(A-030) Use of Real-World Evidence to Satisfy U.S. FDA Postmarketing Requirements and Commitments

Background: Real-World Evidence (RWE) studies to support regulatory filings continue to increase and evolve, mainly driven by time and cost savings of execution. Further, the U.S. FDA has specifically recommended and accepted RWE solutions to address Postmarketing Requirements (PMRs) and Commitments (PMCs). PMR/PMCs are studies conducted after approval to gather additional product safety, efficacy, or optimal use data. PMRs include studies that sponsors are required to conduct under statutes or regulations, while PMCs are studies that sponsors agreed to conduct but not required by a statute or regulation.

Objectives: To understand use of RWE to fulfill PMR/PMCs within FDA’s public database and categorize the RWE approaches.

Methods:

Methods: The FDA PMR/PMC public database was downloaded and filtered by keywords (real-world; real world; sentinel; observational; non-interventional) and Original Application Approval Dates (Jan. 1, 2023 to Jan. 30, 2025). PMR/PMCs with closed statuses (fulfilled & released) for > 12 months at time of database update (Jan. 30, 2025) were not included in the database.

Results: We identified 47 RWE PMR/PMCs (37 PMRs; 10 PMCs) issued for 31 drugs/biologics, including vaccines. Among the 37 RWE PMRs, 2 were required under Accelerated Approvals, while 35 were issued under section 505(o)(3) of the FDA Amendments Act of 2007 to assess safety. Forty-three of the RWE PMR/PMCs were observational studies, while 4 were integrated analyses of multiple data sources including clinical trials, postmarketing reports, RWE, and others. Approximately 60% of the RWE PMR/PMC descriptions contained terms of specific populations such as pediatric, geriatric, pregnant, and other underrepresented groups. Therapeutic areas in which the 31 medical products were developed include: 8 in oncology, 7 in infectious diseases (5 viral and 2 bacterial), 5 neurology, 4 cardiovascular conditions, 2 nephrology, 2 gastroenterology, 2 dermatology, and 1 orthopedics.

Conclusions: Our findings illustrate RWE use cases to (1) better contextualize clinical trial safety/efficacy data versus patients treated with comparators, (2) conduct case-control or exposure cohort studies, or (3) enhance diverse subgroup analyses. Since underrepresentation of various patient subgroups (e.g., age, sex, pregnancy, race/ethnicity, comorbidities, receiving concomitant medications, and gene variations) may challenge generalization of clinical trial findings, additional evidence is needed. An integrated approach applying robust scientific methods and leveraging real-world data may facilitate these efforts.