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Subpart D |
Additional DHHS Protections for Children Involved as
Subjects in Research |
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Source: 48 FR 9818, March 8, 1983; 56 FR 28032,
June 18, 1991. |
§46.401 To what do these
regulations apply?
(a) This subpart applies to all research involving children as subjects,
conducted or supported by the Department of Health and Human Services.
(1) This includes research conducted by Department employees, except that
each head of an Operating Division of the Department may adopt such nonsubstantive, procedural modifications as may be
appropriate from an administrative standpoint.
(2) It also includes research conducted or supported by the Department of
Health and Human Services outside the United States, but in appropriate
circumstances, the Secretary may, under paragraph (i)
of §46.101
of Subpart A, waive the applicability of some or all of the requirements of
these regulations for research of this type.
(b) Exemptions at §46.101(b)(1) and (b)(3) through (b)(6) are applicable to this
subpart. The exemption at §46.101(b)(2) regarding educational tests is also applicable to this
subpart. However, the exemption at §46.101(b)(2)
for research involving survey or interview procedures or observations of public
behavior does not apply to research covered by this subpart, except for
research involving observation of public behavior when the investigator(s) do
not participate in the activities being observed.
(c) The exceptions, additions, and provisions for waiver as they appear in
paragraphs (c) through (i) of §46.101
of Subpart
A are applicable to this subpart.
The definitions in §46.102
of Subpart A shall be applicable to this subpart as well. In addition, as used
in this subpart:
(a) "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.
(b) "Assent" means a child's affirmative agreement to participate
in research. Mere failure to object should not, absent affirmative agreement,
be construed as assent.
(c) "Permission" means the agreement of parent(s) or guardian to
the participation of their child or ward in research.
(d) "Parent" means a child's biological or adoptive parent.
(e) "Guardian" means an individual who is authorized under
applicable State or local law to consent on behalf of a child to general
medical care.
In addition to other responsibilities assigned to IRBs under this part, each
IRB shall review research covered by this subpart and approve only research
which satisfies the conditions of all applicable sections of this subpart.
§46.404 Research not involving greater than minimal
risk.
DHHS will conduct or fund research in which the IRB finds that no greater
than minimal risk to children is presented, only if the IRB finds that adequate
provisions are made for soliciting the assent of the children and the
permission of their parents or guardians, as set forth in §46.408.
§46.405 Research involving greater than minimal risk
but presenting the prospect of direct benefit to the individual subjects.
DHHS will conduct or fund research in which the IRB finds that more than
minimal risk to children is presented by an intervention or procedure that
holds out the prospect of direct benefit for the individual subject, or by a
monitoring procedure that is likely to contribute to the subject's well-being,
only if the IRB finds that:
(a) the risk is justified by the anticipated
benefit to the subjects;
(b) the relation of the anticipated benefit to the risk is at least as
favorable to the subjects as that presented by available alternative
approaches; and
(c) adequate provisions are made for soliciting the
assent of the children and permission of their parents or guardians, as set
forth in §46.408.
§46.406 Research involving greater than minimal risk
and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or
condition.
DHHS will conduct or fund research in which the IRB finds that more than
minimal risk to children is presented by an intervention or procedure that does
not hold out the prospect of direct benefit for the individual subject, or by a
monitoring procedure which is not likely to contribute to the well-being of the
subject, only if the IRB finds that:
(a) the risk represents a minor increase over
minimal risk;
(b) the intervention or procedure presents experiences to subjects that are
reasonably commensurate with those inherent in their actual or expected
medical, dental, psychological, social, or educational situations;
(c) the intervention or procedure is likely to yield generalizable
knowledge about the subjects' disorder or condition which is of vital
importance for the understanding or amelioration of the subjects' disorder or
condition; and
(d) adequate provisions are made for soliciting
assent of the children and permission of their parents or guardians, as set
forth in §46.408.
§46.407 Research not otherwise approvable which
presents an opportunity to understand, prevent, or alleviate a serious problem
affecting the health or welfare of children.
DHHS will conduct or fund research that the IRB does not believe meets the
requirements of §46.404,
§46.405,
or §46.406
only if:
(a) the IRB finds that the research presents a
reasonable opportunity to further the understanding, prevention, or alleviation
of a serious problem affecting the health or welfare of children; and
(b) the Secretary, after consultation with a panel
of experts in pertinent disciplines (for example: science, medicine, education,
ethics, law) and following opportunity for public review and comment, has
determined either:
(1) that the research in fact satisfies the
conditions of §46.404,
§46.405,
or §46.406,
as applicable, or (2) the following:
(i) the research presents
a reasonable opportunity to further the understanding, prevention, or
alleviation of a serious problem affecting the health or welfare of children;
(ii) the research will be conducted in accordance
with sound ethical principles;
(iii) adequate provisions are made for soliciting
the assent of children and the permission of their parents or guardians, as set
forth in §46.408.
§46.408 Requirements for permission by parents or guardians
and for assent by children.
(a) In addition to the determinations required under other applicable
sections of this subpart, the IRB shall determine that adequate provisions are
made for soliciting the assent of the children, when in the judgment of the IRB
the children are capable of providing assent. In determining whether children
are capable of assenting, the IRB shall take into account the ages, maturity,
and psychological state of the children involved. This judgment may be made for
all children to be involved in research under a particular protocol, or for
each child, as the IRB deems appropriate. 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 is not a necessary condition for
proceeding with the research. Even where the IRB determines that the subjects
are capable of assenting, the IRB may still waive the assent requirement under
circumstances in which consent may be waived in accord with §46.116
of Subpart
A.
(b) In addition to the determinations required under other applicable sections
of this subpart, the IRB shall determine, in accordance with and to the extent
that consent is required by §46.116
of Subpart
A, that adequate provisions are made for soliciting the permission of each
child's parents or guardian. Where parental permission is to be obtained, the
IRB may find that the permission of one parent is sufficient for research to be
conducted under §46.404
or §46.405.
Where research is covered by §46.406
and §46.407
and permission is to be obtained from parents, both parents must give their
permission 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.
(c) In addition to the provisions for waiver contained in §46.116
of Subpart
A, if the IRB determines that a research protocol 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), it may waive the consent requirements
in Subpart A of this part and paragraph (b) of this section, 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 law. The choice of anappropriate mechanism would depend upon the nature and
purpose of the activities described in the protocol, the risk and anticipated
benefit to the research subjects, and their age, maturity, status, and
condition.
(d) Permission by parents or guardians shall be documented in accordance
with and to the extent required by §46.117
of Subpart
A.
(e) When the IRB determines that assent is required, it shall also determine
whether and how assent must be documented.
(a) Children who are wards of the State or any other agency, institution, or
entity can be included in research approved under §46.406
or §46.407
only if such research is:
(1) related to their status as wards; or
(2) conducted in schools, camps, hospitals,
institutions, or similar settings in which the majority of children involved as
subjects are not wards.
(b) If the research is approved under paragraph (a) of this section, the IRB shall 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. One individual may serve as advocate for more than one child. The advocate shall 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 as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.