Deborah Zarin, MRCT Center Program Director, co-authored “Completeness of clinical evidence citation in trial protocols: A cross-sectional analysis,” published in Clinical and Translational Report. The authors conclude that “clinical trial protocols undercite accessible, relevant trials and do not document systematic searches for relevant clinical trials. Consequently, ethics review committees often receive an incomplete picture of the research landscape if they review protocols similar to those deposited on ClinicalTrials.gov.”
Industry, academia, non-profit organizations and patient advocacy groups are making strides to improve transparency in sharing clinical trial data, in accord with participant wishes. Key principles for responsible data sharing include protecting the privacy and confidentiality—and wishes—of research participants, balancing risks with benefits, making data disclosure feasible by avoiding undue burdens on data generators and requestors, providing timely access to data in a format convenient for end-users, and ensuring adequate transparency and accountability. In addition, ethical data sharing necessitates careful review of informed consent language to determine whether and how uses of data were originally communicated to trial participants.
The MRCT Center is dedicated to examining barriers to clinical trial data sharing and seeks to develop thoughtful and practical solutions driving through multi-stakeholder participation. Examples of our work and publications can be found on this page.
Global Clinical Trials Data Sharing Platform: Vivli, Inc Founded through an MRCT Center initiative, Vivli was launched in 2017 as an independent not-for-profit entity to promote global clinical trials data sharing. Vivli has established a data platform wherein data are hosted, searched, and accessed. Vivli is now the largest global clinical trial platform with over 6,300+ clinical trials representing 3.8 million participants available to search and request access.
Academic Credit for Data Sharing The current system for recognizing academic advancement is predicated on a track record of peer-reviewed publications. Individuals who share data are rarely rewarded academically for making data available to others for secondary analysis, nor are they formally recognized for data preparation and curation. In response to these structural barriers, the MRCT Center, in collaboration with the New England Journal of Medicine and the Association of American Medical Colleges, formed a working group to advance a system of recognition and academic credit for data generators who opt to share their data.
Balancing Data Anonymization with Data Utility Efforts to facilitate and promote clinical trials data and document sharing rely, in part, on the effective anonymization of clinical study reports. Although existing policy guidelines acknowledge a range of methods to prevent identification of participants after publication of study documents, concrete standards and recommendations for data anonymization are largely absent. Together with the European Medicines Agency (EMA), the MRCT Center has developed a roadmap toward harmonized standards and recommendations for data anonymization.
Tools for Data Sharing Data sharing allows sponsors and investigators to honor the essential contributions and volunteerism of clinical trial participants, to ensure reproducibility, and to enable the maximal use of data by the research community. Supported by and working with the Patient-Centered Outcomes Research Institute (PCORI) Open Science Pilot Project, the MRCT Center worked to lower the barriers to data sharing by creating harmonized governance templates that further clinical trial data sharing, improve interoperability, and preserve participant privacy and autonomy.
Individual Patient Data Sharing Since July 1, 2018 the International Committee of Medical Journal Editors (ICMJE) has required authors to include a data sharing statement at the time of manuscript submission when reporting clinical trial results to journals that follow ICMJE recommendations. More recently, since January 1, 2019 all new clinical trials must include a data sharing statement in the trial’s publicly posted registration. ICMJE recognizes IPD as de-identified, individual participant level data and measurements including tables, figures, and appendices or supplementary material that support the results presented in a manuscript. The MRCT Center has worked to evaluate the understanding and implementation of the ICMJE requirements on the inclusion of data sharing statements at the time of trial registration as well as in patient facing documents, such as the informed consent form.
Advancing the Quality of Clinical Trial Enterprise
Evidence that substantial numbers of trials do not contribute meaningful information to the evidence base raises both ethical and scientific concerns. Participants assume the risks and burdens of a study, while mistakenly believing that they are contributing to medical progress. At the same time, these non-informative trials divert participants, researchers, and other resources from more valuable trials, potentially making it more difficult to reach enrollment targets.
Although others have identified the conduct of non-informative trials as a significant problem, there has been less progress in defining, studying, and attempting to reduce their frequency and thus improve the quality of the medical evidence base. This program focuses on efforts to improve the efficiency and quality of clinical trials, with the overall objective of optimizing the impact of each trial participant and informing key medical and policy decisions. In addition, we build on the established foundation of trial reporting to ClinicalTrials.gov with the aims of improving the timeliness and quality of reports, as well as increasing the use of data from ClinicalTrials.gov by the research enterprise.
Develop “best practices” for the conduct of landscape analyses that enable researchers and other oversight entities to understand what is already known, and what is currently being investigated, about their research question
Analyze large samples of informed consent forms in order to establish better (and worse) practices, and to start to develop tools that might help researchers to write future consent forms
Increase use of data from ClinicalTrials.gov to inform research decisions
April 2021: Served on NASEM committee which released a report on genomic epidemiology data infrastructure; co-authored article “Lack of harmonization of coronavirus disease ordinal scales”
The MRCT Center remains at the forefront of analyzing and understanding the impact of the GDPR and other privacy laws that impact clinical research data and biospecimen sharing. The patchwork of privacy laws that apply to the processing of personal data and in some cases restrict the transfer of such data across national boundaries impedes the progress of science and public health and the use of personal data for secondary research.
