Reflections on Sharing
Clinical Trial Data
Challenges and a Way Forward
PROCEEDINGS OF A WORKSHOP
Theresa Wizemann, Eeshan Khandekar, Jennifer Hinners, and
Carolyn Shore, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Forum on Neuroscience and Nervous System Disorders
National Cancer Policy Forum
Roundtable on Genomics and Precision Health
Board on Health Sciences Policy
Board on Health Care Services
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This activity was supported by contracts between the National Academy of Sciences and AbbVie Inc.; Amgen Inc. (Contract No. GHCCOPS-CSARF-175837); Association of American Medical Colleges; AstraZeneca; Burroughs Wellcome Fund (Contract No. 1020264); Critical Path Institute; Eli Lilly and Company (Contract No. 4900709231); FasterCures, Milken Institute; Foundation for the National Institutes of Health; Friends of Cancer Research; GlaxoSmithKline (Contract No. OTH-PPL-30507 and Contract No. OTH-PPL-32245); Johnson & Johnson; Merck & Co., Inc. (Contract No. MRLCPO-18-2641 and Contract No. MRLCPO-19-106723); National Institutes of Health (Contract No. HHSN263201800029I; Task Order No. HHSN26300007): National Cancer Institute, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Office of Extramural Research, Office of Science Policy; New England Journal of Medicine; Takeda Pharmaceuticals (Contract No. 53108); U.S. Food and Drug Administration (Grant No. 5R13FD005496-04 and Grant No. 5R13FD005496-05); and Wellcome Trust. 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: 978-0-309-67915-2
International Standard Book Number-10: 0-309-67915-X
Digital Object Identifier: https://doi.org/10.17226/25838
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Reflections on sharing clinical trial data: Challenges and a way forward: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/25838.
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PLANNING COMMITTEE ON SHARING CLINICAL TRIAL DATA: CHALLENGES AND A WAY FORWARD1
JEFFREY M. DRAZEN (Co-Chair), New England Journal of Medicine
JOANNE WALDSTREICHER (Co-Chair), Johnson & Johnson
MONICA BERTAGNOLLI, Harvard Medical School; Dana-Farber Cancer Institute and Brigham and Women’s Hospital
TIMOTHY COETZEE, National Multiple Sclerosis Society
PATRICK CULLINAN, bluebird bio
SONALI KOCHHAR, Global Healthcare Consulting; University of Washington; Erasmus MC, University Medical Center
BERNARD LO, The Greenwall Foundation
DEVEN McGRAW, Ciitizen Corporation
DINA PALTOO, National Library of Medicine, National Institutes of Health
LIZ ROBERTS, UCB Biosciences, Inc.
FRANK ROCKHOLD, Duke University Medical Center
SHARON TERRY, Genetic Alliance
DEBORAH ZARIN, Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard
Health and Medicine Division Staff
CAROLYN SHORE, Director, Forum on Drug Discovery, Development, and Translation
JENNIFER HINNERS, Program Officer
EESHAN KHANDEKAR, Associate Program Officer
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
Consultant
THERESA WIZEMANN, Science Writer
___________________
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 Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1
ROBERT M. CALIFF (Co-Chair), Duke University and Verily Life Sciences
GREGORY SIMON (Co-Chair), Kaiser Permanente Washington Health Research Institute and University of Washington
CHRISTOPHER P. AUSTIN, National Center for Advancing Translational Sciences
LINDA BRADY, National Institute of Mental Health
BARRY COLLER, The Rockefeller University
THOMAS CURRAN, Children’s Mercy, Kansas City
RICHARD DAVEY, National Institute of Allergy and Infectious Diseases
JAMES H. DOROSHOW, National Cancer Institute
JEFFREY M. DRAZEN, New England Journal of Medicine
STEVEN K. GALSON, Amgen Inc.
CARLOS GARNER, Eli Lilly and Company
JULIE L. GERBERDING, Merck & Co., Inc.
DEBORAH HUNG, Harvard Medical School
ESTHER KROFAH, FasterCures, Milken Institute
ROSS McKINNEY, JR., Association of American Medical Colleges
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
BERNARD H. MUNOS, InnoThink Center for Research in Biomedical Innovation
KELLY ROSE, Burroughs Wellcome Fund
JOSEPH SCHEEREN, Critical Path Institute
ROB SCOTT, AbbVie Inc.
