TY - JOUR
T1 - Recommendations for the design of therapeutic trials for neonatal seizures
AU - for the International Neonatal Consortium
AU - Soul, Janet S.
AU - Pressler, Ronit
AU - Allen, Marilee
AU - Boylan, Geraldine
AU - Rabe, Heike
AU - Portman, Ron
AU - Hardy, Pollyanna
AU - Zohar, Sarah
AU - Romero, Klaus
AU - Tseng, Brian
AU - Bhatt-Mehta, Varsha
AU - Hahn, Cecil
AU - Denne, Scott
AU - Auvin, Stephane
AU - Vinks, Alexander
AU - Lantos, John
AU - Marlow, Neil
AU - Davis, Jonathan M.
N1 - Funding Information:
The International Neonatal Consortium would like to acknowledge the following people for their review and feedback of the document: Sylvie Benchetrit—Paediatric Committee of the European Medicines Agency (PDCO) and French Medicine Agency ANSM. Teresa Buracchio—US Food and Drug Administration. Maria Donovan—University College Cork. Billy Dunn—US Food and Drug Administration. Wakako Eklund—National Association of Neonatal Nurses; Pediatrix Medical Group of TN/Louisiana Tech University. Pierre Gressens—Diderot University Paris. Richard Haas—University of California, San Diego. Masahiro Hayakawa—Nagoya University Hospital. Kun Jin—US Food and Drug Administration. Carole Kenner—Council of International Neonatal Nurses (COINN). Skip Nelson—US Food and Drug Administration. Philip Sheridan—US Food and Drug Administration. Karen Walker—Australian College of Neonatal Nurses and COINN. Bob Ward—University of Utah, Jennifer Zimmer—Eli Lilly and Company. The International Neonatal Consortium (INC) is supported in part by grant number U18FD005320-01 from the US Food and Drug Administration (FDA) to the Critical Path Institute (http://c-path. org) and through annual dues of member companies.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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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U2 - 10.1038/s41390-018-0242-2
DO - 10.1038/s41390-018-0242-2
M3 - Review article
C2 - 30584262
AN - SCOPUS:85061215146
VL - 85
SP - 943
EP - 954
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 7
ER -