Focus Area: Quality & Transparency

On March 30-31st, 2015 over 70 committed international stakeholders joined together at the Harvard Faculty Club to discuss solutions to Clinical Trial Data Sharing.

Prior to the conference, Deloitte partnered with the MRCT Center to identify common principles, views on data sharing, and methods for sharing of participant level clinical trial data across a cross-section of those anticipated to attend the conference.

Interviews conducted with 21 individuals from industry, foundations, and academia identified common principles for sharing of participant level clinical trial data. Interviewees supported the sharing of data to advance science and improve public health if the following were given:

• Protecting patient rights and privacy
• Ensuring responsible conduct of research and good stewardship of data
• Maintaining incentives for those who generate data to conduct new research

The survey also showed that 100% of respondents supported the value of data sharing and the aggregation of data, but specifics of what data to share varied from making all data available to making data available on request after internal review for legal and competitive risk. A central system that allows for interoperability was widely considered to be the preferred option, however, many challenges needed to be addressed, including:

• Use of common data standard
• Resources to anonymize data
• Data repository for academics
• User friendly system
• Ability to combine data easily
• Common criteria or common review board
• Governance of the central system

Moreover, to improve transparency, interviewees plan to or are currently publishing metrics of data requests and track reasons for denial. Data from respondents show that 93% of data requests have been approved, though the time for approval varied widely. Reasons for denying a request for data include: proposal lacks clear scientific merit, data requested is not appropriate for the study proposal, Data Use Agreement was not signed, out of scope for informed consent, etc. To achieve a shared vision for an interoperable system, key process points should be harmonized such as proposal review, uploading data, system framework, and end of study requirements. The full results may be accessed here.

MRCT Center Pre Conference Survey Slides

MRCT hosted a Data Transparency Conference at Harvard, 30-31 March.

More than 70 participants from academia government, industry, and nonprofit organizations gathered at the Harvard Faculty Club for a 2-day conference focused on how to harness the full potential of participant level data sets for secondary use.

Conference participants developed a vision for a future governance model that envisioned the ideal system as a federated data platform allowing access to data from a variety of sources with broad search capabilities.

Learn More about the MRCT Center’s work in clinical trial data sharing and transparency.

Comments submitted to NIH

In March, we submitted public comments to the National Institutes of Health in response to the Proposed Rule for Clinical Trial Registration and Results Submission. Our comments addressed the need for:

• Providing non-technical summaries that follow health literacy principles and use non-promotional language so that they benefit trial participants and their families
• Extending and coordinating results submission deadlines
• Adopting standard data formats across agencies
• Mandatory expanded access reporting, and
• Extending the timeframe for submitting corrections of clinical trial information.

Learn More

MRCT Center at Harvard was asked to present their efforts on clinical trial data sharing at IOM on February 3, 2014. Both presentations were well received, and the IOM was receptive to suggestions made by MRCT.

Mark Barnes, MRCT Faculty Co-Chair presented “Clinical Trial Data Sharing”.

Barbara Bierer, also MRCT Faculty Co-Chair, presented “Guiding Principles for Clinical Trial Data Sharing”.

Guiding Principles

IOM Presentation

Boston, MA – A new report by researchers from Harvard University and others in a working group convened by the Multi-Regional Clinical Trials Center (MRCT) at Harvard proposes recommendations for addressing a problem that has vexed drug regulators: how to expand public access to data from clinical trials while protecting patients’ privacy and weighing pharmaceutical companies’ business interests.

Recently, the European Medicines Agency (EMA) announced it will provide public access to participant-level data submitted in applications for marketing approval in Europe, prompting questions about whether the U.S. Food and Drug Administration should follow suit. Data releases by the EMA have spurred litigation by drug companies and heated debate about whether clinical trial data should be protected as proprietary information or widely shared.

The report, published online October 21, 2013 in The New England Journal of Medicine, was released to coincide with the first meeting of the Institute of Medicine’s Committee on Strategies for Responsible Sharing of Clinical Trial Data on October 23. The Institute of Medicine convened the committee on an accelerated timetable to develop a framework for expanded public access to clinical trial data. An initial report is expected in January 2014.

“Our experiences with Vioxx, Avandia, and other widely prescribed drugs that were revealed to have serious safety risks show how important it is to give independent scientists access to clinical trial data,” said Michelle Mello, professor of law and public health at the Harvard School of Public Health and lead author of the report. “The question is, how can we achieve the powerful public health benefits of data sharing while protecting research participants’ privacy, avoiding ‘junk science,’ and minimizing burdens on trial sponsors?”

According to the authors, expanding access to participant-level data could both serve as a check on trial sponsors’ characterizations of a product’s safety and effectiveness, as well as open up new avenues of scientific inquiry beyond the scope of the original study. However, there are concerns that research participants’ identities could be discovered, and that competitors and others could use the data to produce flawed analyses. The FDA historically has treated participant-level clinical trial data submitted to the agency as confidential.

The authors recommend that a system of expanded access to clinical trial data apply to trials of all approved prescription drugs, medical devices, and biologics; and treat all trial sponsors and qualified data requesters evenhandedly. It should have mechanisms to ensure that all sponsors and data users adhere to minimum standards—for example, rules should specify what must be shared, and data users should commit to following a scientifically sound analytical plan. If sponsors are permitted to influence which data requests get granted, they should be required to apply explicit decision criteria and publicly explain the reasons for denials. Using an independent intermediary organization to make those decisions, however, may be preferable.

“As in other areas of health care, the push for greater transparency in the area of clinical-trial data appears inexorable,” the authors wrote. “The question is not whether, but how, these data should be broadly shared. The potential risks to research participants and trial sponsors must be thoughtfully addressed in the design of any new data-sharing system but need not block progress toward achieving the promise of ‘big data’ in the clinical trials context.”

“The European Medicines Agency has hastened to impose regulatory mandates for data sharing, which may indeed be needed,” said Mark Barnes, a partner at Ropes & Gray LLP and the Harvard faculty co-director of MRCT, “but such mandates need to be carefully considered, to avoid harms to participants and to preserve commercial incentives for industry to invest in vital research.”

The authors were part of a working group of both academics and pharmaceutical industry experts convened by Harvard’s Multi-Regional Clinical Trials Center, which receives funding from pharmaceutical companies and not-for-profit entities.

“Preparing for Responsible Sharing of Clinical-Trial Data,” Michelle M. Mello, Jeffrey K. Francer, Marc Wilenzick, Patricia Teden, Barbara E. Bierer, and Mark Barnes, NEJM, online October 21, 2013, DOI: 10.1056/NEJMhle1309073