The impact of statistical properties of incremental monetary net benefit and incremental cost-effectiveness ratio on health economic modeling choices

Abstract

ABSTRACT Introduction There is controversy on whether to use incremental monetary net benefit (INMB) or incremental cost-effectiveness ratio (ICER) in health economic evaluations alongside randomized controlled trials. We studied the impact of restricted mean survival time (RMST) on the long-term projection of INMB and ICER. Methods We analyzed the unbiasedness and efficiency of ICER and INMB by (1) deriving the metrics' expected values and variances based on theoretical probability distributions, (2) simulating their 15-year post-trial projections based on between-arm-RMST-gained through a 2 × 4 × 2 factorial experiment of Markov 2-state microsimulations. Simulations and comparison were run on the data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Results Our simulation findings using RMST showed that ICER was more efficient than INMB, regardless of disease populations, time horizon, modeling choices, and underlying probability distributions of incremental mean cost and effect. ICER had a small variance and thus showed its robustness to the choices of models. Conclusion INMB is unbiased, while ICER is biased-but-remediable. INMB’s variance varies with a willingness-to-pay (WTP) threshold value quadratically while ICER’s variance varies with incremental-mean-cost quadratically. A simple and naïve model can sufficiently estimate ICER. Future metrics are expected to be health-economic-meaningful, unambiguous, unbiased, efficient, and statistical-inference-friendly.