Abstract
The primary aim of a phase 1 cancer clinical trial is to determine the maximum tolerated dose of a new drug. Although the continual reassessment method is shown to have better operating characteristics than traditional designs, traditional designs are still widely used in practice. Kang and Ahn (!) developed an algorithm to compute the exact distribution of the maximum tolerated dose (MTD) in traditional designs with dose deescalation and investigated the expected toxicity rate at the MTD with the algorithm. In this paper, using the exact formulae derived by Lin and Shih (2). we study the expected toxicity rate at the MTD and the expected number of patients with toxicity and patients required when the hyperbolic tangent and the logistic functions are used as the unknown dose-toxicity cun’es. We consider the expected toxicity rate both without and with dose deescalation. No further study was done before in cases where dose level zero is chosen as the MTD. Since, in real practice, dose levels are lowered for adjustment and a new trial is conducted when dose level zero is decided as the MTD, we also incorporate this dose adjustment.
Similar content being viewed by others
References
Kang S. Ahn C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Inf J. 2001:35(4):1189–1200.
Lin Y, Shih W. Statistical properties of the traditional algorithm-based designs for phase 1 cancer clinical trails. Biostatistics. 2001;2:203–215.
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.
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.
Faries D. Practical modifications of the continual reassessment method for phase I cancer clinical trials. J Biopharmaceutical Stat. 1994;4:147–164.
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.
Ann 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.
Zohar S, Chevret S. The continual reassessment method: comparing of Bayesian stopping rules for dose-ranging studies. Stat Med. 2001;20:2827–2843.
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.
Smith T, Lee J, Kantarjian H, Legha S, Raber M. Design and results of phase I cancer clinical trial: three-year experience at M.D. Anderson Cancer Center. J Clinical Oncology. 1996;14(1):287–295.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kang, SH., Ahn, C.W. An Investigation of the Traditional Algorithm-Based Designs for Phase 1 Cancer Clinical Trials. Ther Innov Regul Sci 36, 865–873 (2002). https://doi.org/10.1177/009286150203600415
Published:
Issue Date:
DOI: https://doi.org/10.1177/009286150203600415