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/ch emicals based on the interaction index. The test is developed for data resu lting from an experiment involving single-agent exposure groups and s combi nation groups of interest. The testing procedure begins with an overall siz e alpha test of additivity with s degrees of freedom. When this test is rej ected, single degree-of-freedom tests combined with post hoc corrections fo r multiple testing are developed to determine which dose combinations are a ssociated with departure from additivity. The method is illustrated using d ata associated with a patent application for a two-drug combination.