Pharmacometrics and Clinical Trial Design Core

Summary (Pharmacometrics and Clinical Trial Design Core) The Pharmacometrics and Clinical Trial Design (PCTD) Core of the Indiana University-Ohio State University Maternal and Pediatric Precision in Therapeutics Data, Model, Knowledge, and Research Coordination Center (IU-OSU MPRINT DMKRCC) will provide expertise in pharmacometrics and clinical trial design relating to maternal and pediatric therapeutics. The PCTD will also integrate data from the Knowledgebase and Portal Core, Real World Evidence Core, and other collaborators to support development of pharmacometric models in pregnant and lactating women and children to provide mechanistic insight into changes in drug disposition and response across the lifespan and sources of inter- and intra-individual variability. The Aims of the PCTD will 1) bring together pharmacometricians and clinical pharmacologists with expertise in obstetrics and pediatrics to contribute to guidelines for data quality, utilize cutting-edge pharmacometric and data science methods (in conjunction with Knowledgebase Core), and assist in developing and analyzing data from obstetric-pediatric clinical pharmacology research; 2) Facilitate utilization of data and identification of gaps in knowledge from in vitro, preclinical, and clinical studies by incorporating this information into integrative physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) models that encompass dynamic changes in maternal physiology across gestation and postpartum, including lactation models, link to neonates, and describe maturation throughout childhood. PBPK-PD models will incorporate critical sources of inter- and intra-individual variability, including but not limited to pharmacogenomics, obesity, concomitant disease, and disability, to provide a platform to inform precision therapy in maternal and child health; and 3) Serve as a national and international resource by enhancing model informed drug development, clinical study design and personalized pharmacotherapy at various stages of pregnancy and pediatric development through implementation of novel pharmacometric modeling approaches. The PCTD will work with the MPRINT Hub Steering Committee to set research priorities and milestones and with the Outreach, Dissemination and Training Core to disseminate results and provide education on pharmacometric approaches applied to maternal and pediatric therapeutic research.