On This Page:

a. Definitions Specific to the Regulatory Requirements Described in Subpart D
b. Categories of Permitted Research Involving Children
c. OHRP Role in Assessing Proposed Research Not Approvable Under a Permitted Category of Research Involving Children
d. Requirements for Child Assent and Parent/Guardian Permission
e. Requirements for Child Wards in Research

a.  Definitions Specific to the Regulatory Requirements Described in Subpart D 

Children – “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”
Assent – “a child’s affirmative agreement to participate in research.  Mere failure to object should not, absent affirmative agreement, be construed as assent.”
Permission – “the agreement of parent(s) or guardian to the participation of their child or ward in research”
Parent – “a child’s biological or adoptive parent”
Guardian – “an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care”
Ward – a child whose welfare is the responsibility of the State or any other agency, institution, or entity

b.  Categories of Permitted Research Involving Children

Research not involving greater than minimal risk provided that:

(1)   Appropriate provisions are in place for obtaining and documenting the assent of children; and
(2)   Appropriate provisions are in place for obtaining the permission of at least one of the child’s parents
(46.404)

Research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects provided that the following issues are addressed:

(1)   The risk is justified by the anticipated benefit to the subjects;
(2)   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
(3)   Appropriate provisions are in place for obtaining  and documenting  the assent of children and the permission of at least one of the child’s parents
(46.405)

Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects’ disorder or condition provided that the following issues are addressed:

(1)   The risk represents only a minor increase over minimal risk;
(2)   The intervention or procedure presents experiences to subjects that are reasonably commensurate with those encountered in their actual or expected medical, dental, psychological, social, or educational situations;
(3)   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; and
(4)   Appropriate provisions are in place for obtaining  and documenting the assent of children and the permission of both of the child’s parents unless:

• One parent is deceased, unknown, incompetent, or not reasonably available; or
• Only one parent has legal responsibility for the care and custody of the child
  (46.406)

c.  OHRP Role in Assessing Proposed Research Not Approvable Under a Permitted Category of Research Involving Children

For research that is not otherwise approvable that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (46.407), OHRP will:

• Assemble a panel of experts to review the proposed research;
• Provide the public with the opportunity to review and comment on the proposed research via notification in the Federal Register; and
• Compile the public comments and expert reviews, and make a recommendation to the Secretary, HHS.

The Secretary, HHS will then determine:

• That the proposed research, in fact, satisfies the criteria for permitted research (46.404, 46.405, or 46.406);
OR
• That the proposed research:
1. Presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health and welfare of children;
2. Will be conducted in accordance with sound ethical principles;
And that
3. Appropriate provisions are in place for obtaining and documenting the assent of children and the permission of both the child’s parents unless:
• One parent is deceased, unknown, incompetent, or not reasonably available; or
• Only one parent has legal responsibility for the care and custody of the child.

d.  Requirements for Child Assent and Parent/Guardian Permission

Regulatory Requirements for Child Assent
Assent from children must be obtained and documented when they are capable of providing it.  In determining whether children are capable of providing assent, consider ages, maturity and psychological state of the children involved.  This determination can be made for all children to be involved in the research under a particular protocol, or for each child, as appropriate.

• The requirement for obtaining the assent of children involved in the research may be waived if:
• The capability of some or all of the children is so limited that they cannot reasonably be consulted;
• The intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research; or
• The requirements for a waiver of informed consent found in 46.116 are met.
(46.408(a))

Regulatory Requirements for Parent/Guardian Permission
Permission from parent(s) or guardian(s) must be obtained prior to enrolling a child in research.  This permission must meet the requirements for informed consent found in 46.116.

• The permission of one parent may be sufficient for research to be conducted under 46.404 or 46.405.
• Where research is covered by 46.406 and 46.407 and permission is to be obtained by parents, both parents must give their permission unless:
  • One parent is deceased, unknown, incompetent, or not reasonably available; or
  • Only one parent has legal responsibility for the care and custody of the child.
  (46.408(b))

Regulatory Requirements for a Waiver of Parent/Guardian Permission
The requirement for permission from parent(s) or guardian(s) described in 46.116 and 46.408(b) may be waived if:

• The provisions for a waiver of some or all of the elements of informed consent in 46.116 are met;
OR
(1) A research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children);
(2) An appropriate mechanism* for protecting the children who will participate as subjects in the research is substituted; AND
(3) The waiver is not inconsistent with Federal, State or local law
*The choice of an appropriate mechanism depends upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status and condition. (46.408(c)

e.  Requirements for Child Wards in Research

Children who are wards of the State or any other agency, institution, or entity may be included in research approved under 46.406 or 46.407 only if such research is:

• Related to their status as wards; or
• Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of the children involved as subjects are not wards.

If the research is approved under these requirements, an advocate must be appointed for each child in addition to any other individual acting on behalf of the child as a guardian or in loco parentis.  One individual may serve as the advocate for more than one child.  The advocate shall:

• Have the background and experience to act in, and agree to act in, the best interests of the child for the duration of the child’s participation in the research; and
• Not be associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s) or the guardian organization.