Abstract #301770

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JSM 2003 Abstract #301770
Activity Number: 423
Type: Contributed
Date/Time: Wednesday, August 6, 2003 : 2:00 PM to 3:50 PM
Sponsor: Biometrics Section
Abstract - #301770
Title: An Extension of the MFT to Test Synergy in Multiple Drug Combinations
Author(s): Ping Feng*+ and Colleen Kelly
Companies: San Diego State University and San Diego State University
Address: Dept. of Mathematics & Statistics, San Diego, CA, 92182-0001,
Keywords: synergy ; additivity ; multiple drug combinations ; dose-response curves ; drug interactions
Abstract:

Interactions in a combination of drugs or chemicals are important in therapeutics, toxicology, environmental studies, and normal and abnormal physiology. It is important to be able to decide whether the observed effect of a combination is additive, synergistic, or antagonistic. The traditional statistical approaches to the assessment of interactions of n drugs involve the response surface method (RSM), the marginal dose-response curve method (MDRCM). Laska et al. (1994) proposed the MFT, a unique approach to assessing synergy in two-drug combinations that avoids the estimation of any dose-response curve. This method enables the use of simple designs with only three dosages for two drugs: the combination dose of interest and a marginal dosage of each drug. The choice of the marginal dosages depends on the potency ratio of the two drugs at response e, r(e). Since r(e) is usually unknown, an estimate r is used instead. We extend Laska's MFT to assess synergy in three or more drug combinations, and examine the effects of r, different combination dosages and different dose-response functions on the power of the MFT. Additionally, the power of the MFT is compared to the MDRCM.

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