Modeling Order-of-addition Screening Experiments with Applications to Drug Combination

Oregon Convention Center 

There is increasing recognition that the order of administration of drugs in drug combination studies can markedly affect the outcome. Similarly, manufactured products are often sequentially produced and the final quality frequently depends on the order of assembly. Order-of-addition experiments account for the order of administration of the components, and they are quite prevalent, yet research in this area is quite limited, especially in the screening situations where there are more components to choose. We present a series of models for order-of-addition screening experiments and study their properties. We illustrate these models on a drug combination experiment which studies combinations of three antibiotics and two chemotherapy drugs in order to eliminate intracellular microbes.