Cumulative cohort design for dose-finding

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We introduce a new design for dose-finding in the context of toxicity studies for which it is assumed that toxicity increases with dose. The goal is to identify the maximum tolerated dose, which is taken to be the dose associated with a prespecified "target" toxicity rate. The decision to decrease, increase or repeat a dose for the next subject depends on how far an estimated toxicity rate at the current dose is from the target. The size of the window within which the current dose will be repeated is obtained based on the theory of Markov chains as applied to group up-and-down designs. But whereas the treatment allocation rule in Markovian group up-and-down designs is only based on information from the current cohort of subjects, the treatment allocation rule for the proposed design is based on the cumulative information at the current dose. We then consider an extension of this new design for clinical trials in which the subject's outcome is not known immediately. The new design is compared to the continual reassessment method. (c) 2006 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2007-07
Language
English
Article Type
Article
Citation

JOURNAL OF STATISTICAL PLANNING AND INFERENCE, v.137, no.7, pp.2316 - 2327

ISSN
0378-3758
DOI
10.1016/j.jspi.2006.07.009
URI
http://hdl.handle.net/10203/88709
Appears in Collection
MA-Journal Papers(저널논문)
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