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Pediatr Res. 2019 Jun;85(7):943-954. doi: 10.1038/s41390-018-0242-2. Epub 2018 Dec 24.

Recommendations for the design of therapeutic trials for neonatal seizures.

Author information

1
Boston Children's Hospital & Harvard Medical School, Boston, MA, USA. Janet.Soul@childrens.harvard.edu.
2
UCL Great Ormond Street Institute of Child Health, London, UK.
3
Johns Hopkins, Baltimore, Maryland, USA.
4
INFANT Research Centre & Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
5
Brighton and Sussex Medical School, Brighton, England.
6
Novartis Pharma Corp, Cambridge, MA, USA.
7
University of Birmingham, Birmingham, UK.
8
INSERM, UMRS1138, University Paris V and University Paris VI, Paris, France.
9
Critical Path Institute, Tucson, Arizona, USA.
10
C.S.Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
11
Division of Neurology, The Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
12
Riley Children's Hospital, Indiana University, Indianapolis, Indiana, USA.
13
Pediatric Neurology Department & INSERM U1141, APHP, Robert Debré University Hospital, Paris, France.
14
College of Medicine & Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
15
Children's Mercy Hospital, Kansas City, Missouri, USA.
16
UCL Institute for Women's Health, University College London, London, UK.
17
The Floating Hospital for Children at Tufts Medical Center and the Tufts Clinical and Translational Science Institute, Boston, MA, USA.

Abstract

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.

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