Conceptual and organizational barriers to quantitative systems pharmacology modeling of pathophysiological systemic drug hypotheses

Pharmaceutical research and development (R&D) relies on developing good systemic hypotheses about the effect of novel drug mechanisms on pathophysiology. Although quantitative systems  pharmacology (QSP) has been advocated many times for this purpose,1–3 there are still conceptual and organizational barriers hindering the strategic use of this type of computational modeling. In the next sections, we describe these barriers one by one and indicate how they could be overcome. Without loss of generality, we refer to central nervous system (CNS) drug research.