Last Revised: 10.2015
Prior Version: 7.2007
Special Populations in Research
Children
Introduction
Research, including chart reviews, that involves children or the use of Protected Health
Information (PHI) of children must meet the criteria for approval set forth in 45 CFR 46,
Subparts A and D, unless the research has been determined to be exempt from IRB review.
Please note that there are restrictions for approving exempt research involving children.
When children are involved in research, federal regulations require the permission of the
parent(s) or guardian before a child can be enrolled in research. While children may be legally
incapable of giving informed consent, they nevertheless may possess the ability to assent, or
refuse participation in a research study. Assent is a child's affirmative agreement to participate in
research after an explanation of the study in language the child can understand. Failure to object
to participation cannot be construed as assent.
The following guidelines have been established by the IRB to assist investigators who conduct
research involving children. Federal regulations require that assent must be sought from children
unless the requirement is waived by the IRB or is not required under applicable regulations.
Assent must be taken seriously by all investigators who include children as subjects of research.
It is the IRB Chair’s responsibility to have the convened IRB or the IRB Manager to have the
expedited reviewer(s) determine and document whether the following criteria for approval of
research are met when research involves children.
 Category 1 (45 CFR 46.404):
 No greater than minimal risk to children is presented.
 Where parental permission is to be obtained, the IRB must declare whether
one or both parents must give permission for the child’s research participation.
 Category 2 (45 CFR 46.405):
 More than minimal risk to children is presented by an intervention or
procedure that holds out the prospect of direct benefit for the individual
subject, or by a monitoring procedure that 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.
 Where parental permission is to be obtained, the IRB must declare whether
one or both parents must give permission for the child’s research participation.
 Category 3 (45 CFR 46.406):
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More than minimal risk to children is presented by an intervention or
procedure that does not hold out the prospect of direct benefit for the
individual subject, or by a monitoring procedure which is not likely to
contribute to the well-being of the subject.
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 subjects’ disorder or condition which is of vital importance for the
understanding or amelioration of the subjects’ disorder or condition.
Where parental permission is to be obtained, both parents must give
permission unless one parent is deceased, unknown, incompetent, not
reasonably available, or does not have legal responsibility for the care and
custody of the child.
Category 4 (45 CFR 46.407):
 Research not otherwise approvable and presents a reasonable opportunity to
further the understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of children.
 Requires approval by the Secretary of Health and Human Services, as
applicable.
 The federal agency, after consultation with a panel of experts in pertinent
disciplines (for example: science, medicine, education, ethics, law) and
following opportunity for public review and comment, determined either:
 The research fell into categories 1 through 3; 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 and the research will be conducted in
accordance with sound ethical principles.
 Where parental permission is to be obtained, both parents must give
permission unless one parent is deceased, unknown, incompetent, not
reasonably available, or does not have legal responsibility for the care and
custody of the child.
It is the IRB Chair’s responsibility to have the convened IRB determine and document whether
the following criteria for approval of research are met when research in Category 3(45 CFR
46.406) or 4 (45 CFR 46.407) involves wards of the state or any other agency.
 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 involves as subjects are not wards.
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The IRB requires appointment of an advocate for each child who is a ward, in
addition to any other individual acting on behalf of the child as guardian or in loco
parentis.
 The advocate is an individual who has 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
 The advocate is not associated in any way (except in the role as advocate or
member of the IRB) with the research, the investigators, or the guardian.
Definitions
Adult is a person who has 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. Who is an adult may vary depending on the specific treatments or procedures
involved in the research and on the jurisdiction in which the research will be conducted.
Assent means a child’s affirmative agreement to participate in research. Failure of a child to
object to participation cannot be construed as assent. Assent is a process involving
communication with the child. A signature on an assent document is not, by itself, assent.
Child is a person, who has not attained the legal age for consent to treatments or procedures
involved in research, under the applicable law of the jurisdiction in which the research will be
conducted. In most American states, a child is someone who is age 17 years old or younger.
Other countries may define a child differently. For example, in Taiwan, a child is someone who
is 19 years old or younger.
Emancipated minor is a person under the legal age of majority who, usually via a court order,
has the legal rights of an adult. Situations that qualify a person as an emancipated minor vary
from state to state. In Ohio, a person under the legal age of majority becomes an emancipated
minor by order of the court. Grounds for emancipation include marriage or service in the armed
forces. Documentation of emancipation by court order is required before this doctrine can apply
in the research context, in some situations copies of a court order may be required. Please note if
a minor is a parent and has a child of her/his own that does NOT mean that she/he is
emancipated. In this case, investigators would have to collect assent from the minor parent and
parental consent from that minor’s parent/guardian.
Guardian is an individual, who is legally authorized under applicable state or local law, to
consent on behalf of a child to general medical care.
Informed Consent is an individual’s voluntary agreement, based upon adequate knowledge and
understanding of the relevant information, to participate in research either for themselves or for a
child for whom they are the parent, guardian, or legally authorized representative.
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Parent generally means a child’s biological or adoptive parent. Foster parents are not authorized
to give research consent.
Permission or Parental Permission means the agreement of the parent(s) or legally authorized
guardian to the participation of a child in research. This term is often used to emphasize that the
parent is not the subject of the research. In this context permission has the same meaning as
consent.
Policy
It is a requirement that the investigator propose an assent plan as part of a research protocol that
includes children as subjects. If the investigator believes that assent is not appropriate for the
child population being studied, appropriate justification must be provided in the protocol.
Requests for waivers of assent need to be specifically requested and subsequently approved by
the IRB.
The investigator must also describe the additional safeguards in place to protect the rights and
welfare of the children.
Please refer to “Assent from Children”
References and/or Regulatory Citations:
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45 CFR Subpart B
45 CFR 46.404
45 CFR 46.405
Most of the federal regulations relating to research in children are in 45 CFR 46.401-409,
45 CFR 46, Subpart C: Additional Protections Pertaining to Biomedical and Behavioral
Research Involving Prisoners as Subjects
OHRP Guidance Document: “OHRP Guidance on Involvement of Prisoners in
Research,” May 23, 2003
OHRP Guidance: Children: Research with Children FAQ
OHRP Guidance: Information on Special Protections for Children as Research Subjects
Office for Human Research Protections (OHRP), Special Protections for Children as
Research Subjects, Children Involved as Subjects in Research: Guidance on the HHS, 45
CFR 46.407 ("407") Review Process, May 26, 2005
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