Neonatal Safety Information Reported to the FDA During Drug Development Studies

Debbie Avant; Gerri Baer; Jason Moore; Panli Zheng; Alfred Sorbello; Ron Ariagno; Lynne Yao; Gilbert J Burckart; Jian Wang

doi:10.1177/2168479017716713

Neonatal Safety Information Reported to the FDA During Drug Development Studies

Ther Innov Regul Sci. 2017:2017:1-9. doi: 10.1177/2168479017716713. Epub 2017 Jun 28.

Authors

Debbie Avant¹, Gerri Baer¹, Jason Moore^{2

3}, Panli Zheng⁴, Alfred Sorbello⁵, Ron Ariagno^{1

6}, Lynne Yao⁷, Gilbert J Burckart², Jian Wang⁸

Affiliations

¹ Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, USA.
² Office of Clinical Pharmacology, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD, USA.
³ Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.
⁴ University of North Carolina School of Pharmacy, Chapel Hill, NC, USA.
⁵ Office of Translational Sciences, US Food and Drug Administration, Silver Spring, MD, USA.
⁶ Stanford University School of Medicine, Stanford, CA, USA.
⁷ Division of Pediatric and Maternal Health, Office of New Drugs, CDER, US Food and Drug Administration, Silver Spring, MD, USA.
⁸ Office of Drug Evaluation IV, CDER, US Food and Drug Administration, Silver Spring, MD, USA.

Abstract

Background: Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015.

Methods: FDA databases were searched for BPCA and/or PREA studies that enrolled neonates. Studies that enrolled a minimum of 3 neonates were analyzed for the presence and content of neonatal safety data.

Results: The analysis identified 40 drugs that were studied in 3 or more neonates. Of the 40 drugs, 36 drugs received a pediatric labeling change as a result of studies between 1998 and 2015, that included information from studies including neonates. Fourteen drugs were approved for use in neonates. Clinical trials for 20 of the drugs reported serious adverse events (SAEs) in neonates. The SAEs primarily involved cardiovascular events such as bradycardia and/or hypotension or laboratory abnormalities such as anemia, neutropenia, and electrolyte disturbances. Deaths were reported during studies of 9 drugs.

Conclusions: Our analysis revealed that SAEs were reported in studies involving 20 of the 40 drugs evaluated in neonates, with deaths identified in 9 of those studies. Patients enrolled in studies were often critically ill, which complicated determination of whether an adverse event was drug-related. We conclude that the traditional means for collecting safety information in drug development trials needs to be adjusted for neonates and will require the collaboration of regulators, industry, and the clinical and research communities to establish appropriate definitions and reporting strategies for the neonatal population.

Keywords: US FDA; drug development; neonates; safety; serious adverse events.

Abstract

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