OBJECTIVES: Indirect treatment comparisons (ITCs) provide valuable insights into clinical effectiveness, adjunct or in absence of direct evidence, aiding informed decision-making and demonstrating clinical benefit against market-specific comparators. This study aimed to highlight the prevalence of different ITC methodologies in oncology drug submissions to authorities worldwide and assess how widely ITCs are considered as clinical evidence in regulatory approval, reimbursement recommendations, or price implications.

METHODS: In July 2023, a targeted literature review was conducted to identify assessment documents for oncology drug submissions that included ITCs as a source of comparative evidence. This involved manually searching websites of four regulatory bodies (EMA, FDA, Health Canada, and TGA) and four HTA agencies (CADTH, PBAC, HAS, and G-BA) across North America, Europe, and Asia-Pacific for publicly available documents published since 2021 in English.

RESULTS: In total, 185 documents were included. Among these, 188 unique recommendations/decisions were given, and 305 ITCs were evaluated. Although the impact of the recommendations/decisions depends on the authority’s mandate, most were positive (67%), with 30% being negative and 3% deferred. A wide variety of methods were included in submissions, and their proportions aligned with those that were ultimately considered or appraised when making the final recommendation/decision. Given their potential for minimizing bias, authorities more frequently considered results derived from NMAs and MAICs. In contrast, naïve or unadjusted comparisons received significant criticism due to challenging interpretability and susceptibility to bias from confounding factors, which reduces confidence in the results.

CONCLUSIONS: Numerous ITCs in oncology drug submissions have been considered or appraised by various authorities worldwide to inform regulatory approval, reimbursement recommendations, or price implications. Although some methods are preferred over others, the suitability of the ITC method is primarily defined by uncontrollable factors (i.e., data sources, available evidence, and magnitude of benefit/uncertainty) as well as specific local requirements.