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Pediatric Pharmacokinetic Studies Inform Children’s Standard Care: Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (POPS) JOY HOLMES, BSN; LACY MALLOCH, BS; EUGENE MELVIN, MS; JOSEPH MARC MAJURE, MD; DAVID JOSEY, MD; CRYSTAL S. LIM, PHD; LAUREN C. TUCKER, MD; AND ROBERT D. ANNETT, PHD
Abstract Limited information is known about the safety, efficacy, and pharmacokinetics of many medications used in the standard of care of children. Due to the lack of data, drug dosing in pediatrics is often extrapolated from adult studies. In fact, pharmacologic research in adults has been extrapolated to provide recommendations for dosing specifications for approximately 80% of the medications used in standard care in pediatric populations. The Best Pharmaceuticals for Children Act (BPCA) prioritizes therapeutic needs, including support for pediatric labeling, sponsoring pediatric trials, and submitting data leading to labeling changes in pediatric medications. The Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (POPS) utilizes information from medications given in routine care of children to identify the pathophysiologic factors causing changes in the dose-concentration relationship and the extent of changes so that medication labeling can be modified. This article describes POPS, its implementation, and characterizes implementation challenges and successes.
Keywords: Pharmacokinetics, children, standard of care Introduction Approximately 80% of medications used in the standard care of children have not been studied for safety, efficacy, and dosing.1 Pharmacologic research with adults has often been extrapolated to provide dosing specification recommendations for children based on the Food and Drug Administration’s (FDA’s) pediatric study decision tree.2 The most recent reauthorization of the Best Pharmaceuticals for Children Act (BCPA) recognizes the need for the industry to conduct pediatric studies to improve labeling of medications used to treat children. A significant gap exists in our understanding of how medications developed in adult trials can safely be used in the care of
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children. With this legislation in mind, the National Institute of Child Health and Human Development initiated the Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care, or POPS, study. This study is designed to increase our understanding of medications used to care for children through the power of population pharmacokinetics. Specifically, the purpose of POPS is to characterize the pharmacokinetics, explore the pharmacodynamics, and explore biomarkers associated with understudied drugs administered to children as prescribed per standard of care. Thus, findings from POPS will advance the care for children with increased understanding of how medications work among different age groups and may result in modifying labeling for drugs currently widely used in the pediatric population. In an effort to expand recruitment sites, POPS investigators forged a collaboration with the National Institutes of Health (NIH) Environmental Influences on Child Health Outcomes program (ECHO) and specifically the Institutional Development Award (IDeA) program’s pediatric clinical trials network initiative. Mississippi and the University of Mississippi Medical Center (UMMC) have been recipients of funding to establish a local site for the IDeA States Pediatric Clinical Trials Network (the Network), making POPS one of the first pediatric studies to be launched as a result of our local network resources. UMMC is currently one of 17 network sites recruiting participants for POPS, which has been enrolling since 2011. By linking multiple clinical sites, sufficient enrollment of children can occur more efficiently, and the resulting knowledge gained can be rapidly translated and thus provide information for children’s care. In this article we describe the POPS study, how it is being implemented at UMMC, and characterize the challenges and successes related to implementation.
