Exposure-response modeling of clinical end points using latent variable indirect response models.

Exposure-response modeling facilitates effective dosing regimen selection in clinical drug development, where the end points are often disease scores and not physiological variables. Appropriate models need to be consistent with pharmacology and identifiable from the time courses of available data. This article describes a general framework of applying mechanism-based models to various types of clinical end points. Placebo and drug model parameterization, interpretation, and assessment are discussed with a focus on the indirect response models.