Drug-disease modeling in the pharmaceutical industry - where mechanistic systems pharmacology and statistical pharmacometrics meet

Abstract Modeling & simulation (MS and systems dynamics models, which encompass a range of models of (patho-)physiology amenable to pharmacological intervention, of signaling pathways in biology, and of substance distribution in the body (today known as physiologically-based pharmacokinetic models) – which today may be collectively referred to as quantitative systems pharmacology models (QSP). We next describe the convergence – or rather selected integration – of PMX and QSP approaches into ‘ middle-out ’ drug-disease models, which retain selected mechanistic aspects, while remaining parsimonious, fit-for-purpose, and able to address variability and the testing of covariates. We further propose development opportunities for drug-disease systems models, to increase their utility and applicability throughout the preclinical and clinical spectrum of pharmaceutical R&D.