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Activity Number:
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370
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Type:
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Topic Contributed
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Date/Time:
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Wednesday, August 1, 2007 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #309707 |
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Title:
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Experimental Design and Synergy Analysis for Drug Combination Studies Based on Log-Linear Dose Responses
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Author(s):
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Hong-Bin Fang*+ and Ming T. Tan
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Companies:
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University of Maryland Greenebaum Cancer Center and University of Maryland Greenebaum Cancer Center
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Address:
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HSF II S203B, Baltimore, MD, 21201,
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Keywords:
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Additive action ; Combination Index ; Dose-effect ; Experimental design ; Synergy ; Nonparametric model.
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Abstract:
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We propose experimental designs (dose-finding and sample size determination) for detecting departures from additivity of two drugs with log-linear dose responses in a general statistical model that is applicable to both in vivo and in vitro experiments. The design is derived by means of uniform measures that maximize the minimum power of the F-test to detect any departures from additive action, and at the same time minimizes the maximum bias due to lack of fit among all potential departures of a given meaningful magnitude. Furthermore, we propose a nonparametric combination index model to capture the interaction of two drugs. The nonparametric function is estimated using the technique developed in thin plate splines. A study on two anticancer drugs is used to illustrate the method.
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