeats were decorate the booth and share with numerous presentations on how other participants. requested and students asked for to become a DIA member, how a speed networking event of their Patient representatives also to join the Communities, how to own. took advantage of an excellent use ConneX and how to submit opportunity to connect with the abstracts, and providing general EUPATI EuroMeeting 2013 stakeholder support of all kinds to meeting The European Patients’ Academy group at the Connection attendees. on Therapeutic Innovation Reception that included industry John Faulkes, the Project (EUPATI) held a well attended sponsors, regulators and DIA staff Management Community’s new afternoon session on the final day members. In addition, the Poster European leader, had prepared of the EuroMeeting. The session Area hosted posters elicited a 2-minute video encouraging provided a progress report on from patients before the meeting people to join the Community and its first year, outlined activities to contact him. This became an underway to achieve near term example for other communities objectives and how stakeholders and will be published on the DIA can be involved. website. DIA was able to identify a new chair for the Legal Affairs Community, Maria Manley. DIA’s Associate Director, Editorial Services, Judy Connors, made several short video interviews for the web-page at the booth Moreover, leakage of DNA from intact microspheres was not observed. Electrophoresis was performed with de encapsulated samples of DNA and also an aliquot of the particles’ supernatant as an indirect evaluation of DNA not initially encapsulated. The presence of a well defined band of approximately 20Kb for each lane was congruent with DNA molecular weight before encapsulation. Thus, DNA did not suffer any fragmentation throughout the process. No DNA was detected in the lane correspondent to the supernatant of the intact particles which confirms the high encapsulation efficiency of external gelation. It was also determined that there isn’t any step leading to DNA 2013 EuroMeeting denaturation. 73 Student Poster Winners 2nd Prize – Aditi Shah, Topiwala National Medical College, India 1st Prize – Claudia Oliveira, upon mild stirring. Particles’ Faculty of Pharmacy, University of disruption in PBS allowed to Assessment of Disease Activity in Coimbra, Portugal determine the encapsulation Patients of Rheumatoid Arthritis efficiency and to collect samples on Disease Modifying Anti- DNA microencapsulation through to run in an electrophoresis which Rheumatic Drugs (DMARDs) external gelation was performed to assess DNA damage. Abstract: Assessment of Disease DNA Abstract: Activity in Patients of Rheumatoid microencapsulation through The resulting Results: Arthritis on Disease Modifying external gelation microspheres were uniform in Anti-Rheumatic Drugs (DMARDs). size and shape, although no size Keywords: External Gelation, distribution study was performed. Introduction: Rheumatoid Gene Therapy, Microencapsulation The addition of PBS to disrupt the arthritis (RA) is a chronic disease particles is efficient and allowed The purpose of this that leads to inflammation of the Objective: for DNA escape. However, total study is to assess the feasibility joints and surrounding tissues. dissolution was not observed of external gelation for the As the disease progresses, leading to a suspension of encapsulation of DNA, using irreversible joint damage may particles’ skins. only biocompatible reagents, lead to loss of function and to deformity. Recent studies have and thus establishing proof Overall, the encapsulation suggested that the disease is of principle for the use of this efficiency determined was the most aggressive in the first technique to produce polymeric 77,95% of the total amount few years of onset and hence microspheres as non viral means of DNA present in the alginate immediate treatment during this of delivery for gene therapy. solution and only approximately period with a combination of 9% of DNA was lost during bead Microspheres were disease modifying anti-rheumatic Method: formation. Recovery of DNA was prepared by the extrusion of drugs (DMARD) is recommended also effective and little was lost an alginate and DNA solution to improve the long term outcome or absorbed to the particles. through a syringe into CaCl2, of the disease. gf GLOBAL FORUM | REACH
Published Indian data similar to present study is limited. The findings from this study could help sensitize physicians to the benefits of early initiation of DMARD therapy and thus help patients with RA in the long run.
Aims & Objectives: 1. To study whether a delay in starting DMARD therapy from onset of RA has an influence on the disease activity.
2. To study the effect of duration 3rd Prize – Jaroslaw dependence in the Wroclaw of DMARD therapy on disease Jarzebowski, Wroclaw, Medical Substitution Daycare Centre. The activity. University, Poland mean daily dose of methadone for those patients in the clinic is about Method: The study was Socioeconomic costs of heroin 95 mg. In the analysis following conducted in Rheumatology dependence and evaluation of costs of the therapy were outpatient department in tertiary methadone maintenance therapy included: drug, staff, lab tests and care centre in mid-2011. 81 (MMT) from social perspective administration costs;48% of all 74 patients with Rheumatoid arthritis were the costs of methadone. The Socioeconomic on DMARD therapy & who Abstract: mean estimated cost of therapy costs of heroin dependence consented were selected for the per patient was 538,60 zl PLN and evaluation of methadone study. For each patient, disease per month 8,60 zl PLN per day. maintenance therapy (MMT) from activity was assessed using 2 During the interviews following VOL 5 ISSUE 2 social perspective. scoring systems – DAS28 & areas of socioeconomic costs RAPID3. Keywords: methadone were noticed: crime related (thefts, maintenance therapy, robberies), prisons, hospital Results: 81 patients with services, contagious diseases. Rheumatoid Arthritis (RA) on Socioeconomic costs of heroin dependence Disease Modifying Anti-rheumatic Additional areas were law Drugs (DMARD) were assessed Objective: The objective of this enforcement, law courts. for disease activity using scoring work is to compare the costs of The work has shown big systems-Disease Activity Score-28 MMT and drug dependence, in difference between costs of non (DAS 28) & Routine Assessment of order to show that MMT is an therapy approach in comparison Patient Index Data (RAPID3). economically reasonable treatment to methadone maintenance for opioid users in Poland. Patients were segregated into treatment. Those costs were 2 groups. Group1-those who Method: This work is currently mainly divided to government and initiated treatment within 2 years conducted in one of 15 clinics society, and although they are of disease onset (n=36) & group that dispense methadone in difficult to be evenly calculated, 2-those after 2 years (n=45). We Poland. Direct and indirect costs it has been shown that MMT is found that 61.1% (n=22/36) of of the therapy, gathered from the in fact economically reasonable patients who started DMARD Wroclaw Substitution Daycare option for opioid users. therapy within 2 years of onset Center, were compared to the Opioid dependence of disease scored better on both data gathered with forms filled out Conclusion: is probably the most important the scales, compared to 84.4% by patients during an interview form of drug addiction. Currently (n=38/45) who delayed treatment and official data. by more than 2 years after onset in Poland there are about 25 of disease, recording high disease Results: There are currently 30 thousand dependents and activity (p<0.0001). 165 patients treated for heroin only about 5% of them get the opportunity to participate in methadone maintenance UPCOMING therapy (MMT). The reason of this low number is that only EVENTSEUROPE about 25% of budget spending Training Course: Paediatric Investigation Training Course: Advanced GCP Study on drug related problems are Plans (PIP) Monitoring for NHS and from those 25% 15-16 April 2013 5-6 June 2013 Amsterdam, The Netherlands Basel, Switzerland only 8% is to maintenance therapy. These numbers show Meeting: 7th European Forum for Training Course: European Regulatory that the maintenance treatment Qualified Person for Pharmacovigilance Affairs: In-depth Review of Current (QPPV) 17-18 April 2013 Registration Procedures in the in Poland is not used as widely Pre-conference Workshop 16 April European Union as it could be. It is often the London, United Kingdom 6-7 June 2013 last and only option for the drug Basel, Switzerland Training Course: Essentials of Clinical users to come back to normal Study Management Training Course: Good Management life, but is also probably the most 17-19 April 2013 of Medical Devices including In socioeconomically reasonable Vienna, Austria Vitro Diagnostics and Companion Diagnostics: Legal and Practical option at the moment. The Electronic Reporting of ICSRs in the Aspects of Devices answers of patients for the EEA 10-12 June 2013 interview indicate that most social 17-19 April 2013 Amsterdam, The Netherlands San Marino costs of their addiction diminish Training Course: Signal Management in with MMT. The analysis shows Training Course: Premarketing Clinical Pharmacovigilance that in Poland it is economically Safety 10-11 June 2013 18-19 April 2013 Nice, France 75 reasonable to use MMT and the Vienna, Austria findings of the work indicate that Training Course: How to Prepare there should be more facilities EudraVigilance - Electronic Reporting of for Pharmacovigilance Audits and ICSRs in the EEA Inspections that dispense methadone. 22-24 April 2013 11-12 June 2013 Although there sometimes are London, United Kingdom Nice, France ethic arguments against MMT, Training Course: Benefit/Risk EudraVigilance - Electronic Reporting of such as that we should not supply Management ICSRs in the EEA addicts with drugs and that they 13-14 May 2013 12-14 June 2013 are usually never really free of Zurich, Switzerland Madrid, Spain addiction. From medical and EudraVigilance - Electronic Reporting of EudraVigilance: Introduction to purely socioeconomic points of ICSRs in the EEA Pharmacovigilance and Electronic view, it is clear that dispensing 13-15 May 2013 Transmission of Individual Case London, United Kingdom Safety Reports (ICSRs) for the Use of methadone, under proper Eudravigilance supervision, is a great way to EudraVigilance: eXtended 18 June 2013 lower the sum of all drug related EudraVigilance Medicinal Product London, United Kingdom Dictionary (XEVMPD) costs and should be further 16-17 May 2013 EudraVigilance: 1st Information Day continued. London, United Kingdom on Periodic Safety Update Reports -ICH E2C(R2) Periodic Benefit-Risk EudraVigilance: 14th Eudravigilance Evaluation Reports (PBRERs) Information Day 19 June 2013 23 May 2013 London, United Kingdom London, United Kingdom EudraVigilance - Electronic Reporting of Meeting: Impact of the New ICSRs in the EEA Pharmacovigilance Legislation on 19-21 June 2013 Regulatory Affairs London, United Kingdom 4-5 June 2013 London, United Kingdom EudraVigilance - Electronic Reporting of ICSRs in the EEA 26-28 June 2013 Zagreb, Croatia (Hrvatska) gf GLOBAL FORUM | REACH
INDIA Gujarat FDCA Signs MOU with DIA DIA has signed a Memorandum of drugs through efficient and of Understanding (MoU) with the effective regulatory practices in Kaushik Gujarat (India) Food and Drug the state. Desai Control Administration (FDCA) “This strategic partnership Director, DIA to collaboratively strengthen 76 will bring DIA India closer to India the drug regulatory system in the state of Gujarat. Under regulators, and supports our this MoU, each party agrees to objective of imparting training collaborate as a strategic partner programs of the highest quality in organizing training programs, for the betterment of our VOL 5 ISSUE 2 and related knowledge sharing profession and of the patients we and networking initiatives, for professionally serve,” explains the purpose of better monitoring Kaushik Desai, Director, DIA India.
