Presentation (CTI)

OBJECTIVES: Health technology assessment (HTA) frequently requires evidence beyond that generated in registrational trials. Over decades, numerous approaches, such as network meta-analyses (NMAs) and population-adjusted approaches, have been used to bridge these gaps, requiring a structured feasibility assessment to ensure the appropriateness and validity. The framework proposed by Cope et al. (2014) provides a widely recognized, systematic approach to assess the feasibility of conducting NMAs. Since its publication, there have been advancements in methodological approaches such as population-adjusted indirect comparisons as well as increasing use of real-world evidence (RWE). With the introduction of the EU Joint Clinical Assessment (JCA), this study aims to build on the existing Cope et al. framework by identifying opportunities to extend its application.
METHODS: A targeted review of HTA methodological guidance, including EU JCA recommendations, was conducted to identify expectations for comparative evidence generation. These were mapped against the Cope et al. framework to identify potential areas of enhancement and an expanded framework was developed.
RESULTS: The Cope et al. framework remains highly relevant, however several opportunities to expand its scope were identified. Importantly, the framework should consider single-arm trials, external comparator arms, and RWE to reflect current evidence generation practices. Additionally, new methodological approaches when NMAs are infeasible, structured identification of treatment effect modifiers (TEMs) and prognostic variables (PVs), and integration of KOL input should be considered. Finally, pre-specifying target populations, endpoints and intercurrent event definitions will support interpretability and consistency within regulatory frameworks. A general process incorporating these considerations and their sequence in the feasibility assessment is outlined.
CONCLUSIONS: Building on the Cope et al. foundation, the structured identification of TEMs and PVs, the integration of clinical expertise and the consideration of alternative methods with RWE supports more transparent and comprehensive feasibility assessments that meet guidelines for comparative evidence generation.