FDA to clinical trial sponsors: If diverse populations are missing from your pre market data, we may require post market data collection

The FDA has released draft guidance for sponsors of drugs and biological clinical trials focusing on approaches to collecting data on underrepresented populations in post market clinical studies.

In the draft guidance, released on August 8, the agency emphasizes that pre market clinical trials should represent all relevant ages, genders, and racial and ethnic groups. Furthermore, it strongly encourages sponsors to engage early with the agency to seek input on the diversity plan for their pre market clinical development program.

But the FDA also notes that, while a company may strive to obtain a representative population, it is still the case that most pivotal clinical studies are not representative of US racial and ethnic diversity because companies may not have been able to enroll a representative population. When this happens – when populations in a pre-approval clinical study were not sufficiently representative of the US population as a whole – then the agency may request or require post market data collection to gather the relevant safety and efficacy data.

Considerations in post market studies

The guidance describes 1) mechanisms the FDA may use to require post market data collection; 2) the statistical considerations for sub-population analysis in post market study; and 3) approaches drug and biological trial sponsors may use to collect the data on populations that were under-represented in a pre market study. The agency notes that if additional relevant information is collected in a post market study, it may be added to the drug’s label when appropriate.

Much of the content in this document is previously released guidance, but the agency is noting how post market studies can specifically be requested for data on omitted racial or ethnic groups in a pre market study. Among the examples cited:

Post marketing requirements (PMR): For example, the agency may require an applicant to conduct a post market study assessing the rate of adverse events in particular races or ethnic minorities if there is evidence to suggest the risk is higher for those populations (such as the prevalence of a certain genetic trait) if that group was not well represented in the pre market study.

Post market commitment (PMC): Similarly, where there is evidence to suggest there may be a risk or differential efficacy for a certain racial or ethnic sub-group, the FDA may enter into agreement with the applicant to collect additional evidence after the drug is approved.

Next, the agency offers guidance on the approaches an applicant may use to collect post market data, including single arm trials, randomized controlled trials with stratification for certain groups, real-world evidence collection including registries, or meta-analyses where data are pooled across trials.

Finally, the FDA notes that it may approve drugs based on an entirely extraterritorial clinical development program and population, but may ask for additional evidence in a US study if further efforts to characterize the safety and efficacy of the drug are needed.

Building on earlier guidance

This new draft guidance builds upon earlier FDA guidance documents meant to encourage diversity in clinical studies, such as Collection of Race and Ethnicity Data in Clinical Trials (Agency-wide, October 2016), Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs (CDER/CBER, November 2020), and Inclusion of Older Adults in Cancer Clinical Trials (CDER/CBER, March 2022).

Moving forward

The public comment period for this draft guidance is open until October 10, 2023.

For more information on adapting to this evolving regulatory landscape, please contact your DLA Piper relationship partner or the authors of this alert.