Background
In June 2024, the United States Food and Drug Administration (FDA) released draft guidance on Diversity Action Plans for clinical studies. The purpose of the guidance is to improve enrolment of clinical study participants from historically under-represented populations.
Under-represented populations could include certain age groups, sexes, or racial and ethnic demographics. The guidance also suggests that consideration should be given to clinical characteristics, such as the presence of comorbidities and disease aetiology, or whether the clinically relevant population has access to standard preventive and diagnostic care, or standard treatments. Sponsors are also encouraged to consider other factors, for example geographic location, gender identity, sexual orientation, socioeconomic status, physical and mental disabilities, and pregnancy and lactation status.
Once implemented, the guidance will help to ensure that clinical studies appropriately test products in a representative sample of the intended use population. This will better inform the safe and effective use of the medical product for all patients.
For drugs, a Diversity Action Plan is required for Phase 3 and other pivotal clinical studies. For devices, a Diversity Action Plan must be included in the Investigational Device Exemption (IDE) application for clinical studies of the device. For devices for which an IDE application to FDA is not required, a Diversity Action Plan is still required for most clinical study types, with few exceptions. Whilst sponsors are required to submit a plan for the above study types, the FDA strongly recommends they develop and implement a comprehensive diversity strategy across the entire clinical development program, including early phase studies, where possible.
Diversity Action Plans must specify:
- Enrolment goals for under-represented populations
- The rationale for the provided goals
- How the goals will be met
Subsections of the Diversity Action Plan
Enrolment Goals
Enrolment goals must be separated into sub-sections for the race, ethnicity, sex, and age group demographic characteristics of the clinically relevant population. The distribution of the intended use population according to these demographic characteristics should be considered when developing goals. Goals should be informed by the estimated prevalence of the condition in the intended use population in the US for which the product is being studied. Additionally, if a population may have differential effectiveness or safety to a drug or device, a sponsor goal may be to increase the proportional enrolment of a certain population to evaluate outcomes of interest in that group.
Methodology used to derive target enrolment goals should be included. Sponsors are encouraged to utilise registries, publicly available epidemiological surveys, and published literature to obtain information about the estimated prevalence of the condition across the affected population. If available data are limited, using demographic characteristics of a broader disease population, or general US population demographics is an acceptable approach. For multinational clinical studies, enrolment goals for the entire study should be considered and included, and it should not be limited to US-based participants. If the distribution of the condition differs by geographic location across the clinically relevant population, FDA review divisions may be engaged to discuss how best to address these factors in the Diversity Action Plan.
Rationale
In this section of the plan, a rationale must be provided for the proposed enrolment goals. This section must contain sufficient information and analysis to explain how the sponsor determined its enrolment goals. For example, if goals deviate from the estimated prevalence of the condition in the intended use population, a reason for this must be provided. If the Diversity Action Plan will be rolled out across several clinical studies, the plan for each clinical study should reflect a strategy that leads to an overall proportionate representation. If non-publicly available sources such as electronic health records, certain registries, or other privately held information sources are used to derive incidence estimates of the condition across the affected population, sponsors are encouraged to provide the rationale for the approach taken.
The rationale section should also include background information required to understand the condition for which the product is being investigated, as well as any other background information that supports the enrolment goals.
For drugs, data pertaining to possible differences in the pharmacokinetics, pharmacodynamics, safety or effectiveness across the clinically relevant population and by race, ethnicity, sex, and age group should be included. Any population-level or individual characteristics which data suggest could have an impact on the clinical outcomes should also be included.
For devices, the rationale for enrolment goals should describe data relating to possible differential safety and effectiveness of the device across the clinically relevant population and by race, ethnicity, sex, and age group. As for drugs, any population-level or individual characteristics that data suggest could have an impact on the clinical outcomes should also be included. Any data on relevant factors for device performance, such as phenotypic, anatomical, technological, or biological factors should also be evaluated across a diverse population.
How Goals will be Met
This section should detail how the sponsor plans to meet the specified enrolment goals, including enrolment and retention strategies for the study population. Sponsors are encouraged to consult patients and healthcare providers when developing the plan, including for considering enrolment and retention strategies. Enrolment and retention strategies could include community engagement, cultural competency and proficiency training for site staff, improving participant awareness and knowledge of the study, reducing participant burden, improving access to the clinical study, and decentralising the study when appropriate.
This section should also include the sponsor’s plan to monitor enrolment goals during the study to ensure they are met and could include the measures that will be undertaken if the study is not on track to meet enrolment goals.
When to Submit the Plan
For drugs, the FDA recommends that Diversity Action Plans are submitted when the sponsor is seeking feedback regarding the applicable clinical study (ie, typically at the ‘end of phase 2 meeting’). For device studies that require an IDE application, the plan must be included in the IDE application. For device studies that do not require an IDE application, the plan may be submitted as part of the device’s premarket notification (510(k)), PMA application, or De Novo classification request.
Whilst FDA guidance documents are typically not legally binding, they describe the agency’s current thinking on a topic. They are intended to be viewed as recommendations unless specific regulatory or statutory requirements are cited. Once the guidance is finalised, the use of the words must, shall, or required will be binding.
Public Disclosure
To promote transparency, the FDA strongly encourages sponsors to share strategies for meeting Diversity Action Plan enrolment goals with the public using lay language.
Summary
Diversity Action Plans aim to boost the enrolment of participants from historically under‑represented populations in clinical studies. Increasing diversity within these studies will broaden the applicability of the results to a range of patient populations. This approach will offer valuable insights that inform the safe and effective use of medical products for all patients.
The draft guidance can be accessed at this link: Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies | FDA
