A flexible unified approach to the analysis of pre-clinical combination studies

Combinations of drugs are increasingly being used in a variety of diseases. Pre-clinical experiments allow the responses of many drug compounds to be studied in combination with the goal of identifying compounds acting synergistically. This paper presents a unified approach to analysing data from combination studies, calculating a hierarchy of interaction indices to powerfully and flexibly describe the synergistic profile of the combination space studied, utilizing standard statistical software to generate estimates of confidence and provide statistical tests. The approach can work with a wide variety of experimental designs and response patterns and will deal with partial responses and inactive compounds. As well as identifying synergy or antagonism, the same approach can also be used to identify a benefit or detriment to monotherapy. The approach is illustrated with data from an in vitro study. Copyright (C) 2010 John Wiley & Sons, Ltd.