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Three‐dose–cohort designs in cancer phase I trials
Author(s) -
Huang Bo,
Chappell Rick
Publication year - 2007
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3054
Subject(s) - cohort , maximum tolerated dose , medicine , clinical trial , percentile , cancer , oncology , statistics , computer science , mathematics
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 (an extension of the continual reassessment method (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. Copyright © 2007 John Wiley & Sons, Ltd.