Evaluating potential benefits of dose-exposure-response modeling for dose finding.

Dose-regimen selection for confirmatory trials and characterization of dose-response relationship are arguably among the most important and difficult tasks in clinical drug development. Inadequate dose-regimen selection is believed to be one of the key drivers of the high attrition rate in Phase III. Nowadays, drug concentrations are routinely measured in patients in clinical studies throughout the drug development process. This drug exposure information is often used to explain some of the response variability. It could also be used to improve characterization of dose-response, and consequently result in a better dose-regimen selection. A simulation study was undertaken to assess the potential value of dose-response characterization methods that utilize exposure data relative to methods that only require dose and response data. Copyright (c) 2009 John Wiley & Sons, Ltd.