OBJECTIVES: This research aimed to identify trends underlying positive and negative decisions for emerging treatments in England.

METHODS: NICE TA and HST publications in 2023 were identified. Pre-defined topics, including NICE recommendation, clinical and economic evidence submissions, and decision drivers, were extracted with spot checks by a second reviewer.

RESULTS: NICE published guidance on 81 treatments in 2023 (TA:72,HST:9). Although 88% were recommended (71/81;TA:63,HST:8), only 49% of these were recommended in line with EMA marketing authorization (35/71;TA:31,HST:4). Of those experiencing indication restrictions (51%[36/71];TA:32,HST:4), most were to a specific patient subgroup (78%[28/36]) based on age, treatment history/contraindications, or disease-specific measures. Treatments with a restricted indication were frequently critiqued for uncertainty in clinical data (69%[25/36]; long-term/size of benefit, comparative effectiveness) and cost-effectiveness estimates (75%[27/36]). Mean time from EMA marketing authorization to NICE final recommendation was 843 days (TA:764;HST:1459). Assessments in genetic conditions (17%[14/81]) had the largest proportion of positive recommendations (93%[13/14];TA:5;HST:8; restricted indication:4). Overall, 10 treatments were not recommended, all due to lack of cost-effectiveness. Contrastingly, 11% (4/35;all TA) of treatments recommended to authorized indication were not considered cost-effective, with these provided via managed access agreements (MAA) given the substantial unmet need. While most submissions relied on evidence from Phase 3 clinical trials (78%[63/81]), three TAs were recommended based on Phase 1/2 data and an HST gene therapy was recommended based only on real-world evidence (RWE).

CONCLUSIONS: The longer time to recommendation for HSTs reflects the complexity in value assessment within rare diseases. However, the recommendation based on RWE demonstrates openness to accept innovative approaches for conditions facing data generation challenges. Recommendations with early-phase studies suggests a willingness to accept uncertainty, with use of MAA allowing patient access to treatments that do not meet HST criteria. Manufacturers should seriously consider innovative data sources to mitigate inherent uncertainties, particularly for conditions with significant unmet need.