OBJECTIVES: Single-arm trials (SATs) are widely used to evaluate treatments for rare and orphan diseases, and for advanced and refractory cancer where conducting randomized controlled trials is not feasible or ethical. This study aims to evaluate the impact of SATs on treatment recommendations by the National Institute for Health and Care Excellence (NICE) in the UK and the Canadian Agency for Drugs and Technologies in Health (CADTH) in Canada.

METHODS: Publicly available HTA reports and recommendations for oncology drugs using SATs issued by NICE and CADTH over two years (January 2021– December 2022) were identified and reviewed. The product, indication, clinical evidence base, final recommendation, and critique by HTA around SAT were extracted by one reviewer and quality checked by the second reviewer. Eligible studies for the review were those that utilized an SAT design and did not make head-to-head to alternative treatments, placebo, or best supportive care, except when assessing different dosing regimens within the trial.

RESULTS: A total of 130 oncology-related submissions were analysed, with 54% from NICE and 46% from CADTH. The employed in approximately 12% of all oncology-related submissions, with 9 from NICE and 6 from CADTH. In NICE, 22% of submissions received recommended status, 56% were recommended with conditions, and 22% were not recommended. Conversely, all SAT-based submissions from CADTH were recommended with conditions. Among all SAT-based submissions, the most cited critiques by HTAs were concerns regarding population selection bias for external comparators, uncertainty regarding efficacy and safety, and methodological issues related to indirect treatment comparison.

CONCLUSIONS: The acceptance of submissions based on SAT is increasing by the HTA agencies. However, caution should be exercised in the methodological approach used to define the external comparator arm.