FDA Provides Format and Content Recommendations for Trial Diversity Action Plans

J.W. Schomisch
July 1, 2024 at 12:43 PM EST
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The FDA’s new draft guidance on developing Diversity Action Plans takes a deep dive into the recommended format and content of the plans as well as the timing and process for submitting the plans by application or notification type.

The new draft guidance, which replaces an April 2022 draft guidance, also describes the criteria and process by which the FDA will evaluate sponsors’ requests for waivers and provides general recommendations for sponsors who may wish to publicly post key information regarding their Diversity Action Plans.

“Participants in clinical trials should be representative of the patients who will use the medical products,” FDA Commissioner Robert M. Califf, M.D., said in releasing the new draft guidance, which he called “an important step – and one of many ongoing efforts – to address the participation of underrepresented populations in clinical trials to help improve the data we have about patients who will use the medical products if approved.”

Diversity Action Plans are intended to increase enrollment of subjects 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. According to the Food and Drug Omnibus Reform Act of 2022 (FDORA), the plans must specify “the sponsor’s goals for enrollment in a clinical study,” “the sponsor’s rationale for such goals,” and include “an explanation of how the sponsor intends to meet those goals.”

“Generating data for a broader and more representative population early in the clinical development program is among the FDA’s priorities to bring innovative medical products to the public,” added Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “With FDORA, there is now a requirement for sponsors to submit diversity action plans. These plans may help ensure that sponsors are thinking critically and intentionally about the many characteristics of the patient population they aim to treat when designing their clinical study.”

Under FDORA, the requirements for Diversity Action Plans 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 when enrollment commences, FDA does not expect a Diversity Action Plan 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.
  • 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.”

Submission of a Diversity Action Plan is required for:

  • Drugs – a Diversity Action Plan is required for a clinical investigation of a new drug that is a Phase 3 study (21 C.F.R. §312.21), or as appropriate, another pivotal clinical study of a drug (other than a bioavailability or bioequivalence study).
  • 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 (21 C.F.R. §812.3(m)) in an investigation, intends to conduct an investigation that involves an exception from informed consent under 21 C.F.R. §50.24, or if FDA notifies the sponsor that an application is required for an investigation.

The guidance noted that “there are many types of clinical studies that may be conducted as part of the premarket process, representing different stages of device development and testing. Additionally, not all device studies will require submission of an IDE application to FDA; for example, a study may be nonsignificant risk (NSR) and in compliance with 21 C.F.R. §812.2(b)(1)(i) – (vii) or a study may be conducted completely outside the U.S. in such a way that submission of an IDE application is not needed.”

In addition, the agency acknowledged that “a Diversity Action Plan may not be particularly meaningful for certain device studies, such as for small studies conducted during the exploratory clinical stage.” However, the “FDA expects sponsors to develop a Diversity Action Plan for a study that is intended to serve as the primary basis for FDA’s evaluation of safety and effectiveness and benefit-risk determination,”

In addition, the 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. “A study that is exempt from the requirements of the IDE regulations under 21 C.F.R. §812.2(c) does not require the development or submission to FDA of a Diversity Action Plan regardless of whether it is intended to serve as the primary basis for FDA’s evaluation of safety and effectiveness and benefit-risk determination. While sponsors are required to submit a Diversity Action Plan for the studies specified above, FDA strongly recommends that sponsors develop and implement a comprehensive diversity strategy across the entire clinical development program, including in early studies, when possible.”

Addressing Race, Ethnicity, Sex, and Age

Sponsors are required to submit a Diversity Action Plan that specifies goals for clinical study enrollment must be disaggregated by the race, ethnicity, sex, and age group demographic characteristics of the clinically relevant population. “When developing these goals, sponsors should consider the distribution of the intended use population according to these demographic characteristics,” the guidance said.

