Children in Research

 Codes

In general,when soliciting the assent of children, the PI should consider the age of the subjects, their maturity, and their ability to read and comprehend a written document in deciding how the assent will be obtained (e.g. verbally or written).

§46.404 {21 CFR 50.51}- Research not involving greater than minimal risk.

  • If the IRB finds that no greater than minimal risk to children is presented, approval may be given only if adequate provisions are made for soliciting the assent of the children and the permission of the parents or guardians. For this category of research, permission is required of each child’s parents or guardians. Alternatively, the IRB may determine that the permission of one (1) parent/guardian is sufficient.
  • Minimal risk means that the probability and magnitude of the harm 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 exams or tests.

§46.405 {21 CFR 50.52} - Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.

  • If the IRB finds that 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, approval may be given only if the IRB finds that:
  1. the risk is justified by the anticipated benefit to the subjects, AND
  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. adequate provisions are made for soliciting the assent of the children and permission of the parents or guardians. For this category of research, permission is required of each child’s parents or guardians. Alternatively, the IRB may determine that the permission of one (1) parent/guardian is sufficient.

§46.406 {21 CFR 50.53} – Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition.

  • If the IRB finds that 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, approval may be given only if IRB finds that:
  1. the risk represents a minor increase over minimal risk, AND
  2. the intervention/procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations, AND
  3. the intervention/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 conditions, AND 
  4. adequate provisions are made for soliciting assent of the child and permission of BOTH parents/guardians unless one parent is deceased, unknown, incompetent, not reasonably available, or only one parent has responsibility for the care and custody of the child;

§46.407 {21 CFR 50.54} – Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.

  • If the IRB does not believe the research meets the requirement of 404, 405, or 406, approval may be given only if:
  1. the IRB finds that 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 
  2. the Secretary of DHHS, after consultation with a panel of experts in pertinent disciplines and following opportunity for public review and comment has determined either 
  • that the research in fact satisfies the conditions of 404, 405, or 406, 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 and adequate provisions are made for soliciting the assent of children and the permission of both parents/guardians unless one parent is deceased, unknown, incompetent, not reasonably available, or only one parent has responsibility for the care and custody of the child;

§46.408 Requirements for permission by parents or guardians and for assent by children.

Assent of the children

In addition to the determinations required under other applicable sections of this subpart, the IRB shall determine that adequate provisions are made for soliciting the assent of the children, when in the judgment of the

IRB the children are capable of providing assent.

In determining whether children are capable of assenting, the IRB shall take into account

  • the ages,
  • maturity, and
  • psychological state of the children involved.

This judgment may be made for all children to be involved in research under a particular protocol, or for each child, as the IRB deems appropriate. §46.408(a)

When the IRB determines that assent is required, it shall also determine whether and how assent must be documented. §46.408(e)

When can assent be waived (i.e.,the assent of the children is not a necessary condition for proceeding with the research):

If the IRB determines that

  • the capability of some or all of the children is so limited that they cannot reasonably be consulted OR
  • 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,

Even where the IRB determines that the subjects are capable of assenting, the IRB may still waive the assent requirement under circumstances in which consent may be waived in accord with the conditions of the waiver of elements of consent as indicated in §46.116 of Subpart A. §46.408(a)

Permission of each child’s parents or guardian.

In addition to the determinations required under other applicable sections of this subpart, the IRB shall determine, in accordance with and to the extent that consent is required by §46.116 of Subpart A, that adequate provisions are made for soliciting the permission of each child's parents or guardian.

Where parental permission is to be obtained, the IRB may find that the permission of one parent is 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 from parents, both parents must give their permission unless:

  • one parent is deceased,
  • one parent is unknown,
  • one parent is incompetent,
  • one parent is not reasonably available, OR
  • when only one parent has legal responsibility for the care and custody of the child. §46.408(b)

Permission by parents or guardians shall be documented in accordance with and to the extent required by §46.117 of subpart A. §46.408(d)

When parental permission can be waived: §46.408(c)

In addition to the provisions for waiver contained in §46.116 of subpart A, if the IRB determines that 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), it may waive the consent requirements (in Subpart A of this part and §46.408(b) ), provided

  • an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted, and
  • provided further that the waiver is not inconsistent with federal, state, or local law. 

The choice of an appropriate mechanism would depend 

  • 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.