Experiment Designs for the Assessment of Drug Combination Synergism

We review the concepts and the processes leading to the formation of a Combination Index to quantitatively depict combination effects in the evaluation of combination chemotherapies. We raise the important possibility that synergistic results found and published in hundreds, even thousands, of articles on drug combinations maybe over-assessed; many or most results could simply be false positives. We then propose the formation of two Combination Indices to quantitatively depict combination effects in the evaluation of combination chemotherapies; one for the Lowe additive model and one for the Bliss multiplicative model. Within that modeling framework, we will focus on the experiment designs for the assessment of drug combination synergism preceding the formation of a proper combination index.