OBJECTIVES: Orphan Drugs (OD) treat a variety of aetiologically different disorders, which are characterised by low prevalence. Therefore, ODs are an interesting case study from a health technology assessment (HTA) perspective. This research aims to explore recently appraised ODs by HTA bodies (HTABs) in England, Scotland and France, to identify key drivers behind their recommendations.

METHODS: All ODs granted with a European marketing authorisation (MA) between 1^st January 2015 and 30^th April 2017 were identified. Corresponding appraisals from the National Institute for Health and Care Excellence (NICE), the Scottish Medicines Agency (SMC) and the Haute Autorité de Santé (HAS) were identified, reviewed and final decisions were extracted.

RESULTS: A total of 39 MAs for ODs were identified. Consequently, 41 appraisals encompassing 24 ODs were extracted across NICE, SMC and HAS. NICE recommended 5 (86%) out of 7 ODs appraised, SMC recommended 9 (69%) out of 13 ODs appraised and HAS recommended 19 (90%; SMR important or moderate) out of 21 ODs appraised. The main drivers behind OD recommendations by all three HTABs were clinical effectiveness and high unmet need. Furthermore, NICE and SMC considered patient access scheme (PAS) for all the recommended drugs. Additionally, a post-marketing study for 7 of the recommended ODs was requested by HAS. While the main drivers behind lack of recommendations by NICE and SMC were lack of cost-effectiveness and sufficiently robust economic analysis, HAS indicated lack of acceptable methodology to demonstrate efficacy and relevant endpoints, absence of comparator and safety issues.

CONCLUSIONS: Overall, all three HTABs tend to evaluate ODs favourably and have mechanisms to facilitate access, namely PASs (NICE, SMC) and early access through temporary authorisation of use (HAS). NICE and SMC recommended less ODs than HAS due to emphasis on cost-effectiveness. Nonetheless, recommended ODs need to undergo economic negotiation to access French market.