“Sponsors should consider whether certain demographic groups (e.g., older patients, pediatric patients, females, a particular race or ethnic group or combinations thereof) may have a different response to the medical product – either differential effectiveness or safety (e.g., based upon differential pharmacokinetics (PK), pharmacodynamics (PD), or due to possible differences in susceptibility to specific adverse events of concern for a drug or medical device), or due to differential presentation of the disease or condition. In some cases, it may be necessary to increase the proportional enrollment of a certain population in the clinical study to evaluate outcomes of interest or other clinically relevant factors in that group,” the guidance said.

Sponsors must present their enrollment goals across subsets of the population with these demographic characteristics (e.g., for race: Asian, Black/African American, etc.).

“Generally, 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 guidance said. “The FDA recognizes that in some cases, increased enrollment (i.e., greater than proportional) of certain populations may be needed to elucidate potential clinically important differences in drug or medical device response between subsets of the study population.”

A rationale must be provided for the proposed enrollment goals, including when such goals may deviate from the estimated prevalence or incidence of a disease or condition in the intended use population.

“Sponsors must provide in the Diversity Action Plan a description of the general approach and rationale, which should include methodology used to derive target enrollment goals,” the guidance said. The FDA recognized that sponsors may, as part of their clinical development program, plan to conduct several clinical studies to support marketing authorization of a medical product that may be subject to Diversity Action Plan requirements.

“In such cases, the sponsor’s enrollment goals specified in the Diversity Action Plan 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,” the guidance said. “In such a situation, the Diversity Action Plan 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 guidance also noted that some development programs, such as for rare diseases, may include a single, small pivotal study. “Despite enrolling a representative population in that study, participant numbers may be small, potentially precluding the detection of any differences in safety and effectiveness across the study population, should they exist, or limiting the sponsor’s ability to conduct a robust assessment of observed differences,” the guidance said.

“However, consistent representative enrollment may provide opportunities for hypothesis generation and further study,” the guidance said. “Whenever possible, sponsors should utilize appropriate available sources (e.g., certain registries that are reasonably expected to be demographically representative, publicly available epidemiological surveys, published literature, etc.) 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. When using non-publicly available sources (e.g., electronic health records, certain registries, or other privately held information sources) to derive incidence/prevalence estimates, sponsors should provide the rationale for the approach, a synopsis of the analysis used, and citations for the source(s) for these data,” the guidance said.

The estimated prevalence or incidence of the disease or condition by demographic characteristics in the U.S. population for which the medical product is being investigated should generally inform enrollment goals. In certain situations, there may be limited or no data or information available to characterize the incidence and/or prevalence of the disease or condition, or the demographic characteristics of the intended population. In these circumstances, sponsors should consider:

  • For a disease or condition where the prevalence/incidence and distribution in the population by demographic characteristics are known, there may be situations where for a subset of that disease or condition, this information is unavailable or has other limitations precluding its use for the purposes of goal setting. For example, there may be information regarding the distribution of the intended use population by the demographic characteristics of race, ethnicity, sex, and age group for cholangiocarcinoma, but such information may be unavailable for the subset of cholangiocarcinoma for which the medical product is intended, such as cholangiocarcinoma with an FGFR2 fusion. When evaluating a medical product in a such a subset of a disease or condition, it may be acceptable to use prevalence and incidence information for the broader disease and base enrollment on the demographic characteristics of that broader disease population (e.g., the enrollment goal for a study of FGFR2 mutated cholangiocarcinoma cancer could be based on prevalence or incidence information for cholangiocarcinoma).
  • For a clinical study designed to investigate a medical product that is intended for a general use population (e.g., preventive vaccine), it may be acceptable to set enrollment goals based on general U.S. population demographics (i.e., U.S. census data).
  • For a clinical study designed to investigate a medical product in a population for which there are limited or no data or information to characterize the demographic characteristics of the intended use population, it may be acceptable to set enrollment goals based on general U.S. population demographics (i.e., U.S. census data).

