Choice and impact of EQ-5D-5L value set in cost-utility analyses alongside multinational trials: Insights from PREFERABLE-EFFECT and CONVINCE

Objectives: Multinational clinical trials are increasingly common in the European Economic Area, yet no guideline exists on which EQ-5D value set(s) should be used for health economic evaluations alongside multinational trials. Either a single value set or country-specific value sets can be applied, and previous studies have shown that the choice of value set can impact the estimated utility scores. For the EQ-5D-5L, the impact on European pooled cost-utility analyses has not been established. This study evaluates the impact of EQ-5D-5L value sets on cost-utility outcomes in two multinational trials. Methods: Data from two multinational randomized controlled trials were used: (i) supervised exercise compared to usual care for patients with metastatic breast cancer (PREFERABLE-EFFECT), (ii) hemodiafiltration compared to hemodialysis for patients with kidney failure (CONVINCE). EQ-5D-5L was assessed at baseline and during follow-up. Utility scores and quality-adjusted life years (QALYs) were calculated with the country-specific value set for each participant, and with the value set of each included country. The probability of cost-effectiveness was estimated using bootstrapping. Results: Mean assigned utility scores per year alive ranged between 0.762 and 0.889 for PREFERABLE-EFFECT, and 0.673 and 0.806 for CONVINCE. The difference in utility scores is largest when participants report low quality of life. Estimated QALY gains ranged between 0.013 and 0.020 for PREFERABLE-EFFECT and 0.045 and 0.058 for CONVINCE. The maximum difference in probability of cost-effectiveness between the value sets was Δ8.3% at €80,000/QALY in PREFERABLE-EFFECT, and Δ11.1% at €40,000/QALY for CONVINCE. Conclusions: Choice of value set led to substantial variation in absolute utility scores and QALYs, which may influence cost-utility outcomes. This impact could be greater when an intervention prevents or aids recovery of health conditions associated with low quality of life, or results in large mortality differences. Scenario analyses using multiple value sets should be conducted for multinational trials.