Robust Confidence Intervals for Meta-Regression with Correlated Moderators

Mixed-effects meta-regression models provide a powerful tool for evidence synthesis. In fact, modelling the study effect in terms of random effects and moderators not only allows to examine the impact of the moderators, but often leads to more accurate estimates of the involved parameters. Nevertheless, due to the often small number of studies on a specific research topic, interactions are often neglected in meta-regression. This was also the case in a recent meta-analysis in acute heart failure where a significant decline in death rate over calendar time was reported. However, we believe that an important interaction has been neglected. We therefore reanalyzed the data with a meta-regression model, including an interaction term of the median recruitment year and the average age of the patients. The model with interaction suggests different conclusions. This led to the new research questions (i) how moderator interactions influence inference in mixed-effects meta-regression models and (ii) whether some inference methods are more reliable than others. Focusing on confidence intervals for main and interaction parameters, we address these questions in an extensive simulation study. We thereby investigate coverage and length of seven different confidence intervals under varying conditions. We conclude with some practical recommendations.