Inappropriate Evaluation of Effect Modifications Based on Categorical Outcomes: A Systematic Review of Randomized Controlled Trials

Abstract

Our meta-epidemiological study aimed to describe the prevalence of reporting effect modification only on relative scale outcomes and inappropriate interpretations of the coefficient of interaction terms in nonlinear models on categorical outcomes. Our study targeted articles published in the top 10 high-impact-factor journals between 1 January and 31 December 2021. We included two-arm, parallel-group, interventional superiority randomized controlled trials to evaluate the effects of modifications on categorical outcomes. The primary outcomes were the prevalence of reporting effect modifications only on relative scale outcomes and that of inappropriately interpreting the coefficient of interaction terms in nonlinear models on categorical outcomes. We included 52 articles, of which 41 (79%) used nonlinear regression to evaluate effect modifications. At least 45/52 articles (87%) reported effect modifications based only on relative scale outcomes, and at least 39/41 (95%) articles inappropriately interpreted the coefficient of interaction terms merely as indices of effect modifications. The quality of the evaluations of effect modifications in nonlinear models on categorical outcomes was relatively low, even in randomized controlled trials published in medical journals with high impact factors. Researchers should report effect modifications of both absolute and relative scale outcomes and avoid interpreting the coefficient of interaction terms in nonlinear regression analyses.