Design and analysis of drug combination experiments

Roel Straetemans; Timothy O'Brien; Luc Wouters; Jacky Van Dun; Michel Janicot; Luc Bijnens; Tomasz Burzykowski; Marc Aerts

doi:10.1002/bimj.200410124

Design and analysis of drug combination experiments

Biom J. 2005 Jun;47(3):299-308. doi: 10.1002/bimj.200410124.

Authors

Roel Straetemans¹, Timothy O'Brien, Luc Wouters, Jacky Van Dun, Michel Janicot, Luc Bijnens, Tomasz Burzykowski, Marc Aerts

Affiliation

¹ Limburgs Universitair Centrum, Center for Statistics, Biostatistics, Universitaire Campus, B-3590 Diepenbeek, Belgium. [email protected]

PMID: 16053254
DOI: 10.1002/bimj.200410124

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Animals
Biometry / methods*
Clinical Trials as Topic / methods*
Computer Simulation
Data Interpretation, Statistical*
Dose-Response Relationship, Drug
Drug Combinations*
Drug Evaluation, Preclinical / methods*
Models, Biological*
Models, Statistical
Rats
Treatment Outcome

Substances

Drug Combinations