title: Ethics of drug research in the pediatric intensive care unit.
abstract: Critical illness and treatment modalities change pharmacokinetics and pharmacodynamics of medications used in critically ill children, in addition to age-related changes in drug disposition and effect. Hence, to ensure effective and safe drug therapy, research in this population is urgently needed. However, conducting research in the vulnerable population of the pediatric intensive care unit (PICU) presents with ethical challenges. This article addresses the main ethical issues specific to drug research in these critically ill children and proposes several solutions. The extraordinary environment of the PICU raises specific challenges to the design and conduct of research. The need for proxy consent of parents (or legal guardians) and the stress-inducing physical environment may threaten informed consent. The informed consent process is challenging because emergency research reduces or even eliminates the time to seek consent. Moreover, parental anxiety may impede adequate understanding and generate misconceptions. Alternative forms of consent have been developed taking into account the unpredictable reality of the acute critical care environment. As with any research in children, the burden and risk should be minimized. Recent developments in sample collection and analysis as well as pharmacokinetic analysis should be considered in the design of studies. Despite the difficulties inherent to drug research in critically ill children, methods are available to conduct ethically sound research resulting in relevant and generalizable data. This should motivate the PICU community to commit to drug research to ultimately provide the right drug at the right dose for every individual child.
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Niina
authors.initials: N
authors.lastname: Kleiber
authors.forename: Krista
authors.initials: K
authors.lastname: Tromp
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mooij
authors.forename: Suzanne
authors.initials: S
authors.lastname: van de Vathorst
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
mesh_terms: D035843:Biomedical Research / Q000941:ethics*; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D006801:Humans; D007258:Informed Consent / Q000941:ethics; D015278:Intensive Care Units, Pediatric / Q000941:ethics*; D012307:Risk Factors