ABSTRACT
Because complex diseases such as advanced tumors are often resistant to single agents, there is an increasing trend to combine drugs to achieve better treatment effect and reduce safety issues. It is desirable that the combination drugs are synergistic; that is, better activity is achieved at lower dose levels when drugs are combined than when they are individually observed at single drug doses. Depending on component drugs, a combination therapy can yield activity that is synergistic, independent, or antagonistic. Commonly used statistical models to evaluate drug combination efcacy are the Loewe additivity and Bliss independence models (Bliss, 1939). In brief, Loewe additivity model (Loewe and Muischnek, 1926) uses the synergy index τ to describe the effect of combination therapy (see Chapters 2 and 4 for a detailed discussion). When τ < 1, it means that the two drugs in combination achieve better treatment effect than the individual agents with a lower total amount of drugs. Bliss independence model, reliant on probabilistic concept of independence, uses the interaction index I to characterize synergistic effect. When I > 0, the two drugs have positive interaction and produce an effect that is better than those obtained when the components drugs are used individually. In literature, additivity and independence are synonymous with no drug interaction.
