PRIM&R’s Response to FDA’s Draft Guidance on Enhancing the Diversity of Clinical Trial Populations

In June, the Food and Drug Administration (FDA) issued a draft guidance, “Enhancing the Diversity of Clinical Trial Populations—Eligibility Criteria, Enrollment Practices, and Trial Designs.” The issuance of this guidance satisfies a mandate of the FDA Reauthorization Act of 2017 (FDARA), and builds on other recent efforts by the FDA to broaden eligibility criteria for clinical trials and avoid unnecessary exclusions. PRIM&R submitted comments on the guidance this week, and we wanted to share them with you and encourage you to consider submitting your own comments on this important topic—the FDA is accepting comments until August 6.

In our comments, we recognize that the draft guidance represents a significant and welcome step forward in the agency’s efforts to enhance diversity in clinical trial participation and applaud the FDA’s leadership in recommending a wide range of practical strategies that sponsors and other parties can adopt to advance this important goal.

However, we urge the FDA to include in the draft guidance a more robust discussion of the ethics of enhancing clinical trial diversity. In the current version of the guidance, the rationale for enhancing diversity in trial enrollment is presented almost exclusively as a matter of better reflecting the populations most likely to use the study therapy if approved. While we understand the FDA’s focus on the scientific and clinical benefit of increasing diversity in clinical trials, we point out that there are also ethical reasons to widen eligibility criteria and make other efforts to include populations that might otherwise be underrepresented in trials. Primary among these is the Belmont principle of justice, which demands the equitable distribution of burdens and benefits of research, and therefore, as we outline in our comments, calls for the inclusion in research of previously underrepresented communities.

We urge the FDA, furthermore, to make clearer and help stakeholders understand that the inclusion in clinical trials of previously underrepresented groups may involve ethical tradeoffs. While the guidance acknowledges that one reason members of certain populations are intentionally excluded from trials is because they have concomitant chronic conditions, it pays inadequate attention to the fact that those exclusions often serve as protections from the increased risk individuals face as a result of having those conditions. Making a commitment to diversifying trial enrollment and including previously underrepresented groups in research—including those with comorbidities—requires explicitly acknowledging the possibility of heightened risk and implementing appropriate safeguards. The draft guidance should broadly recommend that as sponsors work to enroll historically underrepresented groups, they also consider and make plans to address the full range of risks participants might face. This could include better utilization of community advisory boards, data and safety monitoring boards, risk-based monitoring, and the engagement of participants and their communities across all stages of the research process.

Finally, we make a few additional recommendations, including that the guidance incorporate non-English speakers in its list of populations that are often excluded from clinical trials without scientific rationale, as they can be safely enrolled in research provided certain safeguards are put in place. The FDA should also consider extending the guidance beyond drugs and biologics to include devices.

Enhancing clinical trial diversity is a critical issue, and we are grateful for the FDA’s leadership in addressing it. The FDA is accepting comments on the draft guidance until August 6, and we encourage you to submit comments and let the FDA know what you think, and whether and how the guidance can be improved. You are more than welcome to cite or quote PRIM&R’s comments. If you do, leave us a comment below or send us an email at to let us know!