Stanford IRB • SCRO • APLAC
IRB • SCRO Institutional Review Board IRB • SCRO • APLAC
IRB • SCRO • APLAC

Children in Research

Children are considered a vulnerable population under federal regulations and require additional protections. When a study involves children, the IRB must take into consideration the potential risks and benefits of the research, and the justification for the inclusion of children in the research. In assessing risks, the IRB considers the children’s health status, age, and ability to understand what is involved in the research. In assessing benefit, the IRB considers potential benefits to participants, other children with the same disease or condition, or to society.

This webpage includes the following:

Considerations for Research with Children

When planning research with children, the following should be considered and included in the IRB application:

  • Rationale for the inclusion of children;
  • Whether the children are healthy or have a condition that is being studied;
  • What procedures children will undergo, including what will be done solely for the research versus what is standard of care;
  • Which procedures apply to which group (i.e. healthy controls vs. affected children, treatment group vs. placebo);
  • Whether the research offers the prospect of direct benefit to the children; and
  • A plan for obtaining parental permission and assent from children, as applicable.

Permitted Categories of Research Involving Children

Federal regulations (OHRP and FDA) include four permissible categories for research involving children.  The categories are based on the risks of the research and additional conditions that must be met for the IRB to approve the research activities. The regulations define minimal risk as the probability and magnitude of 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 examinations or tests (45 CFR 46.102(i)).

CategoryRequirementExamples
§46.404/§50.51Minimal Risk Research
  • Blood draw by venipuncture/fingerstick/heelstick
  • Single chest x-ray
  • Bone density test
  • Vision testing/Heart testing
  • Complete neurological exam
  • Oral glucose tolerance test
  • Standard psychological tests
  • Single subcutaneous or intramuscular injection (depending on substance injected)
  • Nasogastric tube insertion
  • Indwelling heparin lock catheter (under certain conditions)
  • MRI (no sedation)
§46.405/§50.52
  1. Research procedures that are greater than minimal risk;
  2. Must include a prospect of direct benefit to the participant; and
  3. Risk must be justified by the expected benefit.
  • Some organ biopsies
  • Phase 1 Pharmacokinetics studies (under certain conditions)
  • Imaging studies
  • Most IND and IDE studies
§46.406/§50.53
  1. Research procedures that are a minor increase over minimal risk;
  2. No direct benefit to the participant; and
  3. Likely to yield important knowledge about the participant’s disease or condition     
  • Urine via catheter
  • Lumbar puncture
  • Skin punch biopsy w/topical pain relief (depending on child’s age, number of biopsies, and size)
  • Bone marrow aspirate w/topical pain relief
  • Small amount of additional tissue obtained at surgery
  • MRI (with sedation, depending on the amount and duration of sedation)
§46.407/50.54
  1. Research procedures do not fall into any of the above categories;
  2. Research presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children; and
  3. Requires approval from HHS Secretary.
  • Muscle biopsies in healthy children
  • Implantation of a venous access port for patients in the placebo arm of a study

Research protocols may include multiple research-related interventions or procedures, some that offer the prospect of direct benefit and some that do not. Any intervention or procedure conducted solely for research should be evaluated separately to determine whether it offers a prospect of direct benefit to the participant (known as component analysis).  If a specific intervention or procedure does not offer a prospect of direct benefit, the risk of the intervention or procedure should be limited to minimal risk (§50.51) or a minor increase over minimal risk (§50.53).

Parental Permission (Consent) Requirements

The categories for research with children include requirements for parental or guardian permission and child assent (45 CFR 46.408) (21 CFR 50.55). Permission means the agreement of parent(s) or guardian to the participation of their child or ward in research (45 CFR 46.402(c)).

CategoryParent Permission Requirement
§46.404/§50.51One parent
§46.405/§50.52One parent
§46.406/§50.53Two parents unless one parent is deceased, unknown, incompetent, not reasonably available, or does not have legal responsibility for the custody of the child
§46.407/50.54Two parents unless one parent is deceased, unknown, incompetent, not reasonably available, or does not have legal responsibility for the custody of the child

See also information on obtaining parental permission in School-Based Research.

Assent Process and Documentation

Children generally are unable to provide informed consent to participate in research, although they might be able to give their assent. Assent is a child's affirmative agreement to participate in research. The regulations state that failure to object should not, absent affirmative agreement, be construed as assent (45 CFR 46.402(b)). When determining if and how assent will need to be obtained, the IRB considers the nature of the proposed research activity and the ages, maturity, and psychological state of the children involved in the research. The research can include children whose age and maturity level limits their ability to fully comprehend the research activities and adolescents whose capacity to understand resembles that of adults. The assent process should reflect a reasonable effort to enable the child to understand what their participation in the research would involve based on their comprehension level.

