The misuse of analysis of variance to detect synergy in combination drug studies

Pain. 1993 Dec;55(3):313-317. doi: 10.1016/0304-3959(93)90006-B.


Drug combination studies often examine the possibility of synergy between drugs. Synergy is defined as an effect of a combination of drugs greater than that expected from the effects of the drugs given individually. One technique used by several investigators is the use of analysis of variance (ANOVA) to determine synergy. In this discussion, the argument is made that due to the pharmacology of drug combination studies the conditions necessary to support the use of ANOVA to detect synergy are typically not met. Therefore, the ANOVA technique is invalid for these drug combination studies.

MeSH terms

  • Analysis of Variance*
  • Dose-Response Relationship, Drug
  • Drug Synergism*
  • Kinetics
  • Receptors, Drug / drug effects
  • Research Design


  • Receptors, Drug