The European Union’s General Data Protection Regulation (GDPR) took effect on May 25, 2018. The regulation governs the processing of personal data of individuals located in any member state of the European Economic Area (EEA) or personal data processed in the context of an entity’s establishment located in an EEA member state. Following “Brexit,” the United Kingdom has enacted national legislation, commonly referred to as the UK GDPR, that is substantially similar to GDPR. Under both GDPR and UK GDPR, personal data are defined broadly as “any information relating to an identified or identifiable natural person (“data subject”); an identifiable person is one who can be identified, directly or indirectly, in particular by reference to an identifier such as a name, an identification number, location data, online identifier, or to one or more factors specific to the physical, physiological, genetic, mental, economic, cultural, or social identity of that natural person. The GDPR had an immediate impact on clinical research generally and multi-regional clinical trials specifically.
In addition to the GDPR, recent years have seen a growing number of sector-specific and omnibus state privacy laws in the U.S., such as the CCPA/CPRA and recently-passed data privacy legislation in Colorado, Utah and Virginia, as well as Florida’s Protecting DNA Privacy Act. Also of note, China enacted an omnibus data privacy law known as the Personal Information Protection Law (“PIPL”), which took effect in 2021, Brazil’s General Data Protection Law (“LGPD”) became subject to enforcement in 2021, and India’s Digital Personal Data Protection Act (“DPDP Act”) was enacted in 2023. The MRCT Center continues to monitor the development of these laws and suggests strategies to help the research community comply with such laws, including through advocacy with relevant public authorities and industry stakeholders.
Identify, explain, and discuss key problems that the GDPR and other privacy laws have introduced for the for the domestic and global research community on clinical research, biobanking, and data banking, as well as big data research.
Highlight the major challenges and ambiguities that privacy laws present for regulators, industry, academia, IRBs/research ethics committees, and researchers.
Engage with the European Commission and EDPB to explore potential solutions.
Share preferred operational practices in each of these areas.
Identify where further guidance or explanations (e.g., FAQs) would be helpful.
key milestones
November 2024: MRCT Center submitted public comments to the U.S. Department of Justice’s proposed rule “Provisions pertaining to preventing access to U.S. sensitive personal data and government-related data by countries of concern or covered persons”
During 2023: Convened experts in the field to assess the ongoing and evolving impact of privacy laws on clinical research and data sharing
December 2022: MRCT Center Research, Development, & Regulatory Roundtable hosted a one-day conference on GDPR and privacy laws in other geographies (China, India, Japan, and South Africa). Dr. Francis Collins, Senior Advisor to the President (Acting) and Former Director of the National Institutes of Health, delivered the keynote address. The five sessions included panelists from academia, pharmaceutical companies, and regulatory bodies.
February 2022: MRCT Center submitted public comments to the National Institutes of Health (NIH) “Request for Information on Proposed Updates and Long-Term Considerations for the NIH Genomic Data Sharing Policy”
September 2021: MRCT Center comments on European Data Protection Board Guidelines 04/2021 on Codes of Conduct as Tools for Transfers
April 2021: MRCT Center comments in response to European Data Protection Board questions on research and GDPR.
October 2020: Co-authored an article in Science Magazine entitled “How to Fix the GDPR’s Frustration of Global Biomedical Research.” The article received significant attention and has been provided as a briefing material to members of the Biden administration seeking to understand international data sharing issues.
May 2020: David Peloquin participated in a webinar organized by ISC that was a follow-up to the November 2019 Brussels conference and discussed the MRCT Center’s comments submitted to the European Commission in April 2020.
April 2020: MRCT Center submitted comments to the European Commission outlining the challenges that GDPR has created for the research community along with potential solutions in response to the European Commission’s call for comments on GDPR.
November 2019: MRCT Center and Ropes & Gray LLP co-organized ISC Seminar on Challenges for Health Research arising from GDPR in Brussels, Belgium.
May 2019: Mark Barnes attended a meeting with the Irish Data Protection Commission to discuss the challenges the GDPR poses to the research community.
February 2019: Mark Barnes and colleagues at Ropes & Gray co-authored an article discussing the challenges in the EDPB’s February 2019 opinion on the intersection of the GDPR and the EU Clinical Trials Regulation.
January 2019: MRCT Center sent a letter to the EDPB commenting on the EDPB’s November 2018 draft guidance on the territorial scope of the GDPR.
July 30, 2018: Application of the GDPR to Research: Legal, Practical and Strategic Implications: The MRCT Center convened over 110 representatives from academia, industry, and government. The conference explored the impact of the EU GDPR on human subjects’ research, biobanking and data banking, and big data research. A letter summarizing the findings was sent to the European Commission Directorate-General for Research and Innovation with a copy to EMA, NIH, and others.