The regulations do not require written documentation of assent. The IRB determines whether assent should be written, verbal, or documented in another way based on the child’s age, maturity, and degree of literacy. Use the Assent Form Templates when applicable.

FAQ's for Research with Children

Children are defined as 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 (state and local) in which the research will be conducted (45 CFR 46.402(a)).

In California, the legal age for consent to treatment or procedures involved in research generally 18 years of age unless one of the exceptions below applies.

In some states children who have not reached the legal age of adulthood may legally consent to certain medical treatments. If the proposed research activity consists of procedures or treatments for which children can give consent outside of the research context, then the children may be considered as adults.  In these cases, the permitted categories of research with children do not apply and children may provide their own informed consent.

In certain circumstances, the California Family Code allows children to consent for themselves in the following situations:

  • Outpatient mental health treatment or counseling for children 12 years of age or older;
  • Medical care for the diagnosis or treatment of reportable infectious, contagious, or communicable/sexually transmitted diseases;
  • Medical care related to alleged rape or alleged sexual assault for children 12 years of age or older;
  • Medical care for the diagnosis or treatment of a drug or alcohol related problem, excluding narcotic replacement drugs;
  • Medical care related to the prevention or treatment of pregnancy for children of any age;
  • When the child is an emancipated minor; and
  • When the child is a self-sufficient minor as defined under Section 6922.

The IRB may waive parental permission if the conditions for a waiver of consent are met, including that the research presents no more than minimal risk of harm to participants. The IRB may also waive parental permission in cases in which the study "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)." In these cases, “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.” (45 CFR 46.408)

The regulations state that the IRB may determine that waiver of children’s assent is appropriate if any of the following apply (45 CFR 46.408(a)):

  1. The capability of some or all of the children is so limited that they cannot reasonably be consulted;
  2. The intervention or procedure involved in the research holds out the prospect of direct benefit to the health or well-being of the children and is available only in the context of the research; or
  3. The research meets the same conditions as those for waiver or alteration of informed consent in research involving adults (45 CFR 46.116(c) or 45 CFR 46.116(d)).

Generally, a researcher may not involve a child in research if the parent(s) or guardian are not available to provide permission and the IRB has not waived parental or guardian permission. In California, a researcher may be able to involve children for research involving treatment under certain circumstances where:

  1. The child is residing with a non-parent relative;
  2. The care of the child has been entrusted by a parent or guardian to an adult; or
  3. The child is in the custody of foster parents, juvenile court, a social worker or probation officer; and

When certain conditions are satisfied (e.g. completion of a “Caregiver’s Authorization Affidavit” or issuance of a court order). 

These laws are complex and guidance from the Stanford General Counsel’s office will be needed.

The regulations provide additional protections for children who are also wards of the State or any other agency, institution, or entity. These protections apply to research approved under 45 CFR 46.406 or 45 CFR 46.407. The research must meet the following conditions (45 CFR 46.409):

  1. The research must be either related to the children’s status as wards; or conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards; and
  2. The IRB must require 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 not be associated in any way with the research, the investigator(s), or the guardian organization. One individual may serve as advocate for more than one child, and must 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.

For research involving medical care for wards of a court, an order from the judge is often required, in addition to permission from the person charged with the care of the child.  Lucile Packard Children’s Hospital (LPCH) Legal Guardianship & Consent policy provides guidelines for authority to consent for medical treatment for various categories of minors, including wards of the state.

A guardian’s authority to consent to research participation is restricted in the following circumstances (in the absence of an affirmative court order):

  • Terms of any letters of guardianship issued by a court (a certified copy of which should be obtained and placed in the medical record);
  • Surgery on a child 14 years or older, unless (i) the child also consents, (ii) the guardian obtains a court order, or (iii) the guardian has determined based on medical advice that an emergency exists in which the child faces loss of life or serious bodily injury if the surgery is not performed;
  • Administering an “experimental drug”; e.g., FDA investigational drug, unless a child 7 years of age or older also consents and the drug is related to maintaining or improving health or obtaining information about a pathological condition of the child;
  • Authorizing electro-convulsive treatment;
  • Admitting the child to a ‘mental health treatment facility’ without the child’s consent;
  • Authorizing antipsychotic drugs except under certain circumstances;
  • Authorizing an elective procedure performed primarily for the purpose of rendering the child sterile (i.e., not treatment which secondarily results in sterilization); and
  • Authorizing psychosurgery under any circumstances.

See Resources below for applicable California laws.

Stanford has strict requirements for the reporting of child abuse and neglect. Researchers should be aware of Stanford requirements and their obligations under California law. See Mandated Reporter Requirements.

Research involving children must not be conducted by VA while on official duty or at VA hospital or approved off-site facilities, unless a waiver has been granted by the VA Chief Research and Development Officer. Waivers are granted only when the study poses no more than minimal risk.

Resources

Page updated July, 2026