Development and comparison of model-integrated evidence approaches for bioequivalence studies with pharmacokinetic end points.

ABSTRACT: By applying nonlinear mixed-effect (NLME) models, model-integrated evidence (MIE) approaches are able to analyze bioequivalence (BE) data with pharmacokinetic end points that have sparse sampling, which is problematic for non-compartmental analysis (NCA). However, MIE approaches may suffer from inflation of type I error due to underestimation of parameter uncertainty and to the assumption of asymptotic normality. In this study, we developed a MIE BE analysis method that is based on a pre-defined model and consists of several steps including model fitting, uncertainty assessment, simulation, and BE determination. The presented MIE approach has several improvements compared with the previously reported model-integrated methods: (1) treatment, sequence, and period effects are only added to ab

SUBMITTER: Chen X 

PROVIDER: S-EPMC11494825 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature