To evaluate methodological challenges and regulatory considerations of indirect treatment comparisons (ITCs) with the analysis of French Transparency Committee (TC) decisions and international health technology assessment guidelines.
We conducted a pragmatic review of ITC guidelines from major health technology assessment bodies and analyzed 138 TC opinions containing 195 ITCs published between 2021 and 2023. We extracted data on ITC methodology, therapeutic areas, acceptability, and limitations expressed by the TC.
ITC submissions increased by 44.7% over the study period, but only 13.3% of these comparisons influenced TC decision making. ITCs were more frequently accepted in genetic diseases (34.4%) compared with oncology (10.0%) and autoimmune diseases (11.1%). Methods using individual patient data showed higher acceptance rates (23.1%) than network meta-analyses (4.2%). Main limitations included heterogeneity/bias risk (59%), lack of data (48%), statistical methodology issues (29%), study design concerns (27%), small sample size (25%), and outcome definition variability (20%). When ITCs were the primary source of evidence, the proportion of important clinical benefit was lower (60.9% vs 73.4%) than when randomized controlled trials were available.
Although ITCs are increasingly submitted, particularly in situations in which direct evidence is impractical, their influence on reimbursement decisions remains limited. There is a need for clear and accessible guides so that manufacturers can produce clearer and more robust ITCs that follow regulatory guidelines, from the planning phase to execution.