The Core Competencies of a Medical Writer: Should a Medical Writer be Medically Qualified? Dr. David Clemow This article includes a set of Clinical Research Scientist, leading questions and the Eli Lilly and Company responses around the skill sets Helle Gawrylewski, MA required of a medical writer, how Senior Director, the roles and the associated Head Medical Affairs & Alliance proficiencies differ across Management, Regulatory geographies, the need for a Medical Writing, Janssen unified competency model, and Research & Development, LLC whether a medical writer really Dr. Nimita Limaye needs to be medically qualified. Vice President, The discussion will be driven by Biometrics and Medical Dr. Nimita Limaye and expert Writing, TCS inputs are provided by Dr. David Q Clemow and Helle Gawrylewski. &A NL: Helle, if you were to NL: Helle, do you feel that a very helpful. Because being able name the top three key young medical writer should to comprehend and communicate competencies that you would first acquire specialization scientific concepts is critical to the consider when recruiting a in a document type or in a medical writer’s role. medical writer, what would therapeutic area, especially those be and how would you keeping in mind the way NL: Helle, what does ‘Lean rate them? pharmaceutical companies Writing’ imply, and what should are structuring themselves a medical writer focus upon HG: While many core these days? if he wants to write a lean competencies are necessary document? for successful professional HG: I’m an advocate of a broad development, I would consider background and grounding HG: Lean writing is only part of a solid scientific or clinical in documents across the lean thinking and processes. It background with a foundation drug development process. includes an assessment of wastes in logical scientific thinking, But certainly a strong level of in a document or in the process exceptional communication skills, experience in organizing and of developing a document. Are and the flexibility to develop writing clinical study reports would unnecessary steps and hand solutions in a changing regulatory be a necessary specialty as a start offs leading to wastes in time environment to be the top three. for a regulatory medical writer. and creating errors? It’s about developing a critical way of NL: Dave, could you please NL: Interpretation and thinking about a document so the comment on the similarities presentation skills are key focus is on a clear but complete and the differences in the competencies of a medical communication of ideas with the 77 skill set of a regulatory writer writer. Dave, what are some audience in mind. What does versus a publication writer? of the things that a writer a particular audience need to should keep in mind while know in the text, what can be DC: While all medical writers, interpreting the data and included by reference? A lean despite their niche, have presenting the results? approach does not develop in overlapping core competencies, a vacuum; it’s a comprehensive there are some focuses for DC: It is critical that the writer way of approaching a project and regulatory versus publication fully understand who their target looking at all opportunities for writers. For example, while audience is and what key content simplification and efficiencies. regulatory writers need to be is needed to meet their needs familiar with guidelines from and to deliver the appropriate key NL: ‘No passion in the world, regulatory authorities and the messages. Everything and the no love or hate, is equal to the International Conference on kitchen sink are not needed! It passion to change someone Harmonization, publication writers is a skill of the medical writer to else’s draft’, said HG Wells. need to be familiar with journal know what is needed, know what What do you think are the key guidelines and publications is not needed, and to concisely attributes of a good reviewer? standards such as Consolidated deliver the message. The writer Standards of Reporting Trials needs to be able to work closely DC: The medical writer must (CONSORT). Regulatory writers with a team (medical, clinical, set expectations for the review, likely need to have a breadth statistics, data management, letting the reviewer know what of knowledge about a broad and regulatory) to deliver the the writer wants out of the review. range of document types, for content to the audience. Being The reviewer must be focused example: study documents such able to digest the team’s input, on the task at hand and be as protocols and study reports; bring them to consensus, and devoted to a critical review; that and compound documents such concisely and accurately write it is, the reviewer should not be as annual safety reports, clinical up is a core skill of the medical thinking they have another shot summaries, and clinical overviews. writer. While a medical writer to look at it when doing their Meanwhile, publication writers are does not have to have a medical review! A reviewer should not more focused on the development degree or necessarily be a pose questions back to the writer of abstracts, manuscripts, posters scientist by background, having but rather provide answers. For and slide kits. the science background can be example, if the reviewer doesn’t gf GLOBAL FORUM | REACH
like the way something is written, NL: Dave, knowing that project segments of information, the she should suggest exactly how management and co-authoring text pieces, the topics as also she wishes to see it written. If she are important skill sets, would data that can be structured in thinks something is missing (eg, you say behavioral or technical a way to add quality, minimize data output or reference), then skills are more important for a errors, and decrease time and she should suggest which data medical writer? effort. As for tools, these are and which reference. The medical changing constantly but at writer cannot be a mind reader. DC: At a very high level, the skill least an openness to consider The reviewer should leave editing sets of a medical writer could be different approaches to building to the medical writer and/or grouped into three categories: documents and submissions is editor, except when something is writing, science, and project/ required. Structured authoring incorrect clinically or scientifically. people management. In my using open Darwin Information opinion, being skilled in all three Type Architecture (DITA) NL: Helle, why do you think areas is important for a medical standards or Health Level 7/ that ‘project management and writer to be successful long term. Clinical Data Interchange co-authoring’ are increasingly Being able to concisely write a Standards Consortium (HL7/ becoming core skills of a good message with tables and text CDISC) models is just finding medical writer? is the core skill set. Being able application, and medical writers to interpret and discuss clinical can provide valuable input as HG: A lead medical writer is the and scientific data and concepts these approaches are rolled out in linchpin of the writing process. is also important for developing the pharmaceutical industry. This is particularly the case clinical/pharmaceutical-based 78 in an industry where there is documents. But, if the writer, NL: Language skills or usually an authoring team of who has to interact with so many scientific proficiency – which experts. Excellent planning individuals to get their work done would you think is the more and management skills drive and has to receive so much input important of the two, Dave? the process and make certain from others to get their work
VOL 5 ISSUE 2 that contingencies are taken done, does not know how to DC: Do medical writers need into account because the manage projects and people, they to be scientists is a question process is unpredictable and are unlikely to be truly successful. debated within the medical writing dynamic. The writer needs to One must have the technical skills community. Most scientists and balance the timeline with the as the base or their behaviors pharmaceutical staff think they content and quality and make will not make up for it, but to be can be a medical writer – not true. sure that steps are in place (or successful long-term, the project Writers often think they can be a resources) to assure both factors management and behavioral medical writer without a science are considered. As for the co- components are very important. background – often not true. I authoring skill, the writer not think that being able to organize only coordinates and drives the NL: Does a medical writer need documents, get the right content writing process but needs to to be IT savvy; if yes, what are in, and write concise content that contribute content. As a scientist, the key tools that a medical flows and tells the scientific story communicator, and problem writer needs to be familiar needs to be the core skill set of solver, contributing content that with? the medical writer. However, when meets the needs of the audience writing scientific documents, to but also the needs of the writing HG: Absolutely! We need to develop the document well, the team of the sponsor is the unique fully embrace the trend to reuse science background can be very value a writer brings to a project. as much standard or routine important. One does not have to In a pressured atmosphere that text as possible and be aware be an expert on a therapeutic area demands increasing speed, a of the technology that can or scientific topic, but needs to writer who can distill ideas quickly leverage effective use of these be able to understand scientific and offer several options for developments. We cannot be talk and concepts. One needs to presenting these ideas is an asset limited by seeing our writing be able to look at data and be to the team. efforts exclusively in terms of able to ask the right questions to documents. We need to see the his or her medical and statistical NL: Dave, what do you think good mentors along the way also colleagues. The writer needs to be are the proficiencies that a is invaluable. able to listen to the answers and medical writer acquires as he be able to interpret them and do moves up the career path? NL: Dave, can you comment something with them; otherwise, on a unified model for the writing team can just spin their DC: Medical writers should build competency mapping across wheels. For me, both writing and their skills across writing, science, geographies for medical science are important, along with and project management as writers, and can there be project management. I would look they grow. If one of those areas some unified assessments for all three when hiring a medical is weak, then that is a likely that would help one compare writer. Don’t forget that we can place to focus on additional writer’s proficiencies across also utilize medical editors, whose training. Gaining understanding of geographic regions? focus can be on format, language, statistical language and concepts DC: I believe there can be a mechanics, grammar, and so is important. From a regulatory unified competency model with forth. writer perspective, gaining depth of experience within a document core competencies important for NL: So does scientific type is important but so is breadth all medical writers globally. In fact, proficiency mean that a of experience across document DIA’s Medical Writing Community medical writer should be types. That is, just because a has developed and published medically qualified, Helle, or do writer did well on one protocol a Medical Writing Competency you think with a qualification does not mean they will on the Model developed by and for in life sciences, the medical next. And just because a writer global medical writers, regardless writer can be trained to has written a ton of protocols, of geography or niche. The model 79 acquire the necessary medical does not mean they can now describes knowledge, skills, and knowledge to be able to write a clinical summary. Writers abilities that are believed to be interpret and represent the generally graduate from study important for successful medical results accurately? reports to protocols to summary writers. The model also touches documents to less template- on skills needed that are specific HG: Actually, it’s not as simple oriented documents such as to regulatory versus publication as I once thought. A medical regulatory responses and briefing writers. or life science degree does documents. Publication writers not necessarily guarantee a grow as they work on slide kits NL: Helle, do you believe that good medical writer. But a solid and other therapeutic areas. India has the potential to understanding of the scientific develop a large pool of medical process and medical knowledge NL: Helle, which do you think writers, and what do you think allows a writer to facilitate the are some of the inherited skills are their core competencies writing process and lead complex of a good medical writer that and their weaknesses? projects successfully. It’s as no training can really develop? HG: The potential is there for much about being able to learn India to develop medical writing on a constant basis and know HG: Attention to detail, as a profession. I am concerned how to collaborate with all the organizational skills, desire to that the new scientifically trained various experts involved in putting learn, patience with a paragraph, students do not acquire realistic a project together. So it’s more ability to self-edit, humility to seek expectations. Bringing the about understanding the data help, large doses of common available competency model and knowing how to acquire the sense, the ability to work well mentioned by David to academia understanding that is the key, I with others – these soft skills play or continuing to discuss the think. Of all the competencies a significant role. But I wouldn’t topic at professional meetings that can be acquired by training, say that no amount of training would serve well in developing probably foundational medical and can develop these. A self-aware awareness of medical writing as scientific knowledge might be the person can learn and hone these a profession. Developing good most difficult. skills given enough opportunities and challenges. Having some writing skills takes time and perseverance, not many seem gf GLOBAL FORUM | REACH
to acknowledge that; there’s need to think about what training NL: Helle, to conclude, do you a great impatience. Certainly they have available for their staff agree that being medically having scientific training and before hiring someone that comes qualified is an asset, but not a medical backgrounds are core into the role without the right requisite to be a good medical competencies that do exist in background. Does the manager writer? India. Weaknesses could be the have a scientific training program impatience, not willing to work – a writing training program? If the HG: I agree that having a solid in a position for many years to applicant is lacking experience, scientific or medical background is grow into it. Also there are still does the applicant have the an asset and a prerequisite. That’s Latin America some challenges with verbal aptitude to learn it? Does the not to say that the background communication and leadership company team have time to let necessarily means a certain ability in the virtual world. Looking the applicant learn it?! I think it is degree. But a balance of skills back over the last several years important to remember that there and knowledge, whether acquired though, I’d say much progress is a difference and some nuance by obtaining a degree or by has been made in increasing the between a medical background experience is a must so there are MW pool, so we’re very much on (eg, doctor or nurse) and a competencies in a broad range the right track. scientific background (eg, PhD). of areas: regulatory information, The question could be ‘Should statistics, editorial skills, project NL: Dave, do you think it a Medical Writer be Scientifically management, relationship is easier to train a medical Qualified.’ If the science is building, leadership talents, professional in writing skills or deemed to be needed, then an strategic thinking, judgment, and the other way around? MD with a research background clear thinking that leads to clear 80 could be better than a PhD in a writing. DC: In my experience there have biological science, who might be been successful medical writers better than someone without a who have come from a liberal science background. References available upon request arts background and successful
VOL 5 ISSUE 2 writers who have come from a scientific background. They picked up the opposite skill set. UPCOMING However, in my experience, it is easier to teach the necessary EVENTSINDIA writing skills to the scientist CONFERENCE than the other way around. But, Meeting: Conference on in reality, it depends upon the Technological Advances in Meeting Regulatory Challenges aptitude and learning agility of April 25, 2013 the hired individual. The best hire Mumbai is the person that has a minimal proficiency in both writing and Meeting: 6th DIA Regulatory science out of the gate. Do not Conference: India, the Upcoming Economy: forget those project management Encouraging Enforcement of skills! The hiring mangers really Regulations May 23-24, 2013 Ahmedabad Generics/APIs July 2013 Hyderabad 8th Annual Meeting in India October 2013 Mumbai Q & Latin America Questions and Answers with Dr. Gustavo Kesselring
Gustavo Kesselring, MD, with the whole community of serves on DIA’s Advisory clinical research professionals that Council for Latin America I have worked with over the last (pACLA). The Council provides 25 years. 81 strategic input and advice to DIA’s Board of Directors, as What is one goal you have set well as input and feedback for yourself as a member of on programs and services in pACLA to advance the mission Latin America. Dr. Kesselring in this area? has been an integral member My goal is to help to increase the of pACLA for 2 years. Below, awareness of DIA membership he offers some insight into benefits and activities within Latin industry in Latin America and America. the goals of pACLA. How do you see the industry What inspired you to apply evolving in Brazil the next 5 for a pACLA voluntary board years? member position? The pharmaceutical industry in I have been involved with DIA Brazil is growing very fast and activities in Latin America will be a major global player in the and USA since 2003 and was medium term. All stakeholders responsible for bringing the DIA involved in drug development Clinical Research Congress to will benefit if we start having Brazil in 2006 and again in 2007. more activities in Brazil in the I have realized that to volunteer next 5 years. for a pACLA board position would benefit and would help connect In your view, what should be the priorities for DIA to address in the Latin American Q region? &A gf GLOBAL FORUM | REACH
Develop online and live training programs in Drug Development Dr. Gustavo Kesselring has been intimately involved in clinical Sciences for the Latin American research in Brazil and internationally for the past two decades. community. Currently, Dr. Kesselring is Executive Director of ViS Research Institute , a research institute for the study of globalization of What are the unique challenges biomedical research and clinical trials with offices in New York, faced by the Latin American São Paulo, and Mumbai.Dr.Kesselring is also Past President of market that differentiate it from Brazilian Society of Pharmaceutical Medicine (SBMF) and a mem- the other global regions? ber of the Executive Committee of the International Federation of JAPAN Associations of Pharmaceutical Physicians (IFAPP). Dr. Kessel- Latin American countries have ring was Director, Clinical Operations of Clinical Research at the not developed an innovative Science Institute at German Hospital Oswaldo Cruz, São Paulo, pharmaceutical industry until Brazil where he has developed the National Clinical Research the 2000´s, but since then some Training Program for the Ministry of Health in Brazil and served countries are speeding up due as its director during 2009/2010.He has been Chairperson and to heavy investments in scientific speaker at the DIA Annual Meeting and currently member of its education and post graduation Latin American Steering Committee and a member of the Bra- programs. The challenges our zilian Medical Association (AMB) at World Medical Association region will face is to develop new (WMA) for the issues related to the Declaration of Helsinki. In medicines for its own diseases March 2011, he was granted by the American Academy of Phar- and for its own public health maceutical Physicians and Investigators (APPI ) with the 2011 needs. Honorary Lifetime Membership Award due to his contribution to 82 What would you advise to clinical research and pharmaceutical medicine. other industry leaders looking into applying for a DIA pACLA position in the future?
