Enhancing Clinical Trial Diversity: FDA’s New Draft Guidance on Enrollment Plans

The US Food and Drug Administration (FDA) has released a draft guidance titled “Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies.” This guidance aims to assist medical product sponsors in creating and submitting Diversity Action Plans (DAPs) for certain clinical studies, which are intended to improve the participation of underrepresented patients and the generalizability of evidence.

FDA commissioner Dr. Robert M. Califf emphasized the significance of this step in the press release, stating, “Participants in clinical trials should be representative of the patients who will use the medical products.”

Improving clinical trial diversity is essential for several reasons. First, it ensures that the trial results are more applicable to a broader spectrum of patients. Second, it enhances the understanding of how diseases and medical products affect different demographic groups.

The draft guidance was developed collaboratively by the FDA’s Oncology Center of Excellence (OCE) Project Equity, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) and Office of Minority Health and Health Equity (OMHHE).

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FDA Guidance on Diversity in Clinical Trials

The FDA draft guidance outlines the required format and content for DAPs. These plans must include the sponsor’s rationale and goals for enrollment, categorized by age group, ethnicity, sex and race of the study population. Additionally, sponsors are encouraged to consider other dimensions of diversity that might affect the treatment outcomes.

The guidance specifies the timing and process for submitting these plans to the FDA and details the criteria for evaluating waiver requests from sponsors who seek exemption from submitting a DAP. The requirement for DAPs stems from provisions in the Federal Food, Drug and Cosmetic Act, amended by the Food and Drug Omnibus Reform Act (FDORA). These provisions apply to Phase III clinical studies and other pivotal studies of drugs, biological products and certain medical devices.

“With FDORA, sponsors are now required 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,” added Dr. Richard Pazdur, director of the FDA’s OCE and acting director of the Office of Oncologic Diseases in the FDA’s CDER.

The FDA requires DAPs for clinical studies with enrollment starting 180 days after the final guidance is published. Stakeholders and the public are invited to submit comments on the draft guidance within 90 days of its publication in the Federal Register.

Lack of Diversity and Underrepresentation in Clinical Trials

A 2022 report by Global Data revealed that among clinical trials that disclosed racial representation data, the overwhelming majority of study participants were white. The National Institute of Minority Health and Health Disparities (NIMHD) stresses that inclusive trials are essential for accurate scientific discovery, as diverse participation ensures different lived experiences and demographics are considered.

For instance, during the early stages of the COVID-19 pandemic, the disease disproportionately affected racial and ethnic minority populations. Including diverse participants in vaccine trials helped ensure the vaccines’ safety and efficacy across different groups. Similarly, understanding asthma disparities requires considering environmental and sociodemographic factors.

A recent analysis highlighted seven threats from lack of clinical trial diversity, including limited applicability of trial results and economic costs of health disparities, projected to reach trillions by 2050 for diseases like diabetes and heart disease. Inadequate representation in trials can lead to missed variations in drug metabolism and overall treatment efficacy among different demographic groups.

Underrepresentation in clinical trials is a persistent issue. Black and Hispanic populations are less represented in trials for conditions like cardiovascular disease and cancer, despite having a higher prevalence of these diseases. According to the CDER’s Drug Trials Snapshots 2019 summary report, Black or African-American participants made up only four percent of oncology trials despite representing 13 percent of the US population. This discrepancy can lead to gaps in understanding how treatments affect these groups, potentially exacerbating health disparities​.

Women are often underrepresented in clinical trials, particularly in cardiovascular research. This is problematic because women can have different physiological responses to treatments compared to men. A study found that only 37.9 percent of participants in cardiovascular trials led by men were women, compared to 44.9 percent in trials led by women. Higher-weight individuals are also frequently excluded from clinical trials. This exclusion can result in a lack of data on the efficacy and safety of treatments for this group, which is critical given the higher comorbidity rates for several conditions.

Access to clinical trials is also often unequal, influenced by geographic, economic and infrastructural factors. Patients in high-income countries have more access to trials than those in low-income countries, leading to disparities in treatment opportunities and outcomes.

Industry Leaders in Clinical Trial Diversity

In light of these challenges, several leading companies are actively working to ensure diversity in clinical trials. GSK, Merck, Johnson & Johnson, F. Hoffmann-La Roche and AbbVie are among those making significant strides.

Notably, Merck’s Diversity & Inclusion in Clinical Trials (DICT) Team was recently awarded the “Champion of Diversity and Inclusion in Clinical Trials” at the 8th annual Citeline Awards for excellence in clinical trial design, technological advancements and outstanding achievements in clinical research and development. This award recognizes exceptional initiatives to promote diversity and inclusion of underrepresented populations in clinical trials. Finalists included Johnson & Johnson/Janssen Research & Development, Medidata (a Dassault Systèmes Company) and The Association of Diversity in Clinical Trials. Merck’s DICT Team was also a finalist for the “Clinical Research Team of the Year” award.

Patient Engagement Is Important

Lack of representation and clinical trial diversity threatens the overarching goals of improving overall health and well-being.

Engaging patients in the planning and execution of clinical trials is a great way to ensure that diverse perspectives are considered. Implementing trial support systems for patients with long travel distances and providing financial support for travel expenses are essential to improving participation rates.

Incorporating decentralized clinical trial (DCT) designs — such as Janssen’s CHIEF-HF Study — can help bring studies closer to patients, reducing the need for travel. This requires collaboration between researchers and local medical teams, supported by digital technologies, to ensure patient safety and compliance.

All in all, measures to include the gender, educational, socioeconomic and ethnic diversity of patients that reflect the demographics of the populations in need will create better products and therapies.