OBJECTIVES: There is significant variation in HTA initiatives implemented for orphan drugs across Europe which has a direct impact on pricing and reimbursement (P&R). We reviewed these initiatives to understand the differences influencing HTA decisions on orphan drugs in European markets.

METHODS: The HTA and P&R pathways in France, Germany, Spain, Italy and UK were reviewed through the relevant organisation websites, with 10 qualitative 1:1 interviews conducted with national and regional experts representing the EU5 to provide details on funding routes, evidence requirements, and pricing negotiations

RESULTS: Some European markets have implemented formal processes to support the assessment of orphan drugs. In the UK a drug is labelled as a highly specialised technology if the treatment population is below <1 in 50,000 and NICE then assesses the effectiveness, safety, and broad cost comparisons rather than utilising cost-effectiveness criteria. In Germany orphan drugs are automatically granted ‘additional benefit’ following marketing authorisation; however, the extent of the benefit is still assessed by the G-BA. Alternatively, some markets (including Italy and France) have not introduced orphan-specific initiatives to date and subsequently orphan drugs are reviewed through the usual P&R pathways, but may be subject to a tailored procedure. Expectations are less stringent regarding clinical or economic evidence and there is greater flexibility for the trial design and the number of patients to enrol due to the small patient population. Furthermore, markets have variable economic thresholds for orphan drugs. In the UK, for example, highly specialised technologies are now being assessed against a maximum threshold of £300,000 per QALY.

CONCLUSIONS: There is a common trend across Europe to streamline HTA processes for orphan drugs. Some markets have implemented formal processes, whereas other markets unofficially adjust evidence requirements. Nuances between markets need to be understood by orphan drugs’ manufacturers in order to achieve optimal P&R.