Assessment of Indirect Comparisons by the HAS Transparency Commission (TC) in France: Systematic Overview and Insights

OBJECTIVES: The increasing number of clinical studies under development for innovative drugs in the same therapeutic area with constantly changing standards of care have increased the necessity to use indirect treatment comparisons (ITCs) to prove a benefit towards standard of care. This work aims to report the characteristics of ITCs that led to an acceptance as well as reasons for rejection by the French HTA body.

METHODS: All evaluation reports containing at least one ITC presented to the Transparency Commission (TC) of the Haute Autorité de Santé (HAS) between January 1, 2021, and December 31, 2023 were systematically screened. The selection of variables to characterize the ITC was the result of preparatory work, where a rigorous review of HTA guidelines was conducted to take into account the evolving changes in the field of ITCs.

RESULTS: Among 1,218 evaluations reviewed, 138 included at least one indirect comparison (for a total of 195 ITCs). The most frequently encountered methods were Network Meta Analysis, weighted approaches (IPTW, SMRW), and population-adjusted methods (MAIC, STC).

13.4% of ITCs were identified as having been taken into consideration by the TC, of which 3.1% were deemed acceptable without limitations and 10.3% were deemed acceptable with limitations. No clear correlation could be confirmed for the impact of the ITC on the finale HTA assessment on SMR, ASMR or the place in the therapeutic strategy.

ITCs conducted in the context of pediatric, rare and genetic diseases had a higher likelihood of acceptance. The main limits highlighted were the heterogeneity / risk of bias, poor data quality, and restrictions in study design.

CONCLUSIONS: In recent years, an increasing number of ITCs have been submitted to TC and supported favorable TC assessments. However, they often entail limitations that could have been anticipated or mitigated.