By Stacey Kusterbeck
Researchers soon will have additional guidance for increasing enrollment of participants from historically underrepresented populations. The U.S. Food and Drug Administration (FDA) has issued a draft guidance, Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies.1 “The draft guidance has been posted for public comment. We would appreciate receiving comments from ethicists, as well as all stakeholders,” says FDA Oncology Center of Excellence Director Richard Pazdur, MD.
Explicit attention to the intentional, proactive inclusion of diverse research participants already should be a critical aspect of institutional review board (IRB) review. “Without inclusion, access to the benefits of scientific discoveries becomes less tenable,” according to Katherine McDonald, PhD, senior associate dean of research and administration, chair of the IRB, and professor of public health at Syracuse University. McDonald says these are important questions for IRBs to consider when evaluating study protocols:
• Eligibility criteria. Do these implicitly or explicitly demonstrate discrimination, which will yield a less diverse sample? Are reasonable, study-specific scientific or ethical justifications provided for exclusion, or is there unjustified categorical exclusion? Do the eligibility criteria presume consent capacity, or do they take a categorical approach to indicate a lack of consent capacity? Do the criteria consider whether someone subject to legal guardianship can be responsibly included? Are there bias-free, valid, standardized screenings and assessments of study-specific eligibility criteria?
• Recruitment approaches, materials, and contexts. Do these explicitly and proactively strive to enhance representation? Are they based on reliable, substantial evidence that will yield diverse samples? Do they account for differences in trust, resources, or social capital to enhance full representation?
• Consent protocols and materials. Do these presume competence and take an educational approach, emphasizing the researchers’ responsibility to enhance understanding? (for instance, reducing literacy requirements by using plain language, text-to-voice or reading materials read aloud?) Do study materials provide support in decision making? Do study investigators offer opportunities for active learning about a research study?
“Ethical principles emphasize that, as a matter of justice, the risks and rewards of research participation should be equally accessible across the spectrum of human variation,” underscores McDonald.
As cofounder of CARER Group, a nonprofit organization dedicated to health equity and diversity in clinical trials, William Fitzsimmons, PharmD, developed a Clinical Trial Diversity scorecard. The scorecard quantifies the age, sex, race and ethnic diversity of study participants in trials leading to FDA approval of novel new drugs. Fitzsimmons and colleagues analyzed FDA-approved novel drugs in 2022-2023 using the scorecard.2 “By assessing all new drug approvals starting in 2022, we are able to assess the current state of diversity — and also determine if current efforts result in improvement in diversity,” explains Fitzsimmons, an adjunct professor in the Colleges of Pharmacy and Medicine at University of Illinois at Chicago.
The scorecard assigned each drug a letter grade between A and F for demographic subgroups including age, sex, race, and ethnicity, taking into account the number of participants from each subgroup that received the novel drug in the clinical trial, and the prevalence of the condition or disease being studied in each subgroup. For the 49 novel new drugs approved during the study timeframe, there was good representation of females and older individuals. “Asian participation was not good overall, but fair, on average. However, Black and Hispanic representation were particularly poor, with Black participation the lowest,” reports Fitzsimmons. For instance, about 20% of novel new drug approvals had no Black participants receiving the new drug. “The results do show that some trials are good overall, so diverse trials are possible,” adds Fitzsimmons.
The study findings suggest that researchers need to take proactive steps to increase enrollment of diverse racial and ethnic groups, particularly Black and Hispanic patients. “It will not happen by chance. It requires planning, execution, monitoring, and corrective actions if there is insufficient representation,” says Fitzsimmons.
In Fitzsimmons’ experience, one of the major reasons that Black patients give for not participating in a clinical trial is “I was not asked.” It is paramount that researchers assess their biases and ensure that they ask patients if they want to participate,” says Fitzsimmons.
Some trials for novel new drugs are the last or only therapeutic option for patients. “If trials are not diverse, we are denying potential lifesaving therapies from these patients,” says Fitzsimmons. As for IRBs reviewing study protocols, Fitzsimmons says these are important questions to ask:
• Is there sufficient renumeration of trial participants to cover all of their costs (travel, childcare, elder care, meals, lost wages, etc.) of participating in trials?
• Are the investigators at the site diverse?
• Do the study procedures discourage diverse participation (for example, too many in-person visits as opposed to virtual visits)?
• Do the inclusion/exclusion criteria unintentionally affect one racial or ethnic group (for example, excluding comorbidities that have a higher incidence in certain populations)?
Does the database for a new drug insufficiently represent certain groups? If so, then the first opportunity to learn whether the therapy is effective and safe in those groups is during the post-market setting. “This may subject patients to risk without the monitoring and informed consent of a clinical trial,” says Fitzsimmons.
- U.S. Food and Drug Administration. Diversity action plans to improve enrollment of participants from underrepresented populations in clinical studies. Published June 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies
- Idris MY, Fitzsimmons WE, Pemu P. Quantifying clinical trial diversity in pivotal registration trials of FDA novel drug approvals. Ther Innov Regul Sci 2024;58:175-183.