VOL 5 ISSUE 2 Get some mentoring about DIA and participate in the Annual Meetings before joining.
Latin American Regulatory Conference (LARC) 2013: “Pharma-Co-Vergence”
May 15-16, 2013 Bogota, Colombia
Register Today! www.diahome.org/LARC2013 JAPAN
Kenji Nagaya
Program Vice- 83 Chair Nippon Kayaku Co., Ltd. Clinical Data Management Workshop in Japan The 16th Annual Workshop however, we can hear the word in Japan for Clinical Data ‘smart’ regarding these changes Management (CDM) was held on - because people don’t hope to February 7 - 8, 2013 in Tokyo. be swayed by them, they hope There were approximately 200 to take advantage of them. attendees in the workshop from We think that the environment Japan, Asia, US and Europe. surrounding the CDM is similar to this. Therefore the theme has This year’s workshop was entitled, been determined as “SMART “SMART CDM.” Changes in CDM” because we would like to ‘Information’ and ‘Technology’ consider the following keywords in are fast-growing, complex, this workshop: global, and massive. Recently,
Standardization, Strategy, Safety, Simplification Management, Metrics, Metadata, Multinational, Assurance, Asia, Accuracy, Adaptive design, Regulation, Reliability, Relationship, Risk based approach, Technology, Teamwork, Terminology, Translate gf GLOBAL FORUM | REACH
The workshop consisted of six In this session, three presenters this workshop. Two presenters sessions over two days. explained how we can use any IT have shown “Integrity” from system with SMART. This session the two different viewpoints of Two sessions were held on indicated that data managers regulator and CDM. After that, the first afternoon. The topic will need to become “Health a panel discussion was held by for Session 1 was “Journey to Informatics Engineers.” Session these presenters where they SMART CDM.” CDM is expected 4 was devoted to “Finding the discussed integrity. The audience to be simple and cool (=SMART!). Right Path for SMART Data also participated in this robust Three presenters have shown Integration and Interoperability” discussion. what constitutes “SMART CDM,” from three different perspectives: from standardization, technology, “Metadata,” “Standardization,” The “CCS (CDM Chatting Session) process, and communication. and “Clinical Data Repository,” Report” was presented before Then we reached a new keyword; which this session considered Session 6. A special program on “Informatics.” The second topic end-to-end clinical data process CCS was held in the morning of of “Approaches for Global to facilitate data integration and the first day in this workshop. This Studies - Asian Challenges” was interoperability. year, we had about 50 attendees. addressed in Session 2. Four They were divided into six topics presenters shared information Session 5 focused on the “Risk of Globalization, Standard, EDC, based on various experiences Based Approach.” Four presenters Career path, Communication, and and exchanged opinions on what explained the concept of risk Oncology, where they discussed Asian CDMs generally consider management from the point of their concerns regarding their daily as a global partner under the view of controlling the quality of work activities. The attendees not 84 circumstances surrounding Asia. clinical data, and the detection only listened, but also actively “Global Standards” and “CDISC” method of the risk. CDM plays a participated. The CCS, therefore, are important keywords. key role in supporting risk-based made a good relationship and monitoring and ensuring data atmosphere among the attendees There were four additional quality with optimization. before the start of the main
VOL 5 ISSUE 2 sessions on the second day. sessions. “Looking at SMART IT” was The final session “Let’s discuss discussed in Session 3. While what the Integrity is!” attracted This workshop closed with great computerization and networking much attention in this workshop. success. We’d like to thank all of every type of information In addition, the program attendees and supporters for related in medical site and clinical committee was pleased to this success. And we are looking study continues to expand, welcome a regulatory authority forward to meeting you at next standardization and integration for PMDA (Pharmaceuticals and annual workshop in Japan for of data have been implemented. Medical Devices Agency) from CDM in 2014.
NOW AVAILABLE DIA 2013 Training Catalog
Education that Fosters INNOVATION diahome.org/trainingcatalog Tetsuomi Takano, RPh
2013 Program 85 Vice-Chair
7th Annual Asian New Drug Development Conference
Since 2007, when DIA presented Conference in Japan for Asian our first Annual Conference New Drug Development, April 15- in Japan for Asian New 16 at Nakano Sunplaza in Tokyo. Drug Development in Tokyo, opportunities for collaborative, Kihito Takahashi, MD, PhD multinational/multiregional clinical (GlaxoSmithKline K.K.), who trials in Japan and surrounding served as Program Chair for countries that benefit patients 2012’s 6th Annual Conference through the region have in Japan for Asian New Drug considerably grown – and so have Development, returns to chair this the challenges that accompany year’s 7th Annual event. Several such trials. DIA’s member and members of the 2012 Program volunteer network in Japan Committee have also returned have ensured that this annual to help develop 2013’s program: conference leads this growth 2013 Program Vice-Chair and helps the drug development Tetsuomi Takano, RPh (Astellas community navigate these Pharma Inc.), 2012 Program Vice- challenges, and comes together Chair Yoshihiko Ono (MSD K.K.), to present our 7th DIA Annual Junichi Nishino (Novartis Pharma gf GLOBAL FORUM | REACH
K.K.), Akio Uemura, PhD (Allergan executive-level viewpoints, future Japan K.K.), and Yoshiaki Uyama, visions, NDA/MAA applications, PhD (Pharmaceutical and Medical Multiregional Clinical Trials Devices Agency, Japan). (MRCTs), health care settings, and UPCOMING day-to-day field operations, in the EVENTS Attendees will receive welcoming, region. JAPAN opening remarks from Ko CONFERENCE June 10 Sekiguchi (Director, DIA Japan), Two comprehensive, extended 2nd CMC Forum in Japan Tatsuo Kurokawa, PhD (Chair, sessions will be devoted to at KFC Hall, Tokyo DIA Advisory Council of Japan; “Exploring Best Practices on Professor, Division of Regulatory Development Regulatory Affairs June 12-13 Sciences, Faculty of Pharmacy, and Clinical Development Related 2nd FDA IND/NDA Training Course in Japan Keio University), and DIA Board to MRCTs in China, Korea and at IVY Hall, Tokyo President Ling Su, PhD (Sidley Taiwan.” Throughout this program, Austin LLP). The conference then speakers and panelists with July 11-12 proceeds through sessions that extensive practical experience 4th Cardiac Safety Workshop in will explore drug development with new drug development in Japan at IVY Hall, Tokyo strategies and practices from Asia will provide insights that global and regional perspectives. promise to be particularly useful Market access, an important to attendees from companies who factor in determining drug are planning to file IND or NDA development strategy, returns applications in China, Korea and/ 86 as an important topic from last or Taiwan. year’s conference; so does the interactive workshop on new drug DIA Japan is pleased to development, which was very present this conference with our well-received at our 2012 event. media partners “The Gold Sheet,”
VOL 5 ISSUE 2 “The Pink Sheet” and PharmAsia The biggest feature of the 7th News. Annual Conference is further focus on “Development Strategy in East Asia” throughout whole two days in comparison with previous conferences. Various analyses and recommendations on development strategies will be presented from multiple aspects, such as NORTH AMERICA
Meryl Comer 87
DIA 2013 Alzheimer’s Call to Action Experts estimate that more than In the US, the National Alzheimer’s 35 million people worldwide, Project Act of 2011 called including more than 5 million for a national plan to combat in the US, currently suffer from Alzheimer’s disease. This plan Alzheimer’s disease related was unveiled by US Health & dementia. The Global Burden Human Services (HHS) Secretary of Diseases, Injuries and Risk Kathleen Sebelius at the May Factors 2010 Study (GBD2010), 2012 Alzheimer’s Research a systematic scientific effort Summit: Path to Treatment & to quantify, over time, the Prevention. The goals of this plan comparative magnitude of health include new research funding, loss by age, sex and geography, new training for clinicians and issued in March 2013, called other health care providers on Alzheimer’s disease “the fastest recognizing disease symptoms, growing threat to health in the and an awareness campaign that US.” encourages caregivers to seek information at the HHS’ new caregiver support website, www. alzheimers.gov. “These actions gf GLOBAL FORUM | REACH
are the cornerstones of a historic advocacy and industry groups are “Our mission is early AD effort to fight Alzheimer’s disease,” pursing to elevate this disease diagnosis, which further Secretary Sebelius announced. on their respective agendas. defines our role as a catalyst “This is a national plan – not a This first forum will serve as the funder for open source ‘Global federal one – because reducing foundation for subsequent forums NeuroDiscovery’ challenges that the burden of Alzheimer’s will that will focus on patient and aim to advance innovation in self- require the active engagement caregiver perspectives (Patient administered mobile applications of both the public and private Advocacy, Caregiver Support for brain health, Alzheimer’s sectors.” and Health Care System Impact clinical trial data mining for sex- [1:45PM]) and on how to advance based differences, and validation On June 26, DIA 2013 49th clinical development in this studies of mobile digital devices Annual Meeting: Advancing specific disease area (Clinical for assessing and tracking early Therapeutic Innovation and Development Successes and cognitive decline.” Regulatory Science will feature Challenges [4:00PM]). The Call three Advancing Alzheimer’s to Action will be chaired by Meryl “Our goal is to ignite and mobilize Innovation Forums developed to Comer, President of the Geoffrey new parts of American society, accomplish this same goal: To Beene Foundation Alzheimer’s and to program new circuits and bring together representatives Initiative. flows of collaboration, in the fight from the scientific, patient against Alzheimer’s, especially in advocacy and industry Meryl has spent most of the past its early and invisible stages where communities and collaboratively two decades as the primary at- experts believe our best hope for engage in the fight against home caregiver for her husband, meaningful treatments and even 88 Alzheimer’s disease (AD). a physician and National Institutes prevention lie,” Meryl says. of Health research scientist “According to the World diagnosed with early onset In December 2012, “The 21st Alzheimer’s Report, 36 million AD at age 57. Meryl is also an Century Brain Trust ™,” a coalition people are currently living with Emmy award-winning broadcast of four nonprofit organizations –
VOL 5 ISSUE 2 dementia. This disease not only journalist with more than three the Geoffrey Beene Foundation places a tremendous burden decades of experience as a Alzheimer’s Initiative, the American on families and financial burden reporter, producer and talk show Health Assistance Foundation, the on our health systems, it has host. She has served two terms USAgainstAlzheimer’s Network changed the very nature of on the National Board of the and the Cleveland Clinic/Lou Rovo generational relationships – in Alzheimer’s Association, serves on Center for Brain Health – won many cases, ‘the child’ must the board of USAgainstAlzheimer’s a $100,000 prize in the Sanofi become ‘the parent’ responsible and is a founding member of “Patient Health Collaborate | for their own mother or father,” the WomenAgainstAlzheimer’s Activate Innovation Challenge.” explains DIA 2013 Annual Meeting Network. This prize will help validate self- Program Chair Sandra Milligan, administered cognitive testing JD, MD (Genentech, Inc., A “The Geoffrey Beene Foundation applications (digital mobile apps) Member of the Roche Group). Alzheimer’s Initiative (GBFAI) (also which individuals could use “We’ll work together and discuss known as the Geoffrey Beene to measure their brain health these issues, and bring those Gives Back® Alzheimer’s Initiative) and establish baselines to help conversations back into not only was launched in November 2007 scientists fight Alzheimer’s and our respective workplaces, but as a charitable beneficiary of the other cognitive disorders long into the lives of the people with Geoffrey Beene Foundation,” before symptoms appear. “This is whom we’ll reunite when we get Meryl explains. “100% of the net science innovation, not science back home.” profits from the global designer fiction. The tools exist today and only menswear brand Geoffrey need a unifying vision and a public- The opening forum, A Call to Beene fund this unique retail/ facing platform,” Meryl emphasizes. Action (10:15AM), will examine philanthropic model that spans “The new alliance of cognitive the global impact of AD and innovative research across major innovators known as ‘The 21st strategies that key industry, diseases from cancer to heart Century Brain Trust ™’ is working disease to Alzheimer’s.” to find, actualize those visions husband who got it at 57, and my efforts that supported real and technologies of the future in mother who got it at 85,” Meryl advances in therapeutic research, the battle against Alzheimer’s and concludes. as well as liberating women across dementia today.” the country to demand more from Does Meryl see the advocacy their healthcare,” she continues. Why bring this battle against AD efforts from the AIDS patient/ “The Alzheimer’s community must to DIA? caregiver communities in the use this heritage, but in new and 1980s and ‘90s as a model for innovative ways for a different “I really believe that your Alzheimer’s patient/caregiver world where medical science organization has embraced advocacy? can do more – a world where collaboration and synergy among the pharmaceutical industry is the health care industry and the “The HIV/AIDS activism of ACT- constrained by different pressures, public and private sectors as UP and the more mainstream and new digital media have again well as patients and caregivers. ‘Pink Ribbon’ campaign to fight redrawn the lines between the What makes DIA important to breast cancer have much to teach personal and political.” the fight against Alzheimer’s is the Alzheimer’s community. Both your integrative approach that of these defining movements Meryl’s extensive journalism and unifies disciplines and innovators incorporated patients, caregivers, broadcast experience also gives across proprietary boundaries that healthcare professionals, her a vision for how broadcast and were once unbreachable,” Meryl researchers and the general public other media can join the battle explains. It’s very hard to get – their lessons are for everyone,” against AD. some of these groups who often she suggests. work ‘in silos’ to work together.” “Mainstream entertainment and 89 “ACT-UP actualized the feminist news media deserve credit for “The basic grammar of Alzheimer’s concept of ‘The personal is being more open and generous research will have to change. For political’ and turned individuals with airtime to confront the too long, data and expertise have living with HIV and AIDS into been siloed away for marketplace. soldiers at the front lines of This may have worked before, the protest for greater medical but not in an era when we need research and overall recognition huge quantities of new data from from the pharmaceutical especially hard-to-reach pre- industry and government. They symptomatic at-risk individuals also set a high bar for patient who will show us how the disease awareness and self-direction, behaves at early stages, before often innovating new care and damage is done,” she continues. treatment methods themselves. And finally, they defined our “DIA exists at the intersection of current approach to working these evolving interests, where with the industry and FDA, scientific innovation and data meet holding them strictly accountable an industry in transition. For DIA, but also developing long-term we provide a very good example collaborative relationships that of a big scientific, societal and facilitated research advances. economic problem. Where better Virtually all patient advocacy to challenge ourselves for new groups today owe something solutions to the Alzheimer’s to these groundbreaking crisis?” strategies.”