A Diversity Action Plan for a multinational clinical study must describe participant enrollment goals for the entire study and should not be limited to U.S.-enrolled subjects, the guidance said. “Additionally, the overall study design, including the selection of study sites, should account for the need to enroll a population representative of the U.S. intended use population as part of the overall medical product development program,” the guidance said.

The FDA recognized the lack of uniformity across the globe in the use of population descriptors such as race and ethnicity may pose challenges when setting enrollment goals for international sites. “For example, it may be challenging to identify corresponding populations defined on the basis of race or ethnicity when describing the affected population outside the U.S. and consequently, when setting enrollment goals for the clinical study. Sponsors should consider FDA guidance when describing and presenting population race or ethnicity for the purposes of setting enrollment goals,” the guidance said.

In setting enrollment goals, sponsors also may consider characteristics, such as geographic location and the socioeconomic status (SES) of the population with the disease or condition in the intended use population if the available data suggest that these characteristics are expected to impact the outcomes under investigation in the study. “As an example, geographic location and SES may affect enrollment and retention of the various subgroups of the population for a clinical study. The Diversity Action Plan should describe if and how these factors may have informed the sponsor’s proposed enrollment goals. Additionally, early identification of barriers and implementation of strategies to mitigate such barriers should be described in the Diversity Action Plan,” the guidance said.

Rationale for Enrollment Goals

The Diversity Action Plan must include the sponsor’s rationale for the enrollment goals. The rationale should include:

  • Background information necessary to understand the disease or condition for which the drug or device is being investigated, including an overview of the natural history of the disease or condition and risk factors, as well as prevalence and incidence estimates, if available.
  • Any other background information that justifies the enrollment goals.
  • If a sponsor plans to conduct several clinical studies to support a single marketing submission, the sponsor may opt to specify enrollment goals across the planned clinical studies. A sponsor’s rationale for having different enrollment goals across planned studies must be included in the Diversity Action Plan; the rationale provided should indicate how individual clinical studies are intended to contribute to the overall enrollment goals for the clinical development program for the medical product (i.e., for a particular indication or intended use).
  • Additionally, for drugs, the rationale should describe 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 PK or PD. Sponsors also should describe available data regarding differences in PK, PD, safety, or effectiveness (e.g., by sex, age, or by genetic variations, which may be more prevalent in certain racial and ethnic populations that impact drug metabolism or susceptibility to adverse reactions) in the 358 Diversity Action Plan.
  • Sponsors should describe, as applicable, the relevancy of other population-level or individual characteristics that available data suggest have an impact on the clinical outcomes (e.g., SES, geographic location, comorbidities). Sponsors should include citations for the sources of data and information (e.g., epidemiological databases, registries, etc.) upon which rationales for enrollment goals are based.
  • For devices, the rationale for enrollment goals should describe data and information about the potential for differential safety and effectiveness of the device across the clinically relevant populations. Sponsors also should describe available data regarding differences expected to impact safety or effectiveness (e.g., by sex, age or by genetic variations, which may be more prevalent in certain racial and ethnic populations that are expected to impact clinical outcomes or susceptibility to adverse events).
  • Additionally, device sponsors should describe, as applicable, the relevance of other population-level or individual characteristics that available data suggest may have an impact on the clinical outcomes (e.g., SES, geographic location, comorbidities). Data on relevant factors for device performance (e.g., phenotypic, anatomical, technological, or biological factors) should be evaluated to characterize any differential effects across a diverse population by the relevant demographic characteristics. The rationale should describe how the sponsor considered the available information when setting the enrollment goals. For example, variations in skin pigmentation that may exist across a diverse population that can affect the performance of certain devices would be a relevant attribute to consider when describing the available data and information in the intended use population. Sponsors should include citations for the sources of data and information (e.g., epidemiological databases, registries, etc.) upon which rationales for enrollment goals are based.