PRoject leadership & Staff
Mark Barnes, JD, LLM, Faculty Co-Director, MRCT Center
Barbara E. Bierer, MD, Faculty Director, MRCT Center
Ensuring the safety of biological products, drugs, and devices in healthcare is the shared responsibility of regulatory, academic and industry-related stakeholders. Safety data are collected and analyzed not only throughout product development but also after approval, through analysis of observational data and/or designated studies. Post-market surveillance more closely represents the real-world setting, and some adverse events only manifest after regulatory approval and adoption as a result of wider dissemination to patients.
Current safety surveillance systems rely upon analysis of spontaneous, voluntary reports and of administrative claims, electronic medical records, and some post-marketing pharmacovigilance studies. A limited number of surveillance systems have utilized innovative analytical and statistical techniques, including data mining, machine learning and artificial intelligence to interrogate real-world data. While these approaches are important and complementary, they fail to harness the full power of cooperation across stakeholders and systems to realize global inclusivity in safety surveillance.
Convened by the MRCT Center in collaboration with others, the Proactive Safety Surveillance initiative (PSS) aims to improve upon current safety surveillance systems by creating a global, cooperative model for a more proactive, predictive safety surveillance system. A partnership with expert stakeholders will aid the selection, evaluation, and adaptation of new technologies, methodologies, and insights to support the medical determination and validity of safety signals. Such a system would also highlight the importance of a thorough benefit and risk analysis and provide better data for the global community. While inevitably challenging, we believe exploration of such a system holds the promise of increasing the timely detection, validation, and communication of important safety information.
OBJECTIVES
Create a framework for an international approach to proactive drug and device safety surveillance, validation, and communication
Engage diverse and international representatives to examine the ethical, social, and political challenges of a global, proactive safety surveillance system
Develop a governance model for the initiative that is respectful of sovereign authorities and differing international laws and regulations
Develop one or more examples of pilot projects appropriate to test the advantages and limitations of a global proactive safety surveillance system
Key Milestones
December 2019: Core Team Conference
September 2019: Methodological Comparison Meeting
May 2019: Visioning Session
Jan – April 2019: Project Core Team established
Program Leadership & STAFF
Barbara E. Bierer, MD, Professor of Medicine, Harvard Medical School and Faculty Director, MRCT Center
Paul Bleicher, MD, PhD, Principal, Evident Health Strategies
Paul Chang, MD, Chief Safety Officer, Johnson & Johnson
William Crown, PhD, Distinguished Research Scientist, Brandeis University
David Madigan, PhD, Provost and Senior Vice President for Academic Affairs, Northeastern University
Sandra Morris, PhD, Vice President Strategy Realization, Johnson & Johnson
Frank Rockhold, PhD, Professor, Duke University
Joseph Ross, MD, Associate Professor of Medicine, Yale School of Medicine
Patrick Ryan, PhD, Vice President of Observational Health Data Analytics, Janssen Research and Development
Jodi Segal, MD, Professor, Johns Hopkins School of Medicine
Paul Stang, PhD, Vice-President Global Epidemiology, Johnson & Johnson
Joanne Waldstreicher, MD, Chief Medical Officer, Johnson & Johnson
MRCT Center Program Director Deborah A. Zarin, MD, and Harry P. Selker, MD, MSP authored “Reporting of Clinical Trial Results: Aligning Incentives and Requirements to Do the Right Thing” in Clinical Therapeutics. The authors argue that FDAAA and other trial reporting policies should be systematically and comprehensively enforced, in order to ensure that results from all clinical trials become available to inform clinical, policy or research decisions in a timely manner.
The MRCT Center submitted public comments to the National Institutes of Health (NIH) “Request for Information on Proposed Updates and Long-Term Considerations for the NIH Genomic Data Sharing Policy,” published in the Federal Register on November 30, 2021.
The MRCT Center appreciates the NIH’s efforts to update its policy on Genomic Data Sharing (GDS) to maintain currency with evolving technology and understanding and commented on multiple issues, including de-identification and evolving concept of “identifiability,” data linkage, data management and sharing principles for NIH-supported resources, harmonization of GDS and NIH Policy for Data Management and Sharing (DMS) plans, and the types of research covered by the GDS policy. In addition, the MRCT Center proposed that the NIH consider several additional issues in its revision including withdrawal of consent, third party risks, harmonization with other federal and international agencies, the increased likelihood of re-identification with future technology advances, sanctions for misuse of data, public education, and the effectiveness and impact of the GDS policy. Read comments
MRCT Center colleagues author an article in JAMA Network Open with Dr. Tony Tse.
Presented on: November 18, 2021
Published by:JAMA Network Open
MRCT Center Executive Director Sarah White, Senior Advisor Luke Gelinas, Project Manager Walker Morrell, Faculty Director Barbara Bierer, and Program Director Deb Zarin authored an article in JAMA Network Open with Dr. Tony Tse: “Characterization of Informed Consent Forms Posted on ClinicalTrials.gov.”