“I don’t want this session to “The ‘Pink Ribbon’ movement be the same old story we’ve built on these approaches heard before. And I bring to it, by further integrating the unfortunately, 18 years of being mainstream American public an at-home caregiver for both my in awareness and fundraising gf GLOBAL FORUM | REACH
American public with difficult mobile applications, you can executives, and Alzheimer’s truths about Alzheimer’s,” she download a brain baseline test caregivers who are often too begins. “You may see this disease from iTunes and track yourself. In exhausted and demoralized for in the headlines, but, there is order to get the longitudinal data yet another fight,” she continues. tremendous stigma – we hide our that researchers need to advance “And yet, even as mainstream loved ones away to protect their the science, people must sign America is beginning to glimpse dignity because the behaviors up for prevention trials. We need just how much of a threat around this disease are so bizarre asymptomatic populations to step Alzheimer’s and other dementias that the general public never really up and say, ‘We’re going to be are to our dreams of vital old age, sees what this disease looks like.” citizen scientists and pioneers Americans largely still sit back and about brain health. Alzheimer’s wait for scientists to do something “We need to move our disease is unacceptable for our to save us. GBFAI challenges conversations away from ‘an old future.’ And mean it!” this complacency and points out person’s disease’ and toward things that every American can a focus on optimal health. For “For too long, this disease and must do to become actively example, few in this country have has been left to under-funded involved in preempting our own their cognitive baseline as part of specialist researchers, over- worst-case old age scenario.” their medical record. Now, through optimistic pharmaceutical industry
Quick facts • A new case of dementia occurs Recommended Reading: somewhere in the world every four Guides: • Dementia is a syndrome that seconds. Mayo Clinic on Alzheimer’s Disease, by 90 can be caused by a number of Ronald Peterson. progressive disorders that affect • The total estimated worldwide The 36-Hour Day: A Family Guide to Car- costs of dementia are US $604 memory, thinking, behavior and ing for People with Alzheimer Disease, the ability to perform everyday billion in 2010. About 70% of the Other Dementias, and Memory Loss in activities. Alzheimer’s disease costs occur in Western Europe Later Life, by Nancy L. Mace and Peter V. is the most common type of and North America. Rabins. VOL 5 ISSUE 2 dementia. By Us For Us Guides, a free series cre- • If dementia care were a country, ated by persons with dementia, available • Dementia mainly affects older it would be the world’s 18th through Murray Alzheimer Research and people, although there is a largest economy, ranking between Education Program. Turkey and Indonesia. If it were growing awareness of cases Bio/Autobiography: that start before the age of 65. a company, it would be the Slow Dancing with a Stranger: A Diary After age 65, the likelihood of world’s largest by annual revenue from the Bedside to the Frontline in the exceeding Wal-Mart (US $414 developing dementia roughly Battle Against Alzheimer’s Disease, by doubles every five years. billion) and Exxon Mobil (US $311 Meryl Comer (expected publication, Sep- billion) tember 2013) • Worldwide, nearly 36 (35.6) million Speaking Our Minds: Personal Reflections people are believed to be living • People with dementia, their from Individuals with Alzheimer’s, by Lisa families and friends are affected with Alzheimer’s disease or other Snyder. dementias, increasing to nearly on personal, emotional, financial Caregiver: A life with Alzheimer’s, by 66 (65.7) million by 2030 and and social levels. Lack of Aaron Alterra. more than 115 (115.4) million by awareness is a global problem. 2050. The number of people with A proper understanding of the Losing My Mind: An Intimate Look at Life with Alzheimer’s, by Thomas DeBaggio. dementia will double by 2030, and societal costs of dementia, and more than triple by 2050. Nearly how these impact upon families, Internet Resources: two-thirds live in low and middle health and social care services Geoffrey Beene Foundation Alzheimer’s income countries, where the and governments may help to Initiative: http://www.geoffreybeene.com/ sharpest increases in numbers are address this problem. alzheimers.html set to occur. Source: Alzheimer’s Disease International The Alzheimer’s Association: www.alz.org World Alzheimer Report 2010 Alzheimer’s Disease International: www. alz.co.uk Alzheimer’s Reading Room: http://www. alzheimersreadingroom.com Source: www.alz.org. Meryl strongly believes that mobile digital technology and June 26: Advancing Alzheimer’s Alzheimer’s Disease Neuroimaging social media networks can help Innovation Program of the Massachusetts Al- zheimer’s Disease Research Center, turn Alzheimer’s research into a A Call to Action Massachusetts General Hospital. personal act of resistance through Forum Chair: Meryl Comer Patient Advocacy, Caregiver Sup- new longitudinal databases of Scheduled Presenters: Peter Neu- port & Health Care System Impact cognitive data from America’s vast man, DrSc: Professor of Medicine; “worried well” population, shared Director, Center for Evaluation of Forum Chair: Robert Feeney, MBA: with clinical trials in ways that data Value & Risk in Health, Tufts Medi- Senior Director, Evidence-Based Reimbursement, Sanofi have never been managed before. cal Center Rudolph E. Tanzi, PhD: Head, Scheduled Presenter: Cynthia “I don’t want our children’s Genetics and Aging Research Unit; Bens: VP, Public Policy, Accelerate generation to pay for my baby Kennedy Professor of Neurology, Cure/Treatments for Alzheimer’s boom generation’s failure to Harvard Medical School, Massa- Disease (ACT-AD); Alliance for Ag- address this issue. The costs chusetts General Hospital ing Research. of Alzheimer’s disease are George Vrandenburg: Co-Founder/ Clinical Development Successes bankrupting to families and President, USAgainstAlzheimer’s & Challenges society,” Meryl explains “On an Reisa A. Sperling, MD: Professor of Forum Chair: Andrew Satlin: Senior even more personal note, once Neurology, Harvard Medical School; VP, Eisai, Inc. you’ve seen this disease up close, Director, Center for Alzheimer Scheduled Presenter: Reisa A. you’re changed forever.” Research and Treatment, Brigham Sperling, MD and Women’s Hospital; Director, 91
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FDA Commissioner Dr. Margaret Hamburg and EMA Executive Director Dr. Guido Rasi share regulatory insights at “Regulatory Collaboration for 21st Century Innovation” during the DIA 2012 Annual Meeting in Philadelphia.
92 Regulators Meeting the Regulated at DIA 2013
VOL 5 ISSUE 2 DIA’s global, neutral forum for View from Health Canada; Dr. A former member of the CDER developing and disseminating Guido Rasi, Executive Director of senior management team and knowledge resources throughout the European Medicines Agency, Program Chair of DIA’s 45th the spectrum of medical product presented the Point of View from Annual Meeting (in San Diego, development makes DIA the EMA; and FDA Commissioner 2009), Dr. Nancy D. Smith educational programs a valuable Dr. Margaret Hamburg presented (Adjunct Professor, Temple meeting place for representatives the Point of View from the FDA. University) will serve as moderator of regulatory agencies, and of the for this CDER Town Hall, reprising industries they oversee, to work Regulators working together her role from last year’s Annual together on common challenges with those they regulate, from Meeting in Philadelphia. and mutually agreeable solutions. regional and global perspectives, will be a prominent feature of our “I’ve been doing this for about For example, last year’s DIA 2012 upcoming DIA 2013 49th Annual fifteen years and the questions Annual Meeting in Philadelphia Meeting: Advancing Therapeutic that are asked, the insight from convened an unprecedented Innovation and Regulatory the audience, and the willingness summit of senior regulatory Science. These special sessions, of FDA’s top leaders to answer executives who discussed summarized below, provide as many questions as possible, Regulatory Collaboration & 21st attendees with opportunities to never cease to amaze me. The Century Innovation: Views of personally discuss issues with questions that are asked are the Heads of Health Canada, an international constellation of what make these Town Halls,” the European Medicines Agency regulatory leadership, mostly Nancy says. “Even when I was on and the US FDA. Paul Glover, consolidated within our Global the senior management team at Assistant Deputy Minister, Health Agency Track, which culminates CDER and knew a lot about what Products & Food Branch, Health in the interactive two-part CDER was going on in the organization, Canada, presented the Point of Town Hall on the meeting’s final day, Thursday June 27. I always learned things at these practical advice for sponsors CDER Town Halls – things going and consultants on regulatory on in areas that I didn’t work with, compliance, as CDER, CBER and issues that had progressed farther CDRH work towards all-electronic than I thought, or new initiatives. environments. It’s a fascinating session.” Challenges for Stable Supply Monday June 24 of Drugs and International Dr. Robert Temple, Deputy Center Director for Cooperation: Representatives European Town Hall: Clinical Science, shares his point of view at the DIA 2012 “CDER Town Hall.” of the EMA, FDA and PMDA will Implementation of New Safety jointly explain issues in the current Legislation & Other Hot Topics: Korea FDA Town Hall; The rapidly globalization of supply chains and The new pharmacovigilance evolving Korea FDA will explain measures against drug shortages, legislation came into force, and and discuss current regulatory and a cooperative scheme among the new Pharmacovigilance Risk system and practices, including regulatory authorities and industry Assessment Committee (PRAC) government R&D investment, in – manufacturers in particular – to started work, in July 2012. This the Republic of Korea. secure a stable drug supply. forum will focus on the first experiences with the new PRAC Wednesday June 26 Latin America Town Hall: and how the PRAC interacts with Regulatory leadership from Brazil, the different EU committees such FDA-Health Canada Regulatory Chile and Mexico will overview as the CHMP and CMDh. Cooperation Council (RCC) Town the evolution of biotechnological Hall: Expert representatives product regulations in the Latin 93 CBER Town Hall: This forum will will discuss the Canada-US American region and discuss how overview CBER’s current work on Regulatory Cooperation Council these regulations are modeled ongoing initiatives, guidances and established by President Obama after and differ from European regulations. and Prime Minister Harper in 2012 (EMA) and US (FDA) regulations. and the projects that the US FDA Tuesday June 25 and Health Canada are pursuing Pharmaceuticals and Medical under this initiative. Devices Agency (PMDA) Town Canadian Approaches to Hall: PMDA leadership will Regulatory Modernization and explain Japanese regulations and International Engagement: PMDA’s current activities and This session will overview the future initiatives for faster and new set of draft regulations for more efficient review of medical orphan drugs, the corresponding products using advanced science guidelines and operational technology. elements, the adoption of A.K. Pradhan, Deputy Drugs Controller of India, at Convergence in Regulatory numerous postmarket ICH the DIA 2012 “India Town Hall.” Science Across the Strait: guidelines and the new Periodic Representatives from the Centers Benefit-risk Evaluation Reports Thursday June 27 of Drug Evaluation from mainland (PBRERs), plus the establishment CDER Town Hall: Parts 1 & 2: China and Taiwan FDA will share of educational networks and Invited panelists who will discuss their views and experience in networks of excellence to facilitate and update regulatory changes Good Review Practice and IND global drug development in and the current hot topics at review as the basis for joint Canada. CDER include the Director, Office panel discussion of collaboration The State of Informatics at CDER, of Surveillance and Epidemiology; opportunities and areas of CBER and CDRH: This session regulatory convergence between will focus on explaining Center Director, Office of New Drugs; these two centers. goals and experiences, and on Associate Center Director for gf GLOBAL FORUM | REACH
But, as you’d A Regulatory Perspective of expect from an Biosimilars in Emerging Markets: Annual Meeting Although they present promising devoted to opportunities and high market Advancing potential, the development of Therapeutic biosimilars presents unique and Innovation and complex challenges. This session Regulatory will provide high-level insight Science, into the regulatory framework for regulatory biosimilar product development in science is key markets of the Latin American Drs. Aginus A. W. Kalis (Executive Director, Medicines Evaluation Board, The consistently (Brazil, Argentina and Mexico) and Netherland), Hans-Georg Eichler (Senior Medical Officer, EMA) and EMA Executive Director Dr. Guido Rasi at the DIA 2012 “European Town Hall.” woven through Asia Pacific (India, China, Korea) the Regulatory regions. Affairs & International Programs; Deputy Submissions Track and other Enhancing Regulatory Science Center Director for Clinical sections of the program, too. A & Expediting Drug Development: Science; and the Director, Office representative sampling of these eClinical & eHealth Tools: This of Communications. related offerings include: interactive FDA panel will focus on FDASIA/PDUFA V commitments “It’s a delight to be able to sit Navigating the Regulatory related to electronic study data on these panels, and it’s always Pathway for Advanced Therapy standards, eSource guidance and been one of my favorite parts of 94 Medicinal Products (ATMPs) its impact on EDC and EHRs, the DIA Annual Meeting. Senior & Combined ATMPs: Experts and various other FDA initiatives CDER staff are just so open and from industry, the EMA and focused on EHRs, study data and so willing to explain the thought Health Canada will discuss therapeutic area standards. processes behind what’s going on implementation of the ATMP
VOL 5 ISSUE 2 at FDA,” Nancy concludes. “That Regulation in the EU, and the Meeting the Challenges of Health openness is so good for everyone. main challenges of a regulatory Care Disparities & Clinical Trial It’s an example of how, during the framework fitted for ATMP Requirements in the Global PDUFA years, we have moved developers, including key issues Environment: Representatives of from being two groups sitting for stem cell product review and the FDA Offices of Minority Health on opposite sides of the table to approval. and Translational Sciences will talk at each other, to two groups clarify expectations regarding sitting down together in a more Electronic Submissions in racial and ethnic clinical trial casual setting to talk with each PDUFA V: Leadership from the enrollment for INDs and marketing other. That’s what makes this so Office of Business Informatics, applications, meaningful inclusion special: It’s more of a dialogue CDER, will report on PDUFA of demographic subgroups than a presentation.” performance goals and (sex, race, ethnicity, age), and requirements, including the demographic analyses. development of clinical and nonclinical terminology standards, related to electronic submissions.
