The blog of the 2009 – 2017 Presidential Commission for the Study of Bioethical Issues

In Safeguarding Children, Commission provides guidance for application of section 407

Most pediatric research can be approved by an institutional review board (IRB) if it poses only minimal risk, offers the prospect of direct benefit, or yields vitally important generalizable information about the participants’ condition. When a pediatric research proposal does not fit within these confines, to move forward, it must be elevated to national-level review under section 407 of 45 C.F.R. Part 46. Section 407 regulates pediatric research that poses higher risk to healthy children without the prospect of direct benefit.

Although some types of pediatric medical countermeasure (MCM) research might be approvable by an IRB as minimal risk, higher risk pediatric MCM research might require national-level review. In its report, Safeguarding Children: Pediatric Medical Countermeasure Research, the Presidential Commission for the Study of Bioethical Issues (the Bioethics Commission) provides much needed guidance for national-level review in the MCM context.  

In order to be approved under section 407, the Secretary of Health and Human Services, in consultation with a national review panel, must find that the research (i) presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children; (ii) will be conducted in accordance with sound ethical principles; and (iii) makes adequate provisions for soliciting parental permission and meaningful child assent.

In formulating the recommendation that was adopted as section 407 three decades ago, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (the National Commission) expressed the view in its report, Research Involving Children, that research presenting more than minimal risk to healthy children without the prospect of direct benefit could only be justified if the research is of major significance, if it addresses a grave and serious health problem, and if the expected benefit is significant.

The serious health problem the National Commission had in mind at the time was polio, and its members did not want their recommendations to be so restrictive that they would have prevented important pediatric research on polio vaccines (http://pediatrics.aappublications.org/content/113/6/1783.full). The National Commission also considered that there might be extraordinary situations in which the dangers of not involving children in more than minimal risk research are so great that it would be unethical to exclude them.

Critics of section 407 argue that its application has not conformed to the intent of the National Commission’s original recommendations.  Instead of reserving section 407 for exceptional situations, for example, IRBs might advance protocols for national-level review simply because they cannot be approved under other provisions that govern the majority of pediatric research. This has resulted in a situation where section 407 has sometimes been treated as a “catchall” for research that should be amended to conform to other approval mechanisms or possibly foregone.

Use of section 407 is further complicated by the fact that it fails to specify the “sound ethical principles” that should govern research under its purview and does not explain how to determine what constitutes a “serious problem.”  While this broad language lends national-level reviewers flexibility to take the particulars of each case into account, it has resulted in uncertainty among panels regarding the interpretation and application of these standards.

In order to successfully address ethical issues in pediatric MCM research, the Bioethics Commission needed to address the ambiguities of section 407 and clarify its guidelines. The recommendations in Safeguarding Children stipulate the circumstances in which a research protocol should proceed to national-level review under section 407, defines the terms and standards provided by section 407, and specifies ethical principles that should be used to assess research under section 407.

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This is a space for the members and staff of the 2009 -2017 Presidential Commission for the Study of Bioethical Issues to communicate with the public about the work of the commission and to discuss important issues in bioethics.

As of January 15th, 2017 this blog will no longer be updated but continues to be available as an archive of the work of the 2009-2017 Presidential Commission for the Study of Bioethical Issues

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