Meta-Analysis of Incremental Net Benefit from Trial-Based Health Economic Evaluations in R: A Tutorial

Systematic reviews of economic evaluations are increasingly used to inform healthcare decision making, yet approaches for a cost-effectiveness meta-analysis vary substantially, and clear methodological guidance remains limited. Differences in country income level, currency, cost reference year, analytic perspective, time horizon, and outcome measures, as well as incomplete reporting of uncertainty, complicate the pooling and interpretation of pooled cost-effectiveness estimates. This tutorial provides a structured reproducible workflow for conducting a cost-effectiveness meta-analysis of trial-based economic evaluations using the incremental net benefit framework. Step-by-step guidance is provided for harmonising costs across countries and time (using purchasing power parity and inflation adjustments, respectively), estimating or imputing missing variances of incremental costs and effects, and pooling incremental net benefits across a range of willingness-to-pay thresholds. Fully annotated R scripts and practical examples are provided to demonstrate the meta-analysis of incremental costs, effects, and net benefits, and the generation of pooled cost-effectiveness acceptability curves to depict decision uncertainty. Stratified and sensitivity analyses are described to explore contextual heterogeneity and assess robustness, respectively. By providing transparent methods and reproducible tools, this tutorial supports a more consistent and interpretable cost-effectiveness meta-analysis, while highlighting important methodological challenges.