JSM 2004 - Toronto

Abstract #301024

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Activity Number: 259
Type: Topic Contributed
Date/Time: Tuesday, August 10, 2004 : 2:00 PM to 3:50 PM
Sponsor: Biopharmaceutical Section
Abstract - #301024
Title: A History of Response Surface Models for Assessing the Nature and Intensity of Interaction among Multiple Agents
Author(s): William R. Greco*+ and Donald B. White and Leonid A. Khinkis
Companies: Roswell Park Cancer Institute and University of Toledo and Canisius College
Address: Elm & Carlton Sts., Buffalo, NY, 14263,
Keywords: synergy ; additivity ; antagonism ; response surface ; pharmacometrics
Abstract:

Pairwise/multiple agent interaction assessment is important for the disciplines of pharmacology, toxicology, epidemiology, food science, and others. Heated disagreements are common in this field. Although it is our view that the future of the field will be dominated by response surface approaches, there is no current consensus on the best RSM. Characteristics for a good RSM for multiple agent interaction include: (a) ability to accommodate arbitrary patterns in dose response slope, maximum effect, and minimum effect parameters; (b) ability to accommodate irregularly shaped isobols at different effect levels, including simultaneous regions of synergism, additivity, and antagonism on the same surface; (c) ability to accommodate antagonism, potentiation, inhibition, and/or coalism between specific agent pairs in a complex mixture; (d) ability to accommodate three or more agents; (e) a hierarchical structure; (f) good statistical characteristics for parameter estimation, model-fitting, and interaction quantitation; and (g) good accompanying graphical procedures. This review will set the stage for reports on current work in the field. Supported by NIH RR10742 and CA16056.

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