A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

Background: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reim‑bursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reim‑ bursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). Methods: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the feld of rare diseases (6 hysicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defned the fnal list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical fnancing scenarios. A multinomial logit model was ftted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process.Results: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and eco‑nomic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efcacy (14.64%), vailability of treatment alter‑natives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%),safety (serious‑ness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining crite‑ria had a<3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-efectiveness (0.83%) and safety (frequency of adverse events) (0.03%).Conclusion: The reimbursement of OMPs in Spain should be determined by its efect on patient’s HRQL, the extent of its therapeutic beneft from efcacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also infuence the decision along with the potential of the treatment to avoid associated costs.This project was carried out with an unrestricted grant from AELMHU (Aso‑ciación Española de Laboratorios de Medicamentos Huérfanos y Ultrahuér‑fanos). AELMHU was not involved in the design of the study and collection, analysis, and interpretation of data and writing the manuscriptYe