503: Research with children
The policy describes the requirements concerning review of research that involves children in regard to autonomy, and who present conditions that may affect risk/benefit determinations or bearing unequal burden in research.
Enrolling children into research studies presents especially difficult considerations for the IRB. Two factors make a case for research in children.
- Children differ markedly from adults; and therefore, adult subject research cannot substitute for testing in children.
- Lack of appropriate research in children will increase their risk of harm from exposure to practices and treatments untested in this population. In addition, new therapies could not be developed for diseases that specifically affect children.
However, research with children requires that the IRB carefully consider assent and parental permission, beneficence, and justice.
The determination of risk (possible harms) and possible benefit to the child is at the core of the concept of beneficence when considering research in a pediatric population.
Therefore, the IRB must consider the degree of risk and discomfort involved in the research in relation to the direct benefits it offers to the child before it can determine whether or not the IRB has the authority to approve the study.
DHHS (45 CFR 46.402(1)): Children are persons who have 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.
FDA (21 CFR 50.3(o)): Children are persons who have 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.
The following exceptions to the general rule apply, where a person underage of 18 does not meet the federal definition of “child” and may provide legally effective consent to participate in research if:
- The child is emancipated;
- The child (a) has entered into a valid marriage, whether or not the marriage is terminated by dissolution;
- Is on active duty with the armed forces of the United States; or
- Has received a declaration of emancipation from a court.
- DHHS 45 CFR 46.402(e): Guardian means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care.
- FDA 21 CFR 50.3(s): Guardian means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care when general medical care includes participation in research. For purposes of subpart D of this part, a guardian also means an individual who is authorized to consent on behalf of a child to participate in research.
3. IRB review
The IRB members will use the checklist: Research Involving Children to determine risk, benefit assessment, and requirements for permission by parents or guardians and assent by children and all other determinations.
When reviewing research conducted on children, risk is defined in terms of minimal and greater than minimal risk, and may only be approved by the IRBs as follows:
|Risk determination||Benefit assessment||IRB’s action|
|Minimal||With or without direct benefit||Approvable|
|More than minimal risk*||Potential benefit to child||Approvable|
|Greater than minimal risk||No direct benefit to child, offers general knowledge about the child’s condition or disorder||Approvable case-by-case*|
|Greater than minimal risk||No direct benefit to child, offers potential to “understand, prevent, or alleviate a serious problem affecting the health and welfare of subjects.”||Not approvable**|
|*The WSU IRB will make determination if consent of one or both parents is required.
* Respect for persons require oral communication with children younger than age seven (7) about the research and what they will experience to the extent their development permits.
**Approval to proceed with this category of research must be made by the IRB coordinator of the HHS with input from selected experts, and following opportunity for public review and comment.
The IRB will determine that adequate provisions are made for soliciting the permission of the child’s parents or guardian.
If the research includes enrollment of subjects in other states or countries, the investigator is responsible for providing the IRB with sufficient information to verify the age at which subjects in such jurisdictions have the ability to consent to participation in research, including any medical treatment or procedures, if applicable.
In general, research involving children will be reviewed at the expedited or full-board level. When the research involves observation of public behavior and the investigator does not participate in the activities being observed an exempt review may be utilized.
The No Child Left Behind Act of 2001
The Act identifies eight (8) categories of protected information for surveys, questionnaires, interview materials, or other testing instruments responses. Research involving any of the eight (8) identified categories requires written parental informed consent prior to participation of a child.
- Political affiliations of student or student’s parents
- Mental or psychological problems of student or student’s family
- Sex behavior or attitudes
- Illegal, anti-social, self-incriminating or demeaning behavior
- Critical appraisals of others with whom students have close family relationships
- Legally recognized privileged or analogous relationships
- Religious practices, affiliations or beliefs of student or student’s parents
Known or suspected child abuse
Investigators are required to report known or suspected child abuse. This must be disclosed on the informed consent form.
Policy on EPA-supported research on children
The IRB may review and approve observational research involving children that does not involve greater than minimal risk only if the IRB finds that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in 40 CFR 26.406.
The IRB may review and approve observational research involving children that involves greater than minimal risk but presenting the prospect of direct benefit to the individual subjects if the IRB finds and documents that:
- The intervention or procedure holds out the prospect of direct benefit to the individual subject or is likely to contribute to the subject’s well-being,
- The risk is justified by the anticipated benefit to the subjects,
- The relation of the anticipated benefit to the risk is at least as favorable to the subjects 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, as set forth in 40 CFR 26.406.
4. Applicable regulations and guidelines
6. Procedures employed to implement this policy & assignment of responsibility
|ORA director, IRB coordinator||Select appropriate reviewers or obtain expert consultant.|
|IRB coordinator||Provide reviewers with appropriate checklists.|
|Reviewers||Present recommendations during convened meeting.
Complete checklists to ensure all determinations are met.
Determine who met the DHHS and state law definitions of child, guardian and ward, if applicable.