Use of normalized prediction distribution errors for assessing population physiologically-based pharmacokinetic model adequacy.

ABSTRACT: Currently employed methods for qualifying population physiologically-based pharmacokinetic (Pop-PBPK) model predictions of continuous outcomes (e.g., concentration-time data) fail to account for within-subject correlations and the presence of residual error. In this study, we propose a new method for evaluating Pop-PBPK model predictions that account for such features. The approach focuses on deriving Pop-PBPK-specific normalized prediction distribution errors (NPDE), a metric that is commonly used for population pharmacokinetic model validation. We describe specific methodological steps for computing NPDE for Pop-PBPK models and define three measures for evaluating model performance: mean of NPDE, goodness-of-fit plots, and the magnitude of residual error. Utility of the proposed evaluati

SUBMITTER: Maharaj AR 

PROVIDER: S-EPMC7293575 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature