Early stopping in seamless phase I/II clinical trials

Abstract

In recent years, seamless phase I/II clinical trials have drawn much attention, as they consider both toxicity and efficacy endpoints in finding an optimal dose (OD). Engaging an appropriate number of patients in a trial is a challenging task. This paper attempts a dynamic stopping rule to save resources in phase I/II trials. That is, the stopping rule aims to save patients from unnecessary toxic or subtherapeutic doses. We allow a trial to stop early when widths of the confidence intervals for the dose-response parameters become narrower or when the sample size is equal to a predefined size, whichever comes first. The simulation study of dose-response scenarios in various settings demonstrates that the proposed stopping rule can engage an appropriate number of patients. Therefore, we suggest its use in clinical trials.

Keywords: continuation ratio model; early stopping; optimum dose; seamless phase I/II trial.