ADVANCING THE
DISCIPLINE OF
REGULATORY SCIENCE
FOR MEDICAL PRODUCT
DEVELOPMENT
An Update on Progress and
a Forward-Looking Agenda
Workshop Summary
Morgan L. Boname, Amanda Wagner Gee, and Anne B. Claiborne,
Rapporteurs
Forum on Drug Discovery, Development, and Translation
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by AbbVie, Inc.; the American Diabetes Association; American Society of Microbiology; Amgen Inc. (Contract No. GHCCOPS-CSARF-63987); Association of American Medical Colleges; AstraZeneca; Baxter BioScience; Burroughs Wellcome Fund (Contract No. 1015149); Critical Path Institute; Doris Duke Charitable Foundation (Contract No. 2015103); Eli Lilly & Co.; FasterCures; Friends of Cancer Research; GlaxoSmithKline (Contract No. 005319); Johnson & Johnson; Merck & Co., Inc. (Contract No. CMO-141224-000649); National Institutes of Health (NIH) (Contract No. HHSN263201200074I; Task Order HHSN26300023): National Cancer Institute (NIH), National Center for Advancing Translational Sciences (NIH), National Institute of Allergy and Infectious Diseases (NIH), National Institute of Mental Health (NIH), and National Institute of Neurological Disorders and Stroke (NIH); New England Journal of Medicine; Pfizer Inc.; Sanofi; Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Contract No. 1R13FD005496-01). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-43884-1
International Standard Book Number-10: 0-309-43884-5
Digital Object Identifier: 10.17226/23438
Additional copies of this report are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2016 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Advancing the discipline of regulatory science for medical product development: An update on progress and a forward-looking agenda: Workshop summary. Washington, DC: The National Academies Press. doi: 10.17226/23438.
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Ralph J. Cicerone is president.
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Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national-academies.org.
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PLANNING COMMITTEE ON ADVANCING THE DISCIPLINE OF REGULATORY SCIENCE FOR MEDICAL PRODUCT DEVELOPMENT: AN UPDATE ON PROGRESS AND A FORWARD-LOOKING AGENDA1
MARTIN PHILBERT (Co-Chair), University of Michigan School of Public Health, Ann Arbor, MI
ALASTAIR WOOD (Co-Chair), Symphony Capital, New York, NY
RUSS ALTMAN, Stanford University, CA
SHARON HESTERLEE, Myotonic Dystrophy Foundation, San Francisco, CA
RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC
EMMA MEAGHER, University of Pennsylvania, Philadelphia, PA
ROBERT MEYER, University of Virginia School of Medicine, Charlottesville, VA
STEPHEN OSTROFF, U.S. Food and Drug Administration, Silver Spring, MD
PAUL SELIGMAN, Amgen Inc., Thousand Oaks, CA
BRIAN STROM, Rutgers, the State University of New Jersey, Newark, NJ
HMD Staff
ANNE B. CLAIBORNE, Forum Director
CHRISTOPHER J. DEFEO, Program Officer
EMILY R. BUSTA, Associate Program Officer
KATHRYN M. HOWELL, Senior Program Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
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FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
RUSS ALTMAN (Co-Chair), Stanford University, CA
STEVEN GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA
MARGARET ANDERSON, FasterCures, Washington, DC
HUGH AUCHINCLOSS, National Institute of Allergy and Infectious Diseases, Bethesda, MD
CHRISTOPHER AUSTIN, National Center for Advancing Translational Sciences, Bethesda, MD
ANN BONHAM, Association of American Medical Colleges, Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, MD
GAIL CASSELL, Harvard Medical School Department of Social and Global Medicine (Visiting), Carmel, IN
ANDREW DAHLEM, Eli Lilly & Co., Indianapolis, IN
JAMES DOROSHOW, National Cancer Institute, Bethesda, MD
JEFFREY DRAZEN, New England Journal of Medicine, Boston, MA
JODIE GILLON, AstraZeneca, Summit, NJ
HARRY GREENBERG, Stanford University School of Medicine, CA (until December 31, 2015)
LYNN HUDSON, Critical Path Institute, Tucson, AZ
S. CLAIBORNE JOHNSTON, Dell Medical School, University of Texas, Austin
JACK KEENE, Duke University Medical Center, Durham, NC (until December 31, 2015)
RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC
KATE KNOBIL, GlaxoSmithKline, Collegeville, PA
RONALD KRALL, University of Pittsburgh, Steamboat Springs, CO (until December 31, 2015)
FREDA LEWIS-HALL, Pfizer Inc., New York, NY
BERNARD MUNOS, InnoThink Center for Research in Biomedical Innovation, Indianapolis, IN
ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation, New York, NY (until December 31, 2015)
