11/23/2020
Image by Gerd Altmann from Pixabay
The Food and Drug Administration (FDA) released a final guidance in November 2020, “Enhancing the Diversity of Clinical Trial Populations - Eligibility Criteria, Enrollment Practices, and Trial Designs.” Certain populations are underrepresented in clinical trials, even though they are part of the target audience for the investigational product once approved. The guidance outlines methods the sponsor can use to support more diverse enrollment that more accurately reflects the target population, in accordance with requirements in the FDA Reauthorization Act of 2017 (FDARA).
Some populations have been excluded out of an abundance of caution or out of concern that complexities may cause difficulties in analysis of safety or effectiveness. There are no scientific reasons for some of the exclusions that are common, such as exclusions for advanced age, obesity, certain infections, or children. The guidance suggests expanding inclusion criteria when possible to increase enrollment of these populations and improve the generalization of results. Another suggestion is to use enrichment strategies, which targets the inclusion of certain populations.
Further recommendations include changing trial design to improve the diversity of the trial population by:
Determining if exclusion criteria are essential or overly restrictive
Broadening eligibility criteria to encompass populations that would use the treatment
Considering using a different trial design that would allow for a broader population, such as:
An adaptive trial design that would start with a narrow population and expand
An expansion cohort for those that would metabolize drugs differently
Additional barriers to participation can be financial costs or inability to travel to study visits due to transportation, job, or caregiver challenges. Considerations for improving enrollment in diverse populations include:
Reducing burdens for study participants, such as only requiring essential study visits and lab work or reimbursing expenses more rapidly
Improving patient centricity in study design
Choosing sites that have more diverse populations
Broadening outreach to and recruitment of diverse populations
Improving transfer of medical records between sites
Other areas the guidance covers are: 1) the expanded access use of investigational drugs, and 2) strategies to broaden eligibility criteria in clinical trials on investigational drugs for rare diseases. You may enjoy our blogs on two draft guidances related to rare diseases: “Rare Diseases: Natural History Studies for Drug Development” and “Rare Diseases: Common Issues in Drug Development Guidance for Industry.”
The guidance focuses on strategies the sponsor can follow in protocol design to broaden eligibility criteria and improve enrollment of populations that are not well represented in clinical trials, despite the fact they are included in the target audience for the drug once approved. Understanding how study requirements can be burdensome to some potential study participants can inform a better design of the trial based on Quality by Design principles, collecting only the data that are essential to primary or secondary endpoints, rather than collecting data because of tradition, while reducing burden. Broadening enrollment to more populations increases the generalizability of study data and improves understanding of the benefit-risk profile.
- The Clinical Pathways Team
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