Measures to Meet Enrollment Goals

The Diversity Action Plan must include an explanation of how the sponsor plans to meet the specified enrollment goals. According to the guidance, the plan should include a description of the enrollment and retention strategies for the study population. “FDA recognizes that inequities in clinical study access and participation for certain populations occur within the context of broader health care inequities,” the guidance said. “While FDA recognizes the value of broad efforts to address healthcare systemic barriers that lead to disparities in clinical study participation rates across various populations (e.g., identification and training of diverse clinical trial investigators and staff, etc.), [the plan] should focus on specific measures that address the enrollment and retention of participants in the particular clinical study for which the Diversity Action Plan is developed. FDA encourages sponsors to consult patients and healthcare providers as part of the process for developing the Diversity Action Plan, including for considering enrollment and retention strategies.” Examples of clinical study enrollment and retention strategies may include, but are not limited to:

  • Implementing sustained community engagement (e.g., through community advisory boards and navigators, community health workers, patient advocacy groups, local healthcare providers, community organizations, etc.).
  • Providing cultural competency and proficiency training for clinical investigators and research staff may help facilitate the building of a trusting relationship with participants, provide a helpful resource for investigators and research staff on how to engage with participants with different backgrounds, help decrease biased communication and behavioral practices, and help avoid the use of cultural generalizations and stereotypes in interactions with participants.
  • Improving study participant awareness and knowledge of the clinical study (e.g., providing language assistance for persons with limited English proficiency).
  • Reducing participant burden (e.g., avoiding unnecessary study-related procedures, imaging, and laboratory tests; employing sites for procedures and laboratory tests that are convenient to the specific populations included in the enrollment goals; providing transportation assistance; providing dependent care; allowing flexible hours for study visits; and reimbursement for costs incurred).
  • Improving access to the clinical study by limiting clinical study exclusion criteria, selecting clinical study site locations that would facilitate enrollment of a representative study population (e.g., initiating the clinical study in sites that serve demographically diverse populations and that have prior experience enrolling diverse study participants in clinical studies), and considering the accessibility needs of persons with disabilities.
  • Employing clinical study decentralization when appropriate.

The Diversity Action Plan also should include a description of the sponsor’s plan to monitor enrollment goals during the clinical study to help ensure goals are met. This can aid prompt intervention to address enrollment barriers. “For example, the sponsor could consider specifying in the Diversity Action Plan the manner and frequency with which study enrollment will be monitored (e.g., when a certain proportion of the study population has been enrolled), and any measures that may be undertaken should the sponsor determine that the study is not on track to meet enrollment goals,” the guidance said, noting sponsors can provide this information in submissions for plan modifications and in briefing packages for meetings related to the clinical study.

Timelines for Submitting Diversity Action Plans

Although sponsors may discuss the Diversity Action Plan with the FDA as soon as practicable during product development, sponsors must submit the plans for certain clinical studies for drugs and devices on statutorily required timelines:

  • For drugs, sponsors must submit the required plan to the relevant IND application as soon as practicable but no later than the date on which the sponsor submits the protocol to the FDA for the Phase 3 study or, as appropriate, other pivotal study. “Because FDA’s review of and feedback on the Diversity Action Plan is most efficient if it occurs in the context of discussions regarding the trial design, study population selection, and other aspects of the clinical study, FDA recommends submission of the Diversity Action Plan when a sponsor is seeking feedback regarding the applicable clinical study for the drug (typically at the End-Of-Phase 2 meeting),” the guidance said.
  • For device clinical studies that require an IDE application to be submitted to the FDA, the plan must be included in the IDE application. Sponsors of studies for which submission of an IDE application is not required must develop a Diversity Action Plan to guide the development of any clinical study with respect to that device and must submit the plan as part of the device’s premarket notification (510(k)), PMA application, or De Novo classification request. In addition, a sponsor may include questions regarding the Diversity Action Plan in a Q-submission submitted to request feedback on questions related to design and conduct of a clinical study prior to its submission in an IDE application or prior to initiating a clinical study for which submission of an IDE application is not required.

