INFERRING SYSTEMIC EXPOSURE FROM A PHARMACOKINETIC SCREEN: MODEL-FREE AND MODEL-BASED APPROACHES

To infer patterns of average systemic exposure and to estimate individual exposures in phase III clinical trials of a new anxiolytic, two statistical methodologies were applied and compared: non‐linear mixed‐effect modelling, and a model‐free approach based on quartiles of dose‐normalized plasma concentrations of the drug. Although the model‐based approach provides more quantitative insight about relationships between average exposure and demographic covariates, the model‐free approach provides qualitatively similar results about average clearance and quantitatively similar results about individual exposures, and the model‐free approach is easy and inexpensive to implement.