Βι¶ΉΣ³»­

230. Research Involving Children

Updated June 7, 2024

The University IRB adheres to the regulatory requirements for research with children as outlined in 45 CFR 46 Subpart D and 21 CFR 50 Subpart D. 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. 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 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.

Introduction

Federal regulations consider children to be a vulnerable population. For research conducted or supported by DHHS or other federal agencies (including research conducted outside of the United States) under Subpart D (45CFR46.401-409) the regulations require additional safeguards for their protection in human research. IRB or consultants with appropriate expertise perform an in-depth review. If there is not at least one person on the IRB with appropriate scientific or scholarly expertise to conduct an in-depth review of the protocol, the IRB will defer review until such expertise can be obtained through consultation.

Through its IRB-Flexibility Policy (IRB-Flex), the University applies Subpart D to greater than minimal risk research involving children regardless of funding; and suspends Subpart D and applies equivalent protections for minimal risk research involving children when the research is not conducted, supported, or otherwise regulated by a federal agency. Specifically, the IRB may:

  • review non-federally funded, minimal risk research involving interview procedures or observations when researchers interact with children under Flex-Exempt Review,
  • alter or suspend DHHS requirements for obtaining and documenting parent/guardian permission and assent from child participants, or
  • allow participation of college students who are 16 or 17 years old in research under the concept of mature minors with a waiver of parent permission (the minor is sufficiently mature to understand, discern and appreciate the benefits and risks of the proposed research).

NOTE: IRB-Flex allows the University IRB to exclude qualifying research from DHHS requirements for informed consent and documentation of consent without requiring IRB approval for waiver/alteration of informed consent or a waiver of signed consent for parent/guardian permission and child/youth assent.

NOTE: All research involving pregnant adolescent females, and biomedical research involving investigational drugs or devices AND non-pregnant adolescent females require additional considerations by researchers and the IRB. These considerations are addressed in subsequent policy sections.

For Research Subject to Subpart D: Requirements for IRB Review and Approval

Composition of the IRB for Review of Research Involving Children

At least one member of the University IRB is knowledgeable about and experienced in working with children. Additionally, for research that may require additional knowledge or expertise related to the condition under study, the IRB may engage the services of a consultant.

IRB Approval for Minimal Risk Research Involving Children (§46.404 and 21 CFR 50.51)

If a University IRB determines that research presents no greater than minimal risk to children, the IRB will ensure that adequate provisions are made for obtaining parent/guardian permission and assent from child-participants, unless the IRB finds and documents (either in the minutes or project records for expedited reviews) the criteria are met for a waiver/alteration of permission, assent, or both.

IRB Approval for Greater than Minimal Risk Research that Presents the Prospect of Direct Benefit to Individual Participants (§46.405 and 21 CFR 50.52)

If a University IRB finds that the risk to child-participants presented by an intervention or procedure is greater than minimal, the IRB may approve the research only if it determines and documents (in IRB minutes) that the research holds out the prospect of direct benefit for individual participants or the monitoring procedure is likely to contribute to each participant’s well-being.

For this determination, the IRB will also confirm and document in the project records that all the following are true:

  1. The risk is justified by the anticipated benefit to the participants.
  2. The relation of the anticipated benefit to the risk is at least as favorable to participants as that presented by available alternative approaches.
  3. Provisions for obtaining parent/guardian permission and assent from child-participants are adequate and comply with regulatory requirements.

IRB Approval for Greater than Minimal Risk Research; No Prospect of Direct Benefit to Individual Participants; the Research Is Likely to Yield Generalizable Knowledge Βι¶ΉΣ³»­ the Participant's Disorder or Condition (§46.406 and 21 CFR 50.53)

If a University IRB finds that the risk to child-participants presented by an intervention or procedure is greater than minimal and neither holds out the prospect of direct benefit to individual participants nor is likely to benefit individual participant’s well-being, the IRB may approve the research only if it determines and documents (in IRB minutes) that the research is likely to yield generalizable knowledge about the participant's disorder or condition.

For this determination, the IRB will also confirm and document in the project records that all the following are true:

  1. The risk represents a minor increase over minimal risk.

NOTE: Variations in risk assessments may result from the ambiguity of the terms minimal risk and minor increase over minimal risk (used to define the federal risk-benefit categories for pediatric research). Federal regulations attempt to address the ambiguity of minimal risk by providing an objective standard for assessing minimal risks, namely, the risks of daily life. However, the regulations do not provide a corresponding standard for what constitutes a minor increase over minimal risk. The University IRB will base determinations about the federal risk-benefit categories for pediatric research on ethical standards concerning the appropriate balance between protecting individual children and allowing important pediatric research.

  1. 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.
  2. The intervention or procedure is likely to yield generalizable knowledge about the participants' disorder or condition which is of vital importance for the understanding or amelioration of the participants' disorder or condition.
  3. Provisions for obtaining parent/guardian permission and assent from child-participants are adequate and comply with regulatory requirements.

IRB Approval for Research that Is Not Otherwise Approvable Which Presents an Opportunity to Understand, Prevent, or Alleviate a Serious Problem Affecting the Health or Welfare of Children (§46.407 and 21 CFR 50.54)

The federal regulations include a risk-benefit category for IRB review of research projects involving children that are not approvable under one of the three previously identified types of research (i.e., §46.404, §46.405, or §46.406). The University will not engage in this type of research activity. If the IRB determines that a research activity meets the criteria for review under §46.407, the Director of Research Integrity & Security and/or the Chair of the IRB will meet with the PI. The purpose of the meeting will be to explore options for review by another IRB in the Western states that regularly reviews pediatric research (e.g., UCSF Benioff Children’s Hospitals in San Francisco or Oakland). The PI will be encouraged and offered guidance to establish an agreement with the external IRB for regulatory review.

