Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Mar 2015
A statistical evaluation of dose expansion cohorts in phase I clinical trials.
Phase I trials often include a dose expansion cohort (DEC), in which additional patients are treated at the estimated maximum tolerated dose (MTD) after dose escalation, with the goal of ensuring that data are available from more than six patients at a single dose level. However, protocols do not always detail how, or even if, the additional toxicity data will be used to reanalyze the MTD or whether observed toxicity in the DEC will warrant changing the assigned dose. A DEC strategy has not been statistically justified. ⋯ Where feasible, a CRM design with no explicit DEC is preferred to designs that fix a dose for all patients in a DEC.