In work package WP1 we will develop novel methodology for improving dose-finding in early phase clinical trials by incorporating data on pharmacokinetics (PK), describing the time-course of drug concentrations in the body, and the pharmacodynamics (PD), describing the time-course of effects, including both the desired pharmacological effect and harmful side-effects of the treatment.
Early phase dose-finding studies are the first trials of a new medicinal product in humans and aim to obtain reliable information on an appropriate dose for use in further clinical trials. Sample sizes for such studies are typically small, and this is particularly true in a small population context. Recent work has led to efficient designs for dose-finding based on the minimum number of participants. These methods have generally relied primarily on observed safety data, however, and there is a growing awareness of the need to better incorporate pharmacokinetic/pharmacodynamic (PK/PD) information in the dose-finding process. In this project our aim will be to extend novel design methods to use PK/PD data more fully to better estimate the best dose level for further evaluation whilst ensuring the sample size for early phase trials is kept to a minimum.