OBJECTIVES: The use of an investigator-choice comparator (ICC) arm is increasing in clinical trials. This approach is supported by regulators in both the US and the EU when a single reference treatment cannot be identified and all ICC options have regulatory approval. The objective of this study was to establish whether the use of an ICC influenced recommendations by the National Institute for Health and Care Excellence (NICE).

METHODS: A published literature review of studies conducted between 2007 and 2021 identified 92 oncology trials with a physician's choice comparator or ICC. All NICE assessments related to those treatments were identified and reviewed to identify whether the use of an ICC arm influenced the final recommendations.

RESULTS: Of the 92 trials, 11 (12%) had been assessed by NICE between 2016 and 2023, with increasing frequency in more recent years. In 7 of these assessments, the ICC was a chemotherapy; the other studies included other therapies in the ICC arm.

Only one assessment resulted in a “not recommended” outcome from NICE (chemotherapy-only ICC arm) and one therapy (with a more complex ICC arm) was made available through the Cancer Drugs Fund. Five therapies were granted unrestricted access, despite criticisms that the ICC arm did not reflect clinical practice in two cases. Four treatments were recommended with restrictions; NICE questioned whether choices made by investigators as part of the ICC arm would align with UK clinical practice.

CONCLUSIONS: ICC arms in clinical trials are becoming more common and can allow various choices. NICE has recommended unrestricted or restricted access for several treatments with pivotal trials that included ICC arms, despite raising concerns about the generalizability and representativeness of the choices. As more data become available, the influence of this factor on assessment outcomes should be further explored in the UK and other markets.