Research with Minors

Requirements When Minors are Research Participants

Children are considered a vulnerable research population because their intellectual and emotional capacities are limited and therefore, they are legally incompetent to give valid informed consent. Investigators interested in enrolling children are required to complete the Special Populations Review Form - Children when submitting an IRB Application or when requesting a modification to an IRB-approved study. Research involving children can be approved by the IRB if it satisfies the following requirements of federal regulations:

When reviewing research involving children as subjects, the IRB considers the risks and discomforts inherent in the proposed research and assesses their justification in light of the expected benefits to the child-subject or to society as a whole.

Federal Regulations regarding "Children" (both 45 CFR 46 and 21 CFR 50) state, "'Children' are 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." Thus, who qualifies as a "child" depends on local laws for consent. In California, 18 is the usual age when people can consent to treatments or procedures, but there are important exceptions, such as when seeking medical care related to the prevention or treatment of pregnancy (see below for further clarifications).

Permitted Categories for Research with Children

Federal regulations classify permissible research involving children into four categories based on degree of risk and type of individual subjects. These categories are described in relation to "minimal risk":

Research not involving greater than minimal risk (45 CFR 46.404 and 21 CFR 50.51):

          • Permission from at least one parent/guardian required

          • Assent of the child (if child is 7 years of age or older) required

          • Expedited level of review necessary

Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects (45 CFR 46.405 and 21 CFR 50.52):

            • The risks must be justified by the anticipated benefits; and
   
            • The risk to benefit ratio must be at least the as favorable as alternative treatments or approaches.

            • Permission from at least one parent/guardian required

            • Assent of the child (if child is 7 years of age or older) required

            • Full Committee review necessary

Research that involves more than minimal risk and presents the prospect of no direct benefit to individual subjects, but generalizable knowledge (societal benefit) (45 CFR 46.406 and 21 CFR 50.53):

            • The risks represent a small increase over minimal risk;

            • The interventions or procedures are commensurate with those associated with the subjects' actual or expected medical, dental, psychological, social or education situations; and

            • The interventions or procedures are likely to yield generalizable information about the subjects' disorder, condition, situation, which is of vital importance to understand or ameliorate.

            • Permission from both parents/guardians required*

            • Assent of the child (if child is 7 years of age or older) required

            • Full Committee review necessary

Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (45 CFR 46.407 and 21 CFR 50.54):

            • Permission from both parents/guardians required*

            • Assent of the child (if child is 7 years of age or older) required

            • Full Committee review necessary

            • Post IRB concurrence, requires submission to the Secretary of the US Department of Health and Human Services who after consultation with panel of experts and following an opportunity for public review and comment must either approve or deny approval of the study.

            • This type of study is very rarely approved.

Parental Permission

Because children cannot legally provide consent for research on their own behalf, permission by at least one parent or legal guardian is required prior to enrollment of a minor in a research study.

            • Research involving no more than minimal risk requires permission from at least one parent (or guardian).

            • Research that involves more than minimal risk but presents the prospect of direct benefit to individual subjects requires permission from at least one parent (or guardian).

            • Research that involves more than minimal risk and presents the prospect of no direct benefit to individual subjects, but generalizable knowledge (societal benefit) requires permission from both parents.*

            • Research that presents an opportunity to understand, prevent or alleviate a serious problem affecting the health or welfare of children, does NOT provide direct benefit to the subject or societal (indirect) benefit requires permission from both parents.*

NOTE: If there are two parents available to give permission but they disagree about allowing their child to participate in the study, the child should not be enrolled unless that disagreement can be resolved. This policy applies to all permissible categories of research involving children.

*Unless 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. If these circumstances are present, the researcher should document this in the subject's research record.

Waiver of Parental Permission

For some expedited research studies the IRB may waive the requirement to obtain written parental permission. See Waiver of Written (Signed) Informed Consent for more information.

In certain cases, research may be designed for conditions or for a subject population for which parental permission for inclusion in research is not a reasonable requirement to protect the subjects (e.g., neglected or abused children).

            • For non-FDA regulated studies, the IRB may waive the requirement to obtain parent(s)/guardian(s) permission 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 laws."

            • For FDA regulated studies, parent(s)/guardian(s) permission cannot be waived for FDA-regulated clinical investigations; FDA regulations lack the provision for wavier of parental permission.

Child Assent


Federal regulation and state statute require that minors assent to participate in research.

        • Assent is defined as a minor's affirmative agreement to participate in research.

        • In most cases, this must be documented in writing if the subjects are at least seven years old.

        • The IRB has authority to require assent from children younger than seven if they are likely to comprehend and appreciate what it would mean to volunteer to participate in a given protocol.

Written Assent Requirements


Assent forms should be written at the appropriate educational and maturity level of the youngest prospective subject in the age range.

            • Techniques such as the use of larger type, simple schema, and pictures may help boost a child's understanding of the text.

            • Depending on the age range of the minors to be involved, the Lead Researcher may be required to develop 2 different assent forms at different reading comprehension levels (e.g., one assent form written for young children ages 7-12 years old, and one assent form written for minors ages 13-17 years old).

            • Alternatively, for children 13-17 years of age, the researcher may develop a joint assent/permission consent form and obtain the signatures of the minor and parent(s) or guardian(s) on one document.

Assent Elements
 
An assent form should contain date and signature lines for the child, a witness, and an investigator. The assent form should cover the following points:

            • what the study is about,

            • why the child is eligible to participate for the study,

            • what procedures will be performed,

            • potential risks and discomforts to the child,

            • potential benefits to the child and society,

            • for non-therapeutic research, a statement that the child can choose whether to participate and may withdraw at any time without negative consequences,

            • an invitation to ask questions any time, and

            • names and phone numbers of whom to contact with questions.

A sample Assent Form is available. Please note: the sample is not meant to serve as a template. Assent forms must be tailored to the reading and comprehension level(s) of the subject populations to be enrolled and will vary widely from study to study.

Waiver of Assent

Assent of the child is not a necessary condition for proceeding with the research under the following conditions:

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

            • The IRB determines 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.

                    • Under such circumstances, a child's dissent which should normally be respected may be overruled by the child's parents at the IRB's discretion.

            • Finally, even where the IRB determines that the child participants are capable of assenting, the IRB may still waive the assent requirement under circumstances in which consent may be waived for adults in accordance with 45 CFR 46.116(d) regarding waiver or alteration of informed consent.