Effect of non-linearity of a predictor on the shape and magnitude of its receiver-operating-characteristic curve in predicting a binary outcome

Area under a receiver-operating-characteristic (AUROC) curve is widely used in medicine to summarize the ability of a continuous predictive marker to predict a binary outcome. This study illustrated how a U-shaped or inverted U-shaped continuous predictor would affect the shape and magnitude of its AUROC curve in predicting a binary outcome by comparing the ROC curves of the worst first 24-hour arterial pH values of 9549 consecutive critically ill patients in predicting hospital mortality before and after centering the predictor by its mean or median. A simulation dataset with an inverted U-shaped predictor was used to assess how this would affect the shape and magnitude of the AUROC curve. An asymmetrical U-shaped relationship between pH and hospital mortality, resulting in an inverse-sigmoidal ROC curve, was observed. The AUROC substantially increased after centering the predictor by its mean (0.611 vs 0.722, difference = 0.111, 95% confidence interval [CI] 0.087–0.135), and was further improved after centering by its median (0.611 vs 0.745, difference = 0.133, 95%CI 0.110–0.157). A sigmoidal-shaped ROC curve was observed for an inverted U-shaped predictor. In summary, a non-linear predictor can result in a biphasic-shaped ROC curve; and centering the predictor can reduce its bias towards null predictive ability.