Design and analysis of drug combination experiments

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


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


  • Drug Combinations