The Food and Drug Administration (FDA) released a draft guidance “Enhancing the Diversity of Clinical Trial Populations - Eligibility Criteria, Enrollment Practices, and Trial Designs.” It is the position of the FDA to enroll subjects who are the target audience for the investigational product once approved. Certain populations are underrepresented in clinical trials, even though they are part of the target audience. The draft guidance outlines methods the sponsor can use to support more diverse enrollment that more accurately reflects the target population, in accordance with requirements in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. The FDA states in the draft guidance that there are no scientific reasons for some of the exclusions that are common, such as exclusions for advanced age, obesity, certain infections, or children. The draft guidance suggests expanding inclusion criteria when possible to increase enrollment of these populations and improve the generalization of results.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, 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
Other considerations for improving enrollment in diverse populations include:
Reducing burdens for subjects to participate
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Other areas the draft guidance covers are: 1) the expanded access use of investigational drugs, and 2) strategies to broaden eligibility criteria in clinical trials on investigational drugs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. There are two draft guidances for rare diseases released for public comment earlier this year. You may enjoy our blogs on them: “Rare Diseases: Natural History Studies for Drug Development” and “Rare Diseases: Common Issues in Drug Development Guidance for Industry.”
The draft 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. Broadening enrollment to more populations increases the generalizability of study data and improves understanding of the benefit-risk profile. Submit your comments on the draft guidance here through August 6, 2019.
- The Clinical Pathways Team
Enjoy this blog? Please like, comment, and share with your contacts.