Generalized Response Surface Models for Assessing Synergistic Effects of Three or More Drugs

• Activity Number: 353
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): John Oleynick*+ and Yong Lin and Dirk Moore and Weichung Joe Shih
• Companies: Janssen Research & Development and University of Medicine and Dentistry of New Jersey and University of Medicine and Dentistry of New Jersey and University of Medicine and Dentistry of New Jersey
• Keywords: synergy

Abstract

Drug synergy occurs when two or more drugs are used in a combination therapy, and the total effect of the drugs is more than would be expected based on their "added" individual effects. Most methods for evaluating synergy are limited to evaluating synergy between two drugs. When more than two drugs are used in a combination, there is an additional complexity not present in 2-drug synergy: determining whether any detected synergy is between all the drugs or only a subset of the drugs.

In this paper, two existing methods for evaluating synergy between two drugs are extended to three or more drugs. The two methods are Plummer and Short's method (1990), which is more appropriate when any synergy is the same at all dose combinations (global synergy), and the parametric method of Kong and Lee (2006), which is more appropriate when the presence and strength of any synergy may vary at different dose combinations (local synergy).

For each method, synergy models are presented for the general case of at least 2 drugs. Implementations for the case of three drugs are described in detail, and an evaluation of their goodness of fit based on simulations is discussed.