Summary of Categories of Research Involving Children That Are Approvable Under Subpart D of 45 CFR 46

Section 46.404: Research that involves no greater than minimal risk to children

Section 46.405: Research that involves greater than minimal risk but the risk is justified by the anticipated benefit to the participants and the relation of the anticipated benefit to the risk is at least as favorable as that presented by available alternative approaches.

Section 46.406: Research that involves greater than minimal risk and no prospect of direct benefit to research participants but (a) the risk represents only a minor increase over minimal risk, (b) the research involves experience reasonably commensurate with those inherent in the child’s medical, dental, psychological, social, or educational situations, and (c) the research is likely to yield generalizable, vitally important knowledge about the child’s disorder or condition.

Section 46.407: Research that is not otherwise approvable but that the IRB and the Secretary of DHHS determine presents an opportunity to understand, prevent, or alleviate a serious problem affecting children’s health or welfare and will be conducted in accordance with sound ethical principles.

NOTE: The corresponding regulations for the FDA are found at 21 CFR 50.51 to 50.54.

protections for child participants are, in general, appropriate for children of different ages. They reasonably defer to state laws that define both the age at which individuals become entitled to make medical care decisions and the special circumstances under which minors may make such decisions in their own right (e.g., for care related to sexually transmitted diseases).

For the most part, the problems with the regulations relate to insufficient government guidance about their interpretation and implementation, shortfalls in data about implementation and compliance, and variability in investigator and IRB interpretations of the criteria for approving research involving children. Some of these criteria include inherently subjective elements that the committee doubts would be substantially and predictably clarified by revising the regulations. As discussed below, one change that the committee does recommend is that FDA make its policies consistent with those of DHHS that allow the waiver of parental permission for children’s, especially adolescents’, participation in research when permission is not a reasonable requirement to protect a child. Another recommendation is that all research that includes infants, children, and adolescents should occur under the umbrella of a formal program for the protection of human research participants (Recommendation 8.1). Because the federal

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