Building a National Framework for the Establishment of REGULATORY SCIENCE FOR DRUG DEVELOPMENT
Workshop Summary
Yeonwoo Lebovitz, Rebecca A. English, and Anne B. Claiborne, Rapporteurs
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.
This project was supported by the Department of Health and Human Services (Contract Nos. N01-OD-4-2139 and 223001003T), the American Diabetes Association, the American Society for Microbiology, Amgen Inc., the Association of American Medical Colleges, Bristol-Myers Squibb, the Burroughs Wellcome Fund, Celtic Therapeutics, LLLP, the Critical Path Institute, the Doris Duke Charitable Foundation, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Novartis Pharmaceuticals Corporation, and Pfizer, Inc. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
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Suggested citation: IOM (Institute of Medicine). 2011. Building a National Framework for the Establishment of Regulatory Science for Drug Development: Workshop Summary. Washington, DC: The National Academies Press.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
Gail H. Cassell (Co-Chair),
Eli Lilly and Company, Indiana
Jeffrey M. Drazen (Co-Chair),
New England Journal of Medicine, Massachusetts
Barbara Alving,
National Center for Research Resources, Maryland
Leslie Z. Benet,
University of California-San Francisco, California
Ann Bonham,
Association of American Medical Colleges, Washington, DC
Linda Brady,
National Institute of Mental Health, Maryland
Robert M. Califf,
Duke University Medical Center, North Carolina
Scott Campbell,
Foundation for the National Institutes of Health, Maryland
C. Thomas Caskey,
University of Texas-Houston Health Science Center, Texas
Peter B. Corr,
Celtic Therapeutics, LLLP, New York
James H. Doroshow,
National Cancer Institute, Maryland
Paul R. Eisenberg,
Amgen Inc., California
Gary L. Filerman,
Atlas Research, Washington, DC
Garret A. FitzGerald,
University of Pennsylvania School of Medicine, Pennsylvania
Elaine K. Gallin,
The Doris Duke Charitable Foundation, New York
Steven K. Galson,2
Amgen Inc., California
Harry B. Greenberg,
Stanford University School of Medicine, California
Stephen Groft,
National Institutes of Health, Maryland
Peter K. Honig,
AstraZeneca, Delaware
Annalisa Jenkins,
Bristol-Myers Squibb, New Jersey
Michael Katz,
March of Dimes Foundation, New York
Jack D. Keene,
Duke University Medical Center, North Carolina
Ronald L. Krall,
GlaxoSmithKline (retired), Colorado
Freda Lewis-Hall,
Pfizer, Inc., New York
William D. Matthew,
National Institute of Neurological Disorders and Stroke, Maryland
Mark B. McClellan,
Brookings Institution, Washington, DC
Carol Mimura,
University of California-Berkeley, California
John Orloff,
Novartis Pharmaceuticals Corporation, New Jersey
Amy P. Patterson,
National Institutes of Health, Maryland
Janet Shoemaker,
American Society for Microbiology, Washington, DC
Ellen V. Sigal,
Friends of Cancer Research, Virginia
Nancy S. Sung,
Burroughs Wellcome Fund, North Carolina
Jorge A. Tavel,
National Institute of Allergy and Infectious Diseases, Maryland
Janet Tobias,
Ikana Media, New York
Joanne Waldstreicher,
Johnson & Johnson, New Jersey
Janet Woodcock,
U.S. Food and Drug Administration, Maryland
Raymond L. Woosley,
The Critical Path Institute, Arizona
IOM Staff
Anne B. Claiborne, Director (from April 5, 2010)
Robert B. Giffin, Director (until February 26, 2010)
Rebecca A. English, Research Associate
Yeonwoo Lebovitz, Program Associate
Genea S. Vincent, Senior Program Assistant
Rona Briere, Consulting Editor
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this report:
STEVEN K. GALSON,1 Amgen Inc., California
PETER K. HONIG, AstraZeneca
CARL C. PECK, University of California, San Francisco
ELLEN V. SIGAL, Friends of Cancer Research
Although the reviewers listed above have provided many constructive comments and suggestions, they did not endorse the final draft of the report before its release. The review of this report was overseen by LESLIE Z. BENET, University of California, San Francisco. Appointed by the National Research Council and the Institute of Medicine, he was
Figures and Boxes
FIGURES
3-1 |
Graphic presentation of the effect of acetaminophen on various mouse gene strains, |
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4-1 |
Breadth of FDA responsibilities by number of establishments as of 2007, |
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4-2 |
Flow of data in an Incubator for Innovation in Regulatory and Information Science (IIRIS)/Centers-of-Excellence (COE) model, |
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5-1 |
Visualization of how the current drug development model is growing disaggregated with involvement of various sectors to reduce risk in innovation, |
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5-2 |
Centers of Excellence in Regulatory Science Network, |
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6-1 |
Shifting opinions on America’s most important health issue, December 2003–February 2010, |
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6-2 |
Americans’ level of confidence in systems for monitoring the effectiveness and safety of new medicines and medical devices, |
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6-3 |
Americans’ views on FDA’s most important role, |
BOXES
2-1 |
Some definitions of regulatory science, |
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2-2 |
Excerpts from the Commissioner’s speech, |
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3-1 |
Potential contributions of regulatory science to cancer therapy, |
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3-2 |
Hamner Institute’s study of inbred mice panels, |
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4-1 |
The IIRIS model, |
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5-1 |
Collaborative models in oncology, |
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6-1 |
The impact of patient advocacy for cancer therapeutics at FDA, |
Acronyms
AHRQ Agency for Healthcare Research and Quality
