Pharmacometrics: A Quantitative Decision-Making Tool in Drug Development

Pharmacometrics—pharmacokinetics/pharmacodynamics (PK/PD) modeling and simulation—has been used to inform drug development decisions for more than two decades and has gained increasing support from the pharmaceutical industry, academia, and regulatory agencies. With the regulatory encouragement on model-informed drug development and the recognition of high-impact emerging applications, pharmacometric analysis currently plays an important role throughout a drug’s life cycle, from the early translational stage to the confirmatory phase 3 and regulatory approval, and even into the post-marketing trials. This chapter provides a brief introduction to pharmacometric analysis approaches including pharmacokinetic models, PK/PD models, physiologically based pharmacokinetic models, quantitative systems pharmacology models, and model based meta-analysis models. Aspects of model development are also discussed such as software, modeling work flow, and major model components, with a focus on population modeling analysis. Finally, case studies are provided to highlight the broad applications of this evolving science in drug development.