In an interview at the NIH Pragmatic Trials Collaboratory's annual Steering Committee meeting and 10th anniversary celebration, we asked Drs. Jeremy Sugarman and Pearl O'Rourke to discuss the role of the Ethics and Regulatory Core in helping the NIH Collaboratory Trial teams plan and implement their pragmatic trials, and the contributions the Core has made to the literature on ethics and regulatory challenges in pragmatic clinical research.

Based on your experience working with the NIH Collaboratory Trials, what are some of the common challenges of the Core?

A common challenge the NIH Collaboratory Trial investigators face is determining their study’s level of risk, specifically whether the research is determined to be “minimal risk.” This issue is important, because it influences the permissibility of using alternatives to conventional written informed consent, such as waiving consent or waiving the requirement to document consent.

A recent focus of the Ethics and Regulatory Core is the challenge some studies face with “collateral findings.” These are findings, whether discovered intentionally or unintentionally, that don’t address the trial’s research questions, but may have implications for the health of patients in the trial. For example, when collecting data from electronic health records, researchers might detect the possible use of contraindicated medications in some patients. We recently completed a multimethod investigation of the ethical and regulatory implications of collateral findings in pragmatic clinical trials.

The Core has also offered advice and guidance on several other issues, including innovative study designs such as cluster randomization and stepped-wedge designs, data and privacy issues, collaborating and communicating with healthcare system representatives and clinicians, and challenges related to conducting research at multiple sites.

What strategies have NIH Collaboratory Trials used to overcome these barriers?

The Ethics and Regulatory Core hosts an initial consultation with each NIH Collaboratory Trial in the planning phase, and then a follow-up consultation when the project transitions to the implementation phase. We also invite the study teams to consult with us to help address any ethical challenges they’re facing. Sometimes these consultations result in changes in study design, partnerships with the Core to nest empirical ethics studies within the NIH Collaboratory Trials, and other approaches.

How are the NIH Collaboratory Trials’ experiences with the Core helping the field of pragmatic research?

The Core’s work with the NIH Collaboratory Trials has created a body of knowledge and guidance that we have made available to help those engaged in pragmatic research. In addition to a series of published articles in the peer-reviewed literature, we have included some related content in the Living Textbook of Pragmatic Clinical Trials.

Can you describe the impact the Core has had on pragmatic trials over the past decade?

The Core’s consultations during the development stage of these trials has improved investigators’ understanding, appreciation, and planning for the relevant ethical and regulatory issues. The result has hopefully been better research design and improved implementation. Likewise, routine conference calls with active studies have provided opportunities for investigators to hear about the challenges encountered and the solutions developed by other study teams. Sharing these experiences has been invaluable.

The Core is available for ad hoc consultation regarding the ethical and regulatory issues facing any of the projects. Such issue-specific consultations hopefully help study teams develop appropriate solutions.

Finally, Core members have generated a substantial amount of empirical and conceptual scholarship related to the ethical and regulatory issues encountered in the NIH Collaboratory. This work is helping to expand understanding of pragmatic clinical research for the broader research community.

What do you think the Core can contribute over the next decade?

The Core’s ongoing consultations during all phases of the NIH Collaboratory Trials will promote improvements to research protocols and offer real-time check-ins for unanticipated challenges. Our regular conference calls, contributions to the Living Textbook, and scholarly publications will continue to provide an important resource for investigators as well as IRBs.