Sharing Clinical Trial Data
MAXIMIZING BENEFITS, MINIMIZING RISK
Committee on Strategies for Responsible Sharing of Clinical Trial Data
Board on Health Sciences Policy
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
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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. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by contracts between the National Academy of Sciences and the U.S. National Institutes of Health (HHSN263201200074I), U.S. Food and Drug Administration, AbbVie Inc., Amgen Inc., AstraZeneca Pharmaceuticals, Bayer, Biogen Idec, Bristol-Myers Squibb, Burroughs Wellcome Fund, Doris Duke Charitable Foundation, Eli Lilly and Company, EMD Serono, Genentech, GlaxoSmithKline, Johnson & Johnson, Medical Research Council (UK), Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Takeda, and The Wellcome Trust. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.
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Suggested citation: Institute of Medicine (IOM). 2015. Sharing clinical trial data: Maximizing benefits, minimizing risk. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
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INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
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COMMITTEE ON STRATEGIES FOR RESPONSIBLE SHARING
OF CLINICAL TRIAL DATA
BERNARD LO (Chair), President, The Greenwall Foundation
TIMOTHY COETZEE, Chief Research Officer, National Multiple Sclerosis Society
DAVID L. DeMETS, Professor and Chair, Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison
JEFFREY DRAZEN, Editor-in-Chief, New England Journal of Medicine
STEVEN N. GOODMAN, Professor, Medicine & Health Research & Policy, Stanford University School of Medicine
PATRICIA A. KING, Carmack Waterhouse Professor of Law, Medicine, Ethics and Public Policy, Georgetown University Law Center
TRUDIE LANG, Principal Investigator, Global Health Network, Nuffield Department of Medicine, University of Oxford
DEVEN McGRAW, Partner, Healthcare Practice, Manatt, Phelps & Phillips, LLP
ELIZABETH NABEL, President, Brigham and Women’s Hospital
ARTI RAI, Elvin R. Latty Professor of Law, Duke University School of Law
IDA SIM, Professor of Medicine and Co-Director of Biomedical Informatics of the Clinical and Translational Science Institute, University of California, San Francisco
SHARON TERRY, President and CEO, Genetic Alliance
JOANNE WALDSTREICHER, Chief Medical Officer, Johnson & Johnson
ANNE B. CLAIBORNE, Senior Program Officer
INDIA HOOK-BARNARD, Study Director (July 2014 to February 2015)
LEIGHANNE OLSEN, Study Director (until November 2013)
REBECCA N. LENZI, Study Director (November 2013 to April 2014)
MICHELLE MANCHER, Associate Program Officer
ELIZABETH CORNETT, Research Assistant (from October 2014)
RACHEL KIRKLAND, Senior Program Assistant (until October 2013)
BARRET ZIMMERMANN, Senior Program Assistant (from October 2013)
MICHAEL BERRIOS, Senior Program Assistant (from September 2014)
SCOTT D. HALPERN, IOM Anniversary Fellow
ANDREW M. POPE, Director, Board on Health Sciences Policy
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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 deliberative process. We wish to thank the following individuals for their review of this report:
Lawrence J. Appel, Johns Hopkins Medical Institutions
Virginia Barbour, PLoS Medicine
Mark Barnes, Multi-Regional Clinical Trials Center at Harvard
Cynthia Dwork, Microsoft Research
Ezekiel J. Emanuel, University of Pennsylvania
David Harrington, Harvard School of Public Health
David Korn, Harvard University
Ronald L. Krall, University of Pittsburgh
Harlan M. Krumholz, Yale University School of Medicine
Christine Laine, Annals of Internal Medicine
Erika Lietzan, University of Missouri School of Law
Alexa T. McCray, Center for Biomedical Informatics
John J. Orloff, Baxter BioScience
Gary Puckrein, National Minority Quality Forum
Sir Michael Rawlins, Royal Society of Medicine
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Enriqueta Bond, Burroughs Wellcome Fund, and Sara Rosenbaum, George Washington University. Appointed by the National Research Council and the Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
Patients and their physicians depend on clinical trials for reliable evidence on what therapies are effective and safe. Responsible sharing of the data gleaned from clinical trials will increase the validity and extent of this evidence. Several large pharmaceutical companies and some academic investigators already are sharing clinical trial data, and the European Medicines Agency will soon do so as well. The issue is no longer whether to share clinical trial data, but what specific data to share, at what time, and under what conditions.
Responsible sharing of clinical trial data raises complex challenges. Key stakeholders—clinical trial participants, sponsors and funders, clinical trialists, and regulatory authorities—have concerns and interests that need to be addressed and balanced. Because clinical trials are conducted worldwide, laws and regulations of different jurisdictions will need to be followed. Moreover, the very nature of clinical trials may change dramatically as data from personal sensors and devices and electronic medical records are increasingly used and new trial designs are introduced. In the face of these changes, sponsors, investigators, clinical trial participants, and regulators may feel that familiar, established practices and expectations are being overturned and that the future is uncomfortably uncertain. If sharing of clinical trial data is to be responsible and sustainable, there will need to be new business models for data sharing, changes in the culture of academic medicine, and incentives for sponsors and investigators to continue to develop new therapies and carry out clinical trials.
