Aggregate-data estimation of an individual patient data linear random effects meta-analysis with a patient covariate-treatment interaction term.

Individual patient-data meta-analysis of randomized controlled trials is the gold standard for investigating how patient factors modify the effectiveness of treatment. Because participant data from primary studies might not be available, reliable alternatives using published data are needed. In this paper, I show that the maximum likelihood estimates of a participant-level linear random effects meta-analysis with a patient covariate-treatment interaction can be determined exactly from aggregate data when the model's variance components are known. I provide an equivalent aggregate-data EM algorithm and supporting software with the R package ipdmeta for the estimation of the "interaction meta-analysis" when the variance components are unknown. The properties of the methodology are assessed with simulation studies. The usefulness of the methods is illustrated with analyses of the effect modification of cholesterol and age on pravastatin in the multicenter placebo-controlled regression growth evaluation statin study. When a participant-level meta-analysis cannot be performed, aggregate-data interaction meta-analysis is a useful alternative for exploring individual-level sources of treatment effect heterogeneity.