JOHN ORLOFF, Baxalta, Deerfield, IL
ROBERT RATNER, American Diabetes Association, Alexandria, VA
MICHAEL ROSENBLATT, Merck & Co., Inc., Kenilworth, NJ
MICHAEL SEVERINO, AbbVie, Inc., North Chicago, IL
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
ELLEN SIGAL, Friends of Cancer Research, Washington, DC
LANA SKIRBOLL, Sanofi, Washington, DC
BRIAN STROM, Rutgers, the State University of New Jersey, Newark
JANET TOBIAS, Ikana Media, New York, NY (until December 31, 2015)
JOHN WAGNER, Takeda Pharmaceuticals, Cambridge, MA
JOANNE WALDSTREICHER, Johnson & Johnson, New Brunswick, NJ
CARRIE WOLINETZ, National Institutes of Health, Bethesda, MD
JANET WOODCOCK, U.S. Food and Drug Administration, Silver Spring, MD
HMD Staff
ANNE B. CLAIBORNE, Forum Director
CHRISTOPHER J. DEFEO, Program Officer (until October 2015)
REBECCA A. ENGLISH, Program Officer
AMANDA WAGNER GEE, Program Officer (as of November 2015)
EMILY R. BUSTA, Associate Program Officer (until December 2015)
MORGAN L. BONAME, Associate Program Officer (as of December 2015)
OLIVIA C. YOST, Senior Program Assistant (as of December 2015)
KATHRYN M. HOWELL, Senior Program Assistant (until November 2015)
ANDREW M. POPE, Director, Board on Health Sciences Policy
Reviewers
This workshop summary has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published workshop summary as sound as possible and to ensure that the workshop summary 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 workshop summary:
Brian Alexander, Harvard Medical School
Jesse Goodman, Georgetown University
Peter Honig, Pfizer Inc.
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the workshop summary before its release. The review of this workshop summary was overseen by Barry S. Coller, The Rockefeller University. He was responsible for making certain that an independent examination of this workshop summary was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this workshop summary rests entirely with the rapporteurs and the institution.
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Contents
2 CHARACTERIZING THE REGULATORY SCIENCE LANDSCAPE
The Role of Data Science in Regulatory Science: A Case Study in Collaboration
Identification and Development of Meaningful Biomarkers
Integrating Clinical Trial Data
Innovative Modeling for Integrating Data
4 REGULATORY SCIENCE INFRASTRUCTURE AND WORKFORCE
Characterizing the Discipline of Regulatory Science
Boxes and Figure
BOXES
3-1 Basic Science of Measurement: Metrology for Principles of Biomarkers
3-2 Potential Concerns for Data Sharing
3-4 Selected Examples of Challenges and Limitations of Web-Based Surveillance
4-1 Examples of Regulatory Scientists as Multidisciplinary Communicators
4-2 Examples of Core Thematic Areas of Regulatory Science
FIGURE
3-1 Pathways to integrate biomarkers in drug development at U.S. FDA
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Acronyms and Abbreviations
AD | Alzheimer’s disease |
ADPKD | autosomal dominant polycystic kidney disease |
API | application program interface |
BLAERS |
Behavioral Log-Based Adverse Event Reporting System |
BQRT | Biomarker Qualification Review Team |
CDER |
Center for Drug Evaluation and Research |
CDISC | Clinical Data Interchange Standards Consortium |
CDRH | Center for Devices and Radiological Health |
CERSI | Center of Excellence in Regulatory Science and Innovation |
COU | context of use |
C-Path | Critical Path Institute |
CPIM | Critical Path Innovation Meeting |
cTAP | collaborative Trajectory Analysis Program |
CTSA | Clinical and Translational Science Award |
DMD |
Duchenne muscular dystrophy |
EHR |
electronic health record |
EMA | European Medicines Agency |
FAERS |
FDA Adverse Event Reporting System |
FDA | U.S. Food and Drug Administration |
FDAAA | FDA Amendments Act of 2007 |
FHIR | Fast Healthcare Interoperability Resources |
fMRI | functional magnetic resonance imaging |
FNIH | Foundation for the National Institutes of Health |
HL7 |
Health Level Seven International |
IND |
Investigational New Drug |
IOM | Institute of Medicine |
IRSA | Innovations in Regulatory Science Awards |
MDEpiNet |
Medical Device Epidemiology Network |
NDA |
New Drug Application |
NIH | National Institutes of Health |
NIST | National Institute of Standards and Technology |
PhRMA |
Pharmaceutical Research and Manufacturers of America |
PK/PD | pharmacokinetic/pharmacodynamic |
PMDA | Pharmaceuticals and Medical Devices Agency |
PSTC | Predictive Safety Testing Consortium |
RCT |
randomized controlled trial |
UCSF |
University of California, San Francisco |