On June 26, 2024, the US Food and Drug Administration (FDA) released its much-anticipated draft guidance on Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. The draft guidance describes which clinical studies would require diversity action plans, what clinical study sponsors should include in their plans, and when FDA may determine that a sponsor can waive the diversity action plan requirement. The draft guidance was issued pursuant to FDA’s obligation under the 2022 Food and Drug Omnibus Reform Act (FDORA) to update its guidance on diversity action plans. Once finalized, this guidance will replace FDA’s April 2022 draft guidance on diversity plans in clinical studies.

The draft guidance provides insight into the actions that FDA expects clinical study sponsors to take to address the historical underrepresentation of certain populations based on age, ethnicity, biological sex and race in clinical studies. It also provides sponsors and other interested parties the opportunity to potentially shape FDA’s expectations by submitting comments on the draft guidance. The obligation to prepare and implement diversity action plans falls primarily on sponsors. However, other stakeholders that support the design and implementation of clinical studies, such as contract research organizations, site management organizations, subject recruitment solution providers and research sites, should consider how the recommendations in the draft guidance may impact their obligations and business strategies.

Comments on the draft guidance must be submitted by September 26, 2024.

IN DEPTH

Minority and underserved populations have long been underrepresented in clinical studies, leading to disparities in the quality and range of treatment options available to them. Diversity action plans are intended to increase the participation of historically underrepresented populations in clinical studies. FDA’s guidance, consistent with section 3602(a) of FDORA, is primarily focused on plans for adequate representation across age groups, biological sexes, and racial and ethnic groups. However, FDA notes that other characteristics could be important to consider when developing a diversity action plan, such as geographic location, gender identity, sexual orientation, socioeconomic status, physical and mental disabilities, pregnancy status, lactation status and co-morbidity.

WHICH CLINICAL STUDIES REQUIRE DIVERSITY ACTION PLANS

According to the draft guidance, diversity action plans would be required for Phase 3 and other pivotal trials (besides bioavailability or bioequivalence studies) for new drugs, including biological products. Most device trials would also require diversity action plans, including those intended to serve as the primary basis for FDA’s evaluation of the safety and effectiveness and benefit-risk determination of the device. If a device study requires submission of an investigational device exemption (IDE) application, the diversity action plan must be included in the IDE application. If a device trial does not require submission of an application for an IDE, the diversity action plan may be submitted with any marketing application (i.e., premarket notification, request for classification or premarket approval application). Diversity action plans are not required for studies exempt from IDE regulations or for device studies that are not designed to collect definitive safety and effectiveness evidence for a specified intended use of a device.

As required by section 3602(c) of FDORA, once FDA’s final guidance is issued, a clinical study sponsor will have to comply with the guidance if the sponsor’s study begins enrollment more than 180 days after the guidance was published. However, FDA does not expect diversity action plans to be submitted for:

• Clinical drug studies with protocols submitted within 180 days following the publication of the final guidance even if enrollment begins more than 180 days after publication of the final guidance.
• Clinical studies of devices received by FDA in IDE applications within 180 days after publication of the final guidance.
• Clinical studies of devices that do not require an IDE application that are approved by an institutional review board or independent ethics committee within 180 days after the publication of the final guidance.

REQUIREMENTS FOR DIVERSITY ACTION PLANS

Diversity action plans should include:

• A study sponsor’s goals for enrollment in the study disaggregated by age group, sex, ethnicity and race.
• The sponsor’s rationale for such goals.
• The sponsor’s explanation of how it plans to meet such goals.

An appendix at the end of the guidance lists the elements of a diversity action plan and notes that a diversity action plan generally should not exceed 10 pages (excluding references).

FDA notes that enrollment goals should generally be informed by the prevalence or incidence of the condition in the US population that is intended to use the product and should consider the sponsor’s overall clinical development program. For example, where a sponsor plans multiple clinical studies, the sponsor should work to achieve proportionate representation across all the studies, even if a single study does not have a proportionally representative population. Diversity action plans for multinational studies should include enrollment goals for the entire study, not just the portions of the study carried out in the United States. Notably, while FDA acknowledges that certain development programs, such as rare disease programs, may have a single, small pivotal study with participant cohorts too small to detect differences in safety and effectiveness across the population, FDA does not exempt these programs from submitting diversity action plans.

The rationale for the study’s enrollment goals must provide sufficient detail and analysis to provide an explanation of how the sponsor determined those goals. This may include any background information necessary to understand the condition or disease addressed by the product being studied (e.g., risk factors for the condition, or incidences or prevalence of the condition). It should also describe any data or information that suggests that the safety or effectiveness of the drug or device being studied may vary across the clinically relevant population.

The diversity action plan must also include a description of the strategies the sponsor plans to use to enroll and retain study participants. FDA notes that the diversity action plan should focus on specific measures taken to address enrollment and retention of participants in the study for which the plan is being submitted. Examples of clinical enrollment and retention strategies referenced in the guidance include sustained community engagement, cultural competency and proficiency training for clinical investigators and staff, participant language assistance, strategies that reduce participant burden (e.g., transportation assistance or dependent care services), and the use of decentralized clinical trial tools to reduce the need for in-person visits to the clinical sites by participants. The diversity action plan should also describe how the sponsor intends to monitor enrollment goals throughout the study. The guidance strongly encourages sponsors to share strategies for meeting enrollment goals with the public, including posting such strategies on sponsors’ websites.

SUBMISSION AND WAIVERS

The guidance includes details about the timeline and process for submitting a diversity action plan and how FDA will provide feedback on submitted diversity action plans. The draft guidance also lists the factors FDA will consider when weighing a request to waive submission of a diversity action plan, noting that such waivers will be rare. These factors include whether a diversity action plan is necessary based on information about the prevalence of the condition, whether conducting a study in accordance with a diversity action plan would be impracticable, and whether a waiver is necessary to protect public health during a public health emergency.

KEY TAKEAWAYS

Although this draft guidance provides valuable information about what steps FDA will expect sponsors to take to promote adequate representation across demographic characteristics in study populations, this guidance has not been finalized. Potential study sponsors and other stakeholders have the opportunity to provide feedback on the draft guidance by submitting comments by September 26, 2024.

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