In this rapidly changing landscape of clinical trials, how can this
report play a constructive and enduring role? The committee that conducted this study could not anticipate, much less try to resolve, the many practical issues that will arise as the sharing of clinical trial data unfolds. Nor could we provide a detailed roadmap for terrain that is unknown and under development. We could, however, provide guiding principles, outline operational considerations, and offer specific recommendations regarding what data should be shared at key milestones in the life cycle of a clinical trial, and we could also recommend conditions that will increase the benefits and minimize the risks of data sharing. Our recommendations represent an attempt to balance the interests of different stakeholders with the public interest of having the best information possible regarding the effectiveness and safety of therapies.
Our committee comprised people with different professional backgrounds and experiences. Their varied interdisciplinary perspectives deepened our discussions and our appreciation for the complexity of clinical trial data sharing. This report is better because of this richness of viewpoints. As chair I wish to thank the committee members for their hard work, their willingness to reconsider their views in light of evidence and persuasion, and their good humor. I believe our deliberations can serve as a model for how stakeholders can learn from each other and find common ground.
This report would not have been possible without the dedicated and expert work of the Institute of Medicine (IOM) staff, including India Hook-Barnard, Michelle Mancher, Anne Claiborne, Andrew Pope, Elizabeth Cornett, and Michael Berrios, whom the committee gratefully acknowledges and thanks. Scott Halpern, IOM Anniversary Fellow, sponsored by the American Board of Internal Medicine Foundation in honor of Dr. John Benson, made many important contributions to the committee’s work as well. I would also like to thank Chelsea Ott for her skilled research assistance.
Bernard Lo, M.D., Chair
Committee on Strategies for Responsible Sharing of Clinical Trial Data
Charge to the Committee and Study Scope
2 Guiding Principles for Sharing Clinical Trial Data
Overview of Key Potential Benefits and Risks
The Committee’s Approach to Applying the Principles
3 The Roles and Responsibilities of Stakeholders in the Sharing of Clinical Trial Data
4 The Clinical Trial Life Cycle and When to Share Data
When Data Packages Should Be Shared
5 Access to Clinical Trial Data: Governance
Approaches to Mitigating the Risks of Data Sharing
6 The Future of Data Sharing in a Changing Landscape
Structure for Collaborative Next Steps
B Concepts and Methods for De-identifying Clinical Trial Data
C Legal Discussion of Risks to Industry Sponsors
D Clinical Trial Data Sharing Policies: Top 1-12 Pharmaceutical Companies Ranked by 2013 Market Capitalization
In response to 23 public- and private-sector sponsors, the Institute of Medicine assembled an ad hoc committee to develop guiding principles and a framework (activities and strategies) for the responsible sharing of clinical trial data. Responsible sharing of clinical trial data will allow other investigators to carry out additional analyses and reproduce published findings, strengthen the evidence base for regulatory and clinical decisions, and increase the scientific knowledge gained from investments by the funders of clinical trials. Data sharing can accelerate new discoveries by avoiding duplicative trials, stimulating new ideas for research, and enabling the maximal scientific knowledge and benefits to be gained from the efforts of clinical trial participants and investigators.
At the same time, sharing clinical trial data presents risks, burdens, and challenges. These include the need to (1) protect the privacy and honor the consent of clinical trial participants; (2) safeguard the legitimate economic interests of sponsors (e.g., intellectual property and commercially confidential information); (3) guard against invalid secondary analyses, which could undermine trust in clinical trials or otherwise harm public health; (4) give researchers who put effort and time into planning, organizing, and running clinical trials adequate time to analyze the data they have collected and appropriate recognition for their intellectual contributions; and (5) assuage the fear of research institutions that requirements for sharing clinical trial data will be unfunded mandates.
With the goal of ensuring responsible sharing of clinical trial data to increase scientific knowledge and ultimately lead to better therapies for
patients, the committee that conducted this study identified the following guiding principles for data sharing: (1) maximize the benefits of clinical trials while minimizing the risks of sharing clinical trial data, (2) respect individual participants whose data are shared, (3) increase public trust in clinical trials and the sharing of trial data, and (4) conduct the sharing of clinical trial data in a fair manner. The committee drew on these guiding principles in developing its recommendations and believes they will be useful in the future as circumstances change and unforeseen issues emerge.
In this report, the committee analyzes how key stakeholders (including participants, sponsors, regulators, investigators, research institutions, journals, and professional societies) assess the benefits, risks, and challenges of data sharing and concludes that all stakeholders have roles and responsibilities in responsible sharing of clinical trial data. The report presents four recommendations designed to maximize the benefits and minimize the risks associated with data sharing:
Recommendation 1: Stakeholders in clinical trials should foster a culture in which data sharing is the expected norm, and should commit to responsible strategies aimed at maximizing the benefits, minimizing the risks, and overcoming the challenges of sharing clinical trial data for all parties.
Recommendation 2: Sponsors and investigators should share the various types of clinical trial data no later than the times specified in this report (e.g., the full analyzable data set with metadata no later than 18 months after study completion—with specified exceptions for trials intended to support a regulatory application—and the analytic data set supporting publication results no later than 6 months after publication).
Recommendation 3: Holders of clinical trial data should mitigate the risks and enhance the benefits of sharing sensitive clinical trial data by implementing operational strategies that include employing data use agreements, designating an independent review panel, including members of the lay public in governance, and making access to clinical trial data transparent.
Recommendation 4: The sponsors of this study should take the lead, together with or via a trusted impartial organization(s), to convene a multistakeholder body with global reach and broad representation to address, in an ongoing process, the key infrastructure, technological, sustainability, and workforce challenges associated with the sharing of clinical trial data.