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Unifying CRM and EWOC designs for phase I cancer clinical trials. (English) Zbl 1284.62651
Summary: 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
Software:
EWOC
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References:
[1] Babb, J.; Rogatko, A., Bayesian methods for cancer phase I clinical trials, (), 1-39
[2] Babb, J.; Rogatko, A.; Zacks, S., Cancer phase I clinical trials: efficient dose escalation with overdose control, Statist. med., 17, 10, 1103-1120, (1998) · Zbl 0903.62064
[3] Babb, J.S.; Rogatko, A., Patient specific dosing in a cancer phase I clinical trial, Statist. med., 20, 2079-2090, (2001)
[4] Carter, S.K., The phase I study, (), 285-300
[5] Cheng, J.D.; Babb, J.S.; Langer, C.; Aamdal, S.; Robert, F.; Engelhardt, L.R.; Fernberg, O.; Schiller, J.; Forsberg, G.; Alpaugh, R.K.; Weiner, L.M.; Rogatko, A., Individualized patient dosing in phase I clinical trials: the role of EWOC in PNU-214936, J. clin. oncol., 22, 602-609, (2004)
[6] Chevret, S., The continual reassessment method in cancer phase I clinical trials: a simulation study, Statist. med., 12, 1093-1108, (1993)
[7] Chu, P.L., 2004. Model-based designs for phase I cancer clinical trials. Ph.D. Thesis, Department of Biostatistics, School of Public Health, University of Medicine and Dentistry of New Jersey, December 2004.
[8] Goodman, S.N.; Zahurak, M.L.; Piantadosi, S., Some practical improvements in the continual reassessment method for phase I, Statist. med., 14, 1149-1161, (1995)
[9] Heyd, J.M.; Carlin, B.P., On sequential designs in nonlinear problems, Biometrika, 85, 2, 496-503, (1998)
[10] Hu, I., On sequential designs in nonlinear problems, Biometrika, 85, 2, 496-503, (1998) · Zbl 0931.62065
[11] Ishizuka, N.; Ohashi, Y., The continual reassessment method and its applications: a Bayesian methodology for phase I cancer trials, Statist. med., 20, 17-18, 2661-2681, (2001)
[12] O’Quigley, J., Continual reassessment design with early termination, Biostatistics, 3, 87-99, (2002) · Zbl 1133.62366
[13] O’Quigley, J.; Pepe, M.; Fisher, L., Continual reassessment method: a practical design for phase I clinical trials in cancer, Biometrics, 46, 33-48, (1990) · Zbl 0715.62242
[14] O’Quigley, J.; Paoletti, X.; Maccario, J., Non-parametric optimal design in dose finding studies, Biostatistics, 3, 51-56, (2002) · Zbl 1133.62367
[15] Shih, W.J., Prediction approaches to sequentially searching for an optimal dose, Biometrics, 45, 623-628, (1989) · Zbl 0715.62249
[16] Shih, W.J., Lee, J.J., Lin, Y., 1999. A hybrid of modified CRM and EWOC approaches for phase-I cancer trials. International Biometrics Society ENAR Spring Meeting.
[17] Storer, B.E., Design and analysis of phase I clinical trials, Biometrics, 45, 925-937, (1989) · Zbl 0715.62241
[18] Tighiouart, M.; Rogatko, A.; Babb, J.S., Flexible Bayesian methods for cancer phase I clinical trials: dose escalation with overdose control, Statist. med., 24, 2183-2196, (2005)
[19] Xu, Z.; Tighiouart, M.; Rogatko, A., EWOC 2.0: interactive software for dose escalation in cancer phase I clinical trials, Drug inform. J., 41, 221-228, (2007)
[20] Zacks, S.; Rogatko, A.; Babb, J., Optimal Bayesian feasible dose escalation for cancer phase I trials, Statist. probab. lett., 38, 215-220, (1998) · Zbl 0903.62064
[21] Zohar, S.; Chevret, S., The continual reassessment method: comparing of Bayesian stopping rules for dose-ranging studies, Statist. med., 20, 2827-2843, (2001)
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