Presentation (CTI)

OBJECTIVES: In France, according to the revised 2022 eligibility criteria for health economic evaluation, Advanced Therapy Medicinal Products (ATMPs) are subject to health economic evaluation by the French National Authority for Health (HAS) whenever an ASMR level I, II or III is claimed, regardless of the expected revenue level.This study aimed to analyze the methodological concerns and sources of uncertainty identified by the French Economic and Public Health Assessment Committee (CEESP) in ATMP economic evaluations.
METHODS: All CEESP economic opinions issued between 2020 and 2026 were reviewed. ATMP and non-ATMP evaluations were compared regarding methodological concerns, uncertainty levels, and evidence maturity.
RESULTS: Among 122 CEESP economic opinions, 16 concerned ATMPs (8 gene therapies, 7 CAR-T therapies, and 1 cell therapy). All ATMPs targeted rare diseases compared with 39% of non-ATMPs. Ten ATMP evaluations were considered non-interpretable by the CEESP, including six due to major methodological concerns and four due to major global uncertainty. Seventy-five percent of ATMP evaluations relied on single-arm clinical trials. Major methodological concerns and uncertainties primarily related to the estimation of comparative effectiveness and health-state utilities, driven by non-robust matching-adjusted indirect comparisons (MAICs), immature clinical data, utility estimates based on small sample sizes, and uncertainty regarding long-term outcomes. Gene and cell therapies appeared more frequently affected by major methodological concerns or uncertainty than CAR-T therapies.
CONCLUSIONS: The findings suggest that many methodological concerns identified in ATMP evaluations stem from evidence limitations that are often unavoidable in rare diseases. As comparative effectiveness and health-state utility estimates frequently rely on indirect evidence and small patient populations, methodological requirements may need to better reflect these constraints. Strengthening real-world evidence generation may also help reduce residual uncertainty and ensure that economic evaluations effectively support healthcare decision-making.