Fig. 4

Schematic diagram of the models for evaluating combination effects. Effect-based models: a Highest Single Agent model : CI = max (EA, EB)/EAB, the significance of a positive combination is given by the P value of the statistical test compared to the HSA. b Response Additivity model : CI = (EA + EB)/EA, the drug combination is positive when EAB is greater than the sum of the individual effects EA and EB. c Bliss Independence model: CI = (EA + EB – EAEB)/EAB, the drug combinations based on the assumption that drugs act independently on distinct action sites. d Concentration-based model: d Loewe Additivity model : CI= a/A + b/B, this flexible model provides isobol representation in addition to the algebraic analysis