Exploring FDA’s toolkit for encouraging study sponsors to meet diversity goals.
When clinical trials fail to enroll a diverse study population, they fail to reveal a thorough understanding of how the drug will work in practice. Researchers also lose the opportunity to improve access to breakthrough therapies and provide better health care to historically underserved communities.
Writing for the Food and Drug Law Journal, industry advisors Sarah Thompson Schick and Kirsten Axelsen suggest that the solution does not lie in industry self-regulation or regulatory mandates. Instead, Thompson Schick and Axelsen consider how the U.S. Food and Drug Administration (FDA) may expand existing regulatory incentive programs to study sponsors upon fulfillment of diversity goals that have eluded the agency for over a decade.
According to a 2020 report of drug trial data published by FDA, only eight drugs approved in 2019 and 2020 included studies with an enrollment of Black and Hispanic participants proportionate to the U.S. population. This under-representation of ethnic and racial minorities remains prevalent even in studies of treatments for conditions that disproportionally affect those groups.
Black and Hispanic patients participate in oncology trials, for example, at rates lower than their proportion of cancer diagnoses, despite higher mortality rates than white patients. Two oncology trials approved by FDA in 2020 reported enrolling zero Black participants.
Thompson Schick and Axelsen attribute this under-enrollment of minority populations to factors such as a long-standing distrust of the medical research community, lack of diversity among study investigators, worries about adherence to clinical trial procedures, common inclusion and exclusion criteria, and sponsor concerns about trial speed and sample size.
Although these factors do not appear discriminatory on their face, as Thompson Schick and Axelsen illustrate, they have the disparate impact of depressing the participation of ethnic and racial minorities as well as low-income communities in clinical drug trials. As an example, Thompson Schick and Axelsen note that certain conditions that are common grounds for exclusion from trials, such as history of heart disease or chronic pain, are also more prevalent in certain non-white groups.
The intersectionality of low-income communities and racial and ethnic minorities exacerbates lack of diversity in clinical trials, according to Thompson Schick and Axelsen. Lack of capital and access to jobs with flexible schedules or private transportation make adhesion to clinical trial procedures requiring multiple visits especially difficult. These hurdles combined with a history of discriminatory behavior and disparity in access to health care have all contributed to the current lack of diversity in clinical trials, according to Thompson Schick and Axelsen.
And this lack of diversity, the Thompson Schick and Axelsen argue, will be costly and difficult to overcome. From recruitment challenges to study size and duration—study sponsors would need to invest significant resources in improving the status quo. Recruitment of non-white participants in clinical trials can cost approximately five times more than white participants.
Relaxing inclusion criteria can lead to study participants that need to drop out of a trial, some for medical reasons and others due to an inability to attend visits according to the study schedule. When participants withdraw from studies, companies not only lose data they can no longer use and resources already spent, but they incur future costs as well. For example, sponsors may need to extend the study to increase the sample size and ensure the trial can demonstrate the requisite safety and effectiveness to garner FDA approval.
It is in part because of the investment required that FDA’s efforts to improve clinical trial diversity over the past decade have yet to produce meaningful change, argue Thompson Schick and Axelsen. The agency’s actions have been persistent, but they have focused on communication and engagement, hoping the industry will fall in line on its own. Some legislators have gone in the other direction and introduced legislation to impose mandates and reporting requirements on sponsors to grapple with the issue.
Instead of self-regulation or burdensome mandates, Thompson Schick and Axelsen would like to see the agency consider expanding some of its existing incentive programs to study sponsors meeting certain diversity criteria. Specifically, Thompson Schick and Axelsen suggest Fast Track Designation, Priority Review, Priority Review Vouchers, and Pediatric Exclusivity as potential models of incentives FDA could offer study sponsors.
Under FDA’s current framework, such programs function to spur drug development for serious conditions, rare diseases, and tropical illnesses. They also encourage research in pediatric populations. In return, the agency offers a range of benefits, including early and proactive interaction with the agency to receive guidance and clarity throughout the approval process and expedited review of applications.
To expand these programs to sponsors seeking to improve clinical trial diversity would require FDA to set certain standards and requirements for qualification that align with diversity of goals. Specifically, Thompson Schick and Axelsen suggest FDA may recommend sponsors enroll participants proportionally to the demographics of the real-world treatment population for a given condition.
Thompson Schick and Axelsen also note that, even though some of FDA’s existing incentive programs are authorized by legislation, others such as the Fast Track and Priority Review programs may be initiated through notice and comment rulemaking. Thompson Schick and Axelsen maintain that the rulemaking route would be preferable to legislation because it would minimize contentiousness and legislative gridlock. Moreover, rulemaking would also allow for public comment and input, which may lead to more creative and innovative viewpoints about how industry and regulators can best collaborate to enhance diversity in drug trial participants.