Statistics in medicine
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Meta-regression has become a commonly used tool for investigating whether study characteristics may explain heterogeneity of results among studies in a systematic review. However, such explorations of heterogeneity are prone to misleading false-positive results. It is unclear how many covariates can reliably be investigated, and how this might depend on the number of studies, the extent of the heterogeneity and the relative weights awarded to the different studies. ⋯ We demonstrate in particular that fixed effect meta-regression is likely to produce seriously misleading results in the presence of heterogeneity. The permutation test appropriately tempers the statistical significance of meta-regression findings. We recommend its use before a statistically significant relationship is claimed from a standard meta-regression analysis.