Action Plans On Diversity: Key Requirements For Certain Clinical Studies

Key Takeaways:

• The Food & Drug Administration (FDA) issued an updated draft guidance on developing action plans to address clinical trial diversity in support of certain studies of drugs and medical devices.
• Sponsors of such clinical studies are required to provide their goals for enrollment in the study, disaggregated by race, ethnicity, sex, and age group of clinically relevant study populations, along with the rationale for those goals.
• These requirements will come into effect 180 days after the guidance is finalized.

On June 26, 2024, FDA issued a new draft guidance on clinical trial diversity, "Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies" (Draft Guidance), to assist medical product sponsors in submitting Diversity Action Plans for the support of certain clinical studies.¹ The Draft Guidance replaces the April 2022 draft guidance for industry: "Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials." Our prior discussion of the 2022 guidance may be found here.

Section 3601 of the Food and Drug Omnibus Reform Act of 2022 (FDORA) added sections 505(z) and 520(g)(9) to the Federal Food, Drug, and Cosmetic Act (FD&C Act), requiring sponsors to submit Diversity Action Plans (DAPs) for certain clinical studies in the form and manner specified by FDA in guidance.² Prior to FDORA, Diversity Action Plans were recommended by FDA but not required. The plans must specify goals for clinical study enrollment, and the goals must be disaggregated by the race, ethnicity, sex, and age group demographic characteristics of the clinically relevant population.

These DAPs are intended to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population. However, the requirements for Diversity Action Plans only apply to clinical studies for which enrollment commences after 180 days from the publication of the final guidance. Because sponsors engage in study planning and implementing study activities prior to the commencement of enrollment, FDA does not expect a DAP to be submitted for clinical studies where the following circumstances are present:

• Clinical studies of drugs with protocols submitted within 180 days following the publication of the final guidance where enrollment is scheduled to begin 180 days after publication of the Final Guidance;
• Clinical studies of devices received by FDA in Investigational Device Exemption (IDE) applications within 180 days after publication of the Final Guidance; or
• Clinical studies of devices that do not require an IDE application to be submitted to FDA that are approved by an institutional review board (IRB) or independent ethics committee (IEC) within 180 days after the date of publication of the Final Guidance.³

FDORA also required FDA to update or issue guidance describing the format and content of Diversity Action Plans (including the timing and process for submitting such plans by application or notification type), the criteria and process by which FDA will evaluate sponsors' requests for waivers from the requirement to submit a DAP, and considerations for sponsors who may wish to publicly post key information regarding their DAPs. The Draft Guidance was issued to fulfill this requirement. This alert provides a general overview of the types of clinical studies that are subject to Diversity Action Plans as well as each of these focal points of the Draft Guidance.

I. Types of Clinical Studies Subject to Diversity Action Plans

For drugs, a DAP 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 DAP 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 is notified by FDA that an application is required for an investigation.

Sponsors of devices for which an IDE application to FDA is not required must develop a DAP for any clinical study with respect to the device, unless the device is exempt from IDE requirements under 21 CFR § 812.2(c). Diversity Action Plans for these devices must be submitted to FDA in any premarket notification submission, De Novo request for classification, or premarket authorization application (PMA) under sections 510(k), 513(f)(2), or 515 of the FD&C Act, respectively.⁴ Notwithstanding this requirement, FDA acknowledges that a DAP may not be particularly meaningful for certain device studies, such as for small studies conducted during the exploratory clinical stage. As specified in the Draft Guidance, while the statute refers to clinical studies broadly, FDA does not intend to receive or review Diversity Action Plans for studies that are not designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use.

II. Format & Content of Diversity Action Plans

A Diversity Action Plan must include:

• the sponsor's goals for enrollment in the clinical study, disaggregated by race, ethnicity, sex, and age group of clinically relevant study populations;
• the sponsor's rationale for such goals; and
• the sponsor's explanation of how the sponsor intends to meet such goals.

A. Enrollment Goals

Per the Draft Guidance, sponsors are expected to present their enrollment goals across subsets of the population with these demographic characteristics (e.g., for race: Asian, Black/African American, etc.). As a matter of course, enrollment goals should be informed by the estimated prevalence or incidence of the disease or condition in the U.S. intended use population for which the medical product is being studied.

The Draft Guidance makes clear that in cases where a sponsor conducts several clinical studies to support marketing authorization of a medical product that may be subject to Diversity Action Plan requirements, the sponsor's enrollment goals specified in the DAP for each study should consider how individual clinical studies may fit into an overall clinical development program for the medical product (i.e., for a particular indication or intended use), and how such individual studies should help generate data representing the clinically relevant population's demographic characteristics consistent with the incidence or prevalence in the disease population for the program. In these instances, the DAP for each clinical study should reflect a strategy that leads to an overall proportionate representation, even though individual clinical studies may not have proportionate representation.

