IMR Press / FBE / Volume 2 / Issue 1 / DOI: 10.2741/E89

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Application and review of the separate ray model to investigate interaction effects
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1 Johnson and Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica N.V., Beerse Belgium

*Author to whom correspondence should be addressed.

Academic Editor: William R. Greco

Front. Biosci. (Elite Ed) 2010, 2(1), 266–278; https://doi.org/10.2741/E89
Published: 1 January 2010
Abstract

In this paper we review the application of the Separate Ray Model to analyze drug combination experiments coming from a fixed ratio design. The idea is the joint fit of separate concentration response curves to each ray under investigation leading to an interaction index for each together with a 95 percent Confidence Interval. The approach is a simple and easy to implement parametric modeling approach and allows estimation and testing of drug interactions based on regularly sampling in the entire space of all combinations going from pure compound A to pure compound B. The analysis is implemented using the SAS/STAT procedure NLMIXED. Two datasets were provided for the modeling exercise. One included different qualitative effects with some rays showing synergy, others antagonism and again others additivity. The second dataset involved the presence of very large synergy together with different observed background effects for the individual rays. The Separate Ray Model is able to handle these practical issues making it a flexible tool to investigate drug interaction experiments using a fixed ratio design.

Keywords
Synergy
Antagonism
Ray Design
Fixed Ratio Design
Loewe
Review
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