ANANTHA SHEKHAR, Indiana University School of Medicine
ELLEN V. SIGAL, Friends of Cancer Research
LANA R. SKIRBOLL, Sanofi
AMIR TAMIZ, National Institute of Neurological Disorders and Stroke
PAMELA TENAERTS, Clinical Trials Transformation Initiative, Duke University
JOANNE WALDSTREICHER, Johnson & Johnson
CARRIE WOLINETZ, Office of Science Policy, National Institutes of Health
ALASTAIR WOOD, Vanderbilt University
JANET WOODCOCK, U.S. Food and Drug Administration
___________________
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 Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
Forum Staff
CAROLYN SHORE, Forum Director
JENNIFER HINNERS, Program Officer
AMANDA WAGNER GEE, Program Officer
EESHAN KHANDEKAR, Associate Program Officer
SYLVIA NCHA, Associate Program Officer
MELVIN JOPPY, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
FRANCES JENSEN (Co-Chair), University of Pennsylvania
JOHN KRYSTAL (Co-Chair), Yale University
SUSAN AMARA, Society for Neuroscience
RITA BALICE-GORDON, Sanofi
KATJA BROSE, Chan Zuckerberg Initiative
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
DANIEL BURCH, Pharmaceutical Product Development, LLC
JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai
SARAH CADDICK, Gatsby Charitable Foundation
ROSA CANET-AVILES, Foundation for the National Institutes of Health
MARIA CARRILLO, Alzheimer’s Association
EDWARD CHANG, University of California, San Francisco
TIMOTHY COETZEE, National Multiple Sclerosis Society
JONATHAN COHEN, Princeton University
ROBERT CONLEY, Eli Lilly and Company
JAMES DESHLER, National Science Foundation
BILLY DUNN, U.S. Food and Drug Administration
MICHAEL EGAN, Merck Research Laboratories
NITA FARAHANY, Duke University School of Law
JOSHUA GORDON, National Institute of Mental Health
RAQUEL GUR, University of Pennsylvania
MAGALI HAAS, Cohen Veterans Bioscience
RAMONA HICKS, One Mind
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, U.S. Department of Veterans Affairs
JONATHAN HORSFORD, National Institute of Dental and Craniofacial Research
YASMIN HURD, Icahn School of Medicine at Mount Sinai
STEVEN HYMAN, Broad Institute of Massachusetts Institute of Technology and Harvard University
MICHAEL IRIZARRY, Eisai Inc.
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
STORY LANDIS, Director Emeritus, National Institute of Neurological Disorders and Stroke
ALAN LESHNER, American Association for the Advancement of Science (Emeritus)
HUSSEINI MANJI, Janssen Research & Development, LLC
JOSEPH P. MENETSKI, Foundation for the National Institutes of Health
CAROLINE MONTOJO, The Kavli Foundation
STEVEN PAUL, Voyager Therapeutics
EMILIANGELO RATTI, Takeda Pharmaceuticals International
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
SANTA TUMMINIA, National Eye Institute
NORA VOLKOW, National Institute on Drug Abuse
ANDREW WELCHMAN, Wellcome Trust
DOUG WILLIAMSON, Lundbeck
STEVIN ZORN, MindImmune Therapeutics, Inc.
Forum Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
PHOENIX WILSON, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
NATIONAL CANCER POLICY FORUM
EDWARD J. BENZ, JR. (Chair), Dana-Farber Cancer Institute and Harvard Medical School
GARNET L. ANDERSON, Fred Hutchinson Cancer Research Center and University of Washington
KENNETH ANDERSON, American Cancer Society and Jerome Lipper Multiple Myeloma Center
KAREN BASEN-ENGQUIST, The University of Texas MD Anderson Cancer Center
LINDA BOHANNON, Cancer Support Community
CHRIS BOSHOFF, Pfizer Inc.
