Validating Physiologically-Based Pharmacokinetic Models Using the Continuous Ranked Probability Score: Beyond Being Correct on Average.

ABSTRACT: Physiologically-based pharmacokinetic (PBPK) models have become increasingly popular for model-informed drug development (MIDD) over the past decade. While several guidelines for model evaluation exist, these are by design often of a general and non-specific nature. It is clear what steps should be carried out but not necessarily how. For instance, a validation step needs to be performed to check if the predictions of a model indeed match with an external dataset. However, how to quantify this is yet unspecified. In this paper, we propose a more thorough validation approach based on the Continuous Ranked Probability Score (CRPS), a popular metric that explicitly quantifies how well a model recreates the distribution of observed data. Crucially, when applied to PBPK modeling, this metric ca

SUBMITTER: Sluijterman L 

PROVIDER: S-EPMC12823297 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature