Presentation (CTI)

OBJECTIVES: Single-arm trials are increasingly used to support HTA submissions, particularly in oncology and rare diseases. Despite literature describing the potential for synthetic approaches to innovate clinical trial design, the real-world application of such techniques in payer submissions remains unclear. This study aimed to explore the methods used to supplement single arm trial data in HTA submissions in England.
METHODS: All technology appraisals published by NICE from May 2023 to May 2025 were screened to identify submissions based on single-arm trials. Final guidance and committee papers were then reviewed in detail to identify the approaches used to provide comparative effectiveness and NICE reactions to those data.
RESULTS: Of the n=156 technology appraisals screened, n=30 presented a single-arm trial as the primary source of efficacy/safety data. Of these, n=7 involved a synthetic control arm. Only two appraisals including synthetic control arms relied on real-world evidence alongside the pivotal single-arm trial; otherwise, clinical inputs for comparator arms were derived from clinical trials using statistical methods, most commonly propensity score matching. Appraisals not including synthetic control arms mostly relied on statistical adjustments to allow matching-adjusted indirect comparisons, naïve indirect comparisons, or both. No appraisals explicitly mentioned the use of machine learning algorithms or artificial intelligence.
CONCLUSIONS: While the potential benefits of innovative techniques like synthetic control arms are widely discussed in the literature, our analysis suggests that standard indirect treatment comparison methods, such as matching-adjusted indirect comparisons, remain the dominant approach for generating comparative evidence in NICE submissions involving single-arm trials. More assessments and further experience of HTA body perspectives are required to determine if the theoretical benefits of synthetic approaches can be realized in practice.