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Updated guidelines aim to improve medical product safety and efficacy through clinical trials that are representative of relevant patient populations 

Published June 26, the U.S. Food and Drug Administration's much anticipated updated draft guidance, "," aims to create more diverse clinical trials by requiring medical product sponsors to submit Diversity Action Plans for biologics, drugs, and medical devices and improve generalizability.

The latest draft guidance broadly describes what sponsors should include in their Diversity Action Plans as mandated by Congress in the 2022 Food and Drug Omnibus Reform Act (FDORA). The guidance was developed by the Oncology Center of Excellence Project Equity in collaboration with the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, the Center for Devices and Radiological Health, the Office of Women's Health, and the Office of Minority Health and Health Equity. 

By increasing the enrollment of participants who are members of historically underrepresented populations in clinical studies through Diversity Action Plans, FDA hopes "to help improve the strength and generalizability of the evidence for the intended use population." The increased diversity will aim to enhance the data supporting premarket applications and advance knowledge about the medical product or disease being studied. 

Which clinical studies are affected?

The guidance mainly focuses on phase 3 clinical studies or pivotal trials as cohort sizes are large enough to ensure trial diversity, but it also addresses clinical studies of biological or drug products and medical devices, especially studies regarding the effectiveness, benefits/risk assessments, and safety of devices. 

Specifically, the guidance describes clinical studies requiring diversity action plans as follows:

"For drugs, a Diversity Action Plan is required for a clinical investigation of a new drug that is a phase 3 study (as defined in 21 CFR 312.21), or as appropriate, another pivotal clinical study of a drug (other than a bioavailability or bioequivalence study).

For devices, a Diversity Action Plan must be included in the Investigational Device Exemption (IDE) application for clinical studies of the device. An IDE application is required if the sponsor intends to use a significant risk (SR) device (as defined in 21 CFR 812.3(m)) in an investigation, intends to conduct an investigation that involves an exception from informed consent under 21 CFR 50.24, or if FDA notifies the sponsor that an application is required for an investigation.

For devices for which an IDE application to FDA is not required, except for a device being studied as described in 21 CFR 812.2(c), section 520(g)(9)(A)(ii) requires sponsors to develop a Diversity Action Plan for any clinical study with respect to the device. Diversity Action Plans for these devices must be submitted to FDA in any premarket notification, request for classification, or application for premarket approval under section 510(k), 513(f)(2), or 515 of the FD&C Act, respectively." 

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If their study fits the above criteria, medical product sponsors of clinical studies that begin enrollment 180 days after publication of the final guidance may be required to submit Diversity Action Plans. In some instances, waivers may be granted, and the guidance establishes a detailed process for evaluating a sponsor's request to waive the Diversity Action Plan.

What's in a Diversity Action Plan?

According to the updated draft guidance, under sections 505(z) and 520(g)(9) of the FD&C Act, a Diversity Action Plan must include the sponsor's enrollment goals for the clinical study, "disaggregated by race, ethnicity, sex, and age group of clinically relevant study populations," as well as the rationale for those goals and a plan for meeting them. In addition to age, ethnicity, sex, and race, the guidance suggests sponsors include other factors that contribute to diversity in clinical trials and that represent patients who will use the approved product. Other factors identified for consideration in this guidance include geographical location, gender identity, sexual orientation, socioeconomic status, physical and mental disabilities, pregnancy and lactation status, and co-morbidities. Appendix 1 of the draft guidance provides a framework for the elements of a Diversity Action Plan.

The latest guidance also specifies that global clinical development programs should reflect enrollment goals for the entire study population. While proportional representation is not required for each study, it is to be met at the level of the overall clinical development program.

FDA has also provided information on procedures for submitting and receiving feedback on Diversity Action Plans. FDA recognizes that there may be circumstances to waive the requirement for a Diversity Action Plan and provides criteria and considerations for when to request a full or partial waiver.

Comments on the draft guidance should be submitted by Sept. 26 to  identified by the docket number, , and guidance title: "."

Currently, FDA's draft guidance on Diversity Action Plans does not specify explicit penalties for non-compliance. However, failure to submit a required Diversity Action Plan could potentially impact the approval process for the clinical study or the medical product being investigated. FDA may also request additional information or impose conditions on the study to ensure compliance with diversity requirements.