Requirements for Parent Permission

Based on information in the project documents, the University IRB must determine that:

  • provisions for obtaining permission from each child’s parent/guardian comply with regulatory requirements at §46.116;
  • the research meets the criteria for a waiver/alteration of consent (i.e., parent permission) at §46.116 items (c) or (d); or
  • the project may be excluded from DHHS requirements for waiver/alteration of informed consent under IRB-Flex (for more information, see IRB policy regarding informed consent for exempt and minimal risk research).

When the IRB determines that parental permission is required, the IRB assesses the requirements for permission from one or from both parents as outlined below.

Permission of One Parent Is Sufficient

The IRB may determine the permission of one parent is sufficient for the following types of research:

  • The research risks are no greater than minimal (i.e., the research is conducted under §46.404 or 21 CFR 50.51);
  • The risks are greater than minimal, but the research presents the prospect of direct benefit to individual participants (i.e., the research is conducted under §46.405 or 21 CFR 50.52). For this research type, parent permission may override child declination to participate.

Permission of Both Parents Is Required

The IRB will require permission from both parents under the following circumstances:

  • The risks are greater than minimal, there is no prospect of direct benefit to individual participants, but the research is likely to yield generalizable knowledge about the participant's disorder or condition (i.e., the research is conducted under §46.406 or 21 CFR 50.53);
  • The research is not approvable under any of the three categories of research identified previously, but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (i.e., the research is conducted under §46.407 or 21 CFR 50.54).

NOTE: Permission from both parents may not be required when one parent is deceased, unknown, incompetent, or not reasonably available; or when only one parent has legal responsibility for the care and custody of the child.

Conditions Under Which Parent/Guardian Permission Is Not a Reasonable Requirement

Under §46.408 item (c), the IRB may determine that the conditions or population for a research project are such that parent permission is not a reasonable requirement to protect participants. The IRB may waive the requirements for parent permission if it determines and documents that:

  • parental permission is not a reasonable requirement to protect participants;
  • an appropriate mechanism will be provided to protect the children who will participate in the research; and
  • the waiver follows federal, state, and local law.

Researchers are required to describe all such alternative mechanisms and the IRB will assess the appropriateness of an alternative mechanism with consideration for the purpose and nature of the research activities, the risk and anticipated benefit to research participants, and participants’ ages, maturity, status, and conditions. The determination and justification for waiving the requirement will be documented in IRB meeting minutes or project records for expedited reviews.

Requirements for Documentation of Parent Permission

When the IRB determines that parent permission is required, the IRB will assess the need for documenting permission, and will determine either:

  • the research meets the criteria for a waiver of documentation of consent (i.e., parent permission) at §46.117 items (c)(1) or (2);
  • the project may be excluded from DHHS requirements for waiver/alteration of informed consent under IRB-Flex (for more information, see IRB policy regarding informed consent for exempt and minimal risk research); or
  • documentation of parent permission is a reasonable requirement for a child to participate in the research.

Requirements for Assent

Based on information in the project documents, the University IRB must determine that the provisions for obtaining assent of the child-participants are adequate and comply with regulatory requirements.

The IRB will consider the ages, maturity, and psychological states of the children involved to assess whether the children can provide assent. The IRB will specify if the determination about the children’s capabilities to provide assent:

  • applies to all children to be involved in a research study, or
  • should be assessed individually, for each child.

If the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted, or 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 and is available only in the context of the research, the assent of the children will not be a necessary condition for proceeding with the research.

When the IRB determines that assent is required, the IRB will determine whether and how assent will be documented.

Additional Requirements for Research Involving Children Who Are Wards

University/Affiliate investigators considering research that may involve wards of the State or any other agency, institution, or entity must comply with DHHS regulations at §46.409, and the relevant Βι¶ΉΣ³»­ Revised Statutes (including definitions of “ward” and “guardian”) available from the Βι¶ΉΣ³»­ Law Library and summarized in IRB policy .

Processes for obtaining parent or guardian permission/consent for a ward’s participation in research must comply with Βι¶ΉΣ³»­ state laws and DHHS regulations at §46.408. Investigators with questions about legal considerations related to obtaining guardian consent are advised to consult with the appropriate authority at their institution (e.g., University Counsel or offices of legal affairs or compliance at affiliate institutions). Investigators must provide the IRB with documentation that identifies the individuals/entities serving as guardians.

Children who are wards may be included in minimal risk research per DHHS regulations at §45.404 and in research posing greater than minimal risk only when the research brings the prospect of direct benefit to the individual participant per DHHS regulations at §46.405.

Children who are wards may be included in research posing greater than minimal risk that does not offer the prospect of direct benefits to participants (per §46.406) or research that is not otherwise approvable, but which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (per §46.407) only under one of the following conditions:

  1. The research is related to their status as wards.
  2. The research is conducted in schools, camps, hospitals, institutions, or similar settings in which many prospective child-participants are not wards.

For research that may involve wards, the IRB requires documentation confirming that an advocate will or has been appointed for each child who is a ward, as follows:

  • The advocate is in addition to any other individual acting on behalf of the child as guardian or in loco parentis.
  • The advocate must have the background and experience to act in the best interests of the child for the duration of the child's participation in the research.
  • The advocate must agree to act in the best interests of the child for the duration of the child's participation in the research.
  • The advocate may not be associated in any way (except in the role as advocate or member of the IRB) with the research, the investigators, or the guardian organization.

NOTE: One individual may serve as advocate for more than one child.

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.