Presentation (CTI)

OBJECTIVES: For interventions with plausible potential to be cost-effective despite clinical and/or economic uncertainty, NICE managed access agreements (MAAs) and SMC ultra-orphan evidence generation periods provide interim access conditional on additional data collection to resolve uncertainties. Evidence generation in rare diseases is constrained by small populations, less conventional study designs and poorly established outcomes, among other challenges. Therefore, we explored whether conditional access periods allow key evidence gaps to be addressed to support routine reimbursement in rare diseases.
METHODS: NICE highly specialised technology (HST) MAA exit appraisals and SMC ultra-orphan reassessments published between January 2022 and May 2026 were identified; appraisals with accessible entry and exit documentation were selected. Key conclusions on changes to the evidence base between entry and exit were extracted.
RESULTS: Eight NICE HST and SMC ultra-orphan exit appraisals were identified. Two SMC and three NICE exit appraisals with corresponding conditional access entry documentation were selected for analysis, with a mean duration of 50 months (range: 10−80) between entry and exit. At entry, principal uncertainties were the lack of evidence for long-term treatment effects and implications for modelling long-term disease progression. Real-world evidence, collected as part of the conditional access or conducted separately, largely reduced the uncertainties. Committees explicitly noted uncertainty remained around long-term treatment effects in two appraisals, although this did not prevent routine reimbursement. Only one appraisal was not approved for routine reimbursement at exit, resulting from commercial considerations rather than persisting uncertainty.
CONCLUSIONS: Only one of five re-appraisals did not achieve routine reimbursement at conditional access exit, suggesting that uncertainty can sufficiently be resolved within current conditional access timelines for rare diseases. Positive re-appraisals were generally based on new or longer-term data becoming available. However, the high rate of positive re-appraisal suggests conditional access agreements may be preferentially applied to technologies already expected to achieve routine reimbursement.