Ethical concerns about federal approval of risky pediatric studies.

The US Federal Code limits research with healthy children to no more than a minimal risk of harm; it restricts research with children who have some disorder or condition to no more than a minor increase over minimal risk, unless potential harms are offset by potential benefits to them, as in therapeutic studies. Higher risk studies require "407 approval," named after the relevant section of the code describing requirements. Rarely used until recently, 407 approval requirements include Institutional Review Board approval and authorization by the Secretary of the Department of Health and Human Services after consultation with a panel of experts; a period for public comment; and assurances that there are adequate permission, consent, and assent. This 407-approval mechanism contains both procedural and interpretative ambiguities, which raise ethical concerns about 1) the expertise represented on advisory panels, 2) the scope of the information offered to the public for comment and its potential conflicts with investigators' intellectual property or commercial interests, 3) whether any upper level of risk exists, and 4) how it conforms with other policies such as the best interest of the child standard in the law or in medical decision making.