What Are the Lessons Learned From the Assessments of Economic Evaluations of Orphan Drugs Submitted by Manufacturers to the French National Authority for Health (HAS) From 2014 to 2024?

OBJECTIVES: In France, economic evaluation of innovative health products has been used in the process of price negotiation of innovative health products since 2014. This study aims to provide a comprehensive review of the economic evaluations of orphan drugs (OD) submitted by manufacturers and assessed by HAS. OD are authorized for rare diseases.

METHODS: We identified all HAS published assessments of economic evaluations (AEEs) of OD from January 2014 to February 2024. The main inputs, aspects and outcomes related to the economic analysis of OD were independently extracted by 2 economists according to a predefined checklist.

RESULTS: We analyzed 59 AEEs of OD including cost effectiveness analyses (CEAs) from January 2014 to February 2024. This represented 20% (59/306) of the total of AEEs. Among OD, the main therapeutic area was oncology (44%, 26/59) and about one fifth corresponded to Advanced Therapy Medicinal Products. Forty-four percent (26/59) of the CEAs were based on Markovian models while partitioned survival models were implemented in 36% (21/59) of the CEAs. Budget impact analyses were submitted in 44 % of the AEEs. Sixty-three percent (37/59) of the CEAs were invalidated due to major methodological limitations (MMLs) or global major uncertainty. Incremental cost effectiveness ratio varied strongly from 7 392 to 2 662 514 €/QALY. The MMLs were associated with all aspects of the modeling. The main concerns were the structure of models and its inputs (61%, 19/31) such as a lack of robust comparative efficacy data and the long-term extrapolation of intervention effect, and the estimation of health state utilities (39%, 12/31).

CONCLUSIONS: We highlighted the issues identified in the published AEEs by HAS. Further efforts for all stakeholders working with OD are needed to overcome the challenges of economic modeling induced by the scarcity of evidence and availability of clinical and quality of life data.