The Emerging Discipline of Quantitative Systems Pharmacology

In 2011, the National Institutes of Health (NIH), in collaboration with leaders from the pharmaceutical industry and the academic community, published a white paper describing the emerging discipline of Quantitative Systems Pharmacology (QSP), and recommended the establishment of NIH-supported interdisciplinary research and training programs for QSP. QSP is still in its infancy, but has tremendous potential to change the way we approach biomedical research. QSP is really the integration of two disciplines that have been increasingly useful in biomedical research; “Systems Biology” and “Quantitative Pharmacology”. Systems Biology is the field of biomedical research that seeks to understand the relationships between genes and biologically active molecules to develop qualitative models of these systems; and Quantitative Pharmacology is the field of biomedical research that seeks to use computer aided modeling and simulation to increase our understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, and to aid in the design of pre-clinical and clinical experiments. The purpose of QSP modeling is to develop quantitative computer models of biological systems and disease processes, and the effects of drug PK and PD on those systems. QSP models allow testing of numerous potential experiments “in-silico” to eliminate those associated with a low probability of success, avoiding the potential costs of evaluating all of those failed experiments in the real world. At the same time, QSP models allow us to develop our understanding of the interaction between drugs and biological systems in a more systematic and rigorous manner. As the need to be more cost-efficient in the use of research funding increases, biomedical researchers will be required to gain the maximum insight from each experiment that is conducted. This need is even more acute in the pharmaceutical industry, where there is tremendous competition to develop innovative therapies in a highly regulated environment, combined with very high research and development (R&D) costs for bringing new drugs to market (~$1.3 billion/drug). Analogous modeling & simulation approaches have been successfully integrated into other disciplines to improve the fundamental understanding of the science and to improve the efficiency of R&D (e.g., physics, engineering, economics, etc.). The biomedical research community has been slow to integrate computer aided modeling & simulation for many reasons: including the perception that biology and pharmacology are “too complex” and “too variable” to be modeled with mathematical equations; a lack of adequate graduate training programs; and the lack of support from government agencies that fund biomedical research. However, there is an active community of researchers in the pharmaceutical industry, the academic community, and government agencies that develop QSP and quantitative systems biology models and apply them both to better characterize and predict drug pharmacology and disease processes; as well as to improve efficiency and productivity in pharmaceutical R&D.