Design and Analysis of Drug Combination Experiments

Roel Straetemans, Timothy E. O’Brien, Luc Wouters, Jacky Van Dun, Michel Janicot, Luc Bijnens, Tomasz Burzykowski, Marc Aerts · Biometrical Journal · 2005

In this paper we present and discuss a novel, simple and easy to implement parametric modeling approach to assess synergy. An extended three parameter log-logistic model is used to analyse the data and calculate confidence intervals of the interaction indices. In addition the model corrects for the bias due to plate-location effects. The analysis is performed with PROC NLMIXED and SAS-code is provided. The approach is illustrated using data coming from an oncology study in which the inhibition effect of a combination of two compounds is studied using 96-well plates and a fixed-ratio design.

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