The Diversity Action Plan: A Critical Step Towards Inclusive Research

Diversity in clinical research is critical to ensure that health interventions and policies are universally representative and effective. Historically, clinical research has often overlooked certain groups based on factors such as age, sex, economic status, and ethnicity in favor of participants from predominantly homogenous groups, disregarding the multifaceted and diverse nature of the global community.

While there are a multitude of issues with disproportionate patient representation — including limited generalisability of findings, exacerbation of health disparities and health inequity, bias, and ethical concerns — many historically marginalised populations continue to be underrepresented in clinical trial patient populations.

As part of the effort to address this ongoing issue, in April 2022, the U.S. Food and Drug Administration (FDA) released a draft guidance on Diversity Action Plans (DAP). In June 2024, in conjunction with the Food and Drug Omnibus Reform Act (FDORA), the FDA updated their guidance document and released Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials⁽¹⁾. This updated guideline applies to all late-stage (Phase 3) submissions and outlines key expectations of the Sponsor to ensure inclusion of underrepresented groups for a more diverse study population.

^{(1) Office of the Commissioner. FDA Guidance Provides New Details on Diversity Action Plans Required for Certain Clinical Studies. FDA. August 9, 2024. Accessed January 14, 2025.}

POST-ARTICLE DISCLAIMER: the FDA Diversity Action Plan guidance document has recently been removed from the website, although the information “holding” pages have been retained – we’ll keep an eye on the latest developments 🌎

The FDA’s DAP guidelines provide an outline of the essential components to be included in the document. These elements include:

1. Enrollment goals where sponsors must identify specific, measurable enrollment targets disaggregated on demographics such as age, sex, and ethnicity
2. Rationale for the study’s methodology and enrollment targets, supported by data on differential safety and effectiveness across clinically relevant populations, genetic variations impacting PK/PD, and other factors such as socioeconomic status or comorbidities that may influence clinical outcomes
3. Measures to meet enrollment goals such as strategies for enrollment and retention of the study population, and a plan to monitor enrollment goals throughout the course of the study

The implementation of DAPs underscores the importance of early planning regarding trial design and participant enrollment. For sponsors, this means that diversity considerations should influence site selection, patient recruitment and retention strategies, and overall trial design from the outset.

For drugs, the DAP must be submitted no later than the day of the Phase 3 protocol submission to the FDA, however, earlier submission is recommended to allow for feedback and adjustments.

For medical devices, the DAP should be submitted with the Investigational Device Exemption (IDE) application, or in cases where there is none, with 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⁽²⁾.

^{(2) Office of the Commissioner. Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. July 3, 2024. Accessed January 16, 2025.}

While the European Medicines Agency (EMA) has not yet adopted and mandated DAPs as part of clinical research, the FDA’s emphasis on diversity is likely to influence European regulatory agencies. Although the EMA does not have a unified document comparable to the FDA’s diversity guidance, there are several guidelines and initiatives that encourage inclusive study populations in clinical research, such as the Clinical Trials Regulation (EU) No 536/2014 within the Good Clinical Practice (GCP) standards⁽³⁾.

The paradigm shift to focus on real-world, diverse data indicates that medical writers in Europe (and globally) may need to proactively think about emerging requirements that prioritise inclusivity in clinical trials. As medical writers, this means the need for increased strategic collaboration, regulatory and guidance awareness, and cultural sensitivity.

^{(3) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC Text with EEA Relevance. Vol 158.; 2014. Accessed January 17, 2025.}