Unifying CRM and EWOC designs for phase I cancer clinical trials.

*(English)*Zbl 1284.62651Summary: The main goal of phase I cancer clinical trials is to determine the highest dose of a new therapy associated with an acceptable level of toxicity for the use in a subsequent phase II trial. The continual reassessment method (CRM) [J. O’Quigley et al., Biometrics 46, No. 1, 33–48 (1990; Zbl 0715.62242)] and escalation with overdose control (EWOC) [J. Babb, A. Rogatko and S. Zacks, “Cancer phase I clinical trials: efficient dose escalation with overdose control”, Stat. Med. 17, No. 10, 1103–1120 (1998)] are two model-based designs used for phase I cancer clinical trials. A few modifications of the (original) CRM and EWOC have been made by many authors. In this paper, we show how CRM and EWOC can be unified and present a hybrid design. We study the characteristics of the approach of the hybrid design. The comparisons of the three designs (CRM, EWOC, and the hybrid design) are presented by convergence rates and overdose proportions. The simulation results show that the hybrid design generally has faster convergence rates than EWOC and smaller overdose proportions than CRM, especially when the true maximum tolerated dose (MTD) is above the mid-level of the dose range considered. The performance of these three designs is also evaluated in terms of sensitivity to outliers.

##### MSC:

62P10 | Applications of statistics to biology and medical sciences; meta analysis |

##### Keywords:

phase I cancer clinical trial; maximum tolerated dose; dose-limiting toxicity; continual reassessment method; escalation with overdose control##### Software:

EWOC
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\textit{P.-L. Chu} et al., J. Stat. Plann. Inference 139, No. 3, 1146--1163 (2009; Zbl 1284.62651)

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##### References:

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