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Abstract:
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Traditional designs for phase I clinical trials assign the same dose to patients in the same cohort. In this paper, we present a new class of designs for cancer phase I trials which initially rapidly escalate by allowing multiple doses (usually 3) to be assigned to each cohort of patients. The class of designs, called the LMH-CRM by administering different percentiles of the maximum tolerated dose (MTD), denoted 'low,' 'medium,' 'high,' is proven to be consistent and coherent (a commonsense property of phase I trials for dose escalation and de-escalation). Three designs (slow, moderate and fast) are derived based on different dose-escalation restrictions. Simulation results show that moderate and fast LMH-CRM combine the advantages of the CRM with one patient per cohort and three patients per cohort: it accurately estimates the MTD; controls overall toxicity rates; and is time efficient.
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