FDA Issues Guidance to Diversify and Expand Participation in Clinical Trials | Mintz – Health Care Viewpoints

On June 28, 2024, the Food and Drug Administration (FDA) published draft guidance for industry titled Diversity Action Plans to Improve Recruitment of Participants from Underrepresented Populations in Clinical Trials (draft guidance), for public review and comment. The draft guidance was issued pursuant to a congressional directive in the Food and Drug Omnibus Reform Act (FDORA), signed into law in December 2022, that required the FDA to issue or update guidance on the diversity action plans that sponsors submit for certain clinical trials of investigational drugs and medical devices. The draft guidance also serves to update guidance that the FDA previously issued on this topic in April 2022.

Background

The United States has made significant progress in clinical trials over the past few decades. However, the populations for which prescription drugs or devices are intended are often underrepresented or not actively recruited to participate in these trials. For example, although blacks make up more than 33% of people with kidney failure, only 9% participate in related clinical trials. Similarly, Latinos, who experience a higher incidence of cancer, make up less than 10% of participants in cancer clinical trials and only 11% of all clinical trial participants in the U.S. The lack of diversity of participants in clinical trials can have negative implications for both individual and public health, because the results of such studies do not reflect the broader population or often even those who would most benefit from the product being studied. This disparity makes these treatments less effective and potentially harmful for some groups.

There are several reasons for the lack of representation of certain communities in clinical trials; we summarize the most important ones below, but we note that there are others as well. These complexities underscore the breadth and scope of the problem that Congress and the FDA are trying to address with the draft guidance.

Historical distrust

• The United States Public Health Service conducted a 40-year clinical trial known as The Tuskegee Experimentin which hundreds of black men with syphilis were experimented on without their informed consent. Although the participants were promised medical care they would not otherwise have received, they were deceived, not informed of their syphilis diagnosis, and were experimented on decades after a cure was known. By exploiting the socioeconomic status of the participants, the researchers conducting the study violated ethical standards, leading to significant distrust of clinical research in the black community. The experiment resulted in 128 deaths from syphilis or related complications, infection of 40 of the participants’ partners, and the birth of 19 children with congenital syphilis.

• Another clinical trial, known as Puerto Rican Pill Testsinvolved women from the poorest areas of San Juan, Puerto Rico, and neighboring towns who were given birth control pills without being told they were taking part in an experiment or clinical trial. When participants reported side effects like nausea, headaches, and depression, researchers often dismissed their claims.

Lack of commitment

• Underrepresented groups are not effectively informed about the opportunity to participate in clinical trials, nor are they provided with sufficient or culturally sensitive information to enable them to make informed decisions about participation.

• One study found that the primary barrier to recruiting minority patients to clinical trials is that patients are not aware that they are eligible for an existing clinical trial. Among the most important factors that facilitate participation are social support and recommendations from physicians.

• Other test A study of black Americans’ reluctance to participate in clinical trials found that there was a belief that research would benefit white Americans more than underrepresented populations. This disparity was cited by survey respondents as a primary reason for their reluctance to participate in clinical trials.

Other issues to consider include scheduling constraints, access to transportation and language barriers.

Which drugs and devices require submission of a Diversity Action Plan?

As detailed in the FDA Draft Guidance, Diversity Action Plans (DAPs) provide an impetus for drug and device developers (also known as clinical trial “sponsors”) to consider and address the factors described above when developing clinical trials for new drugs and devices. For drugs, a DAP is required for a clinical trial of a new drug that is a Phase 3 trial or other pivotal study. For medical devices, a DAP will need to be submitted to the FDA in most cases. If the sponsor is seeking an investigational device waiver or IDE, a Diversity Action Plan must be submitted, whereas in cases where an IDE is not required to continue the clinical trial, a DAP should be included in any premarket notification, application for classification as an investigational device, or all over again device or application for marketing authorisation.

The draft guidance outlines the actual format and content that FDA expects in a DAP and includes an appendix summarizing the required elements. It also describes the timing and process for submitting a DAP and the criteria FDA will use in evaluating a sponsor’s request not to submit a DAP (i.e., a waiver request).

In addition, the draft guidelines identify three cases in which the submission of diversity action plans is not required:

• Clinical trials of drugs for which protocols are submitted within 180 days of publication of the final guidelines, where recruitment is expected to begin 180 days after publication;

• Clinical device studies received by the FDA under IDE requests within 180 days of publication of the final guidance; or

• Clinical device trials that do not require IDE submission and that are approved by an ethics committee or independent ethics committee within 180 days of publication of the final guidance.

Integrating race, ethnicity, gender and age (and more) into diversity action plans

Under FDORA, diversity action plans must identify clinical trial recruitment goals, and these goals must be disaggregated by race, ethnicity, gender, and age group of the clinically relevant population. The sponsor’s rationale, the plan of action to achieve these recruitment goals, and the method for monitoring progress toward the goals must also be detailed in the plan. In other words, recruitment goals must be presented across subgroups of the trial population. Although the draft guidance focuses on race, ethnicity, gender, and age group of the clinically relevant population, it also recognizes that health disparities and access to health care and clinical trials are influenced by a variety of demographics and other social determinants of health. These include, but are not limited to, geographic location, gender identity, sexual orientation, socioeconomic status, physical and mental disabilities, pregnancy status, lactation status, and comorbidities. Sponsors are therefore encouraged to consider these additional demographics when developing recruitment goals.

In developing their DAPs, sponsors must not only consider the clinical impact of their drug or device studies but also anticipate the potential societal impact that the study may have. Indeed, diversifying the clinical trial population will help to provide a more comprehensive understanding of the biological impact that a drug or device may have on the relevant population. However, Congress hopes that the benefits of diversifying recruitment extend beyond clinical outcomes alone. Ideally, developing clinical trials that include diverse populations—especially when those experiences are positive—can help build trusting relationships with participants, promote increased scientific and clinical knowledge, and promote health equity.

Application

FDA will be accepting comments on the draft guidance through Thursday, September 26, 2024, which may be submitted electronically to docket number FDA-2021-D-0798 (link to e-document here ; paper submissions may also be submitted to the address provided in the agency’s notice announcing the availability of the draft guidance). Guidance issued by a federal agency is not generally binding. However, because FDA is required by statute to specify the manner and form in which DAPs are submitted for review, these sections of the guidance (when finalized) will be binding.

The draft guidance presents a new approach for diverse communities to build trust in our health care system, and for drug and device sponsors to build that trust. In addition to the new guidance, FDA’s broader efforts to advance recruitment and retention strategies that include ongoing community engagement through community organizations, health care providers, and patient advocacy groups, and FDA’s support for decentralization of clinical trials, will increase opportunities for broader participation and allow diverse perspectives to be heard and heard. Thoughtful and inclusive recruitment can foster stronger relationships between the medical community and underserved communities, increasing their likelihood of participating in the development of new medicines and medical technologies to treat diseases and conditions. By increasing diversity and inclusion in clinical trials, the medical and scientific community will be better prepared to understand and treat diseases and conditions in all populations.

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