Causally-interpretable meta-analysis: clearly-defined causal effects and two case studies

Abstract

Meta-analysis is commonly used to combine results from multiple clinical trials, but traditional meta-analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently-introduced causally-interpretable meta-analysis methods and apply their treatment effect estimators to two individual-participant data sets. These estimators transport estimated treatment effects from studies in the meta-analysis to a specified target population using individuals' potentially effect-modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated-data meta-analysis methods. In our applications, certain versions of the causally-interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally-interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally-interpretable approach gives meta-analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.