P251: Engagement with FDA’s Advancing Real-World Evidence (RWE) Program: Insights from the First Six Cycles
Poster Presenter
Kristen Miller
Health Scientist Policy Analyst, Office of Medical Policy, CDER
FDA United States
Objectives
Leverage insights from six completed cycles of FDA’s Advancing RWE Program to help guide future submissions and provide actionable strategies for optimizing RWE to support regulatory decision-making.
Method
Data from six completed cycles of FDA’s Advancing RWE Program (March 2023-September 2025) were analyzed to identify drivers of acceptance, non-acceptance, and proposal misalignment with program goals. Findings were used to inform strategies for applicants to enhance clarity and regulatory readiness.
Results
Across six completed cycles of FDA’s Advancing RWE Program, 29 meeting requests were reviewed from various sponsors and six (21%) were accepted.
Accepted proposals consistently demonstrated: (1) a clearly defined regulatory question; (2) a clearly defined role for RWE as primary evidence in regulatory decision-making; (3) feasibility in real-world settings through selection of fit-for-use data sources (4) prespecified (i.e., prior to study initiation) strategies to address confounding, heterogeneity in the disease, missing data, and other sources of bias. Acceptance did not cluster by therapeutic area or data source complexity.
Among the non-accepted submissions, several proposed methods-focused studies or replication studies of ongoing trials and were not decision-enabling. Some were observational trial emulation studies where randomized controlled trials (RCTs) were considered by FDA to be feasible, ethical, or necessary, or where RCTs were already ongoing. Others lacked sufficient scientific rationale to support the new indication or proposed inappropriate novel endpoints not used for regulatory decision making in the disease. Non-acceptance most frequently reflected three themes: (1) RCT were considered feasible despite sponsor concerns, or necessary to support an adequate benefit–risk assessment (9/23, 39%); (2) the proposed study was expected to be only supportive to the main study informing regulatory decision making or to have limited anticipated regulatory impact, and was unlikely to meaningfully influence labeling or regulatory decisions (7/23, 30%); and (3) key study design or data source-related limitations, including missing or inappropriate outcomes or lack of prospectively specified analytic strategies (6/23, 26%).
Conclusion
The Advancing RWE Program is an important initiative that offers early focused discussions on complex study proposals generating RWE. It provides opportunities for shared learning between sponsors and the FDA with the goal of improving the acceptability of RWE related regulatory submissions.
Analysis of the first six cycles provided clarity on the characteristics of submissions more likely to be accepted into the Program. Future submissions should include only studies that are pivotal to the regulatory decision making (methods or replication type studies are not eligible) , clearly define the regulatory question before selecting fit for use data sources, and outline study design and analytic approaches to address potential biases such as confounding, selection and time-related biases. Recurring non-acceptance patterns highlight opportunities to clarify program scope and expectations through more explicit eligibility criteria, targeted outreach, and presentation of successful use cases.
Collectively, these insights offer suggestions to improve submissions, generate evidence that meaningfully informs regulatory decisions, and increase the acceptability and appropriateness of RWE.
