By Clinical Research News Staff 

July 2, 2024 | Last week, the U.S. Food and Drug Administration issued a draft guidance, “Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies,” to assist medical product sponsors in submitting Diversity Action Plans to support certain clinical studies. Comments on the draft guidance should be submitted by September 26, 2024.   

The draft guidance describes the format and content of Diversity Action Plans, which are required as part of the Food and Drug Omnibus Reform Act (FDORA) of 2022. The current draft replaces a similarly-named April 2022 version and details the medical products and clinical studies for which a Diversity Action Plan is required, the timing and process for submitting Diversity Action Plans to the FDA, and the criteria and process the agency will use to evaluate a sponsor’s request not to submit a required Diversity Action Plan (a waiver). 

Diversity Action Plans are intended to increase enrollment of participants of historically underrepresented populations to help improve the data the agency receives about the patients who may potentially use the medical product. Importantly, the DAP focuses not on “numbers but the rate of representation from historically underrepresented populations based on race, ethnicity, sex, and age,” pointed out Esther Krofah, executive vice president of Health at the Milken Institute, an international, independent economic think tank, in an email conversation with Clinical Research News.  

Plan Requirements  

According to the guidance, Diversity Action Plans must specify the sponsor’s rationale and goals for clinical study enrollment (separated by the age group, ethnicity, sex, and race of clinically relevant study populations) and describe how the sponsor intends to meet those goals. The guidance also urges sponsors and investigators to consider the many dimensions of clinical trial diversity, even those that extend beyond age, ethnicity, sex, and race to enroll populations that represent the patients who will be treated if the product is approved.  

“It is a ‘plan,’ and it will require sufficient thinking from both the FDA and the industry,” Krofah added. Some companies have likely invested a good deal of work already around these questions since FDORA passed; others may have more work to do. “It is an opportunity for the stakeholders in the clinical research ecosystem to finally focus on investing in clinical research infrastructures to recruit and retain those who have been set aside in clinical research,” Krofah said. “Research is already planned ahead of time, and teams can now take advantage of data and technologies available for recruitment and retention strategies.” 

DAPs apply to phase 3 clinical studies or, as appropriate, other pivotal clinical studies of a drug or biological product, as well as for certain clinical studies of devices, including those intended to serve as the primary basis for the FDA’s evaluation of the safety and effectiveness and benefit-risk determination of the device. The requirement to submit a Diversity Action Plan applies to any clinical studies for which enrollment begins 180 days after publication of the final guidance.  

Diversity Action Plans can be modified, either in response to FDA feedback or under the sponsor’s own initiative. If the original plan goals are not being met, the current guidance only suggests that an explanation be provided. “If such goals are not being met or are not expected to be met at the conclusion of the study, the status report should include a description of the reason(s) why the sponsor is not currently meeting and/or does not expect to meet enrollment goals and the sponsor’s plan to mitigate such an outcome,” the guidance reads (lines 596-599).  

This is change from the earlier diversity plan guidance, Krofah highlighted. “It would be important to clarify what protocols the FDA would put in place if the enrollment goals were not met despite the best efforts from an industry sponsor,” she said. “The first iteration of the draft guidance states, ‘In the event that recruitment goals are not met despite best efforts, sponsors should discuss with the FDA a plan to collect this data in the post-marketing setting.’ This point is not repeated in the second draft guidance.”  

FDA also strongly encourages sponsors to share their strategies for meeting Diversity Action Plan enrollment goals with the public—in “consumer-friendly language”, to publicly post enrollment goals from their Diversity Action Plans, and to describe the measures they plan to take to achieve the goals.  

Real Progress 

Krofah is hopeful that Diversity Action Plans will positively impact trial diversity, and the Milkin Institute plans to submit comments to FDA suggesting refinements to the guidance, “to maximize the full potential of the Diversity Action Plans,” she said.  

“In principle and practice, the FDA wants to work with sponsors to get medical products approved if sponsors follow requirements and prove that the evidence is scientifically rigorous, supporting the safety and effectiveness of the product for intended populations,” Krofah said. “The DAP implementation should go parallel with the governmental and sponsor investment in clinical research infrastructure and payer’s reimbursement of such studies to recruit and retain in historically underrepresented communities. It might not start perfectly from the beginning, which is why the annual report to Congress, as described in the FDORA Section 504, is important so that all stakeholders involved are accountable for implementing the DAP for safe and effective medical products for all people who will use such products. If FDA continues through its review process to demonstrate how they are using DAPs to make decisions on safety and efficacy to products based on populations that experience the prevalence of this disease in the real world, we will begin to see progress in this area.”