Pharmacologic studies in vulnerable populations: Using the pediatric experience

Abstract

Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics, innovative clinical trial design, use of quantitative clinical pharmacology methods, and pediatric thought leadership and collaboration have successfully overcome many existing barriers. This success has resulted in improved knowledge on pharmacokinetics, safety, and efficacy of therapeutics in children. To date, research in pregnant women has not been characterized by similar success. Wide gaps in knowledge remain despite the common use of therapeutics in pregnancy. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women.

Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children

“…In addition to these advances pediatric clinical trials are incentivized through legislative requirements enacted by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and regulatory bodies in Asia. [1][2][3] In the United States, for example, the Pediatric Research Equity Act permits the FDA to require that pediatric studies be conducted for drugs that are likely to be used in children or from which children are likely to receive significant benefit, whereas the Best Pharmaceuticals for Children Act offers extended patent protection, exclusivity, and governmental authority to request studies of off-patent drugs. 4 Despite advances, 42% of recent pediatric trials failed in achieving labeling indications, highlighting the unique difficulty of establishing drug efficacy and safety in children.…”

An evidence-based review of the use of vasoactive and inotropic medications in post-operative paediatric patients after cardiac surgery with cardiopulmonary bypass from 2000 to 2020

“…6,76 While reasons for the relative lack of studies are likely multifactorial, low consent rates, cost, and current study designs that interfere with the complex and high stakes clinical care delivered in the post-operative setting are likely key drivers. 8,77 Parental, as well as provider, stress, and anxiety, coupled with children being at significant medical and surgical risk while undergoing invasive procedures, is also likely to reduce consent rates. 78,79 Even for those patients who do get enrolled in a trial, study designs with extensive protocol-specific procedures may result in a large number of protocol deviations, study drop-outs, and decreased participation.…”

The Path to Perfect Pediatric Posology — Drug Development in Pediatrics

“…Beyond studying children of all ages, the problem of the correct dose for obese or underweight children is beginning to get attention. Perhaps more importantly, the advances that are being made to support drug development work in children, including in fragile newborns, can be extended to the study of other vulnerable populations such as pregnant and lactating women . The goal of perfect pediatric posology may indeed be at hand.…”