Physicians and others conducting medical research involving children as participants face some incredibly difficult questions. In the United States such research is generally governed by federal regulations known as the Common Rule (45 CFR 46), ie, the regulations governing virtually all medical research in the federal nexus. In particular, research involving children as participants is governed by Part D.
Some remarkably complex issues arise; for example, what are the differences between research associated with interventions resulting in a direct benefit to a participant and research conducted among normal healthy volunteers? How do regulations governing research involving minimal risk differ from those governing research involving a minor increase over minimal risk? What is the difference between minimal risk and a minor increase above that level of risk? What are the circumstances when it is morally and legally acceptable to expose a child to more than this level of risk, and what special rules (called “407 rules”) apply? Is it justifiable to expose a child with a “disorder or condition” to a greater research risk than one without? Do persons at risk for a disease have a condition, or are they merely at risk for a condition? Is it morally preferable to tell children or their parents the results of research or to get their agreement not to be told of the results? What is the difference between permission and assent, and how do each of these relate to consent? When is consent of both parents required, and when will one parent's consent suffice? Can phase 1 trials be said to offer direct benefit to participants?