Uncovering the Hidden Rare Disease Gap within NICE Appraisals

OBJECTIVES: Orphan medicines that miss out on the National Institute for Health and Care Excellence’s (NICE’s) Highly Specialised Technologies (HST) programme are instead assessed by the Single Technology Appraisal (STA) programme which uses a lower cost-effectiveness threshold. Interestingly, previous research has found no significant differences between the proportion of positive NICE STA recommendations for orphan and non-orphan medicines despite the unique challenges faced by orphan medicines. This research aimed to investigate this further by evaluating NICE recommendations for orphan medicines when controlling for different confounding variables.

METHODS: STAs published within the study period (July 2016–January 2022) were identified. Terminated appraisals were excluded. Data including appraisal type, date, decision outcome, end-of-life criteria and orphan status were extracted for each STA. Analysis was conducted to compare decision outcomes.

RESULTS: Orphan and non-orphan STAs had negative recommendation rates of 7.04% and 9.61%, respectively. However, within orphan medicines, non-cancer medicines fared considerably worse than cancer medicines with negative recommendation rates of 13.33% and 5.36%, respectively. When subsequently focusing on cancer medicines, it was identified that 100% of orphan medicines meeting end-of-life criteria (£50,000/quality-adjusted life-year [QALY]) achieved a positive recommendation. When cancer medicines were then excluded, orphan medicines had a negative recommendation rate 2.7 times higher than for non-orphan medicines (13.33% versus 4.85%).

CONCLUSIONS: This research provides evidence of a ‘rare disease gap’ for non-cancer orphan medicines, previously masked by the inclusion of cancer medicines. In 2022, the end-of-life criteria was replaced with a new severity modifier and therefore future work should evaluate the success of this and the new Innovative Medicines Fund (IMF) in reducing inequity in access for orphan medicines. This research also demonstrated that the end-of-life criteria (£50,000/QALY) has potentially influenced access for orphan cancer medicines. Therefore, a higher cost-effectiveness threshold for rare diseases outside of the HST programme might help reduce the ‘rare disease gap’.