Ting-Chao (David) Chou

Memorial Sloan-Kettering Cancer Center & PD Science LLC, USA

Title: Mass-action law pharmacodynamics (MAL-PD) theory/equation/algorithm based general design, analytical computer-simulation for biomedical research techniques and digital/indexed conclusions

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Biography

Prof. Ting-Chao Chou, theoretical biologist, pharmacologist and cancer researcher, was born in Taiwan. He received Ph.D. in Pharmacology from Yale University and Post-Doc. at Johns Hopkins University School of Medicine. He was a Member at Memorial Sloan-Kettering Cancer Center (MSKCC) and Professor of Pharmacology at Cornell University Graduate School of Medical Sciences in 1988. He retired from MSKCC in 2013 and established PD Science LLC. Dr. Chou pioneered the Mass-Action-Law based Pharmacodynamics (PD) General Theory (median-effect equation, algorithm and plot), and the Combination Index (CI) theorem, which quantitatively determine synergy as (CI<1) by computer simulation. His article (1984) introducing the MAL-PD/CI method has 7,371 citations in over 1,420 biomedical journals internationally. Dr. Chou’s published 375 papers have garnered over 38,000 citations with an h-index of 74. Currently, he advocates for MAL based quantitative, cost-effective biomedical R&D/Precision Translational Medicine, and PD/BD-based modernization of basic guidelines-and-regulations for new drug evaluations.

Abstract

Specific-biomedical R&D techniques such protein assay and DNA sequencing are broadly used internationally. Due to complexity and diversity of biological system, the unified general/basic physical, chemical and mathematical principle of the MAL-PD is need as the largest common-denominator to simplify and integrate the complex bio-systems. This paper shares and illustrates that MAL-PD as indicated by (A) the unified median-effect eq. and plot, (MEE and MEP), which also called Doctrine of the Median, DoM) that provides potency (Dm) and shape (m) PD-parameters for individual drugs; and by (B) the general combination index equation (CIE), algorithm, and automated computer simulation, where CI<1, =1, and >1 determined synergism, additive-effect, and antagonism, respectively. Since each terms of both MEE and CIE are “relativity ratio” (dimensionless), therefore, the MAL-PD and CI theory/method is regardless of mechanisms, units, and whether the studies are carried out in vitro (molecular, cellular), in animals or in clinical trial protocol design/data analysis, thus bridging basic sciences with clinical studies under the same theory/principle. In addition, MEP linearizes all PD dose-effect curves (DEC), which lead to the “Minimum Two Dose-data Points Theory” (MTDPT) of MAL-PD and CI, which is especially valuable in animal studies and in clinical trials, where dose-range and dose-density are practically limited.  Thus MAL-PD/CI provide new paradigm for general principle/method for simple, efficient, cost-effective, computer simulation automation and digital/indexed conclusions. MTDPT indicates that single dose of any drug can not satisfy PD studies (i.e., a single point has no shape), and thus impossible to determine synergism or antagonism. Because of simple, flexible features of MAL-PD/CI theory/method, three articles are highly and broadly cited for (i) Original PD/CI theory (TC Chou & P. Talalay, Adv.Enz.Regul. 22:27-55.1984), (ii) General review (TC Chou, Pharmacol.Rev. 58:621-681.2006) and (iii) Perspectives (TC Chou, Can.Res.70:440-446.2010) with a total of 15,866 citations as of October 20,2021.