Dose‐finding approach for dose escalation with overdose control considering incomplete observations

Abstract

We propose a hybrid design, the time‐to‐event dose‐escalation method with overdose control (TITE‐EWOC), introducing the time‐to‐event approach, developed by Cheungit et al., in the EWOC method, developed by Babb et al. The aim of this new design is to decrease the dose‐finding trial duration, without impairing the characteristics of the EWOC design, especially the overdose control ability. We conducted a simulation study, exploring four dose–toxicity relationships and three mean inter‐patient arrival times. Performances of TITE‐EWOC were compared with those of the EWOC method. This study shows that the trial duration can be greatly decreased with the TITE‐EWOC, without impacting the proportion of overdosed patients or the number of dose‐limiting toxicities by trial, for all explored dose–toxicity relationships, except for very short inter‐patient arrival times. The ability of the method to find the true maximum tolerated dose remains unchanged. Copyright © 2011 John Wiley & Sons, Ltd.