Data Monitoring in Adaptive Dose-Ranging Trials

In clinical studies that address dose-finding objectives, the use of trial designs that allow adaptations based upon accruing unblinded data have much potential to introduce added efficiency and to improve the decision making process, compared to traditional designs. In this paper we consider the processes by which such adaptations may be made. Conventions for interim data monitoring and decision making, particularly with regard to restricting access to data, have largely evolved based upon the needs in Phase III nonadaptive studies; as such, they may not be an ideal fit for adaptive dose-ranging studies, because of the different natures of the trials, their placement in the drug development process, and the objectives of the monitoring. In this paper, we specifically discuss what processes for interim monitoring, analysis, decision making and implementation, might be advantageous and appropriate for adaptive dose-ranging studies, and then illustrate how processes were implemented and carried out in a particular case study.