Children as research subjects: moral disputes, regulatory guidance, and recent court decisions.

The millennium has ushered in a new era of oversight for pediatric research, with renewed moral and legal attention to the upper thresholds of potential harms to which children may be exposed in studies. Watershed events discussed include: First, the deaths of two research subjects, allegedly due to insufficient oversight by the investigators and their institutional review boards. Second, the courts expressed concerns about research policies for incompetent persons or children in two cases, T.D. v. N.Y. and Grimes v. Kennedy Krieger Institute, and reinforcement of the principle that the best interest standard must be used for incompetent persons even in research. Third, the Best Pharmaceutical for Children Act and the Pediatric Rule created incentives as well as uncertainty among Institutional Review Boards and researchers about conducting pediatric studies. Fourth, the Office of Human Research Protection signaled the start of more rigorous oversight with its public rebuke and suspension of a National Institute of Child Health and Human Development pediatric obesity study. Failure to clarify the meaning of the pediatric regulations has sometimes misled generally risk-averse institutions and dedicated investigators about what is permissible.