JSM 2004 - Toronto

Abstract #300950

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Activity Number: 221
Type: Contributed
Date/Time: Tuesday, August 10, 2004 : 10:30 AM to 12:20 PM
Sponsor: Biopharmaceutical Section
Abstract - #300950
Title: Looking for Synergism/Antagonism in In-vitro Drug Combination Data
Author(s): Steven Novick*+
Companies: GlaxoSmithKline
Address: Five Moore Drive PO Box 13398, Research Triangle Park, NC, 27709-3398,
Keywords: drug combinations ; hill model ; synergy
Abstract:

A typical drug-interaction investigation starts with an in-vitro study on human cells. Synergism, antagonism, and additivity (the lack of interaction) can be defined by a generalization of Loewe additivity, called the Interaction index. Several methods based on the interaction index have been published, such as by Greco, et al. (1990, 1995), Chou and Talalay (1984), and Berenbaum (1977, 1985). The method that I present extends the ideas put forth by Berenbaum (1985) and the Berenbaum section in Greco, et al. (1995). The method first divides the data into two parts: that which must be Loewe additive and that which may deviate from additivity. Berenbaum modeled the additive portion of the data with an appropriate response surface and then, after fitting the model to the remaining data, informally scrutinized the residuals. At the 2003 JSM, I introduced a formal method of examining the residuals for the simple case of homoscedastic variance. The method has been generalized to the heteroscedastic variance case.

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