Classifying research proposals by risk of harm is fundamental to the approval process and the most pivotal risk category in most regulations is that of “minimal risk.” If studies have no more than a minimal risk, for example, a nearly worldwide consensus exists that review boards may sometimes: (1) expedite review, (2) waive or modify some or all elements of informed consent, or (3) enroll vulnerable subjects including healthy children, incapacitated persons and prisoners even if studies do not hold out (...) direct benefits to them. The moral and social purposes behind this threshold are discussed along with relevant views from the National Commission, NBAC, NHRPAC, Grimes v. Kennedy Krieger Institute, The Nuremberg Code, and The WMA's Declaration of Helsinki. Representative policies from Australia, Canada, South Africa, the U.S., and CIOMS are reviewed revealing different understandings of this sorting threshold. Six of nine frequently cited interpretations of “minimal risk” are untenable. The “absolute” interpretation of the “routine examination” standard is defended as best. (shrink)

United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" (§ 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition (§ 45CFR46.406) (DHHS 2001). During the 25 years since their adoption, these regulations have helped (...) IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations § § 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria. (shrink)

The institutional review board is the social-oversight mechanism charged with protecting research subjects. Performing this task competently requires that the IRB scrutinize informed-consent procedures, the balance of risks and potential benefits, and subject-selection procedures in research protocols. Unfortunately, it may be said that IRBs are spending too much time editing informed-consent forms and too little time analyzing the risks and potential benefits posed by research. This time mismanagement is clearly reflected in the research ethics literature. A review of articles published (...) between 1979 and 1990 in IRB: A Review of Human Subjects Research, for example, reveals a large number of articles on informed consent and confidentiality and considerably fewer on the assessment of risks and potential harms, study design, and subject-selection procedures. (shrink)

To what risks may children participating in research be subjected? Institutional review boards can stand surrogate for parents by filtering out studies whose risk is unacceptably high.

ABSTRACT A complex problem exists about how to promote the best interests of children as a group through research while protecting the rights and welfare of individual research subjects. The Nuremberg Code forbids studies without consent, eliminating most children as subjects, and the Declaration of Helsinki disallows non-therapeutic research on non-consenting subjects. Both codes are unreasonably restrictive. Another approach is represented by the Council for the International Organizations of Medical Science, the U.S. Federal Research Guidelines, and many other national policies. (...) They allow research ethics committees or institutional review boards to authorize studies with acceptable balances of likely benefits and harms, but neither clarify how to balance them nor explain the meaning of pivotal concepts, like “minimal risk.” Paths to the improvement of balancing or consequentialist approaches include improving standardizing of risk assessment, rejecting crude utilitarianism, identifying and justifying normative or moral judg-ments, and acknowledging extra-regulatory thresholds and deontological or non-negotiable duties to children. (shrink)