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Neonatal Safety Information Reported to the FDA During Drug Development Studies

  • Product Safety: Original Research
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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.

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Abbreviations

ADR:

adverse drug reaction

AE:

adverse event

BPCA:

Best Pharmaceuticals for Children Act

FAERS:

FDA Adverse Event Reporting System

FDASIA:

Food and Drug Administration Safety and Innovation Act

NICU:

neonatal intensive care unit

PREA:

Pediatric Research Equity Act

SAE:

serious adverse event

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Author information

Authors and Affiliations

  1. Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, 10903 New Hampshire Ave, Bldg 32, Rm 5153, Silver Spring, MD, 20993, USA

    Debbie Avant RPh, Gerri Baer MD & Ron Ariagno MD

  2. Office of Clinical Pharmacology, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD, USA

    Jason Moore PharmD & Gilbert J. Burckart PharmD

  3. Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA

    Jason Moore PharmD

  4. University of North Carolina School of Pharmacy, Chapel Hill, NC, USA

    Panli Zheng BS

  5. Office of Translational Sciences, US Food and Drug Administration, Silver Spring, MD, USA

    Alfred Sorbello DO, MPH

  6. Stanford University School of Medicine, Stanford, CA, USA

    Ron Ariagno MD

  7. Division of Pediatric and Maternal Health, Office of New Drugs, CDER, US Food and Drug Administration, Silver Spring, MD, USA

    Lynne Yao MD

  8. Office of Drug Evaluation IV, CDER, US Food and Drug Administration, Silver Spring, MD, USA

    Jian Wang PhD

Authors
  1. Debbie Avant RPh
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  2. Gerri Baer MD
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  4. Panli Zheng BS
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  5. Alfred Sorbello DO, MPH
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  6. Ron Ariagno MD
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  7. Lynne Yao MD
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  8. Gilbert J. Burckart PharmD
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  9. Jian Wang PhD
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Correspondence to Debbie Avant RPh.

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Avant, D., Baer, G., Moore, J. et al. Neonatal Safety Information Reported to the FDA During Drug Development Studies. Ther Innov Regul Sci 52, 100–108 (2018). https://doi.org/10.1177/2168479017716713

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  • DOI: https://doi.org/10.1177/2168479017716713

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