ABSTRACT
Model-Informed Drug Development (MIDD) is the most recent term commonly used to describe the application of a wide range of quantitative models in drug development to facilitate the decision-making process. MIDD-related programmatic activities are expected to promote early interactions between drug developers and regulatory scientists on key issues during product development. This chapter describes the development of exposure-response (ER) models. The most challenging issue in drug model development is that how to bridge the ER across patients and healthy subjects. The general framework of disease-drug-trial models is introduced and then an example is employed to illustrate this model development. The disease-drug-trial model contains three major submodels: disease model, drug model, and trial model. The key feature of the model is that saturable, high-affinity binding of the drug to its pharmacologic target is responsible for observable nonlinear pharmacokinetic behavior. A regression approach for continuous variables describing hepatic impairment and pharmacodynamic parameters is recommended by Food and Drug Administration.
