OBJECTIVES

: Studies of orphan drugs typically have inferior clinical evidence compared with treatments in common diseases. This can lead to uncertain cost-effectiveness modelling and difficulties for payers to determine whether an orphan treatment provides value for money. This research aims to identify challenges in cost-effectiveness modelling of rare disease treatments within the United Kingdom (UK) and the United States of America (USA) by reviewing National Institute for Health and Care Excellence (NICE) highly specialised technologies (HST) appraisals and Institute for Clinical and Economic Review (ICER) value assessments.

METHODS

: NICE HST guidance and ICER assessments were searched without time limitation through January 15, 2020. While all NICE HST appraisals were included in the analysis, ICER assessments were included only if an indication qualified as a rare disease following the definition of the Rare Disease Act of 2002. Submission documents were then screened in a peer-reviewed process.

RESULTS

: Twelve NICE HST appraisals and three ICER value assessments in various indications were identified. Across all NICE HST appraisals, limited and uncertain clinical data was the most prevalent issue (12/12). Similarly, all ICER value assessments identified showed limited and uncertain clinical data (3/3). Challenges with quality of life (QoL) assessment was the second most common issue in NICE HST appraisals (7/12) and ICER value assessments (1/3). Less common were technical challenges in cost-effectiveness modelling such as capturing all important aspects of a rare disease within the model structure and difficulties with statistical analysis of trial evidence. Despite these challenges, most NICE HST appraisals resulted in a positive guidance recommendation.

CONCLUSIONS

: Cost-effectiveness modelling of rare disease interventions has several challenges such as limited and uncertain trial data, QoL assessment and technical modelling challenges. NICE has given positive guidance recommendation for most orphan treatments to date contingent upon commercial arrangements with manufacturers reflecting the decision uncertainty.