Trends Underlying Positive and Negative Decision-Making for New Treatments Targeting Rare Diseases (RD) Appraised by the National Institute for Health and Care Excellence (NICE) in 2023

OBJECTIVES: Value demonstration in RD is complex due to challenges in data collection, impacting patient access to potentially effective treatments. This research aimed to identify trends underlying positive and negative decisions for treatments targeting RD in England to anticipate potential challenges in future submissions.

METHODS: NICE technology appraisals for medicines with orphan designation published in 2023 were identified. Pre-defined topics, including NICE recommendation, clinical and economic evidence submissions, and decision drivers, were extracted by a single reviewer with spot checks by a second reviewer.

RESULTS: NICE published guidance on 27 medicines with orphan designations in 2023. Although 81% were recommended (22/27), only 59% of these were recommended in line with EMA marketing authorization (13/22). Of those experiencing indication restrictions (41%;9/22), most (78%;7/9) were restricted to a specific patient subgroup by age, disease stage, treatment contraindications, or performance measure. 67% (6/9) of restricted indication treatments were critiqued for clinical data uncertainty (long-term benefit, size of treatment benefit, potential bias) compared to only 38% (5/13) of treatments recommended in line with the EMA indication. Many of the full EMA indication recommendations critiqued for uncertainty were dependent on a managed access agreement (MAA;3/5;60%). Only 1 medicine was recommended according to marketing authorization, without the use of a MAA or discount patient access scheme. This submission included evidence from 5 Phase 2-3 studies demonstrating a similar benefit to standard of care while offering a comparable cost and reduced administration burden.

CONCLUSIONS: The uncertainty inherent in RD affects the likelihood of a positive, unrestricted recommendation due to the impact of uncertain clinical data on the reliability of cost-effectiveness estimates. Population restrictions alongside MAA and discounts allow decision-makers to accommodate a degree of uncertainty, supporting patient access. However, there is a need to optimize the evidence base to achieve unrestricted access at a price reflective of the product’s value.