Ethical challenges in neonatal research: Summary report of the ethics group of the newborn drug development initiative

Abstract

Background: The Newborn Drug Development Initiative (NDDI) was established to address the lack of substantive data supporting efficacy and safety of drugs in the neonate. Objective: This commentary summarizes some of the ethical issues involved in neonatal drug development. Methods: At the NDDI workshop held March 29 and 30, 2004, in Baltimore, Maryland, members of the Ethics Group were dispersed among the subspecialty groups before convening to discuss common ethical themes. The Ethics Group then met together to identify and discuss those ethical themes that were both important and shared among the groups. These themes are discussed and illustrated with the other NDDI group reports. This workshop was cosponsored by the National Institute of Child Health and Human Development and the US Food and Drug Administration. Results: Neonatal drug research is scientifically and ethically necessary to establish the efficacy and safety of drugs widely used in newborn medicine. However, research involving neonates must be carefully designed to balance potential risks and benefits, with consideration given to the component analysis of risk. The protocols proposed by the NDDI groups would be considered greater than minimal risk and offering prospect for direct benefit, thus adhering to the Department of Health and Human Services' pediatric research regulations (Subpart D). The NDDI groups all proposed randomized controlled clinical trials, with careful attention to scientifically and ethically appropriate control groups. Multiple regulatory bodies have affirmed that in the absence of proven effective treatment or when a proven treatment offers marginal benefits, study designs with placebo controls are ethical. Obtaining parental permission is a complex issue, with a paucity of evidence describing the feasibility of informed and voluntary consent under conditions of duress and a short therapeutic window. The Subpart D regulations offer sufficient protection to critically ill neonates. The application of the revised Subpart B regulations would restrict the use of a waiver of consent for minimal risk research and for emergency research, and would not allow research that offers no direct benefit and no more than a minor increase over minimal risk. Conclusions: Multisite collaboration involving standards of care and institutional review board procedures may be important for establishing scientific and ethical consistency. Ongoing dialogue among researchers, clinicians, parents, and other interested parties is essential to promoting ethically and scientifically sound neonatal clinical research.