Excerpted From: Sarah Thompson Schick and Kirsten Axelsen, Considering Modifications to Existing FDA Regulatory Incentives to Achieve Greater Racial and Ethnic Diversity in Pivotal Clinical Trials for Drug Approvals, 77 Food & Drug Law Journal 246 (2022) (76 Footnotes) (Full Document)


SchickAxelsenIn November 2020, the U.S. Food and Drug Administration (FDA) issued the final guidance, “Enhancing the Diversity of Clinical Trial Populations-- Eligibility Criteria, Enrollment Practices, and Trial Designs,” providing recommendations on how clinical trial sponsors can approach enrollment of underrepresented patient populations. This effort builds on more than a decade of initiatives to increase racial and ethnic diversity in clinical trials at both FDA and the National Institutes of Health (NIH). However, despite guidance to and investment in clinical trial sponsors and researchers, the FDA data shows that most pivotal clinical trials for new drug approvals do not enroll participants that reflect the racial and ethnic diversity of the U.S. population. There are several reasons for a lack of racial diversity in pivotal clinical trials for drug approval, including historical distrust of the medical community, limited participation and engagement of diverse healthcare professionals as investigators, typically used inclusion and exclusion criteria in trials, concerns about adherence to clinical trial procedures, and sponsor focus on rapid enrollment and expected treatment effect size.

While FDA has discussed and assessed clinical trial diversity at length, many of its stated goals are centered around further dialogue and communication with sponsors, patients, and other community-level stakeholders. The agency has recommended changing criteria for including participants in studies that have the effect of disproportionately excluding people who are not white. With the legacy of racism in the United States and its effect on health and the expectation of health outcomes from a treatment, diverse trials are costlier and more time-consuming for sponsors. The issue goes beyond recruitment and trust; it also includes managing co-morbid conditions and changing trial sizes due to the expected efficacy of treatment. These are changes that can have a meaningful effect on the cost and duration of a trial. As a result, guidance to make certain changes may not be a sufficient incentive. We believe the additional step of establishing regulatory incentives (as opposed to any regulatory mandates) is a feasible option for the agency.

Specifically, we suggest that FDA consider extending regulatory incentives that currently offer sponsors access to certain expedited programs or to extended data protection. Certain types of expedited programs could also be an available option where sponsors are establishing and executing plans, in good faith, to recruit and retain racial and ethnic minorities in their clinical trials. We argue that, if sponsors are provided regulatory incentives, there may be a more marked change in sponsor behavior to ensure more substantial recruitment and retention of racial and ethnic minorities. This can also be of benefit to racial minorities and the healthcare system: providing opportunities for increased access to patient care, expediting the development of an investigational product candidate, and generating data on a more representative patient population to better anticipate how the drug will work in practice.

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As there is continued discussion on how to increase clinical trial diversity, regulatory incentives can serve as a catalyst for more innovation, collaboration, and to another extent, competition in the industry. Indeed, regulatory incentives are market incentives. Additionally, while regulatory incentives can impact clinical trial diversity, there are other potentially positive outcomes, especially racial and ethnic minorities participating in clinical trials having access to highly trained and experienced physicians in the healthcare system that may not be readily available to some depending on the geographic area in which they reside. This is not a long-term remedy, although opportunities for more constructive interactions with the healthcare system and healthcare professionals in a clinical trial setting could provide solutions to address disparate health outcomes beyond development of new drug products and therapies. Further, by establishing regulatory incentives for clinical trial diversity, beyond stated goals and policy or guidance documents, FDA has an opportunity to fulfill its mission in an inclusive manner by truly “advancing the public health.”

Overcoming the barriers to racial and ethnic minority participation in clinical development will be expensive, although there are existing regulatory incentives that FDA can leverage to encourage drug development and data collection for certain diseases and patient populations. These regulatory tools, including Fast Track Designation, Priority Review, PRVs, and Extended Data Exclusivity, should be considered as potentially viable incentives to sponsors for expanding clinical trial diversity. Because of the legacy of racism and disenfranchisement in the United States, there is significant variability in the health status and presence of disease in different races and ethnicities, even if there are not clearly defined biomarker or genetic differences. Differential living environment, access to capital, and access to healthcare means that the expectation of an outcome from a particular treatment is heterogenous across different groups in a way that affects pivotal trial size and costs. Even with advances in clinical trial approaches, such as digitally enabled trials and community-level outreach, without additional incentives to change current behavior, the environment will continue to work against diversity in clinical development.

Sarah Thompson Schick is a Senior Associate at Hogan Lovells on the Pharmaceuticals and Biotechnology team, and most recently is a former Associate at DLA Piper.

Kirsten Axelsen is a Senior Policy Advisor to DLA Piper, and she is also a Health Innovator Fellow with the Aspen Institute, and a Visiting Scholar with the American Enterprise Institute.