Scientific Publications by FDA Staff

Clin Pharmacol Ther 2015 Sep;98(3):328-35

A survey of neonatal pharmacokinetic and pharmacodynamic studies in pediatric drug development.

Wang J, Avant D, Green D, Seo S, Fisher J, Mulberg AE, McCune SK, Burckart GJ

Conducting clinical trials in neonates is challenging, and knowledge gaps in neonatal clinical pharmacology exist. We surveyed the Food and Drug Administration databases and identified 43 drugs studied in neonates or referring to neonates between 1998 and 2014. Twenty drugs were approved in neonates. For 10 drugs, approval was based on efficacy data in neonates, supplemented by PK data for four drugs. Approval for neonates was based on full extrapolation from older patients for 6 drugs, and partial extrapolation was the basis for approval for four drugs. Dosing recommendations differed from older patients for most drugs, and used body-size based adjustment in neonates. Trial failures were associated with various factors including inappropriate dose selection. Successful drug development in neonates could be facilitated by an improved understanding of the natural history and pathophysiology of neonatal diseases and identification and validation of clinically relevant biomarkers.