Presentation (CTI)

OBJECTIVES: Single-arm trials (SATs) present methodological challenges due to possible biases and a lack of comparative data. Nonetheless, SATs are employed in specific contexts, such as rare diseases or when randomised controlled trials are impractical or unethical. This review examines the acceptance of SATs in health technology appraisal (HTA) evaluations by four HTA agencies: National Institute for Health and Care Excellence (NICE) in England, Canadian Agency for Drugs and Technologies in Health (CADTH), National Centre for Pharmacoeconomics (NCPE) in Ireland, and Haute Autorité de Santé (HAS) in France.
METHODS: A systematic review analysed appraisal reports for 229 drugs with decisions made in 2024 from NICE (n=82), CADTH (n=87), HAS (n=32), and NCPE (n=28). The study reviewed characteristics of the drugs and disease areas that utilised SATs and examined mitigation strategies implemented by manufacturers to address the absence of a control arm within pivotal studies.
RESULTS: The review identified 35 SATs (15.3%) in the combined analysis, split near-equally between orphan (48.6%) and non-orphan (51.4%) drugs. A key theme in the acceptance of SATs was the use of indirect treatment comparisons (ITCs). Most submissions (88.6%) utilised an ITC, with unanchored matching-adjusted indirect comparisons being the predominant method (70.6%). Other methods included naïve comparison (17.6%), unanchored simulated treatment comparisons (8.8%), and synthetic control arms (2.9%). Reimbursement rates of studies employing SATs varied, with 42.9% achieving reimbursement, 48.6% achieving reimbursement with conditions, and 8.6% not achieving reimbursement in the relevant country.
CONCLUSIONS: SATs can be accepted in HTA evaluations when robust methods, such as ITCs, address the absence of a control group. However, acceptance often depends on conditions such as price adjustments or a narrowed population. Aligning evidence generation strategies with the forthcoming EU HTA guidance is essential, including by carefully selecting of ITC methods and justifying SAT-based evidence, to optimise outcomes in EU joint scientific consultations.