Pharmacometrics in pharmaceutical industry; Perspective in pharmacology

Abstract

The term pharmacometrics originally covers wide scope of quantitative modeling and simulation (M&S) concept and discipline, which emerged from academic interest about a century ago, then, have been applied to drug research and development since about 30 years ago. During the period, diversity of M&S methods have come up and provided industry R&D with various aids for business success. An EFPIA working group published a white paper "Good Practice in Model-Informed Drug Discovery and Development", or briefly "MID3" paper in CPT Pharmacometrics Systems Pharmacology, in which M&S methods being applied to drug R&D are comprehensively classified and characterized for their roles and values. In this paper, M&S is classified into two groups, one is "pharmacometrics" in narrower sense, while the other is "systems pharmacology". The former is based mostly on conventional compartment model, including so-called PKPD, population PK(PD), etc. This group of model is developed with assuming a conceptual model and fitting it to PK(PD) data obtained in vivo. The latter group (systems pharmacology) is based on systems data relevant to drug actions which are obtained independently regardless of dosing drug(s) to animals or human. The model is not specific to a certain drug but used generally for the same mechanism of drugs, thus, capable to accumulate and utilize vast scope of knowledge-/data-base. These two groups of models are also called "top-down" and "bottom-up" approaches. They differ in their strength and weakness, but have a common trend in the last decade, that is, both are increasingly used for drugs' pharmacologic actions, efficacy and safety. For pharmaceutical industry, the most business critical milestone is Phase II, thus, designing, conducting the pivotal study optimally and assessing the results wisely are key practices. "Disease models" are proposed and exercised in both types of models, supporting drug development differently, also evolving rapidly particularly as the "quantitative systems pharmacology" (QSP) approach.