BACKGROUND: One-third of medicines pending European Commission decision are Orphan Drugs (OD). The increase in Marketing Authorizations (MA) is challenging for the Health Technology Assessment (HTA) agencies who often deal with high uncertainties of ODs evidence package.

OBJECTIVES: This study aims to examine disparities in HTA decision-making for ODs, as issued by two prominent European agencies employing distinct decision-making processes. One agency, the Haute Autorité de Santé (HAS) in France, adopts a clinically driven approach, while the other, the Scottish Medicines Consortium (SMC) in Scotland, follows an economically driven model.

METHODS: The European public assessment reports (EPARs) database was screened to identify ODs approved between 2018 and 2022. HAS reports for these ODs were extracted then the corresponding SMC report for the same indication was examined.

RESULTS: A total of 30 ODs with HAS and SMC reports were identified. The HTA decisions were consistent between the two agencies in 70% of cases (18 recommendations and 5 restrictions). Ten indications were subject to disparities between the agencies (HAS recommended/SMC not recommended (N=1); HAS recommended/SMC restricted (N=1); HAS restricted/SMC not recommended (N=1); HAS restricted/SMC recommended (N=7)). Overall, the HAS recommended all assessed indications for reimbursement, while SMC did not recommend two for use within the NHS for being not-cost effective despite considering decision modifiers.

CONCLUSIONS: HTA recommendations differ between the two agencies. In France, the focus primarily centers on clinical evidence alongside disease severity and unmet need. Conversely, the Scottish agency's decision depends on the drug's cost-effectiveness, considering decision modifiers.