Early Completion of Model-Assisted Designs for Dose-Finding Trials

Abstract

We propose a novel early completion method for phase I dose-finding trials using model-assisted designs. The trials can halt when a maximum tolerated dose (MTD) is estimated with sufficient accuracy. Early completion can reduce the average number of patients treated relative to the planned number, thereby allowing the trial to proceed to enrolling an expansion cohort for efficacy and enabling the trial to reach the next phase faster. Early completion is conducted on the basis of a dose-retainment probability using dose-assignment decisions. We evaluated early the completion for two actual trials. In addition, we performed a computer simulation to confirm the percentage of correctly selected MTDs, the early completion percentage, and the average number of patients treated. In the evaluation of the two actual trials, we confirmed that the trials completed early. In the simulation results, we confirmed that the percentages of correct MTD selection were maintained relative to the original model-assisted designs. The early completion percentages ranged from 50% to 90%, and the number of patients treated reduced from 20%-60% relative to the planned number of patients. We conclude that the early completion method can be applied unproblematically to the model-assisted design of phase I dose-finding trials.