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Simultaneously Optimizing Dose And Schedule Of A New Cytotoxic Agent, Thomas M. Braun, Peter F. Thall, Hoang Nguyen, Marcos De Lima

The University of Michigan Department of Biostatistics Working Paper Series

Traditionally, phase I clinical trial designs determine a maximum tolerated dose of an experimental cytotoxic agent based on a fixed schedule, usually one course consisting of multiple administrations, while varying the dose per administration between patients. However, in actual medical practice patients often receive several courses of treatment, and some patients may receive one or more dose reductions due to low-grade (non-dose limiting) toxicity in previous courses. As a result, the overall risk of toxicity for each patient is a function of both the schedule and the dose used at each adminstration. We propose a new paradigm for Phase I …