FDA’s Expedited Drug Development and Review Programs: Leadership from FDA and EMA explain FDA’s expedited drug development and review programs to speed the development and review of drugs for serious or life-threatening diseases for patients who lack alternative therapies. Marketing Pharmaceuticals 2013 Workshop
Over 250 regulatory, legal and review team to ensure compliance and enforcement; the use of the communications professionals with FDA and other policies and latest technologies to promote attended DIA’s 2013 Marketing regulations. products; and how to establish Pharmaceuticals Workshop, held internal systems within companies in Washington, DC, February “Early involvement of the FDA to make promotional reviews more 20-21. The annual conference is the key to optimizing your efficient. As always the audience 95 provides a forum for industry goals,” emphasized Elaine Hu benefitted from the active professionals to interact with Cunningham, Senior Regulatory participation of many FDA staff senior regulators at the FDA and Review Officer at the FDA, who members. foster a common understanding of presented during a session how marketing is conducted in a on Substantial Evidence in “This meeting has always been highly regulated environment. Promotion. Cunningham one of the best attended meetings stressed early communications in the industry. The reason is The recent 2nd Circuit court with the FDA to ease the process because it enables people to decision US vs. Caronia was a and reduce the likelihood of get caught up to date on the hot topic in many of the sessions. enforcement actions from latest FDA policies, enforcement The FDA representatives at the FDA. acts, and other developments the workshop announced the in the quality promotion of government’s decision not to Day two of the conference pharmaceuticals as well as appeal the case and said the featured breakout sessions medical devices,” said Wayne case would not affect FDA policy on “Product Communications Pines, President, Regulatory or enforcement. A number in the Pre-Approval Stage,” Services and Healthcare, APCO of lawyers who represent the “Fundamental Issues in the Worldwide Inc. Pines served on industry discussed their views of Regulatory Evaluation of Health the Program Committee for the the case’s implications. Economic Information,” and conference . “Disease State and Unbranded The conference opened with Materials.” The final session of Next year marks the 25th Annual three sessions featuring panelists the workshop was a Question Marketing Pharmaceuticals representing the FDA, including and Answer Session with three Workshop. Be sure to monitor updates on recent enforcement FDA panelists who addressed www.DIAhome.org as more details actions and new and proposed any remaining questions from the become available guidances. Many of the presenters audience. provided practical advice for all members of the promotional The panels also presented updates on government policies gf GLOBAL FORUM | REACH
FDASIA, PDUFA & DIA On July 9, 2012, the Food and (Please see the related article Panelists who will discuss key Drug Administration Safety in this issue for DIA’s efforts in PDUFA V commitments, current and Innovation Act of 2012 specific response to PDUFA V implementation plans, and related (S. 3187), including the fourth Title X, “Structured Approach to topics of particular interest to reauthorization of the Prescription Benefit-Risk”) statisticians are scheduled to Drug User Fee Act – PDUFA include Theresa Mullin, PhD V – was signed into law. This On September 20, DIA and (Director, Office of Planning legislation also encompassed the Food & Drug Law Institute & Informatics, CDER); Robert User Fee Acts for biosimilars (FDLI) teamed to collaboratively O’Neill, PhD (Senior Statistical (BsUFA), generic drugs (GDUFA) present Unwrapping FDA’s Advisor, Office of Translational and medical devices (MDUFA). UFA Package. DIA and FDLI Sciences [OTS], CDER); Stephen “S. 3187 is the culmination of followed with DIA/FDA Industry E. Wilson, DrPH, CAPT USPHS the work of the administration PDUFA V Conference in October. (Director, Division of Biometrics and Congress, in partnership These conferences facilitated III, Office of Biostatistics, OTS, with patients, the pharmaceutical foundational discussions among CDER); and Jay P. Siegel, MD and medical device industries, FDA, industry, technology (Chief Biotechnology Officer and the clinical community, and other vendors and representatives of Head, Global Regulatory Affairs, stakeholders, to provide the Food the patient, consumer and health Jansen Research & Development 96 and Drug Administration with the care advocacy and professional LLC). tools needed to continue to bring communities, about their shared drugs and devices to market PDUFA V commitments and What points does Dr. Siegel safely and quickly and promote implementation strategies. If hope to stress, as an industry innovation in the biomedical you missed these conferences, representative, which will benefit VOL 5 ISSUE 2 industry, and to help secure the or attended and would like to not only the attending audience jobs supported by drug and revisit their presentations, you but the regulatory representatives device development,” said US can purchase synchronized audio on this panel? Health & Human Services (HHS) recordings and powerpoint slides “The NBA/BLA review process Secretary Kathleen Sebelius from both conferences within under PDUFA V involves several in a statement issued upon its “Online Learning” under “Meetings changes including: Two month signing. “While enactment of S. & Training” on www.diahome. longer initial review cycles, 3187 marks an important moment org. Individual sessions are also broader FDA authority to extend for innovators across industry, available for purchase (see box at the first cycle, a new late cycle research and clinical care settings, end of article). meeting including FDA officials its most important beneficiaries Looking ahead, the first session responsible for decision making, are the patients and families of our DIA/FDA Statistics Forum and enhanced efforts to resolve that will be helped by the next 2013: PDUFA V Statistical Topics issues within the first review generation of affordable medical and Emerging New Issues (April cycle. It is hoped that better issue products this bill will help to 28 to May 1 in Bethesda, MD), communication and resolution will foster.” developed by the DIA Statistics lead to more first cycle approvals Since then, industry and Community, will provide a “PDUFA and shorter average times to regulatory professionals have V Overview.” This session will approval,” he explains. “Given worked to implement and comply be co-chaired by Stephen J. the improved FDA performance with its requirements, and DIA has Ruberg, PhD (Distinguished metrics in these areas in the last worked to develop corresponding Research Fellow; Global Statistical two years of PDUFA IV, further educational and networking Sciences, Eli Lilly & Company) and improvement may be challenging; opportunities to help lead these Lisa M. LaVange, PhD (Director, but documentation of benefits of efforts. Office of Biostatistics, Office of the new review process will be Translational Sciences, CDER). critical to ensuring support for continuing it in PDUFA VI.” Those attending our DIA 2013 eSource guidance, its impact permanent reauthorization of the 49th Annual Meeting: Advancing on electronic data capture US Pediatric Research Equity and Therapeutic Innovation and and electronic health records, Best Pharmaceuticals for Children Regulatory Science, June 23- therapeutic area standards and Acts, and joint EMA/FDA pediatric 27 in Boston, will also discover related electronic study data program review numerous sessions devoted to standards FDASIA, PDUFA V and related FDA’s Electronic Drug Registration topics. These are currently FDASIA: Impact of New Legislative & Listing System: Updates: scheduled to include: Provisions on Innovative Drug Regulatory overview of drug Development: Detailed overview establishment registration, drug Pediatric Drug Development: A of this legislation’s impact on listing requirements, annual New Paradigm Under FDASIA: regulatory professionals working in registration changes, and recent Comprehensive review of the the drug and device development updates to the Electronic Drug legislation’s impact on pediatric and/or review processes Registration & Listing System and drug development the National Drug Code Directory FDASIA Patient Provisions One Electronic Submissions in Year Later: Summary overview Impact & Interventions Related PDUFA V: Update on electronic of the provisions that enhanced to FDASIA: Increasing Diversity submissions and the development patient input into FDA decision in Clinical Trials: Symposium on of clinical and nonclinical making, as well as an update from tailoring informed consent to terminology standards from FDA and the patient community enhance clinical trial recruitment the CDER Office of Business on their implementation of diverse populations, key Informatics sociological concepts that impact 97 Global Pediatric Development: minority participation in clinical Enhancing Regulatory Science Next Steps: Senior leadership trials, and the impact of FDASIA & Expediting Drug Development: from industry, the EMA and on recruiting diverse clinical eClinical & eHealth Tools: FDA discuss the impact of the subjects. Interactive discussion of the EU Pediatric Legislation, the
Presentations available from Presentations available from Unwrapping FDA’s UFA Package: DIA/FDA PDUFA V Conference What’s Inside the Statute – What’s Next? • New Review Program for NME NDAs/Original BLAs and Enhanced Communication Between • PDUFA, GDUFA and BsUFA Highlights FDA & Sponsors During Drug Development • MDUFA Highlights • Enhancement & Modernization of the FDA Drug Safety System • Beyond Review Management: Additional Provisions for Regulatory Science, Enhanced • Structured Benefit-Risk Assessment in Regulatory Communications and Transparency Decision Making, Patient-Focused Drug Development, and Advancing the Use of Patient • Enhanced Drug Development: Greater Access Reported Outcome Measures to Experts, Pediatrics, Breakthrough Therapies, • Efficiency of Human Drug Review through GAIN/Antibacterials Required Electronic Submissions • FDASIA Provisions to Enhance Drug • Regulatory Science Enhancements: Meta- Development: Drug Shortage & Supply Chain Analysis, Pharmacogenomics & Biomarkers, and • Other Device Reforms Rare Diseases • Standardization of Electronic Drug Application Data: A Critical Factor in Improving the Effectiveness & Efficiency of the Regulatory Review Process • Ensuring the Success of PDUFA V: FDA, Industry & Stakeholder Perspectives Please visit “Online Learning” within “Meetings & Training” on www.diahome.org for these and related offerings. gf GLOBAL FORUM | REACH
Courtney Ingram 98 Manager, DIA North America Marketing
VOL 5 ISSUE 2 Exploring Social Me-DIA In December 2012, FDA sent The online patient community a Warning Letter to a company PatientsLikeMe (www. who was marketing a drug patientslikeme.org) recently product through the use of announced a new collaboration Facebook testimonials, for with a pharmaceutical company “Liking” a Facebook claim about that hopes to help members of this product. (Facebook allows PatientsLikeMe with the rare lung users to express their approval condition idiopathic pulmonary or recognition of a posting by fibrosis (IPF). “Rare diseases clicking a “Like” button which are sometimes called ‘orphan displays a “thumbs-up” icon.) diseases’ because they affect This Warning Letter explained so few people, and don’t attract that, in the absence of FDA significant research attention or approval, the products these funding. Our website is where testimonials represent are not patients count,” explained recognized as safe and effective, PatientsLikeMe Co-founder and and are therefore being improperly President Ben Heywood. “They’re marketed as unapproved drugs. contributing their real-world experience to help others living with IPF and advance research.” featured the panel discussion Medical Writing track, examined “Safety & Social Media: Is This new disclosure models that The Question or The Answer?” will compliantly communicate Chaired by Elizabeth E. Garrard, scientific information in a digital PharmD, RPh (Garrard Safety age that gives people instant Solutions) and featuring access to information through pharmacovigilance experts from Facebook, YouTube, Twitter and the industry, regulatory and other social media platforms and academic perspectives, this forum applications. Chaired by Patrick explored what social media can Reilly (Bristol-Myers Squibb) within do to improve drug safety, what the Medical Communications must change for industry and track, “Digital & Social Media: regulatory professionals to realize What Should You Know…And the value that social media can Be Thinking About It?” examined bring to drug safety, and what how health care professionals are each stakeholder can do to make using this new digital landscape this happen. We need to rethink to effectively keep themselves and Pamela Loughner, PhD, MEd (Loughner & regulations; to envision new ways their patients informed. Associates) will chair the Mobile Learning & Social to collect data; and to move away Media Symposium at our DIA 2013 49th Annual from an assembly-line model and Looking forward, DIA will offer Meeting: Advancing Therapeutic Innovation and ivory tower mentality, toward an the webinar Regulating a Social Regulatory Science on June 27. interactive transparent approach, World on July 18. Planned by the concluded one panelist. Planning DIA Regulatory Affairs Community, 99 Current estimates suggest that is underway to reprise this session this webinar will focus on how there will be more than 2.1 billion as a standalone webinar later in to incorporate