Ethical assessment of pediatric research protocols.

Specific regulations regarding oversight of research in children vary from country to country, but most share common principles derived from major consensus documents. Whereas the permissibility of research on adults depends heavily upon the informed consent of the subject, the regulation of research in pediatrics is focused primarily upon protection of the subjects from research risks. Since patients who require intensive care are commonly at high risk for complications related to the severity of their illnesses, justifying the risks of research on critically ill children may therefore be particularly challenging. Use of an approach known as "component analysis" can be very helpful in separating the risks attributable to the medical care itself from those that should be ascribed to the research. After identifying and isolating the research interventions, a three-step approach is helpful for evaluating the "net risks" of the research: (1) Separate each component of the research into discrete interventions. (2) Any intervention for which the benefits equal or exceed the risks is ethically justified. (3) For interventions in which the risks exceed the benefits, the "net risk" for each intervention needs to be justified, as follows: (a) the interventions may not exceed the locally defined threshold for pediatric research (e.g., not greater than a minor increment more than minimal risk, as in the U.S. regulations); and (b) the scientific value of the study for improving the care of future children must be sufficient to justify the sum of the net risks of the research interventions.