Presentation (CTI)

OBJECTIVES: Single-arm trials are frequently used in orphan oncology because randomized controlled trials are often infeasible. However, the absence of direct comparative evidence creates uncertainty in both clinical and economic evaluations. This study compared NICE-recommended and non-recommended oncology appraisals of orphan drugs supported by single-arm trials to assess indirect treatment comparison (ITC) methodologies, economic modelling structures, External Assessment Group (EAG) critiques, and the impact of uncertainty on cost-effectiveness outcomes and reimbursement decisions.
METHODS: NICE technology appraisals (January 2021-March 2026) were screened against the MHRA Orphan Register. Of 71 orphan appraisals identified, 29 were in oncology, of which 11 based on single-arm trials met the inclusion criteria. ITC methodologies, economic modelling structures and outcomes, EAG critiques, and final NICE recommendations were extracted and descriptively summarized.
RESULTS: The 11 appraisals covered 10 therapies across 8 oncology indications; 7 (64%) were recommended. All appraisals used ITCs; most commonly matching-adjusted indirect comparison (MAIC; 8/11) with propensity score methods used in 6/11. Common EAG concerns included population mismatch (8/11), inadequate adjustment for prognostic factors (7/11), limited methodological transparency (7/11), and low effective sample sizes (6/11). For economic evolutions, partitioned survival models were used in 10/11 appraisals with survival extrapolation uncertainty was noted in almost all. Despite uncertainty in comparative clinical effectiveness across all appraisals, NICE considered it acceptable in recommended appraisals, as the estimated incremental cost-effectiveness ratios (ICERs) remained within the acceptable range for NHS England resource use. In contrast, uncertainty in non-recommended appraisals led to cost-effectiveness estimates being considered either too high or too uncertain for routine NHS use.
CONCLUSIONS: NICE decisions in orphan oncology were influenced not only by the presence of single-arm evidence but also by whether the resulting uncertainty was considered acceptable for decision making and produced cost-effectiveness estimates within acceptable thresholds. This highlights a key consideration for HTA submissions.