Testing for Excess Over Highest Single Agent with an Application to High-throughput Screening of Pairs of Compounds
John J. Peterson
Abstract: Combination drug therapy offers much promise for discovering pharmaceutical treatments that are efficacious and safe. A key efficacy criterion for a combination of two compounds is that the combination is superior to both of its component compounds used alone. This article proposes a simultaneous testing procedure, based upon step-down trend tests, that identifies dose combinations for pairs of compounds that produce efficacy results with excess over highest single agent (i.e. the combination is superior to both of the component compounds). This testing procedure is applied to data from experiments for a pilot high-throughput screening study for pairs of compounds evaluated at nine dose levels using 9×9 factorial experiments. This procedure is easily automated and can be computed using the SAS® MULTTEST procedure.
