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CODE OF FEDERAL REGULATIONS
TITLE 45
PUBLIC WELFAREDEPARTMENT
OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
OFFICE FOR PROTECTION FROM RESEARCH RISKS
PART 46
PROTECTION OF HUMAN SUBJECTS
* * *
Revised November 13, 2001
Effective December 13, 2001
* * *
Subpart A -- |
Federal
Policy for the Protection of Human Subjects (Basic DHHS |
Sec. |
|
To what does this policy apply? |
|
Definitions. |
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Assuring compliance with this policy--research conducted or supported by any Federal Department or Agency. |
|
[Reserved] |
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IRB membership. |
|
IRB functions and operations. |
|
IRB review of research. |
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Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research. |
|
Criteria for IRB approval of research. |
|
Review by institution. |
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Suspension or termination of IRB approval of research. |
|
Cooperative research. |
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IRB records. |
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General requirements for informed consent. |
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Documentation of informed consent. |
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Applications and proposals lacking definite plans for involvement of human subjects. |
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Research undertaken without the intention of involving human subjects. |
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Evaluation and disposition of applications and proposals for research to be conducted or supported by a Federal Department or Agency. |
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[Reserved] |
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Use of Federal funds. |
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Early termination of research support: Evaluation of applications and proposals. |
|
Conditions. |
Subpart B -- |
Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research |
Sec. |
|
To what do these regulations apply? |
|
Definitions. |
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Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. |
|
Research involving pregnant women or fetuses. |
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Research involving neonates. |
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Research involving, after delivery, the placenta, the dead fetus or fetal material. |
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Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women, fetuses, or neonates. |
Subpart C -- |
Additional DHHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects |
Sec. |
|
Applicability. |
|
Purpose. |
|
Definitions. |
|
Composition of Institutional Review Boards where prisoners are involved. |
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Additional duties of the Institutional Review Boards where prisoners are involved. |
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Permitted research involving prisoners. |
Subpart D -- |
Additional DHHS Protections for Children Involved asSubjects in Research |
Sec. |
|
To what do these regulations apply? |
|
Definitions. |
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IRB duties. |
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Research not involving greater than minimal risk. |
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Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects. |
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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. |
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Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. |
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Requirements for permission by parents or guardians and for assent by children. |
|
Wards. |
Authority: 5 U.S.C. 301; Sec. 474(a), 88 Stat. 352 (42 U.S.C. 2891-3(a)).Note: As revised, Subpart A of the DHHS regulations incorporates the Common Rule (Federal Policy) for the Protection of Human Subjects (56 FR 28003). Subpart D of the HHS regulations has been amended at Section 46.401(b) to reference the revised Subpart A.The Common Rule (Federal Policy) is also codified at
7 CFR Part 1c |
Department of Agriculture |
10 CFR Part 745 |
Department of Energy |
14 CFR Part 1230 |
National Aeronautics and Space Administration |
15 CFR Part 27 |
Department of Commerce |
16 CFR Part 1028 |
Consumer Product Safety Commission |
22 CFR Part 225 |
International Development Cooperation Agency,Agency for International Development |
24 CFR Part 60 |
Department of Housing and Urban Development |
28 CFR Part 46 |
Department of Justice |
32 CFR Part 219 |
Department of Defense |
34 CFR Part 97 |
Department of Education |
38 CFR Part 16 |
Department of Veterans Affairs |
40 CFR Part 26 |
Environmental Protection Agency |
45 CFR Part 690 |
National Science Foundation |
49 CFR Part 11 |
Department of Transportation |
TITLE 45
CODE OF FEDERAL REGULATIONS
PART 46PROTECTION OF HUMAN
SUBJECTS* * *Revised June 18, 1991
Effective August 19, 1991* * *
Subpart A |
Federal Policy for the Protection of Human Subjects (Basic DHHS Policy for Protection of Human Research Subjects) |
Source: 56 FR 28003, June 18, 1991. |
§46.101
To what does this policy apply?(a)
Except as provided in paragraph (b) of this section, this policy applies
to all research involving human subjects conducted, supported or otherwise
subject to regulation by any Federal Department or Agency which takes
appropriate administrative action to make the policy applicable to such
research. This includes research conducted by Federal civilian employees
or military personnel, except that each Department or Agency head may
adopt such procedural modifications as may be appropriate from an administrative
standpoint. It also includes research conducted, supported, or otherwise
subject to regulation by the Federal Government outside the
(i) information obtained is recorded in such a manner that human subjects
can be identified, directly or through identifiers linked to the subjects;
and (ii) any disclosure of the human subjects' responses outside the research
could reasonably place the subjects at risk of criminal or civil liability
or be damaging to the subjects' financial standing, employability, or reputation.(3)
Research involving the use of educational tests (cognitive, diagnostic, aptitude,
achievement), survey procedures, interview procedures, or observation of
public behavior that is not exempt under paragraph (b)(2) of this section,
if:
(i) the human subjects are elected or appointed public officials or candidates
for public office; or (ii) Federal statute(s) require(s) without exception
that the confidentiality of the personally identifiable information will
be maintained throughout the research and thereafter.(4) Research involving
the collection or study of existing data, documents, records, pathological
