A statistical test for detecting and characterizing departures from additivity in drug/chemical combinations

In this paper, we propose a test of additivity in a combination of drugs/chemicals based on the interaction index. The test is developed for data resulting from an experiment involving single-agent exposure groups and s combination groups of interest. The testing procedure begins with an overall size alpha test of additivity with s degrees of freedom. When this test is rejected, single degree-of-freedom tests combined with post hoc corrections for multiple testing are developed to determine which dose combinations are associated with departure from additivity. The method is illustrated using data associated with a patent application for a two-drug combination.