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Activity Number:
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233
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Type:
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Contributed
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Date/Time:
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Monday, August 3, 2009 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #304960 |
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Title:
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A Bayesian Approach to Dose-Response Assessment and Synergy
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Author(s):
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Violeta G. Hennessey*+
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Companies:
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The University of Texas M.D. Anderson Cancer Center
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Address:
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2222 Maroneal Unit 316, Houston, TX, 77030,
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Keywords:
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Drug interaction ; Hierarchical models ; Combination index method ; Loewe additivity ; Emax model ; Interaction index
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Abstract:
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We propose a Bayesian approach to dose-response assessment and drug interaction analysis between combined agents. We focus on in vitro dose-response studies that include repeated experiments with multiple replicates. We limit our work to combination studies that use a single-ray experimental design, that is, agents are combined using a fixed-dose ratio. We have developed a Bayesian hierarchical model that accounts for sources of variability inherent in the data and uncertainty in parameter values. The model consists of a modified Hill's equation (Emax model) with an additive residual error on the logarithmic scale. In addition, we have developed a method based on Loewe additivity that allows one to assess the presence of synergy with honest accounting of uncertainty. We apply the proposed model and method to a motivating data set from an in vitro ovarian cancer research study.
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