D. Children

By regulatory definition, a child is a person who has not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted (45 CFR 46.402(a)).  By FDA definition, a child is a person who has not attained the legal age for consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted.  For purposes of research conducted in the state of Iowa, the term “child” as used in both the DHHS and FDA definitions is analogous to “minor” under Iowa Code and is viewed as “an unmarried person under the age of eighteen years.”  (Iowa Code 600A.2(13))

In cases of human subjects research under the authority of the UI IRB(s) but conducted outside of the state of Iowa, the UI IRB confers with the UI Office of General Counsel regarding the applicability of other state, national, or international laws to the particular project.  In general, the UI IRB will apply the law of the state in which the research is being conducted.  For example, if a project involves children and one of the recruitment sites is in a bordering state, the laws of the bordering state will be evaluated to which individuals meet the DHHS and FDA definition of “children” at that site.

Federal regulations permit IRBs to approve a research project involving children after determining which of the following categories applies, and only if the project satisfies all of the conditions in the applicable category (45 CFR 46, Subpart D (DHHS) and 21 CFR 50 Subpart D  (FDA)):

1. Research that does not involve greater than minimal risk may be approved if the IRB finds that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians.  The IRB may determine that permission of one parent or guardian is sufficient.
2. Research involving greater than minimal risk, but presenting the prospect of direct benefit to an individual subject, or a monitoring procedure that is likely to contribute to the subject's well- being, may be approved if the IRB finds that:

•  the risk is justified by the anticipated benefit to the subject;
•  the relationship of anticipated benefit to risk is at least as favorable as that presented by available alternative approaches; and
• adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

3. Research involving greater than minimal risk with no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition, may be approved if the IRB finds that:

• the risk represents a minor increase over minimal risk;
• the intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;
• the intervention or procedure is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance for the understanding or amelioration of the subject's disorder or condition; and
• adequate provisions are made for soliciting assent of the children and permission of their parents or guardians.

4. Research that is not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children may be approved if the IRB and the Secretary of DHHS, after consultation with a panel of experts in pertinent disciplines and following an opportunity for public review and comment, find that:

• the research satisfies one of the above three conditions; or
• the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;
• the research will be conducted in accordance with sound ethical principles; and adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

In compliance with federal regulations, the IRB must determine that permission of both parents is required, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless only one parent has legal responsibility for the care and custody of the child.

Federal regulations (45 CFR 46.409(b)) also indicate that children who are wards of the state, or any other agency, institution, or entity can only be included in research in this category if the research is related to their status as wards or conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.  If one of these criteria is met and the research is approved, the IRB must require appointment of an advocate for each child who is a ward in addition to the person acting as guardian or in loco parentis.  One person may serve as the advocate for multiple wards, however this advocate must have the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child’s participation in the research and cannot be associated in any way (except as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

Research involving children is only permitted at the VA with the approval of the Facilities Director. This approval must be attached to any research proposals at the VA which propose to involve children. The research participation of children must be no greater than minimal risk.