The NEMO consortium will carefully address all ethical, legal, social and safety issues as they arise. Given the particular importance attached to ethical issues in neonatal research, a separate work package for the NEMO Study, Study Monitoring and Ethics has been developed (WP 05). A Data Monitoring Commitee (DMC) have been established to oversee all activities relating to study ethics.
The neonatal population is a particularly vulnerable group, thus it is our priority to ensure that all participating NEMO centres are in full compliance with EU, national and local ethical guidelines. We carefully consulted the Recommendations of the Ad Hoc group for the development of implementing guidelines for Directive 2001/20/EC "Ethical considerations for clinical trials performed in children" when designing the work packages for clinical trial conduct and study monitoring and ethics. We are very aware of the need for rigorous ethical standards in neonatal research. Neonatal seizure treatment is an area, which has been neglected for too long. The main reasons why there are no larger, controlled studies are because of the ethical and logistic difficulties involved. By making ethics an ongoing concern throughout the project will we be able to do justice to the needs of these babies and their families.
The research activities in this study will include participation of full term newborn infants with seizures, and infants considered to be at high risk of developing seizures. Research into improving our ability to treat neonatal seizures is urgently needed. Neonatal seizures are very different to those in older children and adults, both clinically and electrographically. Therefore only research conducted in newborn babies can inform us on the efficacy and safety of bumetanide as an adjunct therapy for neonatal seizures.
The coordinator and co-coordinator of the NEMO study will implement the research project in full respect of the legal and ethical European /institutional requirements and codes of practices. The coordinator and sponsors will provide copies of Ethical approval documentation to the Commission and all approvals will be submitted prior to the commencement the trial. Procedures involving newborn infants will conform to the Helsinki Declaration (1975).
Informed consent will be obtained from the parents or guardians of all infants in the participating centres. The leader of the study monitoring and ethics work package (WP 05) will ensure that participating centres are trained in ethical and safety issues associated with the study via a one day workshop before recruitment begins in all centres (WP 02).
Placebo treatment in the neonate is ethically unacceptable. The protocol we propose for NEMO-2 would treat babies with seizures with the standard antiepileptic drug (phenobarbitone) in addition to bumetanide (study drug) or placebo. This means that at no point during the study would a baby only receive placebo or would treatment be withheld or delayed. Placebo in NEMO-2 is not equivalent to absence of treatment, but rather used as an add-on to standard care (as suggested by the "Recommendations of the Ad Hoc group for the development of implementing guidelines for Directive 2001/20/EC on "Ethical considerations for clinical trials performed in children").
"Development of safe and effective treatment strategies relies on future studies of high quality randomized controlled trials (with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden."