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, 85 (7), 943-954

Recommendations for the Design of Therapeutic Trials for Neonatal Seizures


Recommendations for the Design of Therapeutic Trials for Neonatal Seizures

Janet S Soul et al. Pediatr Res.


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.

Conflict of interest statement

Two co-authors are employees of a pharmaceutical company, as noted in the list of affiliations. No products are discussed in this article. The consortium aims to improve methods that can be applied to evaluating the safety and effectiveness of any medical product for neonates and is consequently drug agnostic.


Fig. 1
Fig. 1
Seizure workgroup collaborators
Fig. 2
Fig. 2
Delphi process to develop neonatal seizure trial recommendations
Fig. 3
Fig. 3
Seizure treatment diagram

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