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Activity Number:
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248
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Type:
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Invited
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Date/Time:
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Tuesday, August 5, 2008 : 10:30 AM to 12:20 PM
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Sponsor:
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ENAR
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| Abstract - #300270 |
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Title:
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Controversy and Convergence on Modeling Synergism in Drug Combination Studies
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Author(s):
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Ming T. Tan*+ and Hong-Bin Fang
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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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MSTF 2nd Floor, Room 261, Baltimore, MD, 21201,
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Keywords:
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Drug Combination ; Synergy ; Experimental design ; Interaction Index ; Loewe Additivity ; Sample size
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Abstract:
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Preclinical experiment on multi-drug combination has an increasingly important role in (especially cancer) drug development. We propose a general method based on the uniform scattered points in the experimental domain for dose finding and sample size determination for combination studies of multiple drugs in a semi-parametric statistical model applicable to both in vivo and in vitro experiments. The design maximizes the power to detect departure from additivity. We demonstrate the application of the method to a study on SAHA and Ara-C where subsequent data collected according to this design have identified synergistic combinations that would been missed with more classic designs. We also validate the design utilizing the combinations of two enzyme inhibitors where comprehensive data are available on the dose response.
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