OBJECTIVES: The European (EU) Regulation on Health Technology Assessment will apply from January 2025. From that date, all new medicines for oncology and advanced therapy medicinal products will have their relative clinical effectiveness evaluated via an EU Joint Clinical Assessment (JCA). Between 2006 to 2021, the European Network for Health Technology Assessment (EUnetHTA) pioneered methods and procedures, fostering cross-border collaboration on joint relative efficacy assessments (REAs). Indirect treatment comparisons (ITCs) were a core element of REA submissions as they were required to evaluate the relative effectiveness against different standards of care. Extracting ITC-specific insights from EUnetHTA assessments may provide insights for understanding their impact on future EU JCAs.

METHODS: All EUnetHTA assessments including ITCs for pharmaceutical therapies were reviewed. Information related to the population/intervention/comparator/outcome (PICO), submitted ITCs methods, limitations and critiques, and relative effectiveness conclusions were gathered.

RESULTS: Between 2006 and 2021, EUnetHTA conducted 23 REAs of medicinal products, with twelve assessments including an ITC. Following the PICO scope, 64 treatment comparisons were required, with a median of four comparators per assessment (range 1-18). Direct evidence covered 17% (11/64) of the required comparisons, while 39% (25/64) relied on indirect evidence. In 44% (28/64), comparisons were not feasible. Eight Bucher ITCs and seven population-adjusted ITCs were used. Seven REAs incorporated network meta-analyses. While the acceptance level of submitted ITCs by EUnetHTA remains unclear in many assessments, the ITC results were still presented. EUnetHTA critiqued the ITCs in most assessments with respect to their indirect nature or limitations related to the underlying evidence, leading to inconclusive findings on relative effectiveness in several cases.

CONCLUSIONS: The EU HTA regulation signifies a transformative shift in evaluating medicinal products. ITCs evaluated by EUnetHTA offer valuable insights for future EU JCAs, where in order to address the PICOs, ITCs will need to be included as a relevant component of evidence.