Research Involving Children

The University of Pittsburgh adheres to the regulatory requirements for research with children as outlined in 45 CFR 46 Subpart D and 21 CFR 50 Subpart D. When reviewing research with children, the IRB membership includes at least one member who is knowledgeable about or experienced in working with children.

Definitions

Children - Federal law defines "children" as persons who have not attained the legal age for consent to treatment for procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. Under Pennsylvania law, persons under the age of eighteen (18) generally meet this definition of "children" with the exceptions noted below. As a result, permission of the child’s parent(s) or guardian(s) must generally be obtained prior to the participation of that child in research.

• The provisions that permit a minor to be considered emancipated vary depending upon the circumstance. In the Commonwealth of Pennsylvania, a minor can be considered emancipated for one purpose (for example, obtaining birth control) but not for others. Unless a minor has been emancipated by court order, which should be confirmed by requesting a copy of the order, a minor should NOT be considered emancipated for purposes of consenting to participation in research.

Guardian - Under federal law, "guardian" means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care.

• A child’s "guardian" may provide legally effective informed consent for participation in research. If a guardian provides consent, the court order or legal authorization to consent to general medical care should be copied and included in the research records with the consent document. It is important to note that physical custody and legal guardianship may not be the same for some children, and that courts may only grant partial or joint custody in some cases. Review of the court order or other legal documentation establishing the guardianship is necessary to determine who may provide consent for participation in research on behalf of the child.
• Under the laws of the Commonwealth of Pennsylvania, foster parents or Children and Youth Services cannot consent to general medical care on behalf of a child, unless a court order or the consent of the parent has been obtained. Therefore, such persons do not meet the federal definition of “guardian” and cannot provide consent for the participation of a foster child in a research study. Only the birth or adoptive parent(s) can provide the legally authorized consent to participation in research. In addition, a child who is in the custody of Children and Youth Services is considered a ward of the state, and the procedures set forth below for enrolling wards must be followed.

Permission - The agreement of parent(s) or guardian to the participation of the child in research.

Assent - An affirmative agreement by the child to participate in research. Mere failure to object should not be construed as assent without an affirmative agreement.

Parent - A child’s biological or adoptive parent.

Applicable Categories of Research

The IRB reviews all research involving children as participants and approves only research that satisfies all of the conditions of applicable federal regulatory subpart sections. The IRB assesses the potential risks and benefits for each research proposal, and the provisions for permission and assent, to determine if the activity satisfies the conditions for a category of research permitted for children, as specified in DHHS 45 CFR 46.404, 46.405, 46.406, 46.407 and 46.409 and FDA 21 CFR 50.51, 50.52, 50.53, 50.54 and 50.56.

The research categories are described as follows:

(45 CFR 46.404 and 21 CFR 50.51) 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.

(45 CFR 46.405 and 21 CFR 50.52) Research involving greater than minimal risk, but presenting the prospect of direct benefit to an individual participant, or a monitoring procedure that is likely to contribute to the participant’s well-being may be approved if the IRB finds that:

• The risk is justified by the anticipated benefit to the participant;
• 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.

(45 CFR 46.406 and 21 CFR 50.53) Research involving greater than minimal risk with no prospect of direct benefit to individual participants, but likely to yield generalizable knowledge about the participant’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 participants 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 participant’s disorder or condition which is of vital importance for the understanding or amelioration of the participant’s disorder or condition; and
• adequate provisions are made for soliciting assent of the children or permission of their parents or guardians.

(45 CFR 46.407 and 21 CFR 50.54) Research that is not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health of welfare of children may be approved if the IRB and the Secretary of Health and Human Services (DHHS), after consultation with a panel of experts in pertinent disciplines and following an opportunity for public review and comment, find that the research in fact satisfies one of the above three categories; or satisfies all of the following requirements:

• the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health and 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.

If the research study is not Federally-supported or subject to FDA regulation, the IRB Office will request review by a panel of pediatric experts to determine the applicability of approval under Section 45 CFR 46.407.

Wards of the State

Children who are wards of the state or any other agency, institution, or entity can be included in research approved under 45 CFR 46.406 and 45 CFR 46.407 or 21 CFR 50.53 and 21 CFR 50.54 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 children involved as participants are not wards (45 CFR 46.409 or 21 CFR 50.56).