CATHY J. BRADLEY, Colorado School of Public Health and University of Colorado Cancer Center
OTIS W. BRAWLEY, Johns Hopkins University
CYNTHIA BROGDON, Bristol-Myers Squibb Company
ROBERT W. CARLSON, National Comprehensive Cancer Network
GWEN DARIEN, National Patient Advocate Foundation
NANCY E. DAVIDSON, Seattle Cancer Care Alliance; Fred Hutchinson Cancer Research Center; and University of Washington
GEORGE D. DEMETRI, Harvard Medical School; Dana-Farber Cancer Institute; and Dana-Farber/Harvard Cancer Center
JAMES H. DOROSHOW, National Cancer Institute
NICOLE F. DOWLING, Centers for Disease Control and Prevention
SCOT W. EBBINGHAUS, Merck Research Laboratories
KOJO S. J. ELENITOBA-JOHNSON, University of Pennsylvania
STANTON L. GERSON, Case Western Reserve University and University Hospitals Seidman Cancer Center
LORI HOFFMAN HÖGG, U.S. Department of Veterans Affairs
HEDVIG HRICAK, Memorial Sloan Kettering Cancer Center
ERIN HUFMAN, Novartis Oncology
ROY A. JENSEN, Association of American Cancer Institutes; The University of Kansas Cancer Center; and Kansas Masonic Cancer Research Institute
LISA KENNEDY SHELDON, Oncology Nursing Society
SAMIR N. KHLEIF, Georgetown University Medical Center
MICHELLE M. LE BEAU, University of Chicago Medicine Comprehensive Cancer Center
MIA LEVY, Rush University Cancer Center and Rush System for Health
J. LEONARD LICHTENFELD, American Cancer Society
NEAL J. MEROPOL, Flatiron Health
MARTIN J. MURPHY, CEO Roundtable on Cancer
RANDALL A. OYER, Penn Medicine Lancaster General Health
RICHARD L. SCHILSKY, American Society of Clinical Oncology
JULIE SCHNEIDER, U.S. Food and Drug Administration
DEBORAH SCHRAG, Harvard Medical School and Dana-Farber Cancer Institute
LAWRENCE N. SHULMAN, University of Pennsylvania
DAN THEODORESCU, Cedars-Sinai Medical Center
GEORGE J. WEINER, The University of Iowa
ROBERT A. WINN, Virginia Commonwealth University Massey Cancer Center
Forum Staff
ERIN BALOGH, Senior Program Officer
EMILY ZEVON, Associate Program Officer
CYNDI TRANG, Research Associate
KATE HAWTHORNE, Senior Program Assistant
ANNALEE GONZALES, Administrative Assistant
ADEGBOYEGA AKINSIKU, Mirzayan Fellow
SHARYL NASS, Director, National Cancer Policy Forum, and Senior Director, Board on Health Care Services
ROUNDTABLE ON GENOMICS AND PRECISION HEALTH
GEOFFREY GINSBURG (Co-Chair), Duke University
MICHELLE PENNY (Co-Chair), Biogen
NAOMI ARONSON, Blue Cross Blue Shield Association
ARIS BARIS, Regeneron Pharmaceuticals
KARINA BIENFAIT, Merck & Co., Inc.
VENCE BONHAM, National Human Genome Research Institute
ANN CASHION, National Institute of Nursing Research
ROBERT B. DARNELL, The Rockefeller University
STEPHANIE DEVANEY, All of Us Research Program, National Institutes of Health
KATHERINE DONIGAN, U.S. Food and Drug Administration
W. GREGORY FEERO, Journal of the American Medical Association
JESSICA GILL, National Institute of Nursing Research
MARC GRODMAN, Genosity
JILL M. HAGENKORD, Color Genomics
EMILY HARRIS, National Cancer Institute
RICHARD HODES, National Institute on Aging
PRADUMAN JAIN, Vibrent Health
SEKAR KATHIRESAN, Massachusetts General Hospital
MUIN KHOURY, Centers for Disease Control and Prevention
DAVID LEDBETTER, Geisinger
CHARLES LEE, The Jackson Laboratory for Genomic Medicine
THOMAS LEHNER, National Institute of Mental Health
DEBRA LEONARD, The University of Vermont Medical Center
PATRICK LOERCH, Johnson & Johnson
JAMES LU, Helix
SEAN McCONNELL, American Medical Association
MONA MILLER, American Society of Human Genetics
JENNIFER MOSER, U.S. Department of Veterans Affairs
ANNA PETTERSSON, Pfizer Inc.
VICTORIA PRATT, Association for Molecular Pathology
NADEEM SARWAR, Eisai Inc.
SHERI SCHULLY, Office of Disease Prevention, National Institutes of Health
JOAN A. SCOTT, Health Resources and Services Administration
SAM SHEKAR, Northrop Grumman Information Systems
NONNIEKAYE SHELBURNE, National Cancer Institute
NIKOLETTA SIDIROPOULOS, The University of Vermont Health Network Medical Group
KATHERINE JOHANSEN TABER, Myriad Women’s Health
RYAN TAFT, Illumina
JACQUELYN TAYLOR, New York University
SHARON TERRY, Genetic Alliance
JOYCE TUNG, 23andMe
JAMESON VOSS, Air Force Medical Support Agency
MICHAEL WATSON, American College of Medical Genetics and Genomics
KAREN WECK, College of American Pathologists
CATHERINE WICKLUND, National Society of Genetic Counselors
HUNTINGTON F. WILLARD, Geisinger National Precision Health
JANET WILLIAMS, American Academy of Nursing
SARAH WORDSWORTH, University of Oxford
ALICIA ZHOU, Color Genomics
Roundtable Staff
SARAH BEACHY, Senior Program Officer and Roundtable Director
SIOBHAN ADDIE, Program Officer
MEREDITH HACKMANN, Associate Program Officer
MICHAEL BERRIOS, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
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Reviewers
This Proceedings of a Workshop was 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 National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
TIMOTHY COETZEE, National Multiple Sclerosis Society
ALEXA T. MCCRAY, Harvard Medical School
JOHN ORLOFF, Alexion
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by DANIEL MASYS, University of Washington. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
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Acknowledgments
Sponsorship from the Wellcome Trust helped make this workshop possible. Support from the sponsors of the National Academies of Sciences, Engineering, and Medicine’s Forum on Drug Discovery, Development, and Translation; Forum on Neuroscience and Nervous System Disorders; National Cancer Policy Forum; and Roundtable on Genomics and Precision Health is crucial to support this and other work of the National Academies.
