Abstract
A main purpose of Phase I cancer clinical trials is to identify the maximum tolerated dose (MTD) of a new agent for experimentation in Phase II and III studies. The continual reassessment method has been shown to be superior to the standard design. However, in practice, the standard design has still been widely used. Therefore, it is important to investigate the performance of the standard design accurately. In this paper, we develop an algorithm to compute the exact distribution of the recommended dose level in the standard design. The algorithm is a better tool than simulation in the investigation of the operating characteristics of the standard design, because it does not involve any sampling error and computing time is much shorter than simulation. With the algorithm, the expected toxicity rate at the MTD in the standard design is investigated extensively for some dose-toxicity curves in a certain range.
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References
Faries D. Practical modifications of the continual reassessment method for phase I cancer clinical trials. J Biopharma Stat 1994;4;147–164.
O’Quigley J, Chevret S. Methods for dose finding studies in cancer trials: A review and results of a Monte Carlo study. Stat Med 1991;10;1647–1664.
O’Quigley J, Pepe M, Fisher M. Continual reassessment method: A practical design for phase I clinical trials in cancer. Biometrics 1990;46;33–48.
Goodman S, Zahurak M, Piantadosi S. Some practical improvements in the continual reassessment method for phase I studies. Stat Med 1995;14;1149–1161.
Moller S. An extension of the continual reassessment methods using a preliminary up-and-down design in a dose finding study in cancer patients, in order to investigate a greater range of doses. Stat Med 1995;14;911–922.
Ahn C. An evaluation of phase I cancer clinical trial designs. Stat Med 1998;17;1537–1549.
Korn E, Midthune D, Chen T, Rubinstein L, Christian M, Simon R. A comparison of two phase I trial designs. Stat Med 1994;13;1799–1806.
Reiner E, Paoletti X, O’Quigley J. Operating characteristics of the standard phase I clinical trial design. Computat Stat Data Analysis 1999;30;303–315.
Goldsmith M, Slavik M, Carter S. Quantitative prediction of drug toxicity in human from toxicology in small and large animals. Cancer Research 1975;35;1354–1364.
Storer B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925–937.
Gorden N, Willson J. Using toxicity grades in the design and analysis of cancer phase I clinical trials Stat Med. 1992;11;2603–2075.
Mick R. Phase I Clinical Trial Design. In Schilsky R, Milano G, Ratain M, eds. Principles of Antineoplastic Drug Development and Pharmacology. New York, NY: Marcel Dekker, 1996;29–36.
Smith T, Lee J, Kantarjian H, Legha S, Raber M. Design and results of a phase I cancer clinical trial: Three-year experience at M.D. Anderson Cancer Center. J Clin Oncology 1996;14(1);287–295.
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Kang, SH., Ahn, C. The Expected Toxicity Rate at the Maximum Tolerated Dose in the Standard Phase I Cancer Clinical Trial Design. Ther Innov Regul Sci 35, 1189–1199 (2001). https://doi.org/10.1177/009286150103500416
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DOI: https://doi.org/10.1177/009286150103500416