What Drives the Limited Scope of French National Authority for Health (HAS) Economic Opinions for Rare Diseases in France?

OBJECTIVES: Innovative treatments of Rare Diseases (RD) expected to have a significant impact on healthcare expenses must be assessed through an economic evaluation reviewed by the French National Authority for Health (HAS). We conducted an analysis of the methodological aspects resulting in significant uncertainties and major methodological reservations (MR) from HAS.

METHODS: We reviewed economic opinions published by the HAS in 2020 and 2021, focusing on cost-effectiveness analyses (CEAs), and analysed the MR formulated in the context of CEA’s main methodological choices and the products’ clinical trial data available.

RESULTS: Thirteen CEAs in eleven indications (25% of HAS’ opinions in 2020-2021) were identified with ICERs ranging from €50K to €2.5M/QALY. HAS issued major MR in 3 cases but concluded that the scope of results was limited or that they were uninterpretable in 7 other cases, thus limiting their impact on pricing negotiations in 90% of cases.

Although lacking robust and/or mature clinical data to model and extrapolate treatment effect was a key determinant of these reservations, lacking evidence on the RD landscape (appropriate definition of the analysed/reimbursed population; natural history of the disease and efficacy of standard of care, allowing robust indirect comparisons; lacking costs and utility data) was a bigger hurdle to the acceptability of the dossiers, preventing accurate modelling of the disease and validation of modelled outcomes in the population where the products demonstrated value and will be used.

CONCLUSIONS: HAS’ expectations towards RD and treatment effect modelling for France require vast amounts of evidence on the indication landscape. Innovative treatments for RD are particularly suited for pre- and post-marketing authorisation early access programmes in France. Manufacturers should leverage such programmes to generate data informing cost-effectiveness models through clinical development and real-world evidence generation in order to improve opinions’ scope and help leverage health-economics rationale in pricing negotiations.