The very high costs of orphan drugs, together with the uncertainties regarding their (cost-)effectiveness raise questions regarding the efficiency and legitimacy of their health technology assessment (HTA) and appraisal process. The aim of the present, qualitative study was to investigate how experts on the reimbursement of these treatments perceive the HTA and appraisal process in their country. Moreover, it aimed to provide specific conditions and practical recommendations for their improvement.

Twenty-two European experts from 19 different countries were included in a qualitative survey and semi-structured interviews. Transcripts were analyzed using the qualitative data analysis software Nvivo. A grounded theory approach was adopted to develop a set of well-defined concepts from the cyclic analysis of the empirical data.

First, analysis of the expert interviews yielded five good practices for an efficient HTA and appraisal of orphan drugs: a high level of transparency, patient involvement, a clear decision-making structure with room for flexibility, mechanisms to minimize bias and an explicit consideration of the opportunity cost. Meanwhile, participants highlighted several barriers to the overall process, such as a lack of trust between the different stakeholders and imbalances in negotiation power. In addition, the results allowed to identify a number of ‘contextual’ determinants that may undermine the legitimacy of the final decision, such as bias and the perverse effects of the orphan drug legislation. Drawing from the experts’ experiences, a toolkit was developed that includes an extensive number of specific recommendations (and conditions) for decision-makers to improve the legitimacy and efficiency of their HTA and appraisal of orphan drugs.

Overall, the results showed that decision-makers should focus on limiting the impact of the contextual determinants rather than improving the methods included in the HTA. This will contribute to further legitimize reimbursement choices for orphan drugs towards the wider public.