The Draft Guidance encourages sponsors to use appropriate available sources (e.g., certain registries that are reasonably expected to be demographically representative, publicly available epidemiological surveys, published literature) to obtain information about the estimated prevalence or incidence of the disease or condition across the affected population, by race, ethnicity, sex, and age group.

B. Rationale for Enrollment Goals

To meet the statutory requirement, a sponsor must include sufficient information and analysis to explain how the sponsor determined its enrollment goals. The Draft Guidance suggests that a sponsor's rationale for the enrollment goals should include:

• Enough background information (to aid understanding) about the disease or condition for which the drug is being investigated;
• Any other background information that justifies the enrollment goals;
• In cases where sponsors plan to conduct several clinical studies to support a single marketing submission, the sponsor can opt to specify enrollment goals across the planned clinical studies;
• For drugs—among other things, a description of data and information that suggest a potential for differential safety and effectiveness of the investigational drug across the clinically relevant population (such as possible differences in pharmacokinetics (PK) or pharmacodynamics (PD); and
• For devices—among other things, a description of data and information about the potential differential safety and effectiveness of the device across the clinically relevant populations.

C. Measures to Meet Enrollment Goals

To meet this statutory requirement, Diversity Action Plans should include a description of the enrollment and retention strategies for the study population—with the plan focusing on specific measures that address the enrollment and retention of participants in the particular clinical study for which the DAP is developed. The Draft Guidance encourages sponsors to consult patients and healthcare providers as part of the process for developing DAPs (including for considering enrollment and retention strategies) and provides various examples of clinical study enrollment and retention strategies. In an effort to track progress, the Draft Guidance states that DAPs should also include a description of the sponsor's plan to monitor enrollment goals during the conduct of the clinical study to help ensure that goals are met.

III. Timelines for Submitting Diversity Action Plans

The Draft Guidance elucidates the following timelines for the submission of Diversity Action Plans:

• For drugs, sponsors must submit the required DAP to the relevant IND application as soon as practicable but no later than the date on which the sponsor submits the protocol to FDA for the phase 3 study or other pivotal study; and
• For device clinical studies that require an IDE application to be submitted to FDA, the DAP must be included in the IDE application. Sponsors of certain studies for which submission of an IDE application is not required must develop a DAP to guide the development of any clinical study with respect to that device and must submit the DAP as part of the device's premarket notification (510(k)), PMA application, or De Novo classification request.

According to the Draft Guidance, the process for Submitting DAPs will vary depending on the medical product type. In general, to ensure that FDA can conduct a timely and efficient review of a DAP, sponsors should describe the required elements clearly and concisely, with limited cross-referencing to previously submitted documents, with a length not exceeding 10 pages (excluding references).

IV. Criteria & Process for Waiver Requests

Under the statute, FDA may waive the requirement to submit a DAP, or any part thereof, either on the Agency's initiative or at a sponsor's request if certain criteria are met. In determining whether to grant a waiver, FDA will evaluate whether—

• A waiver is necessary based on what is known or what can be determined about the prevalence or incidence in the U.S. of the disease or condition for which the new drug or device is under development (including in terms of the patient population that may use the drug or device);
• Conducting a clinical investigation in accordance with a DAP would otherwise be impracticable; or
• A waiver is necessary to protect the public health during a public health emergency.

V. Recommendations for Sponsors in Posting Diversity Action Plan Key Information

The Draft Guidance includes some considerations for sponsors wishing to post key information from their Diversity Action Plans, namely their clinical study enrollment goals disaggregated by race, ethnicity, sex, and age group, and a brief description of the measures taken to achieve the stated goals. In addition to using consumer-friendly language, FDA recommends that sponsors should consider:

• Linking from such a posting to a recruitment website for the trial or to a commonly used repository for clinical trial information; or
• Linking to the sponsor's website posting from a recruitment website for the trial or from a commonly used repository for clinical trial information because patients and the public may be searching for clinical studies in clinical trial databases such as ClinicalTrials.gov.

Footnotes

1 See https://www.fda.gov/media/179593/download.

2 See 21 U.S.C. § 355(z) and 21 U.S.C. § 360j(g)(9)(A).

3 See section 3602(c) of the Food and Drug Omnibus Reform Act of 2022 (FDORA) included as part of the Consolidated Appropriations Act (December 2022) (P.L. 117-328).

4 See 21 U.S.C. §§§ 360(K), 360c(f)(2), and 21 U.S.C. § 360e.

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