Children as Research Subjects
Assent – a child’s affirmative agreement to participate in research. Mere Parent – a child’s biological or adoptive parent.
failure to object, absent affirmative agreement, should not be construed
as assent. Minimal Risk - that level of risk associated with the daily activities of a
normal, healthy, average child.
Children – persons who have not attained the legal age for consent to
treatments or procedures involved in the research under the applicable Minor increase over minimal risk - risks that are a little more than
law of the jurisdiction in which the research will be conducted minimal and pose no significant threat to the child's health or well-being.
Guardian – an individual who is authorized under applicable State or Wards – Wards of the State or any other agency, institution, or entity.
local law to consent on behalf of a child to general medical care.
Permission – the agreement of parent(s) of guardian to the participation
of their child or ward in research.
When research involves children, federal regulations require the IRB to determine what “risk category” it falls into and to
approve the research only if it satisfies the approval criteria that apply to the particular risk category.
Category Approval Criteria Additional Detail/Requirements
One: Clinical investigations not involving 1. Adequate provisions are made to Only one parent need give consent
greater than minimal risk. solicit assent of the children and
permission of parents or guardians.
Two: Clinical investigations involving 1. The risk is justified by the anticipated Only one parent need give consent.
greater than minimal risk but benefit to the subject
presenting the prospect of direct 2. The relation of the anticipated
benefit to individual subjects. benefit to the risk is at least as
favorable to the subjects as that
presented by available alternative
3. Adequate provisions are made for
soliciting the assent of the children
and permission of parents or
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Category Approval Criteria Additional Requirements
Three: Clinical Investigations involving 1. The risk represents a minor increase 1. Both parents or legally appointed
greater than minimal risk and no over minimal risk. guardians must give consent unless
prospect of direct benefit to 2. The intervention or procedure one parent or guardian is deceased,
individual subjects, but likely to yield presents experiences to subjects unknown, incompetent, not
generalizable knowledge about the that are reasonably commensurate reasonably available, or does not
subject’s disorder. with those inherent in their actual or have legal responsibility for the
expected medical, dental custody of the minor.
psychological, social or educational 2. Wards may participate only if the
institutions. research is related to their status as
3. The intervention or procedure is wards; or conducted in schools,
likely to yield generalizable camps, hospitals, or similar settings
knowledge about the subject’s in which the majority of the children
disorder that is of vital importance for are not wards. (An advocate must
the understanding or amelioration of be appointed for each child who is a
the disorder. ward in addition to any guardian.)
4. Adequate provisions are made for
soliciting the assent of the children
and permission of parents or
Four: Clinical investigations not otherwise All of the above PLUS 1. Requires approval by the Secretary
approvable that present an of health and Human Services.
opportunity to understand, prevent, 1. MUST CONSULT WITH FDA: 2. Requires consent of both of the
alleviate a serious problem affecting approval requires consultation with a parents or guardians (unless as
the health or welfare of children. panel of experts determining that the detailed above for Category 3.)
investigation in fact satisfies the criteria, 3. Wards may participate as above (for
and a give opportunity for a public review Category 3.)
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In general, the rule for obtaining the required assent from children is that the IRB must determine whether the children are capable of
providing assent based upon their age, maturity, and psychological state.
The judgment may be made on a case-by-case basis or under one protocol. Assent is not required if the IRB determines that the
capability of some or all of the children is so limited that they cannot be reasonably consulted, or that the intervention or procedure 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
Age of Consent
Under the Interim Rule definition of children, the IRB must determine the oldest legal age of consent for any treatment or procedure
involved in the investigation and use that age as a baseline for determining whether “children” are participating in the study. Age of
consent is 18 years in all states except Alabama and Nebraska, where the age of consent is 19 years. Also, in Kentucky the age of
consent for children with disabilities is 21 years.
Under current law, the IRB is to conduct continuing review of research at intervals appropriate to the degree of risk of the research, but
not less than once per year. The FDA expects that the degree of risk posed to children will be considered by the IRB in determining
when to conduct a continuing review of an ongoing trial for compliance with the Interim Rule.
Minimal Risk *
Risks include all harms, discomforts, indignities, embarrassments, and potential breaches of privacy and confidentiality associated with
the research. The minimal risk standard defines a permissible level of risk in research as the socially allowable risks that parents
generally permit their children to be exposed to in non-research situations. Healthy children, ranging from newborns to teens,
experience differing levels of risk in their daily lives. Indexing the definition of minimal risk to the socially allowable risks to which normal,
average children are exposed routinely should take into account the differing risks experienced by children of different ages.
In the final report to the National Human Research Protections Advisory Committee (NHRPAC), the interpretation of minimal risk is that
level of risk associated with the daily activities of a normal, healthy, average child. If certain groups of children are routinely exposed to
greater risks as part of their ordinary lives because of the circumstances in which they live, their level of increased risk ought not be
interpreted as minimal risk just because it is part of the common experience of these otherwise healthy children.
Minor Increase Over Minimal Risk*
The IRB is responsible for determining what level of risk constitutes a minor increment over minimal. In making the determination, the
IRB should only permit risks that are a little more than minimal and pose no significant threat to the child's health or well-being. While
the definition of minimal risk is indexed to the risks encountered in the daily lives of normal, healthy, average children, the permissible
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level of risk associated with a minor increase over minimal should be just a bit more than that level and also commensurate with the
risks of interventions or procedures having been experienced or expected to be experienced in the lives of children with a specific
disorder or condition. This concept of commensurability is important to allow the child and parents to have a basis upon which to make
thoughtful judgments about assent and permission. The fact that children may experience invasive procedures with considerable risk
and discomfort during the care and treatment of a disease does not justify risks greater than a minor increase over minimal in a
research study that provides no prospect of direct benefit to the individual subjects.
*Excerpt from DHHS regulations. 66 Fed. Reg. 20589. Pediatric Interim Rule April 30, 2001
DHHS regulations. 66 Fed. Reg. 20589. Pediatric Interim Rule April 30, 2001
63 Federal Register 66632, December 2, 1998. Pediatric Rule
Public Law 105-115. FDA Modernization Act of 1997
Final Report to National Human Research Protections Advisory Committee (NHRPAC) from the Children’s Workgroup.
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