Isotonic designs for phase I trials

Leung, D. H. Y. & Wang, Y-G. (2001) Isotonic designs for phase I trials. Controlled Clinical Trials, 22(2), pp. 126-138.

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The purpose of a phase I trial in cancer is to determine the level (dose) of the treatment under study that has an acceptable level of adverse effects. Although substantial progress has recently been made in this area using parametric approaches, the method that is widely used is based on treating small cohorts of patients at escalating doses until the frequency of toxicities seen at a dose exceeds a predefined tolerable toxicity rate. This method is popular because of its simplicity and freedom from parametric assumptions. In this payer, we consider cases in which it is undesirable to assume a parametric dose-toxicity relationship. We propose a simple model-free approach by modifying the method that is in common use. The approach assumes toxicity is nondecreasing with dose and fits an isotonic regression to accumulated data. At any point in a trial, the dose given is that with estimated toxicity deemed closest to the maximum tolerable toxicity. Simulations indicate that this approach performs substantially better than the commonly used method and it compares favorably with other phase I designs.

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43 citations in Scopus
38 citations in Web of Science®
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ID Code: 90607
Item Type: Journal Article
Refereed: Yes
Additional Information: ISI Document Delivery No.: 421TE
Times Cited: 33
Cited Reference Count: 15
Leung, DHY Wang, YG
Elsevier science inc
New york
Keywords: continual reassessment method, dose escalation, isotonic regression, maximum tolerated dose, phase I trials, up-and-down method, continual reassessment method, clinical-trials, dose-escalation, cancer, improvements
DOI: 10.1016/s0197-2456(00)00132-x
ISSN: 0197-2456
Divisions: Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright Elsevier Science Inc. 2001
Deposited On: 20 Nov 2015 04:27
Last Modified: 26 Jun 2017 10:01

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