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.

A Literature Review of the Pharmacokinetics and Pharmacodynamics of Dobutamine in Neonates

“…The influence of critical illness, such as renal or liver failure, release of vasoactive cytokines, as well as specific therapies such as extracorporeal membrane oxygenation will influence dosing regimens [35]. For example, in neonates undergoing total body cooling there is animal evidence that dobutamine will accumulate, presumably due to a reduction in the activity of catechol-O-methyl transferase [70].…”

“…Both the European Medicines Agency in their priority list for studies into off-patent pediatric medicinal products and the US National Institutes of Health in their Best Pharmaceuticals for Children Act have highlighted dobutamine as a drug that requires further investigation [18,35].…”

Pregled poticaja za razvoj pedijatrijskih lijekova i broja pedijatrijskih kliničkih ispitivanja faze III u izabranim državama

“…Podaci o primjeni lijekova ekstrapoliraju se iz podataka za odraslu populaciju, zbog čega doziranje predstavlja glavni izazov u terapijama pedijatrijske populacije [3][4] . No, svaki lijek korišten u praksi, koji nije ispitan u kliničkim ispitivanjima, može se smatrati eksperimentom 5 . Zakonodavni čimbenici, manjak gospodarskog interesa farmaceutske industrije, odraz negativnih rezultata na upotrebu lijeka u odrasloj populaciji te odgođene neželjene reakcije na lijekove uzrok su nedostataka podataka o primjeni lijekova u pedijatrijskoj populaciji, što tu populaciju dovodi do statusa 'terapijske siročadi' [6][7][8] .…”

Uncertainty in Antibiotic Dosing in Critically Ill Neonate and Pediatric Patients: Can Microsampling Provide the Answers?

“…There are challenges associated with performing pharmacokinetic studies in neonatal and some pediatric patients due to their small blood volumes and the psychological burden associated with blood sampling. 25 Studies have found that pediatric intensivists are in ethical conflict about performing potentially life-saving drug research, even while identifying them as ethically acceptable. 25 Yet, this information is important for optimizing the treatment of their patients.…”