Abstract:
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The primary goal of a dose-finding trial for the novel anticancer agents is to identify an optimal dose (OD), defined as the tolerable dose having adequate efficacy under the unpredictable dose-toxicity and dose-efficacy relationships. It is also quite important to accelerate early-stage trials to shorten the entire period of drug development. To solve these issues, we propose the time-to-event Bayesian optimal interval design to accelerate dose-finding based on cumulative and pending data of both efficacy and toxicity. The new design, named “TITE-BOIN-ET” design, is nonparametric and a model-assisted design. A simulation study shows that the TITE-BOIN-ET design has advantages compared with the model-based approaches in both the percentage of correct OD selection and the average number of patients allocated to the ODs across a variety of realistic settings. In addition, the TITE-BOIN-ET design significantly shortens the trial duration compared with the designs without sequential enrollment and therefore has the potential to accelerate early-stage dose-finding trials.
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