social media mobile devices in use by the 2013. technologies into successful year 2016, a nearly twenty-fold and compliant marketing and increase from 2010. All these “Social Media: Digital Tools & communication plans, including facts clearly illustrate how social Considerations in Compliant adverse event reporting, from the media has become inextricably Development,” presented at regulatory perspective. woven into the scientific, Marketing Pharmaceuticals academic, clinical, industrial and 2013, chaired by Dale A. Cooke And before that webinar, our regulatory aspects of therapeutic (Digitas Health), divided into DIA 2013 49th Annual Meeting: development, and, at the same two parts: An overview of the Advancing Therapeutic Innovation time, into the personal lives of the current state of digital media and and Regulatory Science will patients for whom these therapies of tools that industry can use to present several opportunities are intended. In response, DIA work with it, and an interactive to learn more about social has presented and continues to discussion forum where panelists media in these various contexts. present educational opportunities and attendees shared important These include: Social Media, aimed to help all these experiences and points to Mobile Applications & Patient stakeholders understand and consider when developing mobile Support Programs: Challenges & make the most of social media digital platforms and applications, Solutions for Handling Drug Safety and other digital communication from multimedia news releases Information; Data from Everyone: technologies. with video and external links to Using Smartphones & the Internet smartphone apps for monitoring to Connect with Subjects (both According to the Pew Internet blood pressure. June 25); and Clinical Trial Visit of Project, eight in ten internet users the Future: Leveraging Emerging look online for health information, More recently, Medical & Scientific Technologies to Crack the Patient making it the third most popular Communications 2013 focused Recruitment Challenge (June 26). online activity among those on similar, related topics. “Medical surveyed. Pharmoacovigilance & Writing for Social Media,” chaired In addition, Pamela Loughner, Risk Management Strategies 2013 by Jennifer L. Riggins, PharmD PhD, MEd (Loughner & (Eli Lilly and Company) within the Associates) will chair the gf GLOBAL FORUM | REACH
Mobile Learning & Social Media Symposium on June 27. This symposium will focus on the social How to Manage Cross-Channel Social media platform Twitter, and how to use it to improve your conference Campaigns and career experiences. Pamela It seems like social media is everywhere, and every marketer is will focus her presentation on clamoring to get in the game. It’s no surprise why: the time most “Learning on the Go: Making global consumers spend on social media has grown more than the Most of Mobile Learning 250% in just the past two years. Therefore, it is becoming more Technologies.” and more evident that companies must engage with individuals on these multiple channels. The difficulty now is that one com- “My PhD is in Instructional pany may have to maintain and engage its audience on three, Systems and Technology, so four, five, or even more social networks at once. This can be a I’m all about looking at what daunting task if you aren’t a so-called social media expert. technology can do. Our challenge But that doesn’t mean you simply ignore social media. Clearly is that there’s so much technology there’s value to being present and effectively using, these plat- hype or ‘glitz and glamour’ out forms. here are steps you can take to help extend your brand there that people don’t look at presence across multiple social networks without a huge time its underlying importance – it’s investment. strategic value. There isn’t always 1. Aggregate Content to Accelerate Your Brand Awareness a great deal of substantive planning when new technologies Running social campaigns across multiple channels is a simple 100 become available: Everybody way to extend reach. You can ramp up participation across all flocks to them and tries to use networks by “investing” in a social media aggregator, a tool that them for everything. But we’re pulls in feeds from all these sites (and others, too) and central- trying to ask, and to answer, izes them in one place. Here are a few to choose from: ‘What makes good sense?’” Pam • TweetDeck VOL 5 ISSUE 2 explains. • HootSuite “Our other session presenters • Seesmic will be very hands-on with Twitter: One will teach you how 2. Study Personalities to tweet from the conference, Every social network has its own personality. Study what’s and the other will more or less unique about the way people use each channel and create demonstrate how to use Twitter to content that reflects that. This sounds like a lot of upfront work, network and even look for a job. but by sharing relevant engaging content you can post less My presentation will come from frequently and still grow your following. a more strategic vantage point: Mobile devices are not going 3. Sing the Same Song away; in fact, their use continues Become a brand that evokes the spirit of a given social chan- to rise. How can we be thoughtful nel. Don’t just blend in. Aim to be fun and authentic while still about this? How do we integrate showcasing your brand. this technology into what we do? 4. Don’t Get Lured by New Technologies What are the capabilities of mobile Just because it exists doesn’t mean you have to use it. Track learning? Instructionally, how the Key Performance Indicators (KPIs) for every channel and do we match the technology’s use your findings to determine where you spend your time. capabilities to our learning needs, You also need to figure out whether the extra effort is worth it. content and users?” Continuous research and testing will help you nail the social marketing mix. At DIA, we engage our stakeholders across multiple social media channels. Follow us on Twitter, Facebook, LinkedIn, You- Tube, Flickr, Google+, and Pinterest. 101
Structured Approach to Benefit-Risk Monitoring and assessing benefit- postmarket drug review process risk is such a critical step in by the end of the fourth quarter clinical trials, therapeutic product 2013. development, regulatory approval and postmarketing safety, that After determining that a structured Title X of the 2012 PDUFA qualitative approach best reauthorization (PDUFA V) was reflects the reality that benefit- entirely devoted to “Enhancing risk assessment is a qualitative Benefit-Risk Assessment in exercise grounded in the Regulatory Decision Making.” quantification of various data, FDA Among other topics, Title X published their plan, “Structured directed FDA to create a five Approach to Benefit-Risk year plan for developing and Assessment in Drug Regulatory implementing a structured benefit- Decision Making” on March 5. risk assessment: To publish a draft This plan notes that while FDA plan for public comment by the is charged to approve drugs end of the first quarter 2013, and that are both safe and effective, to begin execution of that plan neither “safe” or “effective” are and implement this structured defined by regulation or statute. framework in the pre- and “There are two areas where we intend to focus efforts beginning in gf GLOBAL FORUM | REACH
FY2013,” wrote the FDA. “The first On April 28, the DIA/FDA is characterizing the uncertainty Statistics Forum 2013: PDUFA V in how well the benefit-risk Statistical Topics & Emerging New assessment based on premarket Issues will present a “Benefit- clinical trial data translates to the Risk Evaluation” tutorial that postmarket setting after the drug will discuss the challenges of is approved and used in a much evaluating benefit-risk, the need wider patient population.” behind this structured approach, and methods for incorporating “The second area pertains to patient preferences and outcomes our level of uncertainty about a in this structure. Premarket and result or finding, particularly a new postmarket assessment of benefit- finding that becomes available in risk are also on the agenda for the the postmarket setting where the luncheon roundtable discussion basis for the finding comes from scheduled for April 30, which sources of varying levels of rigor.” will be followed by a more formal session that examines the positive Though the FDA is responsible for impact that statisticians can have most of the activity directed by on “Benefit-Risk Assessment in Title X, their actions will impact Clinical Development & Regulatory professionals working in every Review.” corner of the therapeutic product 102 development, approval and The “Structured Benefit-Risk marketing continuum, as well as Assessment in Regulatory the patients they serve. DIA has Decision Making, Patient- presented and will continue to Focused Drug Development, and present professional development Advancing the use of Patient
VOL 5 ISSUE 2 and networking opportunities to Reported Outcome (PRO) help these professionals work Measures” session from the more efficiently and effectively in October 2012 DIA/FDA PDUFA V this new environment. Conference was recorded and is available as an archived webinar Last year, DIA’s Clinical Safety & within “Online Instruction” under Pharmacovigilance Community “Meetings & Training” on www. unveiled a special Benefit-Risk diahome.org. Working Group dedicated to benefit-risk assessments and In addition to chairing this the structures and processes Benefit-Risk Working Group, Dr. that support them. “We see Noel serves as chair for several these changes creating a installments of DIA’s ongoing, broader audience and a widening eight-part Assessing the Benefits audience of practitioners that & Risks of Medicines webinar need fundamental understanding series (see accompanying box of benefit-risk assessment,” says for the schedule of the remaining Rebecca Noel, DrPH, MSPH (Eli sessions). What complexities led Lilly & Company), who chairs this to segmenting this educational working group. “So we need a series into eight topics? global cooperative, collegial forum where all stakeholders can come “Benefit-risk encompasses a together to share information broad array of topics that range on methods and tools and best from the very qualitative to the practices.” very quantitative. This webinar series attempts to give a high- level overview of that breadth, and breadth and complexity of Eight-Part Webinar as it progresses from the more what’s been developing within this Series: Assessing qualitative elements of benefit-risk emerging space. First, you have the Benefits and assessment down through some to orient people to those changing Risks of Medicines of the more specific quantitative expectations, and then provide methodologies that someone them with an overview of the tools April 24: Part 5: Stated Choice might want to use within a pharma we have to help meet these new Methods for Valuing Benefits and company or regulatory agency,” expectations. This way, hopefully, Risks Rebecca explains. it doesn’t seem as daunting a May 22: Part 6: Multicriteria task: It gives people a grounding Decision Analysis to Assist in the “These eight sessions are laid place that they can start from, and Decision Making Process out in that order. We start with can then learn more about specific June 12: Part 7: A Structured, an overview to help people who topics as they have a need,” Quantitative Health Outcomes are new to the topic or to the Rebecca concludes. Approach to Drug Benefit-Risk field understand key issues: Analysis Why benefit-risk is emerging as Planning is already underway for July 24: Part 8: Visualization & a separate, standalone topic; another educational event, titled Communication of Benefit-Risk why benefit-risk has become Benefit-Risk Assessment from The first four parts of this increasingly important; and when Inception to Maturation: Making series are available as archived and where and how we use the Critical Decisions, tentatively webinars: structured approaches to benefit- scheduled for the fall of 2013. Part 1: Introduction to the risk assessments.” Benefit-Risk – Why is Everyone In the meantime, benefit-risk Talking about Benefit-Risk? 103 “The second session provided a is also the subject of several high level overview of key industry sessions at DIA 2013 49th Annual Part 2: Benefit-Risk Assessment a Changing Regulatory initiatives: What was important Meeting: Advancing Therapeutic Landscape about, and how benefit-risk was Innovation and Regulatory Science a key component of, the recent in Boston. A On June 25, Stuart Part 3: Framing for Benefit-Risk iteration of PDUFA; current FDA Walker, PhD (Founder, Centre for Assessment and Communication activities around benefit-risk Innovation in Regulatory Science, Part 4: Clinical Judgment and assessment, including the recent UK) will chair a panel of experts Pragmatic Considerations for publication of the FDA draft from Europe, Asia and the US Endpoint Selection and Display in plan for how they will develop FDA to examine Implementing Benefit-Risk and implement their benefit-risk an Internationally Acceptable Please look within “Online assessment framework; what’s Framework for Benefit-Risk Instruction” under “Meetings & happening with the European Assessment of Medicines: How Training” on www.diahome.org. Medicines Agency and the Close Are We To This? Susan Register for the full webinar series Innovative Medicines Initiative; P. Duke, MS (GlaxoSmithKline) and save 20%! and what’s happening with the will chair Structured Benefit- new Good Pharmacovigilance Risk in the Current Regulatory Practices legislation in the EU, and Environment and the Implications this whole new paradigm that we for Clinical Statisticians in North face with the switch from Periodic America and Europe, on June 26. Safety Update Reports to Period Benefit-Risk Evaluation Reports,” she continues.
