Abstract
BACKGROUND: Historically, neonatal therapeutic interventions were derived from adult therapeutics, and tragedies resulting from this approach have demonstrated differences in the pathophysiologic and developmental processes between neonates and older patients. Over the past 3 decades, researchers and collaborative research networks have made progress in the systematic evaluation of neonatal therapies, yet most neonatal therapeutic products have been incompletely assessed for safety and efficacy, and remain unlabeled and unapproved. APPROACH: This work describes the legislative initiatives that have stimulated an increase in pediatric and neonatal studies. It highlights examples of successful neonatal drug studies that have resulted in informative neonatal labeling changes, as well as studies that have produced incomplete information. Strategies that support the design of successful studies, including targeting specific subpopulations, modeling and simulation to inform dose selection, innovative design strategies, biomarkers, and endpoints are discussed. Multi-stakeholder consortia such as the International Neonatal Consortium (INC), are working to improve the tools needed for the development of neonatal therapies. These research tools may be used by trial networks to inform consistent and efficient multicenter studies. CONCLUSION: More data are needed to support safe and effective use of drugs in neonates, and to obtain these data, a thorough understanding of pathophysiology, drug disposition, biomarkers, and clinically-meaningful endpoints is required. This information will be derived from clinical trials, registries, real-world evidence, and the medical literature. Collaboration of consortia and the development of research networks are essential to achieving these goals.