Design and analysis of drug combination experiments.
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.
Straetemans
Roel
R
Limburgs Universitair Centrum, Center for Statistics, Biostatistics, Universitaire Campus, B-3590 Diepenbeek, Belgium. Roel.Straetemans@luc.ac.be
O'Brien
Timothy
T
Wouters
Luc
L
Van Dun
Jacky
J
Janicot
Michel
M
Bijnens
Luc
L
Burzykowski
Tomasz
T
Aerts
Marc
M
D000465:Algorithms; D000818:Animals; D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008954:Models, Biological; D015233:Models, Statistical; D051381:Rats; D016896:Treatment Outcome
D004338:Drug Combinations