Presentation (CTI)

OBJECTIVES: To assess how cost-effectiveness outcomes differ depending on whether the ICER is calculated against the comparator used in the pivotal trial (direct comparison) or an alternative treatment (indirect comparison), focusing on ASMR III evaluations in France.
METHODS: A retrospective analysis was conducted on CEESP evaluations published since 2014 for medicines with an ASMR III rating. Only valid assessments, without major methodological reservations or global uncertainty, were included. The analysis covered drugs evaluated for initial market access or indication extension, excluding pediatric-only uses. Evaluations were classified by comparator type: trial-based (direct) or external (indirect). Outcomes included ICER in €/QALY, delta QALY, delta life-years (LY), and delta cost. Mann-Whitney U tests were used to compare distributions between groups (N=45; 35 direct, 10 indirect), with a significance threshold set at α = 0.05.
RESULTS: ICER values showed greater dispersion in the indirect group (median €118,914; SD €203,378) than direct (median €93,519; SD €107,126), although the difference was not statistically significant (p = 0.135). Delta QALY was significantly higher and more consistent in the direct comparison group (median = 0.58, SD = 0.47) than indirect (median = 0.31, SD = 0.99; p = 0.005), partly explaining the ICER variability. High ICERs in indirect comparisons may reflect the use of comparators with higher clinical efficacy than the trial control, mechanically reducing the incremental benefit. No significant differences were found for delta LY (p = 0.34) or delta cost (p = 0.70), though costs > €1M occurred only in the direct group.
CONCLUSIONS: Variations in ICERs between direct and indirect comparisons reflect structural differences in comparator availability. Introducing a reference ICER value in France without accounting for this may disproportionately penalize indications with multiple alternatives or concurrent developments. A more nuanced integration of comparator context into cost-effectiveness interpretation is essential to ensure fair and coherent HTA-based pricing decisions.