OBJECTIVES: Reimbursement decisions made by NICE or SMC may result in differential patient access to orphan medicines in the UK. This study identifies instances where NICE and SMC recommendations related to EMA-authorised medicines for rare diseases differ, and investigates the reasons for such differences.

METHODS: EMA-authorised medicines for rare diseases were identified and categorised based on availability of NICE and SMC assessments. For completed assessments with differing decisions, available guidance documents were reviewed to establish the factors influencing the decision-makers’ judgements on value-for-money, including: robustness of clinical and cost-effectiveness evidence; plausibility of inputs and assumptions; range and plausibility of the ICERs; levels of uncertainty; patient access schemes (PAS’s); and modifiers considered for decision-making.

RESULTS: From 96 EMA-authorised medicines for rare diseases, 23 had completed assessments by both agencies, 5 with differing recommendations. Four medicines were recommended by NICE and rejected by SMC; the opposite for the remaining medicine. Factors related to positive NICE recommendations included supplemental clinical and cost-effectiveness evidence presented during the appraisals to reflect decision-makers’ preferred approaches. Companies offered PASs for four medicines, and further financial arrangements were agreed as part of managed access agreements (MAAs) for two medicines. Rejections by SMC were related to uncertainty and high costs compared to health benefits, while the NICE rejection was related to lack of cost-effectiveness. An improved PAS and the evidence provided by the Patient and Clinician Engagement (PACE) process seemed key for the acceptance of one medicine by the SMC and not by NICE.

CONCLUSIONS: Among orphan medicines with opposing recommendations between NICE and SMC, factors linked to positive NICE recommendations included: flexibility to present supplemental data and economic analyses during the appraisal; and agreed PASs and MAAs. The SMC’s acceptance of one orphan medicine seemed mainly related to an improved PAS and the consideration of PACE.