Presentation (CTI)

OBJECTIVES: Real-world evidence (RWE) is increasingly used to complement randomized controlled trials in regulatory decision-making and medical product communication. The FDA’s Consistent With FDA-Required Labeling (CFL) pathway permits dissemination of certain studies or analyses (e.g., RWE) when it meets the scientifically appropriate and statistically sound (SASS) criteria and the three factors as described in the CFL guidance. However, there is limited understanding of what constitutes SASS for RWE. This study aimed to develop multistakeholder expert consensus to clarify how RWE can meet SASS standards when intended for CFL communication.
METHODS: The CFL-SASS Collaborative for RWE employed a mixed-methods approach, including a modified Delphi process, to address methodological and regulatory considerations for RWE generation under CFL guidance. Existing RWE standards were reviewed across the literature, established frameworks, and FDA guidance. Eight RWE and regulatory experts participated in interviews and evaluated draft consensus statements addressing CFL-related gaps through four virtual modified Delphi sessions involving independent voting, structured feedback, and facilitated discussion. Consensus was defined a priori as > = 75% agreement.
RESULTS: The CFL-SASS Collaborative for RWE developed the CFL-SASS Principles for RWE Informed by Multistakeholder Expert Consensus (CFL-SASS PRIME), a set of expert and consensus-derived, principles that define expectations for study design, data sources, analytic methods, interpretation, and transparent communication of RWE under the CFL pathway. Twenty draft consensus statements were evaluated. Consensus was achieved on 17 statements which were incorporated into the recommendations that aligned existing RWE methods while addressing practical considerations specific to CFL communication.
CONCLUSIONS: Inconsistent approaches to generating RWE that meets the SASS standard have limited its practical use for CFL communication. CFL-SASS PRIME provides expert-endorsed, consensus-based recommendations to support consistent and appropriate generation and communication of RWE under the CFL pathway, complementing existing FDA guidance and established RWE reporting standards.