Estimating target population treatment effects in meta-analysis with individual participant-level data

Meta-analysis of randomized controlled trials is commonly used to evaluate treatments and inform policy decisions because it provides comprehensive summaries of all available evidence. However, meta-analyses are limited to draw population inference of treatment effects because they usually do not define target populations of interest specifically, and results of the individual randomized controlled trials in those meta-analyses may not generalize to the target populations. To leverage evidence from multiple randomized controlled trials in the generalizability context, we bridge the ideas from meta-analysis and causal inference. We integrate meta-analysis with causal inference approaches estimating target population average treatment effect. We evaluate the performance of the methods via simulation studies and apply the methods to generalize meta-analysis results from randomized controlled trials of treatments on schizophrenia to adults with schizophrenia who present to usual care settings in the United States. Our simulation results show that all methods perform comparably and well across different settings. The data analysis results show that the treatment effect in the target population is meaningful, although the effect size is smaller than the sample average treatment effect. We recommend applying multiple methods and comparing the results to ensure robustness, rather than relying on a single method.