AIDS acquired immune deficiency syndrome
ARRA American Recovery and Reinvestment Act of 2009
BC Biomarkers Consortium
CBER Center for Biologics Evaluation and Research
CDC Centers for Disease Control and Prevention
CDER Center for Drug Evaluation and Research
CERTS Centers for Education and Research on Therapeutics
COE Centers of Excellence
COERS Centers of Excellence in Regulatory Science Network
CPI Critical Path Initiative
CTTI Clinical Trials Transformative Initiative
DARPA Defense Advanced Research Products Agency
FDA Food and Drug Administration
FDAAA FDA Amendments Act of 2007
FDAMA FDA Modernization Act of 1997
FNIH Foundation for the National Institutes of Health
GAO Government Accountability Office
HHS Department of Health and Human Services
HIV human immunodeficiency virus
ICT-21 Information Communication Technology for the 21st Century
IIRIS Incubator for Innovation in Regulatory and Information Science
IND Investigative New Drug Application
IOM Institute of Medicine
IOTF NCI–FDA Interagency Oncology Task Force
IT information technology
NCI National Cancer Institute
NDA New Drug Application
NIH National Institutes of Health
NIST National Institute of Standards and Technology
OMOP Observational Medical Outcomes Partnership
OODP Office of Oncology Drug Products
PDUFA Prescription Drug User Fee Act
PhRMA Pharmaceutical Research and Manufacturers of America
SAE serious adverse event
Preface
Regulatory agencies worldwide are tasked with a difficult mandate to provide large populations with efficient access to drugs that are both safe and effective. They must also balance this task while adapting to new technologies in medicine and information technology. These demands are further complicated by the increasing globalization of drug development and regulatory relationships. These challenges, along with problems with contaminated supplies, serious adverse events, and other compounding issues that accompany changes in administration, contribute to the over-burdening of a regulatory system whose resources have not increased along with its demands. We urgently need to ensure that our regulatory bodies have the autonomy, resources, and scientific support needed to function effectively to promote public health and safety.
The U.S. Food and Drug Administration (FDA) is a science-based agency responsible for regulating 80 percent of Americans’ consumable goods and a quarter of the U.S. economy. It is imperative that every one of FDA’s regulatory decisions be based on the best scientific evidence. Unfortunately, this has not always been possible due to several factors, including—but not limited to—inadequate human capital, leadership support, and funding. Above all, a weakening science base at the agency has threatened its ability to support its core regulatory functions and decisions. FDA needs to resolve this gap between scientific and regulatory decision making to ensure continuity of its duties in an environment of heightened public scrutiny on drug safety and rapid scientific advancements.
The public increasingly recognizes the importance of regulatory science. The notion of basing regulatory decisions on the best scientific knowledge
available is not new, but never before have funds been deliberately appropriated for the accomplishment of this task. FDA’s 2011 budget proposal includes $25 million specifically allocated to the building of a regulatory science infrastructure at the agency. In anticipation of this event and as an acknowledgment of the “reform-ready” political atmosphere, the Institute of Medicine’s Forum on Drug Discovery, Development, and Translation held a public workshop with the following goals in mind:
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Establish a clear definition of regulatory science, and engage the public and the policy community in a discussion of its challenges and opportunities.
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Increase awareness of inadequate funding for regulatory science and the impact on the development of new therapies on patients.
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Articulate priorities and strategies for building or rebuilding the infrastructure for regulatory science.
The one-day workshop featured leaders from government, such as Representative Rosa DeLauro (D-CT); Department of Health and Human Services Deputy Secretary, William Corr; and FDA Commissioner, Margaret Hamburg. Speakers from academia, industry, and patient advocacy groups provided a variety of perspectives and illuminated examples of the urgent need of a regulatory science infrastructure. Leaders in emerging technologies, such as genomics, biostatistics, and information technology—whose fields of study are influenced daily by regulatory decisions—deliberated on potential consequences arising from the failure to establish a robust scientific base at the agency level. In addition, moderated panels considered mechanisms for building a regulatory science infrastructure at FDA, analyzed existing implementation models, and posed strategies for engaging the public and policy makers.
This was a timely workshop that provided a valuable opportunity to bring together a diverse group for thoughtful discussion about improving drug development and strengthening regulatory science. I would like to thank all of the individuals—speakers, moderators, and panelists—who contributed to and participated in the workshop. In particular, I would like to thank a small team of participants in the workshop who spent many hours in advance of the workshop discussing the merits of Centers of Excellence in Regulatory Science and the critical characteristics of these centers including: K. Ahlport, M. Anderson, L. Benet, R. Califf, G. FitzGerald, S. Kim, J. Kramer, R. Nerem, D. Nordenberg, M. Osterholm, K. Schneeman, J. Shoemaker, E. Sigal, N. Sung, and J. Tobias. I would also like to thank the members of the Forum and Forum staff for their dedication and commitment to developing and executing this workshop.
Gail H. Cassell, Co-Chair
Forum on Drug Discovery, Development, and Translation