Critique of the Two-Fold Measure of Prediction Success for Ratios: Application for the Assessment of Drug-Drug Interactions

Drug Metab Dispos 39(2):170-173 (2010) PMID 21036951

Current assessment of drug-drug interaction (DDI) prediction success is based on whether predictions fall within a two-fold range of the observed data. This results in a potential bias towards successful prediction at lower interaction levels (ratio of the area under the concentration-time profile (AUC) in the presence of inhibitor/inducer compared to control is <2). However, inclusion of variability increased the prediction success at these levels by 2-fold. The trend of lower prediction accuracy at higher potency of DDIs reported in previous studies is no longer apparent when predictions are assessed via the new predictive measure. Thus, the study proposes a more logical method for the assessment of prediction success and its application for induction and inhibition DDIs.