[Speech]

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need be requirements to conduct studies in children concomitantly with those in adults. It is
better to expose children to the risks of research than the risks of unscientific clinical
practice.
Conceptual vagueness of the regulations. Let me turn to the federal
regulations, as this will provide a framework for understanding some of the remaining
problems for the participation of children in research. The regulations stipulate that if
research is not greater than minimal risk, then the permission of the parent and the assent of
the child, to the extent capable, is sufficient. There are two issues to note. First is the
acknowledgment that depending on their maturity level, children should have a greater role
in the decision to participate in research. More conceptual work may be needed to flesh out
how this should work operationally.
The second point is that if studies involve greater than minimal risk, the IRB is to
make a normative decision that the potential risks are balanced by the benefits of the study,
prior to parents being given the option of permitting their children to participate. The IRB
should attempt to "track those decisions that would be made by informed and scrupulous
parents."
The threshold criteria for IRBs to make this moral assessment is "minimal risk",
defined as "the magnitude and probability of harms or discomfort anticipated in the research
are not greater in and of themselves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examinations or tests" (45 CFR
46.102 (I)). There has been great attention to this definition of minimal risk, with no clear
consensus. For example, even though a risk of everyday life for a child might include a
bicycle accident, it wouldn't justify a study involving children riding bikes in heavy traffic.
If the risk is greater than minimal, the regulations provide the IRB with different
necessary criteria, depending upon whether the research offers the prospect of direct benefit
to the child. If there is a prospect of direct benefit, then two additional criteria must be
determined by the IRB. First, the risk must be justified by the anticipated benefit, and
second the relationship between benefits and risks must at least be as favorable as other
alternatives. The regulations are not clear about whether studies with placebos should fall
under this category of direct benefit. In placebo controlled studies, it is possible that a child
will not benefit because the study drug is no better than placebo, or because they have
received the placebo. Yet the study offers the prospect of direct benefit, even though not all
children in the study will benefit. This points to one of the potential problems with
informed consent for studies of direct benefit; the tendency of investigators to overstate the
benefits of participation. Even with review of the consent form by an IRB, it is possible

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