Abstract
The regulations dictating acceptable levels of risk in pediatric research were developed to protect pediatric research participants from unnecessary or excessive harms. These special protections were adopted in 1983 by the Department of Health and Human Services (DHHS) as part of what is generally referred to as Subpart D of the Common Rule, and have not undergone any evaluation or substantive revision in over 35 years. As pathways for drug development become more complex and with more innovative interventions, investigators and institutional review boards (IRBs) are increasingly evaluating complex protocols with research interventions for children that may represent, “a minor increase over minimal risk, without the potential for direct benefit.” Determinations of what interventions represent a minor increase are subjective, and as evidenced by the two research ethics cases in this issue, the pathway for approving studies that may involve more than a minimal increase in risk, without potential for immediate direct benefit, is poorly defined.