In a country characterised by its racial and ethnic diversity, but where less than 5 percent of clinical trial data includes racial and ethnic factors, clinical trial diversity has become a key issue for the US FDA. Drug and medical device makers recognise the importance of diversity but find their goals complicated by historical mistrust and healthcare inequities among certain communities. In response to the new clinical trial diversity draft guidelines the FDA issued in June, pharma and medical device industry organisations demand clarity.
New Guidance
In June the FDA issued new clinical trial diversity draft guidelines, including “Diversity plans to improve enrolment of participants from underrepresented racial and ethnic populations in clinical trials.” These new rules represent requirements for the racial and ethnic Diversity Action Plans (DAP) companies will need to include in their clinical trials, focusing on the types of products that require a DAP, submission guidelines, and proposed approaches to meeting diversity goals.
“The agency’s draft guidance is an important step—and one of many ongoing efforts—to address the participation of underrepresented populations in clinical trials to help improve the data we have about patients who will use the medical products if approved,” said FDA commissioner Robert Califf.
While the draft guidance is not legally binding, under the 2022 Food and Drug Omnibus Reform Act (FDORA), the agency will require companies to file plans on how they intend to increase diversity once the final guidelines have been published for studies that begin enrolment 180 days later. Until then, the FDA has been collecting feedback from stakeholders and the public, a process that was set to end on September 26.
Call for Clarity
Among the research community, reactions to the new proposed rules have been largely positive. “This is a very important development that’s moving us in the right direction towards improving and increasing clinical trial diversity and making sure that the safety and efficacy data that we get from both device and drug studies is more representative of the populations that will receive those drugs and devices as they roll out,” said Wayne Batchelor, co-chair of the steering committee for the American College of Cardiology’s Clinical Trials Research programme.
Industry stakeholders have also welcomed the guidelines yet called for more explicit information on several fronts. What kinds of studies will require a DAP? How will new race and ethnicity categories align with established definitions? What about global trials? What if companies are unable to meet the stipulated requirements?
In its comments on the FDA proposal, the Biotechnology Innovation Organization (BIO) requests illustrative examples of a DAP “with enrolment goals disaggregated by the required categories (Race, Ethnicity, Sex and Age Group)” and raises the challenges of recruiting a more diverse patient population. “Despite extensive efforts, it has long proven challenging to increase diversity in clinical trials. There will inevitably be circumstances when sponsors cannot meet their enrolment goals despite their good faith efforts.” BIO also seeks further clarification about international studies, claiming that the guidelines appear to be “based on prevalence and incidence in the US.”
Meanwhile, the Pharmaceutical Research and Manufacturers of America (PhRMA) argued in its feedback that for global studies there may be varying race and ethnicity definitions and data collection practices in other countries. “We recommend that FDA define key terminology in the final guidance and initiate a process to achieve longer-term international harmonization on these terms.” PhRMA too requested a more explicit definition of terms such as “new drug” and “pivotal study” used in the draft guidelines. “The definitions of these terms are critical to allowing sponsors to evaluate which clinical studies will require a DAP.”
Other stakeholders questioned the lack of reliable data on which to base their DAPs. “We recognize that the Agency recommends that enrolment goals for a diversity action plan should be informed by the estimated prevalence or incidence of the disease or condition in the U.S. population for which the device is being studied, allowing sponsors to utilize claims data as an available source to obtain information about the estimated prevalence or incidence of a disease or condition. However, a lack of appropriately disaggregated data sources may present challenges for developing diversity action plans under this approach,” said the Medical Device Manufacturing Association (MDMA).
Roadblocks to Diversity
While the pharma industry is aware of the need to increase clinical trial diversity, there are perhaps few companies that genuinely “walk the talk” when it comes to increasing the representation of non-white male groups in their trials. GSK, for its part, did introduce diversity plans into all of its phase III studies in 2022 and 2023. Along with its industry members, PhRMA developed a set of principles for clinical trial diversity and funded Equitable Breakthroughs in Medicine Development, an initiative aimed at addressing the barriers to participation from minority populations.
But beyond these efforts, the fact remains that in the United States large segments of the population are systematically underrepresented in clinical trials. According to the FDA drug trial snapshot for 2020, black people made up just 8 percent of clinical trial participants, despite representing 13 percent of the total US population while Hispanics represented 11 percent, despite being 19 percent of the total US population. This lack of diversity has led to the absence of representation, in many cases, of groups where a particular disease is most prevalent, creating huge gaps in the understanding of these diseases and in how they are treated.
There are historical factors that continue to impact clinical trial participation. Minority groups have been known to distrust the healthcare system and lack knowledge of clinical research processes whereas in a country without universal coverage many poorer minority communities have limited access to healthcare. “Despite sponsor efforts, enrollment [in clinical trials] will continue to be affected by factors outside the control of sponsors, including systemic racism, historical mistrust in clinical research, healthcare inequities, and differences in health literacy,” read BIO’s comments to the new FDA draft guidelines.
