Pharmacokinetic and pharmacodynamic data and models in clinical trials.

There is current emphasis for extended integration of pharmacokinetics (PK) and pharmacodynamics (PD) into all phases of new drug development, including large-scale clinical trials. In this paper, we focus on study design and data analysis issues for the investigation of pharmacokinetic/pharmacodynamic and blood level/effect relationships in patients. The application of descriptive and model-based regression statistical methodology for including sparse drug systemic concentration data in the analysis of efficacy and safety is illustrated by examples chosen from diverse therapeutic areas. The population approach, based on mixed-effects modelling, is one such methodology, which also provides new tools for analysis of response vs dose and response vs time data. The existence of a variety of statistical techniques for handling complex PK/PD time-varying data should increase the impact of such data analysis on future drug development.