title: The promises of quantitative systems pharmacology modelling for drug development.
abstract: Recent growth in annual new therapeutic entity (NTE) approvals by the U.S. Food and Drug Administration (FDA) suggests a positive trend in current research and development (R&D) output. Prior to this, the cost of each NTE was considered to be rising exponentially, with compound failure occurring mainly in clinical phases. Quantitative systems pharmacology (QSP) modelling, as an additional tool in the drug discovery arsenal, aims to further reduce NTE costs and improve drug development success. Throughin silicomathematical modelling, QSP can simulate drug activity as perturbations in biological systems and thus understand the fundamental interactions which drive disease pathology, compound pharmacology and patient response. Here we review QSP, pharmacometrics and systems biology models with respect to the diseases covered as well as their clinical relevance and applications. Overall, the majority of modelling focus was aligned with the priority of drug-discovery and clinical trials. However, a few clinically important disease categories, such asImmune System DiseasesandRespiratory Tract Diseases, were poorly covered by computational models. This suggests a possible disconnect between clinical and modelling agendas. As a standard element of the drug discovery pipeline the uptake of QSP might help to increase the efficiency of drug development across all therapeutic indications.
authors.affiliation: Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: V R
authors.initials: VR
authors.lastname: Knight-Schrijver
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: V
authors.initials: V
authors.lastname: Chelliah
authors.affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: L
authors.initials: L
authors.lastname: Cucurull-Sanchez
authors.affiliation: Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: N
authors.initials: N
authors.lastname: Le Novère
keywords: Drug discovery; Modelling; New therapeutic entity; QSP; Quantitative systems pharmacology; Systems biology