Louise Baschet | Searcharxiv

arXiv2026

Indirect Comparisons For Health Technology Assessment: A Practical Methodological Guide And Tips With Insights From The French Transparency Commission

Context: Indirect treatment comparisons (ITC) are essential when direct head-to-head evidence is unavailable. Their reliability depends on rigorous methodological choices and careful assessment of underlying assumptions. Appropriate methodological choices can help address challenges such as cross-country variations in treatment practices, ethical constraints, and evolving treatment landscapes during trial conduct. This opinion and perspective paper provides practical guidance to strengthen the quality, robustness and accuracy of ITCs in the context of health technology assessment (HTA) in France. Methods: A panel of experts in ITCs and French market access environment developed the present strategic guidance, informed by previous work reviewing HTA methodological guidelines and complemented by a systematic review of Transparency Committee opinions from the French National Authority for Health (HAS). Results: Key considerations include early anticipation of ITCs, justification of potential confounding factors, and rigorous assessment of similarity and transitivity in randomized trial-based comparisons. In network meta-analysis, the structure of the evidence network should be adapted to the specific decision context. Population-Adjusted Indirect Comparisons require careful reporting and interpretation of the effective sample size. When evidence relies on non-randomized clinical trials, comparisons between single-arm studies and external control arms may be appropriate under different scenarios, depending on the feasibility of conducting subsequent randomized studies. Conclusions: Robust and reliable ITCs require methods consistent with the validity of their assumptions and the strength of the available evidence. This practical guidance supports the development of rigorous ITCs to inform decision-making in complex medical contexts where direct comparisons are not feasible.

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arXiv2025

Methodological Advances and Challenges in Indirect Treatment Comparisons: A Review of International Guidelines and HAS TC Case Studies

To evaluate methodological challenges and regulatory considerations of indirect treatment comparisons (ITCs) with the analysis of international health technology assessment guidelines and French Transparency Committee (TC) decisions. We conducted a pragmatic review of ITC guidelines from major health technology assessment (HTA) bodies and multistakeholder organizations. Then, we analyzed TC opinions published between 2021-2023. We extracted data on ITC methodology, therapeutic areas, acceptability, and limitations expressed by the TC. The targeted review of the main guidelines showed mainly agreements between HTA bodies and multistakeholder organizations, with some specificities. 138 TC opinions containing 195 ITCs were analyzed. Only 13.3% of these ITCs influenced TC decision-making. ITCs were more frequently accepted in genetic diseases (34.4%) compared to 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. While ITCs are increasingly submitted, particularly where direct evidence is impractical, their influence on reimbursement decisions remains limited. There is a need for clear and accessible guides so manufacturers can produce clearer and more robust ITCs that follow regulatory guidelines, from the planning phase to execution.

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