Where the proposed research involves Wards of the Commonwealth of Pennsylvania or any other agency, institution, or entity; an advocate will be appointed 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 (i.e., see 45 CFR 46.409 (b) and, if applicable, 21 CFR 50.56).

• One individual may serve as an advocate for more than one child-Ward.
• The advocate will be 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 and who is not associated in any way (except in the role of advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

Consent Requirements

If a research study is designated as meeting the criteria for (45 CFR 46.404 or 21 CFR 50.51); or (45 CFR 46.405 or 21 CFR 50.52), the IRB will determine whether adequate provisions have been made to solicit the permission of each child’s parents or guardians, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless one parent has sole legal responsibility for the care and custody of the child. Where parent permission must be obtained, the IRB may determine that the permission of one parent is sufficient.

If a research study is designated as meeting the criteria for (45 CFR 406 or 21 CFR 50.53); or (45 CFR 46.407 or 21 CFR 50.54), the IRB requires the permission of both parents, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless one parent has sole legal responsibility for the care and custody of the child.

The permission of the child’s parent(s) must be documented by the inclusion of a signature on the consent form indicating that the child is under the age of 18 and therefore cannot provide direct consent.

Waiver of Parental Consent for Abused or Neglected Children

The IRB may waive the requirement for parental consent if it determines that the research study is designated for conditions or for a subject population (e.g., neglected or abused children) for which parental or guardian permission is not a reasonable requirement to protect the subjects (see 45 CFR 46.408). If the IRB grants this type of waiver based on this criterion, it must substitute an appropriate mechanism for protecting the children-subjects. The choice of such mechanism will depend on the nature and purposes of the proposed research activities; the risk and anticipate benefit to the children-subjects; and the age, maturity, status, and condition of the proposed subject population.

The IRB will not waive the requirement to obtain parent or guardian permission based on the above-stated criterion if the research study is subject to FDA regulations (21 CFR Parts 50 and 56) governing human subject protections (i.e., the research study involves an evaluation of any article regulated by the FDA).

Consent for Continued Participation

If the research study involves children (age < 18 years old) who will continue to undergo research interventions (including the collection of identifiable private information) after they become adults, the IRB research protocol should address a mechanism (e.g., addendum informed consent document with copy of originally signed consent form attached; new consent form) whereby direct consent for continued participation in the research study will be obtained from these individuals at the time they reach adult status.

Consent for Children Participating in Non-Local Research

If the research includes enrollment of participants in other states or countries, the principal investigator is responsible for providing the IRB with sufficient information to verify the age at which participants in other jurisdictions have the ability to consent to participation in research, including any medical treatments or procedures if applicable. The IRB may, if it appears advisable, require the submission of an opinion rendered by an attorney from any applicable jurisdiction on age at which an individual can consent to participation in research. Non local research is addressed in Chapter 25.

Child Abuse Statement

The following statement should appear under the Confidentiality section of all informed consent documents involving research studies conducted with children: "If the researchers learn that you or someone with whom you are involved is in serious danger of harm they will need to inform the appropriate agencies as required by Pennsylvania law." There may be instances where alternate language is appropriate.

Assent Requirements

Adequate provisions must be made for soliciting the assent of the children-subjects when, in the judgment of the IRB, the children-subjects are capable of providing assent. In determining whether children-subjects are capable of providing assent, the IRB will take into account the ages, maturity, and psychological state of the involved children. This judgment may be made for all children to be involved in given research study, or for each child, as the IRB deems appropriate. The assent of a child-subject will not be a necessary condition for proceeding with the child’s research participation if the IRB determines:

• that the capability of some or all of the children-subjects is so limited that they cannot reasonably be consulted;
• that 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-subjects and is available only in the context of the research; or
• the IRB finds and documents that:
  • the research involves no more than minimal risk to the children-subjects;
  • the waiver of assent will not adversely affect the rights and welfare of the children-subjects;
  • the research could not practicably be carried out without the waiver; and
  • whenever appropriate, the children-subjects will be provided with additional pertinent information after participation.

Children who are developmentally able to provide written assent will sign the consent document in addition to the parent(s). For children who are not determined to be developmentally able to sign the consent document, the investigator must certify that the purpose and nature of the research was explained in age appropriate language and that the child provided positive affirmation to participate.