OBJECTIVES: Ultra orphan drugs pose challenges in the health technology assessment (HTA), reimbursement, and pricing due to limited patient population and data, resulting in high decision uncertainty. Considering these challenges, we aim to examine the outcomes for ultra orphan drugs appraised by NICE, GBA, and HAS.

METHODS: All highly specialised technologies (HST) appraisals submitted to NICE between 2015 to 2023 were reviewed. The identified interventions were further searched on the GBA and HAS websites. Final recommendations along with the justification and categories for additional clinical value (Major, Considerable, Minor, Non-quantifiable, No benefit, and Less benefit for GBA and Major, Substantial, Moderate, Minor, and No improvement for HAS) were recorded. Only dossiers available in English language were considered.

RESULTS: Out of the 22 drugs appraised by NICE, 64% were fully recommended (i.e., in line with their marketing authorisation), and 36% were recommended with restrictions. All recommendations included a simple discount-based patient access scheme. There were 13 matched pairs for NICE versus GBA and of these, 23% were given Considerable/Major rating by GBA, while 62% had Non-quantifiable additional clinical benefits. Similarly, for the 18 drugs assessed by both NICE and HAS, clinical benefit was rated by HAS as Minor improvement/No improvement in 44% and as Substantial improvement in 22% submissions. Of the 10 matched pairs for all three agencies, 60% were rated Non-quantifiable by GBA while the same was considered as Minor (30%), Moderate (20%) and Substantial improvement (10%) by HAS. Overall, high uncertainty regarding the clinical effectiveness of the drugs was observed across the three agencies.

CONCLUSIONS: Despite similar clinical data, there is inconsistency in recommendations across different HTA bodies which can impact the pricing and reimbursement decisions. A Joint clinical assessment can potentially harmonise these inconsistencies and ensure equal access to innovative treatments for patients with ultra orphan diseases across Europe.