Pediatric research posing a minor increase over minimal risk and no prospect of direct benefit: challenging 45 CFR 46.406

Subpart D of the Common Rule establishes 4 categories of research that may be conducted on children. One category, 45 CFR 46.406, permits research posing a minor increase over minimal risk and no prospect of direct benefit but expected to yield vital knowledge about the subjects' disorder or condition. To include other children in research posing a minor increase over minimal risk and no prospect of direct benefit requires federal review and approval of the Secretary of Health and Human Services under 45 CFR 46.407. It is widely held that children generally should not be exposed to more than minimal risk in research without the prospect of direct benefit. To justify deviating from this norm, as 406 allows, two claims must be true: (1) When there is vital knowledge to be gained from studying children, it is permissible to expose some children to a minor increase over minimal risk with no prospect of direct benefit; (2) It is permissible for locally reviewed and approved research to expose only children with the disorder or condition under investigation to greater risk with no prospect of direct benefit. The justification for (1) appears to be grounded in the magnitude of benefit to society combined with the need to study children. This article demonstrates that, even if the necessity and magnitude of benefit to society justify exposing children to increased risk, the decision to categorically restrict participation in such research to children with the disorder or condition under investigation (unless the study is federally reviewed and approved) is not justified. Subpart D should be revised.