“The intent behind the series is to help people who are new, or are turning their attention, to the area, understand the depth gf GLOBAL FORUM | REACH
UPCOMING NOREVENTSTH AMERICA April 3-4, 2013 April 25 & 26, 2013 May 23, 2013 Regulatory Information Management Two-Part Webinar Series: Webinar: Certificates of 2013 Impact of the New European Pharmaceutical Products for Baltimore Marriott Inner Harbor at Pharmacovigilance Legislation and Regulatory Submissions Camden Yards, Baltimore, MD Important Updates May 29-30 & June 5-6, 2013 April 9, 11, 16 & 18, 2013 April 29-May 1 2013 Online Training Course: Good Online Training Course: DIA/FDA Statistics Forum 2013: Clinical Practices for Clinical Fundamentals of Project PDUFA V Statistical Topics and Research Professionals Management for Nonproject Emerging New Issues Managers Bethesda North Marriott Hotel & June 4, 2013 Convention Center, Bethesda MD Online Training Course: Regulatory April 10, 2013 Aspects of Prescription Drug/ Online Training Course: Conflict April 29-May 1, 2013 Biologics Advertising and Management Training Course: Pragmatic Promotional Labeling Approaches to Drug Safety across April 15-17, 2013 the Premarketing and Postmarketing June 5, 2013 CMC Workshop: From Drug Continuum Online Training Course: Essentials of Development to Global Supply to DIA Headquarters - Horsham, PA Comparative Effectiveness Research Patients for Medical Affairs and Healthcare 104 Washington Marriott Hotel, May 1, 2013 Professionals Washington, DC 3rd Annual State of Clinical Development Cost Conference June 12, 2013 April 15, 2013 McNeil Science & Technology Online Training Course: Training Course: Introduction to Center, University of Sciences, Supplements and Other Changes to Signal Detection and Data Mining Philadelphia, PA an Approved Application DIA Headquarters - Horsham, PA VOL 5 ISSUE 2 May 1-3 & 8-10, 2013 June 12, 2013 April 15, 2013 Online Training Course: Basics of Eight-Part Assessing the Benefits Training Course: Overview of Drug the IND Phase and Risks of Medicines: Webinar Development Series Part 7: A Structured, DIA Headquarters - Horsham, PA May 6-8, 2013 Quantitative Health Outcomes Online Training Course: Who’s Approach to Drug Benefit-Risk April 16-17, 2013 Monitoring the Monitor? Analysis Training Course: Global Considerations for Regulatory May 14 & 16, 2013 July 16-18 & 23-24, 2013 Strategy Development Online Training Course: Developing Online Training Course: Advanced DIA Headquarters - Horsham, PA Standard Operating Procedures Clinical Statistics for Nonstatisticians (SOPs) April 22-23, 2013 July 18, 2013 Training Course: Essentials of May 20-22 & 29-31, 2013 Webinar: Regulating a Social World Project Management Online Training Course: Basics of DIA Headquarters - Horsham, PA the NDA Phase July 23 & 25, 2013 Online Training Course: Interactions April 23, 2013 May 22, 2013 with the FDA during IND/NDA Online Training Course: Strategies Eight-Part Webinar Series: Phases for Comparative Effectiveness Assessing the Benefits and Risks Research for Regulatory, of Medicine: Part Six: Multi-criteria July 24, 2013 Compliance and Legal Professionals Decision Analysis to Assist in the Eight-Part Webinar Series: Decision Making Process Assessing the Benefits and Risks of April 24, 2013 Medicines: Part Eight: Visualization Eight-Part Webinar Series: May 22, 2013 and Communication of Benefit-Risk Assessing the Benefits and Risks of Webinar: Connecting the Right Medicine: Part Five: Stated Choice Sites to Promising Trials: The Role of July 30, 31 & August 1, 2013 Methods for Valuing Benefits and Web-based Feasibility Assessment Online Training Course: Adverse Risks Event Reporting Requirements: IND May 22, 2013 and Postmarketing Webinar: Connecting the Right Sites to Promising Trials: The Role of Web-Based Feasibility Assessment. ASIA PACIFIC
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DIA, IFPMA & HSA Singapore Present Asia Regulatory Conference 2013 From January 28-30, the Health access to new and improved Sciences Authority (HSA) of medicines. DIA and IFPMA co- Singapore hosted Asia Regulatory presented the first Asia Regulatory Conference 2013, co-organized by Conference in 2011 with the Asia- the HSA, DIA and the International Pacific Economic Cooperation Federation of Pharmaceutical (APEC) Harmonization Center Manufacturers and Associations (AHC) in Seoul, Korea. (IFPMA). Developed on the theme “Regulatory Convergence and “This three-day conference Cooperation to Improve Access offers a unique opportunity for and Quality,” this conference key stakeholders from health brought together more than 300 authorities, local and multinational experts from health authorities, pharmaceutical companies, and pharmaceutical companies and clinical research to meet and academia across almost 30 exchange views, discuss topics countries in the Americas, Asia of interest and identify focus and Europe to identify specific areas for ongoing efforts to areas that will enhance patient increase patient access to new gf GLOBAL FORUM | REACH
In his opening remarks, HSA Chief Executive Officer and Associate Professor John Lim spoke extensively about regulatory and industry collaboration for safer and better access to medicines. “We are living in a period of enormous innovation in the biological sciences. Genomics, proteomics and other ‘omics’ are being linked to technology and statistical modeling that allow Dr. Amy Khor, Minister of State for Health and researchers an unprecedented Associate Professor John Lim, CEO of the Health Manpower, Singapore, delivers remarks at Asia view of the inner workings of Sciences Authority, Singapore, addresses attendees at Regulatory Conference 2013 human biology. The ascendant Asia Regulatory Conference 2013 biopharmaceutical industry has and improved medicines,” said because of traditional regulatory embraced this knowledge and DIA Board President Ling Su, frameworks or outdated risk companies are rushing to translate PhD, in his welcoming remarks. concerns.” new discoveries into powerful, “We are honored to have Dr. Amy potentially safer, more effective Khor, Minister of State for Health “Strategic engagement and and personalized therapies,” he and Manpower in Singapore, collaborative platforms to began. 106 speaking at the event as well as stimulate scientific discussion about emerging issues in speakers from top-level regulatory “We are all faced with valid regulatory science, and fostering authorities in several Asian concerns that our traditional binary co-creation of solutions with countries and leading experts in approval for drugs is too much of stakeholders, is important in this the International Conference of a ‘one size fits all model,’ and that
VOL 5 ISSUE 2 dynamic environment,” Professor Harmonization process.” certain promising candidates for Lim concluded. more circumscribed indications “Countries like Japan, Korea and and populations are being lost. Singapore face the increasing During this conference, the Taking into consideration evolving challenge of appropriately Singapore HSA signed a new science and technology, managing the healthcare needs Memorandum of Understanding is there a better model for drug of a rapidly aging population (MOU) with the Medicines regulatory approval – one that and the rising incidence of Evaluation Board (MEB) of the is adaptive, robust, yet able to chronic diseases. It is therefore Netherlands to advance public reduce cost and time to access?” important to look at more public- health services, and further Prof. Lim asked. private partnerships to ensure enhance access to safe and effective medicines, needed by better utilization of resources “To cope with the rapid advances their respective populations. This to meet national healthcare in emerging sciences that are MOU will further collaboration needs, as well as to create the increasingly deployed during between the two agencies on right environment for ongoing drug R&D, there is a pressing pharmacovigilance and risk life science innovation,” said Dr. need to ensure that regulatory management strategies and Khor at this opening ceremony. expertise is equally cutting practices, improved benefit/risk “Greater collaboration among edge,” he continued. “Regulatory assessment of medicinal products, industry players and regulators will frameworks must be robust joint education and training of not only ensure more effective and enough to cater to the pace of regulators and postgraduate efficient drug development, and new drug development and ensure students, and other initiatives. This provide early access to safe and thatregulations facilitate the safe MOU was signed by Professor high quality products to markets, and effective deployment of the Lim and by Professor Hubert but will also ensure more effective latest science. This has to be Leufkens, Chairman of MEB, and surveillance of medicines already achieved without impeding new was witnessed by Dr. Khor. in the market.” therapy development and access DIA 2013 Advancing Therapeutic Innovation and Regulatory Science
49th Annual Meeting | June 23-27 | Boston, MA | Boston Convention and Exhibition Center
FEAtURED SESSIONS: Defining Clinical Trial Innovation: Challenges and Opportunities for 2013 SpeakerS: Susan K. Nunchuck, Craig H. Lipset PhD, MSN Head of Clinical Senior Clinical Innovation, Research Associate Worldwide Actelion Clinical Research and Research Development Pfizer Inc
Andreas Koester Jeffrey S. Kasher, Head of Clinical PhD Development Vice President, Johnson & Johnson Global Clinical Development Eli Lilly and Company
Making CRO-Sponsor Partnerships Work: Largest, Executive Roundtable Global SpeakerS: Multidisciplinary Kenneth I. Kaitin, PhD Ciaran Murray Event Professor and Chief Executive Director, Center for Officer the Study of Drug ICON Plc DevelopmentTufts University School of Medicine
Jamie Macdonald Jonathan B. Zung, Chief Executive PhD Officer Vice President, INC Research Head of Global Development Operations Bristol-Myers Squibb
SESSION HIgHlIgHtS: • Reinventing the R&D Business Model: Heeding the President’s PCAST Report on Innovation • Leveraging In-Pharmacy Education to Improve Patient Comprehension and Access to Clinical Trials • Big Data: Impact on Innovation • Advancing Alzheimer’s Innovation: A Call to Action • The State of Clinical Outsourcing: Managing Risk in Outsourced Clinical Trials
Visit diahome.org/DIA2013gF for more details. EDUCATEEDUCATE ggff
EDUCATE does just that: Keeps
you abreast of the association,
membership, regulatory, and
legislative news while including
features such as career advice,
book reviews, patient perspectives
and more. EPSA Intern Reflects on DIA 2013 EuroMeeting
Milos Stojkovic EPSA Vice 109 President of Public Rela- tions
Since 2012, DIA Europe has teamed with the European Pharmaceutical Students’ Association (EPSA) to provide an internship in our Basel, Switzerland, office. Milos Stojkovic, EPSA Vice President of Public Relations, was the most recent EPSA representative selected to serve as this intern. Working in our Basel office, Milos was actively involved in preparations for our recent 25th Annual EuroMeeting: Amsterdam 2013, where he delivered an overview of the EuroMeeting program to a special student session, and also made a presentation about his experience to the DIA Advisory Council of Europe (ACE). “Having an intern from EPSA working full time at DIA offices has been an important experience for DIA Europe,” Jytte Lyngvig, Director, DIA Europe, explained in the February 2013 edition of the EPSA Newsletter (Volume 20, Issue 2). “Aims of opening DIA events more to students and young professionals have benefitted from this move, and with the high level of professionalism shown by the intern, we are very satisfied how the partnership with EPSA is developing.” Milos shares his thoughts about these experiences in the following article. gf GLOBAL FORUM | EDUCATE
The Place Where It All Young Professionals Networking demographics can collaborate. Came Together Reception just after this meeting. 90 minutes of informal roundtable They were happy to join the event discussion between patients, Even though my internship and inspired DIA’s European patient representatives and ended just some weeks before, Director and DIA Board President advocates on one side, and the EuroMeeting was the place to welcome the attendees. Dr. students, representatives of where it all came together. This Ling Su told the story about student associations and other was where the majority of the his path from a student poster participants on the other side, office’s work in the last few presenter years ago to the DIA touched upon topics of better months, including mine, came President of today. mutual understanding and to realisation. Are students shaped some concrete ideas of and young professionals aware It was my pleasure to have the institutional collaboration. From of all the aspects developed first speaker slot on Monday both sides, it seemed that this for them? Is the smart phone morning and officially kick-start session is only the beginning of application well-synchronised with the meeting by presenting to closer contact between the two the programme (the task I was students the possible aspects demographics brought together working on)? Will the new session where they can get engaged, the by Fellowship programmes of DIA between students and patients background between EPSA and Europe. about collaboration possibilities go DIA, and how can they utilise as planned? These were some of the EuroMeeting in the best way In the end, from both my the questions running through my possible. Providing them with personal perspective and as mind when arriving in Amsterdam. personal comment, I was able a representative of EPSA, this 110 But all of them went away as the to give advice to myself, as I sat DIA EuroMeeting brought me busy schedule started to unwrap in the same audience one year great satisfaction from knowing and I was already heading to my ago for my first EuroMeeting, that students are not only the first meeting. impressed with the diversity and healthcare stakeholders of amount of activities but at the tomorrow, but that we can be
VOL 5 ISSUE 2 Kicking off with a big start was my same time intimidated by them. respected members of this presentation about the internship Discussion started to heat up as community whose ideas and experience to the Advisory Council the session speakers changed, insight equally count, even in the of Europe: Well-accepted among but it is my joy to report that the highly professional environment of this group of select individuals, message I hoped to transmit DIA and its EuroMeeting. interested in what feedback I was received: Be open and am able to provide from the communicate, and you will be perspective of a DIA intern and impressed with what will you take representative of European home with you. pharmacy students, but ultimately from the general perspective Time flew by and the third day of a student and emerging saw the last two EuroMeeting professional. This proved to sessions with special focus be a big motivational boost for on students. After the student me, knowing that the next day’s feedback session, EPSA “How to Get the Best Out of the and EURORDIS hosted the EuroMeeting” session is not just session about how these two a couple of enthusiasts who are interested in bringing students and young professionals closer to this event, but that this general feeling is shared by many. The biggest note for me most certainly was when the ACE members decided to join the Student and Engaging the Patient: Birth of the DIA Patient Engagement Community
Patient engagement may be “the new big thing” in the world of health care, but for the patient advocates who are part of DIA’s new Patient Engagement Community, it has been front and center from day one at each of their organizations. The new DIA Patient Engagement Community provides opportunities for representatives of patient organizations to collaborate with policymakers, members of the medical and scientific communities, industry representatives and academics, to advance therapeutic innovation and 111 regulatory science with the patient in mind, all in a neutral environment.
