FDA Diversity Requirement: Impact on Rare Disease Drug Manufacturers

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Increasing clinical trial diversity presents unique challenges for rare disease treatments due to population size, disease heterogeneity, and low awareness.

Many clinical trials underrepresent the diversity of the real-world population that may benefit from the product once marketed. Historically, factors such as race, ethnicity, age, gender, socioeconomic status, disability, and others, have been passive data points captured as a result of a clinical trial, and have not been used to align the enrollment to the intended real-world patient population. This has led to gaps in understanding of treatment safety, efficacy, and long-term outcomes in specific patient populations, and in part has motivated statutory interest to increase diversity of clinical trial programs and ensure representative enrollment in trials. The Food & Drug Administration (FDA) now has increased authority to monitor the diversity of late-stage clinical trials, which introduces new sponsor trial design and enrollment planning decisions that have unique impacts on stakeholders in the rare disease community.

Demographics of Clinical Trial Participation

In response to mandates from the 2012 FDA Safety and Innovation Act, the FDA’s Center for Drug Evaluation and Research has been reporting clinical demographic data for new drugs and biologics. The 2015–2019 Drug Trials Snapshots Summary Report provides aggregated data on trial participation across demographic groups.

Figure 1. Demographics of Trial Participation
Figure 1. Demographics of Trial Participation

Source: 2015–2019 Drug Trials Snapshots Summary Report

The 2020 Report highlighted that clinical trial participants were mostly white, non-Hispanic females under the age of 65, and the 2021 Report indicated that even though some improvements have been made, broad enrollment of diverse cohorts remains a challenge.

FDA Initiatives Designed to Increase Diversity

The FDA has focused on increasing clinical trial diversity over the past few years, but authority has been maintained via regulatory rather than statutory changes. In April 2022, the agency issued draft guidance for sponsors developing medical products outlining how to enroll adequate numbers of trial participants from various racial and ethnic groups. This guidance aligned to language on Diversity Action Plan (DAP) requirements in the Prescription Drug User Fee Act VII commitment letter. The DAP policy became a law as part of the 2023 Consolidated Appropriations Act.

The included diversity provision applies to sponsors of a new drug or device and must include enrollment goals, rationale for those goals, and an explanation of how a sponsor will achieve them. This plan must be submitted to the FDA by the beginning of a phase 3 or pivotal study. Relevant information could include prevalence and incidence of the disease, current pharmacokinetic and pharmacogenomic data, or patient demographics.

However, the Health and Human Services Secretary can waive the DAP requirement for instances such as difficulty identifying patients due to the small size of the testable population, multifactorial diagnosis that complicates eligibility, or the potential for a disease to affect a specific subset of the general population. Sponsors requesting a DAP waiver must have it granted by the FDA, whereas submitting a DAP does not require acceptance or rejection.

DAP information will become part of a new mandate that will begin by 2025, whereby updated demographic information will be aggregated to demonstrate whether applicants met their DAP-established enrollment goals. This information will be made available in annual reports published by the FDA.

Impact on Stakeholders in Rare Disease Community

The DAP provision impacts rare disease community stakeholders in unique ways.


  • Requires data collection and education to regulators on disease epidemiology (e.g., assessment of real-world evidence and claims data)
  • Poses operational burden, including potential changes to clinical study protocols, enrollment practices, and retention resources to operationalize DAP
  • Exposes existing tracking deficiencies that rare diseases experience (e.g., no diagnostic code available), which may require alternative approaches to determining prevalence and incidence numbers


  • Allows historically underrepresented patients a stronger opportunity to have investigational access to treatments
  • Requires safety and effectiveness data in real-world target population be on hand during drug review, providing more clarity on accurate product outcomes
  • Requires accounting for logistical aspects of conducting a study with underrepresented groups (e.g., travel and monitoring)

While payers may not be directly affected by the policy, they will need to have a broader understanding of rare disease life-long patient journey and patients’ needs when transitioning between care systems (e.g., pediatrics to adults). Plans may also need to identify diverse data points from clinical trials that could be helpful in creating patient-centric framework which would lead to cost reduction.

How Avalere Can Help

Avalere’s subject matter expertise across product lifecycle in the rare disease landscape lends in-depth perspectives to support a variety of stakeholders interested in product that target rare diseases. For more information on how Avalere can support your goals, connect with us.

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