The National Academies staff wish to express their gratitude to the speakers whose presentations helped inform workshop discussions on the state of clinical trial data sharing; to the members of the planning committee for their work in developing the workshop agenda and shaping the discussions; and to the many other National Academies staff without whom this workshop and the accounting thereof would not have been possible: Jeanay Butler, Robert Day, Sadaf Faraz, Greta Gorman, Anna Isabel Camilo Javier, Bardia Massoudkhan, Bettina Seliber, Lauren Shern, Victor Stewart, and Taryn Young.
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4 STRIKING A BALANCE BETWEEN BENEFIT/VALUE AND RISK/COST
5 DATA INTEROPERABILITY AND PLATFORM USABILITY
6 INFRASTRUCTURE SUSTAINABILITY
7 CHALLENGES AND DISINCENTIVES FOR SHARING AND REUSE OF DATA
8 FINDING VALUE IN SHARING CLINICAL TRIAL DATA: OVERCOMING USABILITY AND SUSTAINABILITY CHALLENGES
Data Generator/Sharer Perspective
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Boxes and Figures
BOXES
1-1 Workshop Statement of Task
2-1 Independent Review Panel Perspective: Suggestions to Enhance Data Sharing
3-1 Goals and Principles of Open Science at the Duke University School of Medicine
6-1 Proactive Clinical Trial Data Sharing by Lilly
FIGURES
1-1 Functions of the Trial Reporting System
3-1 Status of data requests by quarter (as of November 1, 2019)
Acronyms and Abbreviations
| ACCENT | Adjuvant Colon Cancer End Points |
| ADaM | CDISC Analysis Data Model |
| ALS | amyotrophic lateral sclerosis |
| APC | Adenoma Prevention with Celecoxib |
| APPROVe | Adenomatous Polyp Prevention on Vioxx Trial |
| BMS | Bristol-Myers Squibb |
| BRIDG | Biomedical Research Integrated Domain Group |
| CARE | Collective benefit, Authority to control, Responsibility, and Ethics |
| CDISC | Clinical Data Interchange Standards Consortium |
| CSDR | ClinicalStudyDataRequest.com |
| CTSU | Clinical Trial Services Unit and Epidemiological Studies Unit |
| CTT | Cholesterol Treatment Trialists’ Collaboration |
| dbGaP | database of Genotypes and Phenotypes (National Center for Biotechnology Information) |
| DCRI | Duke Clinical Research Institute |
| DSA | data sharing agreement (used interchangeably with DUA) |
| DSMB | Data and Safety Monitoring Board |
| DUA | data use agreement (used interchangeably with DSA) |
| EHR | electronic health record |
| FAIR | findable, accessible, interoperable, and reusable |
| FDA | U.S. Food and Drug Administration |
| FHIR | Fast Healthcare Interoperability Resources |
| ICMJE | International Committee of Medical Journal Editors |
| ICTRP | International Clinical Trials Registry Platform (WHO) |
| IDDO | Infectious Diseases Data Observatory |
| IOM | Institute of Medicine |
| IPD | individual participant data or individual patient data |
| IRB | institutional review board |
| IRP | independent review panel |
| ITT | intention to treat |
| LDL | low-density lipoprotein |
| MIT | Massachusetts Institute of Technology |
| MRC | Medical Research Council (United Kingdom) |
| NCI | National Cancer Institute |
| NCORP | NCI Community Oncology Research Program |
| NCTN | National Clinical Trials Network (NCI) |
| NHLBI | National Heart, Lung, and Blood Institute (NIH) |
| NIH | National Institutes of Health |
| NMA | network meta-analysis |
| PEER | Platform for Engaging Everyone Responsibly |
| SDMC | Statistics and Data Management Center |
| SDTM | CDISC Study Data Tabulation Model |
| SOAR | Supporting Open Access for Researchers |
| SPRINT | Systolic Blood Pressure Intervention Trial |
| TRS | Trial Reporting System |
| TSC | Trial Steering Committee |
| UCL | University College London |
| WHO | World Health Organization |
| WWARN | WorldWide Antimalarial Resistance Network |
| YODA | Yale University Open Data Access Project |
