Under federal regulations, some research that would be approvable for adults involves more risk than is allowable for children. The regulations recognize children’s greater vulnerability and need for protection. Unfortunately, the concepts of risk on which decisions about approvable research hinge have significant subjective elements. The same applies to several other key concepts in the regulations. Reasonable people may disagree when interpreting these concepts, especially when little or no evidence is available to inform judgments. Nonetheless, if investigators and IRB members apply the definitions presented here, judgments about similar protocols should be more consistent. They should also conform more to the ethical principles underlying the regulations.
In addition, the consistency and quality of evaluations can be improved if investigators and IRB members pay more systematic attention to all the requirements (not just the provisions related to risk) included in the four sections of the DHHS and FDA regulations that set criteria for permissible research involving children. Applications for IRB approval and IRB records should include rationales related to each of the key concepts. The last chapter of this report recommends that IRBs and federal agencies provide clear, easily located guidance that will help both investigators and IRB members understand and fulfill their responsibilities.