OBJECTIVES: Increasing numbers of orphan drugs are in development for treatment of rare diseases. Orphan drug studies often have lower quality evidence versus nonorphan drugs, and economic evaluations are associated with greater uncertainty, making application of general health technology assessment (HTA) rules challenging. This review identified special HTA and reimbursement considerations introduced for assessment of orphan drugs and implications for manufacturers.

METHODS: A targeted review of published literature and Internet sources was undertaken from January 2016 to April 2018 to capture the most recent information. Countries included were England, France, Germany, the Netherlands, Sweden, Scotland, and Wales.

RESULTS: Three countries (Germany, France, and Scotland), have special HTA considerations for orphan drugs. These include flexibility regarding level of evidence (Scotland and Germany) and acceptance of proven additional benefit if the annual budget impact is below a threshold (€30 million and €50 million/year for France and Germany, respectively)

Special reimbursement conditions for orphan drugs are considered in the Netherlands, where hospitals can apply for additional funding. In Sweden, the Tandvards-och Lakemedelsformansverket can take a flexible approach to reimbursement, based on level of unmet need and uncertainty, and may consider a higher cost-effectiveness threshold for orphan drugs. In Germany, there are no specific pricing considerations, but lack of therapeutic alternatives often results in a continued free-pricing approach.

In England, the National Institute for Health and Care Excellence developed guidance for ultra-orphan conditions (prevalence <1 in 50,000) under the Highly Specialised Technology Programme, where reimbursement decisions are based on broader criteria.

CONCLUSIONS: Although several European countries have introduced special considerations for assessment and reimbursement of drugs for rare diseases, evidence guidelines for orphan versus nonorphan drugs are similar. Manufacturers should utilise a range of evidence sources and techniques, including comparative real-world information, to bridge data gaps and address uncertainty to enable equitable decision-making.