“With all the changes that we are and representation across seeing in healthcare development all disciplines within DIA. Its and delivery, the patient is objectives include sharing what becoming the primary driver works best for patients; promoting behind drug development, access patient-centered outcomes; and to drugs and health policy,” former initiating and promoting authentic DIA Worldwide Executive Director collaborations with patients Paul Pomerantz explained in the throughout all aspects of drug December 2012 Global Forum development, as well as health (Volume 4, Issue 6). “It’s through care policy and practice. There the engagement of patients in our is no other forum where these global multi-stakeholder network advocates can learn about the that we are able to adequately nuances, issues and trends that address and in fact get to the affect their organizations and heart of these matters.” ultimately their constituents. The Patient Engagement Community The mission of the Patient hopes to not only energize Engagement Community is patient advocates but more to improve health outcomes fully engage representatives of with patient engagement pharma, biotech, government, and academia who want to see the patient voice become more prominent. gf GLOBAL FORUM | EDUCATE
Through our Patient Fellowship “The Patient Engagement Programs in Europe and Community is so important at so North America, DIA continues many levels. We want to see an JOIN A COMMUNITY! to enthusiastically embrace enhanced patient voice in drug Joining a Community is easy, convenient, patients and patient advocates discovery and drug development. and free as part of your DIA membership. as stakeholders, and welcomes We really look forward to advising their increasing participation DIA members about patient- DIA Communities allow members to as speakers and chairs at our centered outcomes and issues exchange information, explore industry hot topics, and build a professional educational events, and as patient to address during the course network through a discipline-specific, representatives on our Regional of clinical trials,” she continues. global or regional Community. Network Advisory Councils for Europe and “We are so proud of the fact and share information and ideas North America, a trend we look that several program alumni are through state-of-the-art online forward to advancing in other DIA now part of the Patient Centered media and forums. regions, too. Outcomes Research Institute (PCORI) grant reviewing process.” “I had the privilege to be among Go to the first patient representatives “The recent addition of a Patient www.diahome.org/Community to speak at the DIA EuroMeeting Engagement Community affords to join the Community of your choice. in the 1990s and the first to be a any DIA member the opportunity member of the DIA EuroMeeting to interact with patient advocates. Programme Committee, thereafter It is a win-win-win situation!” a Theme Leader, and later a concurs Amye L. Leong, MBA, To become a DIA member, go to www.diahome.org/membership. 112 member of the DIA Advisory Patient Fellow Class of 2012 Council of Europe,” explains Yann (President & CEO, Healthy Le Cam, CEO of EURORDIS, Motivation). the European Organisation for Rare Diseases. “All my efforts, To learn more about the new DIA
VOL 5 ISSUE 2 with the support of EURORDIS Patient Engagement Community, colleagues and DIA colleagues please explore “Global Patient as well as the essential support Initiatives” within “Networking & of Dr. Yves Juillet and other Communities” on www.diahome. leaders in the DIA, were focused org. We also invite you to visit the on increasing the participation Patient Advocate Fellowship booth of patient representatives in DIA in the exhibit hall, to speak with activities, as a full stakeholder, a Marcia and other Patient Fellow full actor of the drug development program leadership, if you’re and regulatory processes, and planning to attend our DIA 2013 a partner in the value creation 49th Annual Meeting: Advancing chain.” Therapeutic Innovation and Regulatory Science in Boston. “We want the Patient Engagement Community to be open to all “The synergy that Patient Fellows global DIA stakeholders. The feel when they get together at Patient Engagement Community DIA conferences is astounding,” is the place to be to hear the explains Donna Mayer, Manager all-important patient voice across of Stakeholder Engagement. so many different areas.” said “Everyone realizes how much they Marcia Horn, Chair of this new could learn from one another and Community (and CEO of the conversations have continued long International Cancer Advocacy after the Fellows return home.” Network). What difference has the DIA Patient Engagement Community made?
“Rare disease conditions can be life-altering, and in some cases, life-ending, and having that voice for those people and having a group that is willing to listen to us and wants to learn more about it, it’s so meaningful, it’s very hard to describe.” – Daniel Smith, National Dysautonomia Research Foundation
“The experience of being interviewed by The New York Times at the DIA 2012 Annual Meeting was a game-changer for our organization. It has made a tremendous difference to the Mastocytosis Community and that is all thanks to the platform that DIA gave me to brief the media about an agonizing and complex rare disease.” – Kelli Foster, Mastocytosis Society
“By fostering global collaboration and innovative campaigns, DIA provides the necessary 113 platform to help overcome the challenges faced by the rare disease patient community.” – Marion Schwartz, Cholangiocarcinoma Foundation
“The Parkinson’s Advocates in Research (PAIR) Learning Institute provides training to people living with Parkinson’s so that they can partner with the research community in developing new treatments at a faster pace. Within 18 months, we have doubled the number of PDF Research Advocates, now over 200 strong around the country. The sup- port of the DIA was central to this effort.” – Veronica Todaro, Parkinson’s Disease Foundation
“The disease I represent [Autosomal Recessive Polycystic Kidney Disease (ARPKD) and Congenital Hepatic Fibrosis (CHF)] is symptom managed, which means that as symp- toms occur, they are treated; there are no therapeutic treatments or standards of care. Research, development and discovery are happening at a faster and faster rate. But genuine progress always includes the patient’s voice, expressed through patient ad- vocacy organizations like the ARPKD/CHF Alliance, from the beginning to the end. For patient- centered care and research, knowledgeable patient input is critical. I was given access to a wealth of enlightening educational sessions that offered distinctive new perspectives from industry and drug companies, and from policy makers and regulators. I was also exposed to fascinating information about research positioning, study designs and precision medicine. As a result, I better understand bringing drugs to market, fast- tracking medications, funding and incentives for all parties, consortiums, protocols, and improving patient outcomes.” – Colleen Zak, ARPKD/CHF Alliance gf GLOBAL FORUM | EDUCATE
Philanthropy Grant Recipients Report
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VOL 5 ISSUE 2 With the awarding of the 2012-2013 Philanthropy Grants, the DIA Philanthropy Grant Program comes to a close. Through this program, DIA awarded research and event grants to applicants whose charitable cause benefits the public, helps to fulfill the DIA mission and vision, and helps fulfill DIA’s responsibility as a nonprofit section 501(c)(3) tax-exempt charitable, educational and scientific association. DIA will, however, continue to support these causes through Patient Fellowships, Student Fellowships and similar means.
Earlier this year, DIA received International reports from two of the 2011-2012 Alliance of Patients’ Philanthropy Grant recipients. The Organizations (IAPO) following highlights were extracted from these reports. The IAPO is the only global alliance representing patients across all disease areas and promoting patient-centered health care around the world; IAPO has over 200 members, representing over 50 disease areas and over 50 countries, in a network that connects over 4,000 organizations and represents an estimated education and public advocacy; and the process that brings new 365 million patients worldwide. the PDF has dedicated over therapies to market, as well as DIA’s Grant supported the IAPO’s $96 million to fund the work of leadership and advocacy skills 5th Global Patients Congress: leading scientists throughout the so that they can more confidently Achieving Patient-Centered world, and over $40 million to interact with the scientific, clinical Healthcare: Indicators of Progress support national education and and advocacy communities. & Success, their annual flagship advocacy initiatives that help the event, presented in London in nearly one million people who “On behalf of the PDF, I cannot March 2012. Other Congress live with Parkinson’s Disease in thank DIA enough for supporting sponsors and grant providers the US. DIA’s Grant supported this important initiative. It gets included the International the program presented by at the heart of what DIA is Federation of Pharmaceutical the Parkinson’s Advocates in encouraging and doing – including Manufacturers & Associations Research (PAIR) Learning Institute, patients in the clinical research (IFPMA), the Medtronic Southern Region, in March 2012. process,” wrote Veronica Todaro, Foundation, and the National These Learning Institutes are MPH, the Foundation’s Director of Health Council. three-day education and training National Programs, in their report. events designed to prepare “Within the last 18 months, we Parkinson’s Disease people living with Parkinson’s, have doubled the number of PDF Foundation (PDF) and their caregivers, for work as Research Advocates, now over research advocates. They learn 200 strong around the country. Founded in 1957, the PDF has from experts in the field about the The support of DIA was central to been a leading national presence science of Parkinson’s disease this effort.” in Parkinson’s disease research, 115
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Thousands of volunteers from around the globe provide the foundational support to DIA’s mission of furthering innovation in the pharmaceutical, biotech- nology, and medical device fields. DIA volunteers shape the health care in- dustry, network with indus- try leaders, confront major issues, share expertise, exchange knowledge and collaborate with other pro- fessionals. We are grateful for all of our volunteers, 116 who support DIA’s mission and their colleagues world- wide by participating in our Communities, submitting articles to our publications, acting as speakers or VOL 5 ISSUE 2 program committee mem- bers for our meetings and workshops, and serving on our Regional Advisory Councils, Board of Direc- tors, and Editorial Boards. Thank you for all you do. To learn more about vol- unteer opportunities with DIA, please visit the “Get Involved” section of www. diahome.org. 117 118 VOL 5 ISSUE 2 g g f f GLOBAL FORUM|ASSOCIATION NEWS Amendments atMarchMeeting GOVERNANCE Corner • • General Changes These changesare summarized andexplainedbelow: these revisions duringitsmeetingofMarch 3,2013. to theBoard ofDirectors, whichreviewed andapproved recommended thefollowing revisions oftheDIABylaws The DIAGovernance &LeadershipCommitteehas simply reads “DIA.” the phrase“theDIA”andnow removed from allinstancesof The word “the”hasbeen Director Bylaws toWorldwide Executive been corrected throughout the The ExecutiveDirector’s titlehas Board Approves Bylaws Board ApprovesBylaws • • “Publications” cle IV,Changes toArti order. Editor’s dutiesinamore logical been re-arranged topresent the Paragraph B:Sentenceshave Regulatory Science Therapeutic Innovation& to Drug InformationJournal has beenchangedfrom the of DIA’s official publication Paragraph A:Thename
Changes to Article V, • Paragraph 8: Elections: Except Changes to Article XIII, “Membership” for the opening sentence, the “Amendments to Bylaws” rest of this Paragraph is an • Paragraph A3 was changed to internal procedure captured in • Language was changed to specify that voting is done by the Nominations and Elections eliminate the Board review proxy ballot and to remove the SOP approved by the Board in timeframe and thereby offer a specific means of that proxy. November 2012, and so need more timely decision-making not appear in the Bylaws. process Changes to Article VI, “Officers & Board of Changes to Article VIII, • Language was added to clarify Directors” “Standing Committees” how Bylaws amendments are distributed to the membership. • Language was added to specify • The Compensation Committee full terms and to consistently and Philanthropy Committee If you have any questions about define officer and director terms have been disbanded, and these changes, please contact removed from the Bylaws: DIA’s Governance Administrator at • Paragraph 9: Fiduciary Duties: Duties of the Compensation [email protected]. Fiduciary Duties was moved Committee will be undertaken up to Paragraph 4, to keep by the Executive Committee, all paragraphs pertaining to and its charter will be “duties” together (the Paragraph incorporated into the Executive itself was not changed) Committee Charter; the DIA • Paragraph 5: Vacancies: Philanthropy Committee 119 Language was added to has disbanded because the describe who decides if a Philanthropy Grant Program has vacancy on the Board shall be been discontinued. filled.
Cast Your Vote for the 2013 DIA Board of Directors Please remember to take the time to vote in our DIA 2013 Board of Directors Election. Eligible members will receive an email from DIA_Election_Admin which contains a personal link to your 2013 Election ballot and secure electronic voting. Don’t miss your chance to help steer DIA into the future! (Please check your ‘spam filters,’ too.)