OBJECTIVES : Since economic evaluation is required for innovative drugs in France, 97 efficiency opinions were published by the French Health Technology Assessment “HAS/CEESP” between February 2014 and May 2019. Efficiency opinions focus on the methodological consistency of the dossier in reference to the HAS guidelines , towards a three-level scale limitations including minor, important and major limitations on the structural choices, clinical data presented and main assumptions. A major objection leads to the invalidation of the dossier. This analysis aims to describe the determinants of important and major limitations from the CEESP.

METHODS : For each of the 97 efficiency opinions, all limitations were extracted and analyzed as well as clarification questions sent by the CEESP. Only important and major objections were described.

RESULTS : Sixty-eight major limitations were distributed among 40 opinions and 299 important objections was notified in 77 opinions. Data sources or transition probabilities led to 44% of major limitations (27/68) mostly because of a lack of robustness of clinical trial results or limited data available. Comparators and sensitive analyses represented 14% (9/68) and 13% (8/68) of major limitations respectively. Important objections were mainly associated to data sources and lack of sensitive analyses with 19% (56/299) and 18% (52/299) respectively. Only 74% (50/68) of major objections and 61% (182/299) of important objections were discussed during clarification questions.

CONCLUSIONS : This analysis highlights that avoiding major limitations could be achieved particularly with robust clinical data to feed efficiency analysis. Limitations on lack of sensitivity analyses may reflect CEESP’s preference for unrestricted number of sensitivity analyses in order to reduce uncertainty. It also appears that clarification questions do not always help identifying risks of major/important limitations limiting the possibility for companies to adjust their dossiers.