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P102: Call for Representative Oncology Trials: FDA Racial & Ethnic Diversity Postmarket Requirements Sep 2022 - Aug 2023

Poster Presenter

Scarlett Yang

Senior Regulatory Affairs Associate
Gilead Sciences
United States

Objectives

Issuing Postmarket Requirements (PMRs) and Postmarket Commitments (PMCs) are among several approaches for the US FDA to advance evidence generation and diversity in clinical research. This analysis examines recent oncology PMR/PMCs relevant to race and ethnicity over a 12-month period.

Method

FDA’s public PMR/PMC database was searched for records from Sep 1, 2022 to Aug 31, 2023. Results were filtered by keywords (race; racial; diversity) and manually reviewed for malignant indications. FDA oncology approvals and product labels on Drugs@FDA were also examined.

Results

From Sep 2022 to Aug 2023, US FDA approved 17 novel oncology products. Of these, there were 11 PMR/PMCs related to diversity, specifically race and ethnicity, across 10 approvals. Nine were accelerated approvals (AAs), while 1 (elacestrant) was a traditional approval. Six were PMRs and 5 PMCs. Among the PMRs, 5 were requirements to fulfill AAs, while 1 was required under FDAAA Section 505(o)(3) to assess safety. Talquetamab-tgvs for multiple myeloma (MM) received 2 diversity PMRs, 1 required under AA and the other under FDAAA Section 505(o)(3). The diversity PMR/PMCs were for lymphoma (n = 4), MM (n = 4), breast cancer (n = 1), cholangiocarcinoma (n = 1), and epithelial ovarian, fallopian tube, or primary peritoneal cancer (n = 1). Hematologic malignancies (n = 8 out of 11; 73%) accounted for the majority. MM disproportionately affects African Americans, recognized in the FDA’s analysis of racial disparities in MM trials (Kanapuru et al. Blood Adv. 2022), while White Americans have the highest incidence rate for non-Hodgkin lymphoma (NCI SEER). Next, we explored if underrepresentation of racial and ethnic minorities in pre-market studies correlated with issuance of PMRs over PMCs. Study demographics were collected from the Clinical Studies section of the 10 oncology product labels. Among the 11 PMR/PMCs, there was no correlation between reported demographics and types of postmarket studies requested (PMC v. PMR). FDA specified enrollment demographics, primary, and secondary efficacy endpoints of the PMRs. The PMCs were issued to characterize efficacy, PK, PD, and/or safety in US racial and ethnic minority patients. In 2 PMCs, real-world evidence was noted as a potential data source.

Conclusion

Our findings illustrate FDA’s focus on promoting clinical studies representative of the US population. To enhance diversity, equity, and inclusion in clinical research, FDA undertook multifaceted pre- and post-approval efforts including providing guidance documents, requesting diversity plans, and issuing PMRs and PMCs at the time of approval. In April 2022, FDA issued draft guidance on diversity plans. Furthermore, the Food and Drug Omnibus Report Act (FDORA) was signed into law in December 2022 and required FDA to release new guidance on diversity action plans. Our results demonstrate that through PMRs mandated by AA, FDA exercised its authority to require confirmatory trials to include subjects from racial and ethnic groups representative of US patients with the disease. FDA’s PMR description could specify enrollment requirements, in addition to other design elements, such as primary/secondary endpoints and treatment arms. FDA’s PMR/PMC measures were applicable to drug development programs for indications with the highest incidence among White populations, as well as those where minority populations are disproportionately impacted. The diversity PMR/PMCs will address clinical questions in racial and ethnic populations underrepresented in pre-approval oncology trials. More efforts on evidence generation are needed to better characterize benefit-risk profiles of oncology drugs in demographic subgroups that reflect the prevalence of the disease. An integrated approach leveraging real-world data may facilitate these efforts, as directed by the 21st Century Cures Act and FDA’s Framework for Real-World Evidence Program.