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...

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Veröffentlicht in:	Biometrical journal 2005-06, Vol.47 (3), p.299-308
Hauptverfasser:	Straetemans, Roel, O'Brien, Timothy, Wouters, Luc, Van Dun, Jacky, Janicot, Michel, Bijnens, Luc, Burzykowski, Tomasz, Aerts, Marc
Format:	Artikel
Sprache:	eng
Schlagworte:	96-well plates Algorithms Animals Antagonism Biometry - methods Clinical Trials as Topic - methods Computer Simulation Data Interpretation, Statistical Dose-Response Relationship, Drug Drug combination Drug Combinations Drug Evaluation, Preclinical - methods Drug interaction Fixed-ratio design Hill model Interaction index Models, Biological Models, Statistical Pharmacology Plate-location effects Rats Ray design Synergy Treatment Outcome
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Beschreibung
Zusammenfassung:	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. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
ISSN:	0323-3847 1521-4036
DOI:	10.1002/bimj.200410124