Source:http://linkedlifedata.com/resource/pubmed/id/16596575
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2006-12-28
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| pubmed:abstractText |
This paper proposes a statistical method for determining the therapeutic dose of a test drug in a confirmatory clinical trial based on a phase II clinical trial using 3 or 4 doses of the drug. This method assumes the primary variable has a normal distribution with a common variance, that a test-drug effect is seen when the population means show a response pattern indicating a monotonic increase with dose, and that there is a prior distribution for the population means. Under the proposed method, multiple contrast statistics are determined, such as contrast statistics for linear increase and plateau, and a response pattern is selected based on the maximum contrast statistic. The posterior probability that the selected response pattern is the true one is evaluated, and if this exceeds the cut-off value a therapeutic dose is selected based on the estimated response pattern. To select the appropriate cut-off value, a simulation study was conducted using a loss function for which the loss due to overestimation is greater than the loss due to underestimation. It was found that, as a rule, the appropriate cut-off value to reduce the expected loss for various response patterns is 0.75 for a 3-group trial and 0.70 for a 4-group trial. Using these cut-off values, the proposed method was applied to a previous clinical trial of a leukotriene receptor antagonist in patients with bronchial asthma. The method enabled the selection of what are considered appropriate response patterns and a therapeutic dose. Thus, the proposed method appears reasonable.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0277-6715
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| pubmed:author | |
| pubmed:copyrightInfo |
2006 John Wiley & Sons, Ltd.
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| pubmed:issnType |
Print
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| pubmed:day |
10
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| pubmed:volume |
26
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
498-511
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16596575-Asthma,
pubmed-meshheading:16596575-Clinical Trials, Phase II as Topic,
pubmed-meshheading:16596575-Data Interpretation, Statistical,
pubmed-meshheading:16596575-Dose-Response Relationship, Drug,
pubmed-meshheading:16596575-Humans,
pubmed-meshheading:16596575-Leukotriene Antagonists,
pubmed-meshheading:16596575-Models, Statistical,
pubmed-meshheading:16596575-Peak Expiratory Flow Rate
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| pubmed:year |
2007
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| pubmed:articleTitle |
A method for therapeutic dose selection in a phase II clinical trial using contrast statistics.
|
| pubmed:affiliation |
Graduate School of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. akirawa@mar.rikadai.jp
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| pubmed:publicationType |
Journal Article
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