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Article
Data sources: zbMATH Open
Biometrics
Article . 1997 . Peer-reviewed
Data sources: Crossref
Biometrics
Article . 1997
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A Random Walk Rule for Phase I Clinical Trials

A random walk rule for phase I clinical trials
Authors: Durham, Stephen D.; Flournoy, Nancy; Rosenberger, William F.;

A Random Walk Rule for Phase I Clinical Trials

Abstract

We describe a family of random walk rules for the sequential allocation of dose levels to patients in a dose-response study, or phase I clinical trial. Patients are sequentially assigned the next higher, same, or next lower dose level according to some probability distribution, which may be determined by ethical considerations as well as the patient's response. It is shown that one can choose these probabilities in order to center dose level assignments unimodally around any target quantile of interest. Estimation of the quantile is discussed; the maximum likelihood estimator and its variance are derived under a two-parameter logistic distribution, and the maximum likelihood estimator is compared with other nonparametric estimators. Random walk rules have clear advantages: they are simple to implement, and finite and asymptotic distribution theory is completely worked out. For a specific random walk rule, we compute finite and asymptotic properties and give examples of its use in planning studies. Having the finite distribution theory available and tractable obviates the need for elaborate simulation studies to analyze the properties of the design. The small sample properties of our rule, as determined by exact theory, compare favorably to those of the continual reassessment method, determined by simulation.

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Keywords

Likelihood Functions, Biometry, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, Drug-Related Side Effects and Adverse Reactions, up-and-down designs, toxicity studies, Applications of statistics to biology and medical sciences; meta analysis, small sample distribution theory, Sequential statistical design, Random Allocation, adaptive designs, Pharmaceutical Preparations, Humans, quantile estimation, Cyclophosphamide, Bone Marrow Transplantation, Randomized Controlled Trials as Topic

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
148
Top 1%
Top 1%
Top 10%
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