Journal of Probability and Statistics
Volume 2012 (2012), Article ID 692725, 16 pages
Research Article

Number of Patients per Cohort and Sample Size Considerations Using Dose Escalation with Overdose Control

Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA

Received 29 June 2012; Accepted 15 September 2012

Academic Editor: Yichuan Zhao

Copyright © 2012 Mourad Tighiouart and André Rogatko. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The main objective of cancer phase I clinical trials is to determine a maximum tolerated dose (MTD) of a new experimental treatment. In practice, most of these trials are designed so that three patients per cohort are treated at the same dose level. In this paper, we compare the safety and efficiency of trials using the escalation with overdose control (EWOC) scheme designed with three or only one patient per cohort. We show through simulations that the number of patients per cohort does not impact the proportion of patients given therapeutic doses, safety of the trial, and efficiency of the estimate of the MTD. Additionally, we present guidelines and tabulated values on the number of patients needed to design a phase I cancer clinical trial using EWOC to achieve a given accuracy of the estimate of the MTD.