Review of the Economic Evaluations of Advanced Therapy Medicinal Products (ATMPs) Assessed by the French National Authority for Health (HAS)

OBJECTIVES: Economic evaluation of ATMPs submitted by the manufacturers with a claimed clinical added value (qualified as major or substantial or moderate) has become mandatory since 2023. This study aims to review all the assessments of economic evaluations (AEEs) of ATMPs published by HAS.

METHODS: We developed a checklist including the principal elements of the economic evaluations (e.g. inputs, decision models, assumptions about treatment effects and cure, results of the AEEs, identified uncertainties, methodological limitations). The extracted items were independently checked by 2 authors.

RESULTS: We identified and analyzed 15 AEEs of ATMPs with unique administration from January 2019 (date of the first evaluated ATMP) to April 2024. ATMPs were mostly gene therapy (14/15, 93%) including CAR-T-cell therapies (9/15, 60%). Only one AEE corresponded to somatic-cell therapy (1/15, 7%). The main therapeutic area was hematological malignancies (10/15, 67%). All AEEs included cost-effectiveness analyses (CEAs), with a time horizon varying from 7 to 85 years. Budget impact analyses were submitted in 67% of the AEEs. Partitioned survival models were implemented in 47 % (7/15) of the CEAs, while 40% (6/15) of CEAs were based on Markovian models. 53% (8/15) of the CEAs were invalidated due to either major methodological limitations or overall major uncertainty. Incremental cost-effectiveness ratio of validated CEAs varied from 108 833 to 351 511 €/QALY. The main reasons leading to CEAs invalidation were a lack of availability of both robust efficacy and quality of life data, and the concerns related to the extrapolation of treatment durability and cure assumptions.

CONCLUSIONS: Our review highlighted the challenges of economic evaluations of ATMPs such as the uncertainty related to the middle and long-term effectiveness of potential curative therapy. New frameworks to tackle these challenges are needed to address a suboptimal valuation of ATMPs and to facilitate price negotiation in France.