The impact of neglected confounding and interactions in mixed-effects meta-regression

Abstract: Analysts seldom include interaction terms in meta-regression model, what can introduce bias if an interaction is present. We illustrate this in the current paper by re-analyzing an example from research on acute heart failure, where neglecting an interaction might have led to erroneous inference and conclusions. Moreover, we perform a brief simulation study based on this example highlighting the effects caused by omitting or unnecessarily including interaction terms. Based on our results, we recommend to always include interaction terms in mixed-effects meta-regression models, when such interactions are plausible.