On April 13, 2022, the U.S. Food and Drug Administration (“FDA”) issued a draft guidance providing specific recommendations to the industry on how to improve diversity in clinical trials. The FDA’s focus on increasing racial and ethnic diversity in clinical trials is not new, with the agency issuing several guidances since 2016 on this topic. However, the recent draft guidance sets out new expectations for sponsors conducting clinical trials intended to support marketing authorization of drugs, biologics, and medical devices.
The FDA has explained that certain racial and ethnic populations are frequently underrepresented in clinical research, despite, in some instances, having a disproportionate disease burden relative to their proportional representation in the general population. To help address this disparity, the FDA now recommends that sponsors proactively develop a plan to increase racial and ethnic diversity for trials conducted under an Investigational New Drug Application (“IND”) or investigational device exemption (“IDE”). In addition, a plan is recommended for medical products for which clinical studies are intended to support a device marketing submission, whether a premarket notification (“510(k)”), premarket approval (“PMA”) application, a De Novo classification request, or a humanitarian device exemption (“HDE”). For studies of drugs and biologics, sponsors should develop and submit the plan to the relevant IND “as soon as practicable,” but no later than when the sponsor is seeking feedback on the pivotal trial (generally by the End of Phase 2 meeting). For studies of medical devices, the FDA recommends that sponsors submit the plan as part of the investigational plan submitted with the IDE. Where an IDE is not required for clinical studies of a medical device, sponsors can obtain feedback on the plan through the Q-submission process.
When developing a diversity plan, the FDA recommends that sponsors start by assessing “any data that may indicate the potential for a medical product to have differential safety or effectiveness associated with race or ethnicity.” Where sponsors identify such data, the plan should describe the study design features that will support the assessment of safety and effectiveness of the medical product in the relevant racial and ethnic populations. Even where there are no data indicating potential for differential safety or effectiveness, the FDA recommends that enrollment in the trial reflects the epidemiology of the disease.
The draft guidance provides the FDA’s expectations for the elements of a diversity plan, although the agency notes that this is not an exhaustive list of steps that may be taken to improve diversity in clinical trials:
- Overview of the disease/condition: Describe the available data on the disease/condition in underrepresented populations, including any differential application or use of prevention, screening, or diagnostic strategies across different racial and ethnic populations.
- Scope of medical product development program: Briefly describe the studies planned to support the application for marketing authorization, including an outline of the study design, study population, endpoints, and expected geographic locations of the trials, and how these features of the trials may address inclusion of underrepresented populations. Sponsors should also summarize any findings from clinical pharmacology studies that may indicate any differences applicable to certain racial and ethnic populations.
- Goals for enrollment of underrepresented racial and ethnic participants: Specify underrepresented populations (based on the assessment done to provide an overview of the available data on the disease/condition, as noted above), and provide goals for enrollment of participants from these populations.
- Specific plan of action to enroll and retain diverse participants: Sponsors should provide detailed steps that will be implemented to enroll and retain participants from underrepresented racial and ethnic groups, as well as how data will be used to characterize safety, efficacy, and optimal dosage in these participants (when applicable). The FDA provides examples of strategies sponsors might utilize to achieve these goals, such as making sites more accessible and providing language assistance, engaging with community health resources (e.g., community health workers and patient advocacy groups), and reducing the burdens of study participation (e.g., reducing study-related procedures and using local laboratory/imaging services or telehealth). The plan should include metrics to ensure that the trial achieves goals for diverse enrollment and steps to be taken if enrollment goals are not met.
- Status of meeting enrollment goals (as applicable): Sponsors should provide updates on the status of meeting enrollment goals. If, despite the sponsor’s best efforts, the sponsor cannot meet these goals, the sponsor should “discuss a plan and justification for collecting data in the post-marketing setting.” We note that although the guidance does not provide additional details on how the FDA would require such data to be collected, the agency has recently included language in approval letters for oncology products approved under the accelerated approval pathway to “include sufficient representation of racial and ethnic minorities to better reflect the U.S. patient population” when conducting confirmatory studies.
The FDA notes that the agency may request periodic updates to specific components of the plan throughout the development of a medical product, and a description of the successes and challenges in implementing the plan should be included as part of the marketing application.
The draft guidance represents a step forward by the FDA in explaining how sponsors can build diversity into clinical development from the outset. Like all of the FDA’s guidances for industry, the draft guidance contains “nonbinding recommendations,” and it is not yet clear how strongly the FDA will advance these recommendations in interactions with sponsors. However, the guidance signals a willingness to engage early with sponsors and provide substantive feedback, which may be useful to sponsors in understanding what the FDA will ultimately expect from their clinical trials — either prior to approval or in the post-marketing setting.
Relatedly, on April 28, 2022, the FDA proposed in the Federal Register to amend the form used by physicians to request expanded access, Form FDA 3926, to include an option to add “Race and Ethnicity” in the “Clinical Information/Brief Clinical History” field. Such information could help the agency track how racial and ethnic groups benefit from expanded access. This client alert provides additional background on the FDA’s expanded access program.
Comments on the FDA’s draft guidance are due by June 13, 2022.
See Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs (November 2020); Collection of Race and Ethnicity Data in Clinical Trials (October 2016); and Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies (September 2017).
See, e.g., FDA Approval Letter for Brukinsa, available at https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2021/213217Orig1s005ltr.pdf.