For the clinical development of a new drug, the determination of dose-proportionality is an essential part of the pharmacokinetic evaluations, which may provide early indications of non-linear pharmacokinetics and may help to identify sub-populations with divergent clearances. Prior to making any conclusions regarding dose-proportionality, the goodness-of-fit of the model must be assessed to evaluate the model performance. We propose the use of simulation-based visual predictive checks to improve the validity of dose-proportionality conclusions for complex designs. We provide an illustrative example and include a table to facilitate review by regulatory authorities.
This is the peer reviewed version of the following article: Wolfsegger, MJ, Bauer, A, Labes, D, et al. Assessing goodness‐of‐fit for evaluation of dose‐proportionality. Pharmaceutical Statistics. 2020; 1– 10. https://doi.org/10.1002/pst.2074 which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/pst.2074 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