How to Submit the Diversity Action Plan and Receive Comment

The process for submitting Diversity Action Plans varies depending on the medical product type. “To ensure that FDA can conduct a timely and efficient review of a Diversity Action Plan, sponsors should describe the required elements of the Diversity Action Plan clearly and concisely, with limited cross-referencing to previously submitted documents,” the guidance said. “In most cases, the Diversity Action Plan should be succinct, its length generally not exceeding 10 pages, excluding references,” the guidance said.

For Drugs:

  • The plan must be submitted to the IND under which the applicable clinical study will be conducted.
  • Sponsors should include relevant administrative information on the title page, including the drug name, IND number, proposed indication(s), clinical study identification information (e.g., NCT number, title, study ID) and the plan version number and date.
  • The cover letter should alert the FDA that the submission includes a Diversity Action Plan and denote whether the plan is new or revised. “Sponsors should indicate in the cover letter accompanying a new or revised Diversity Action Plan, ‘DIVERSITY ACTION PLAN-Initial’ or ‘DIVERSITY ACTION PLAN-Revised,’ respectively, written in large, bolded type. If a partial waiver has been granted for the clinical study that is the subject of the Diversity Action Plan, sponsors should alert FDA in the cover letter accompanying the Diversity Action Plan, and in the relevant section(s) in the Diversity Action Plan.”
  • Depending on the specifics for each clinical development program, the relevant Division in CDER or CBER may or may not provide feedback on the plan. “FDA feedback on a new or revised Diversity Action Plan may be at FDA’s initiative or per the sponsor’s specific request for feedback. Sponsors with specific questions regarding a planned or submitted Diversity Action Plan may include them as a topic for discussion in meetings with FDA,” the guidance said.
  • Following submission of an initial plan, a sponsor may, as appropriate, submit modifications, which may be based on feedback from the FDA or at the sponsor’s own initiative. “In such instances, the submission must include a copy of the Diversity Action Plan with changes tracked as well as a clean version,” the guidance said. As part of the submission, sponsors also must include a “Summary of Modifications and Justification” section that outlines the modifications to the plan and provides the rationale for the changes.
  • For an IND that is required to be submitted in eCTD format, plan submissions must be submitted in eCTD module 2.5, Clinical overview.
  • The status of the plan submission and as appropriate, any discussions and correspondence with the agency regarding the plan, including with respect to partial waiver requested or granted, should be included in the regulatory history for milestone meetings (i.e., in the meeting briefing document), as well as in marketing submissions.
  • Sponsors should provide an update in their IND annual reports on their progress toward meeting plan enrollment goals and submit the plan update in the annual report section pertaining to clinical study participant demographics. “If such goals are not on track for being met at the conclusion of the study, the status report should include a description of the reason(s) the sponsor is not currently meeting or does not expect to meet enrollment goals and the sponsor’s plan to mitigate such an outcome,” the guidance said.
  • In marketing application submissions, sponsors should provide a brief overview of the plan pertaining to the Phase 3 or other pivotal clinical study, an assessment of whether the plan enrollment goals were met in the context of the relevant clinical study or the overall Phase 3 development program, and as appropriate, an explanation of what measures may have contributed to the observed outcomes with respect to the enrollment goals. “If a waiver from the requirement to submit a Diversity Action Plan has been granted, the sponsor should clearly indicate such in the marketing application submission and cite the correspondence granting the waiver,” the guidance said. Sponsors should include information regarding the plan in module eCTD 2.5 of the NDA or BLA submission.

For Devices:

  • FDA considers the Diversity Action Plan as a constituent part of the overall process for generating clinical evidence for the subject device. “As such, a sponsor may submit a pre-submission to request written feedback or a meeting with FDA regarding the Diversity Action Plan for a clinical study,” the guidance said.
  • A plan must be submitted as part of the IDE application for clinical studies of significant risk (SR) devices.
  • For device studies that require development of a plan, but do not require an IDE, the plan must be submitted as part of a 510(k), PMA application, or De Novo classification request. “While FDA encourages sponsors to seek agency feedback when appropriate, consistent with existing approaches to developing clinical evidence, FDA anticipates that many Diversity Action Plans for studies not requiring submission of an IDE application may be developed without FDA’s input,” the guidance said. “A pre-submission may be appropriate when FDA’s feedback on specific questions is necessary to guide product development and/or submission preparation. For example, if submission of an IDE application is not required, a sponsor may opt to request FDA’s feedback on the enrollment goals of the clinically relevant population for a proposed pivotal clinical study intended to support a particular intended use.”
  • The cover letter accompanying a submission that includes a plan (e.g., an IDE application, marketing submission, or a Q-submission seeking feedback on a plan) should alert FDA that the submission includes a Diversity Action Plan and, denote whether the plan is new or revised. Sponsors should state in the cover letter “DIVERSITY ACTION PLAN-Initial” or “DIVERSITY ACTION PLAN-Revised” in large, bolded type.
  • Sponsors should include relevant administrative information on the title page, including device name; sponsor contact information; relevant submission number(s) including as appropriate, IDEs, Q-submissions, and/or marketing submissions, proposed indication or indications for use statement, and intended use, clinical study identification information (e.g., NCT number, title, study ID), and the plan version number and date.
  • Following submission of an initial plan, a sponsor may, as appropriate, submit modifications, which may be based on feedback from the FDA or at the sponsor’s own initiative. In such instances, the submission must include a copy of the plan with changes tracked as well as a clean version. As part of the submission, sponsors must also include a “Summary of Modifications and Justification” section that outlines the modifications to the plan and provides the rationale for the changes.
  • For modifications to the plan for a SR study following approval of the IDE application under which an applicable SR medical device study will be conducted: FDA considers changes to the plan included in an approved IDE to be similar to other types of changes made to the approved study. Such modifications may be in response to feedback from the FDA or at the sponsor’s own initiative. “In such instances, sponsors should follow the processes discussed in the 2001 guidance on Changes or Modifications During the Conduct of a Clinical Investigation.”
  • For modifications to the plan for a study intended to support FDA’s evaluation of a medical device and which does not require an IDE application: if the sponsor considers FDA’s feedback on the modification to be necessary to guide product development and/or submission preparation, the sponsor should submit a pre-submission. FDA anticipates that most modifications to a Diversity Action Plan for studies that do not require an IDE will not require agency feedback.
  • Marketing submissions, IDE applications, and requests for feedback or meetings should include a summary of any discussions and correspondence with FDA regarding a relevant plan, including with respect to any waiver requests. If a waiver has been granted, “the sponsor should clearly indicate such in the cover letter and provide a copy of FDA’s correspondence granting the waiver.”
  • As part of periodic reporting requirements under applicable FDA regulations, sponsors should include an update on their progress toward plan enrollment goals. “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.”
  • In marketing submissions that contain clinical data from studies conducted under an approved IDE application submitted to the FDA, sponsors should provide a brief overview of the plan pertaining to the relevant clinical studies that generated data to support the marketing submission. Sponsors also should provide an assessment of whether the plan enrollment goals were met in the context of the applicable study or the development program and, as appropriate, an explanation of what measures may have contributed to the observed outcomes with respect to the enrollment goals.
  • In marketing submissions for which the device study did not require an approved IDE application and was not exempt from IDE requirements under 21 C.F.R. §812.2(c), sponsors must provide the Diversity Action Plan for the study. Sponsors should include an assessment of whether the plan enrollment goals were met in the context of the relevant clinical study or the development program and, as appropriate, an explanation of what measures may have contributed to the observed outcomes with respect to the enrollment goals.
  • In circumstances where a Diversity Action Plan is required to support marketing authorization, the FDA recommends sponsors provide a clear and concise description of the plan for inclusion in the public-facing summary documents (e.g., De Novo Summary, 510(k) Summary, PMA Summary of Safety and Effectiveness).

Requesting Diversity Action Plan Waivers

The FDA may grant a full or partial waiver of the requirement to submit a Diversity Action Plan either on the agency’s initiative or at a sponsor’s request. “While the appropriateness of a waiver is a case-specific determination and will depend on factors relevant to a specific development program, FDA will evaluate whether any of the following statutory criteria are satisfied when considering whether a waiver is appropriate”:

  • 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 Diversity Action Plan would otherwise be impracticable; or
  • A waiver is necessary to protect public health during a public health emergency.

“Given the importance of increasing enrollment of historically underrepresented populations in clinical research, including in clinical studies of drugs and devices, in order to detect potential differences in product performance and improve the generalizability of the results, full or partial waivers from the requirements around the submission of a Diversity Action Plan will only be granted in rare instances,” the guidance said.

If the FDA determines that the statutory criteria for granting a waiver are met and that granting a waiver on the agency’s initiative is appropriate, the agency will notify interested parties through appropriate channels. For example, to the extent permitted under applicable disclosure law, FDA may consider public communications and/or post relevant information on FDA’s website regarding the decision to issue the waiver.

Sponsors should consider the following in determining whether to submit a request for a full or partial waiver:

  • The FDA generally does not intend to waive the requirement to submit a Diversity Action Plan even if the disease or condition under study is relatively homogenous with respect to race, ethnicity, sex, or age group. If supported by relevant data and information, sponsors should indicate in their rationale supporting their enrollment goals why the targeted population is homogenous.
  • The FDA is required to issue a written response granting or denying a waiver request within 60 days of receiving the request. “Sponsors should submit requests for a waiver (if warranted) as early as feasible, and no later than 60 days before the Diversity Action Plan is required for submission. FDA strongly encourages sponsors to discuss plans to request a waiver early in the planning stages of the clinical study or clinical development program. Sponsors should request a waiver early enough to allow sufficient time for preparation and submission of the Diversity Action Plan as required, should FDA deny the waiver request. Sponsors should not submit waiver requests less than 60 days before the Diversity Action Plan is required,” the guidance said.
  • Sponsors may decide to include different enrollment goals across multiple planned Phase 3 or other pivotal studies. “FDA recognizes that under these circumstances, the enrollment goals for each individual study may not be fully reflective of the enrollment goals across all studies. In these cases, sponsors should not seek a waiver for each study. Rather, in their Diversity Action Plans, sponsors should specify how the enrollment goals are expected to be met across the development program and provide a rationale for the enrollment goals for a specific study.”
  • For drugs, a waiver request should be submitted electronically to the IND, in eCTD module 1.12.5, Request for a waiver, and should be submitted to the IND application under which the clinical study that is subject to the requirement of a plan will be conducted. The accompanying cover letter should include “DIVERSITY 678 ACTION PLAN-Waiver Request” written in large, bolded type. The waiver request submission should include IND number, applicable clinical study name or identification number and a justification for the waiver request, including relevant data and information.
  • For devices, a waiver request should be submitted as a standalone submission with an  accompanying cover letter that includes “DIVERSITY ACTION PLAN-Waiver Request” written in large, bolded type. The waiver request should include submission number(s) if available, information about the device including a device description and proposed intended use, the applicable clinical study, the type of marketing submission that the clinical study is intended to support and a justification for the waiver request, including relevant data and information.

Public Posting of Key Plan Information Encouraged

“FDA strongly encourages sponsors to share strategies for meeting Diversity Action Plan enrollment goals with the public,” the guidance said. “Sponsors may consider publicly posting on their website 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.”

For medical products or uses that are not approved, licensed, cleared, or classified, such key information should be available in the same location as other content regarding such products.

The guidance noted that although sponsors can post such key information at any time, while the study is still open for recruitment, sponsors may wish to 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.

The FDA recommended using consumer-friendly language when sharing key information from Diversity Action Plans.

Submit electronic comments on the draft guidance by Sept. 26 to Docket No. FDA-2021-D-0789 at www.regulations.gov.

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