The combination index (CI < 1) as the definition of synergism and of synergy claims

The unified theory of the median-effect equation (MEE) of the mass-action law (MAL) indicates that dose and effect are interchangeable, and all dose-effect curves can be transformed into straight-lines by the median-effect plot. Therefore, it allows pharmacodynamics (PD) analysis using small size experimentation for in vitro and in vivo studies. Further, extension of MEE has proven that the Combination Index Equation (CIE) which defines Synergism (CI < 1), Additive Effect (CI = 1) and Antagonism (CI > 1), can be automatically simulated by CompuSyn software within one second after data entries. With adequate experimental accuracy of measurements, the minimum number of only 10 data points are required for quantitative synergy determination in two-drug combinations, even in animals or in clinical trials. Three articles introducing the CI method (in 1984), the review (2006), and the perspectives (2011) have been well recognized and cited 5516, 2382, and 1701 times in 1117, 768 and 530 biomedical journals, respectively (as of 2.10.2018) [Google Scholar Citations- Ting-Chao Chou]. However, the academic societies and governmental regulatory agencies are still lack of guideline on synergy definition, despite over 20 arbitrary, non-quantitative synergy definitions are still applied and reported. As drug combination is the most widely used therapies for the most dreadful diseases such as cancer and AIDS, a call for open forum on scientific credibility and accountability in these matters is warranted.