ISSUE: The growing number of highly specialized products, including cell-based and gene therapies, is an accelerating, likely permanent trend in drug development. These products often achieve regulatory approval based on single-arm trials due to ethical considerations or difficulty of recruiting patients. HTA agencies must then assess highly specialized products based on single-arm pivotal trials alongside historical study data or prospective local real-world evidence (RWE) on standard care. Several manufacturers have already supported regulatory and HTA filings using single-arm trials alongside historical trial data and/or prospective RWE.

This development challenges the established role of NMAs in HTA processes. NMAs are a core tool to establish comparative value of healthcare interventions, both from clinical and societal perspectives, given that it is not feasible to conduct head-to-head studies for every treatment. HTA bodies rely on NMA techniques to derive necessary estimates of comparative effectiveness for use in economic models. The question therefore arises regarding the outlook for use of NMAs in determining the comparative effectiveness for highly specialized products given the growing use of single-arm trials.

OVERVIEW: Dr Naci will introducing the topic and present current and evolving approaches to comparative effectiveness research, including those relevant to single-arm pivotal trials (10 min). Next, the panelists will present their perspectives (10 min each). Dr. Dawoud will argue for the continuing place of NMAs and the evolution of innovative methodological approaches, including those relating to using single-arm trials. Dr. Heeg will argue that single-arm trials can be acceptable for HTAs under certain conditions, including that the RWE control arm must be considered in the single-arm trial protocol. Dr. Cappelleri will argue for the necessity of approving highly specialized products based on single-arm trials to expedite access. Next, panelists or the moderator will pose challenges to begin the debate section (10 min). General Q&A will follow (10 min).