specimens, or diagnostic specimens, if these sources are publicly available
or if the information is recorded by the investigator in such a manner that
subjects cannot be identified, directly or through identifiers linked to
the subjects.(5) Research and demonstration projects which are conducted
by or subject to the approval of Department or Agency heads, and which are
designed to study, evaluate, or otherwise examine:
(i) Public benefit or service programs; (ii) procedures for obtaining benefits
or services under those programs; (iii) possible changes in or alternatives
to those programs or procedures; or (iv) possible changes in methods or levels
of payment for benefits or services under those programs.(6) Taste and food
quality evaluation and consumer acceptance studies, (i) if wholesome foods
without additives are consumed or (ii) if a food isconsumed that contains
a food ingredient at or below the level and for a use found to be safe, or
agricultural chemical or environmental contaminant at or below the level
found to be safe, by the Food and Drug Administration or approved by the
Environmental Protection Agency or the Food Safety and Inspection Service
of the U.S. Department of Agriculture.(c) Department or Agency heads retain
final judgment as to whether a particular activity is covered by this policy.(d)
Department or Agency heads may require that specific research activities
or classes of research activities conducted, supported, or otherwise subject
to regulation by the Department or Agency but not otherwise covered by this
policy, comply with some or all of the requirements of this policy.(e) Compliance
with this policy requires compliance with pertinent Federal laws or regulations
which provide additional protections for human subjects.(f) This policy does
not affect any State or local laws or regulations which may otherwise be
applicable and which provide additional protections for human subjects.(g)
This policy does not affect any foreign laws or regulations which may otherwise
be applicable and which provide additional protections to human subjects
of research.(h) When research covered by this policy takes place in foreign
countries, procedures normally followed in the foreign countries to protect
human subjects may differ from those set forth in this policy. [An example
is a foreign institution which complies with guidelines consistent with the
World Medical Assembly Declaration (Declaration of Helsinki amended 1989)
issued either by sovereign states or by an organization whose function for
the protection of human research subjects is internationally recognized.]
In these circumstances, if a Department or Agency head determines that the
procedures prescribed by the institution afford protections that are at least
equivalent to those provided in this policy, the Department or Agency head
may approve the substitution of the foreign procedures in lieu of the procedural
requirements provided in this policy. Except when otherwise required by statute,
Executive Order, or the Department or Agency head, notices of these actions
as they occur will be published in the Federal Register or will be
otherwise published as provided in Department or Agency procedures.(i) Unless
otherwise required by law, Department or Agency heads may waive the applicability
of some or all of the provisions of this policy to specific research activities
or classes or research activities otherwise covered by this policy. Except
when otherwise required by statute or Executive Order, the Department or
Agencyhead shall forward advance notices of these actions to the Office for
Protection from Research Risks, National Institutes of Health, Department
of Health and Human Services (DHHS), and shall also publish them in the Federal
Register or in such other manner as provided in Department or Agency
procedures.11 Institutions with DHHS-approved assurances on file will
abide by provisions of Title 45 CFR Part 46 Subparts A-D. Some of the other
departments and agencies have incorporated all provisions of Title 45 CFR
Part 46 into their policies and procedures as well. However, the exemptions
at 45 CFR 46.101(b) do not apply to research involving prisoners, fetuses,
pregnant women, or human in vitro fertilization, Subparts B and C. The exemption
at 45 CFR 46.101(b)(2), for research involving survey or interview procedures
or observation of public behavior, does not apply to research with children, Subpart D, except for research involving observations of
public behavior when the investigator(s) do not participate in the activities
being observed.§46.102
Definitions.(a) Department or
Agency head means the head of any Federal Department or Agency and any
other officer or employee of any Department or Agency to whom authority has
been delegated.(b) Institution means any public or private entity
or Agency (including Federal, State, and other agencies).(c) Legally authorized
representative means an individual or judicial or other body authorized
under applicable law to consent on behalf of a prospective subject to the
subject's participation in the procedure(s) involved in the research.(d) Research means
a systematic investigation, including research development, testing and evaluation,
designed to develop or contribute to generalizable knowledge. Activities
which meet this definition constitute research for purposes of this policy,
whether or not they are conducted or supported under a program which is considered
research for other purposes. For example, some demonstration and service
programs may include research activities.(e) Research subject to regulation,
and similar terms are intended to encompass those research activities for
which a Federal Department or Agency has specific responsibility for regulating
as a research activity, (for example, Investigational New Drug requirements
administered by the Food and Drug Administration). It does not include research
activities which are incidentallyregulated by a Federal Department or Agency
solely as part of the Department's or Agency's broader responsibility to
regulate certain types of activities whether research or non-research in
nature (for example, Wage and Hour requirements administered by the Department
of Labor).(f) Human subject means a living individual about whom an
investigator (whether professional or student) conducting research obtains(1)
data through intervention or interaction with the individual, or
(2) identifiable private information.Intervention includes both physical procedures by which data are
gathered (for example, venipuncture) and manipulations of the subject or
the subject's environment that are performed for research purposes. Interaction includes
communication or interpersonal contact between investigator and subject. Private
information includes information about behavior that occurs in a context
in which an individual can reasonably expect that no observation or recording
is taking place, and information which has been provided for specific purposes
by an individual and which the individual can reasonably expect will not
be made public (for example, a medical record). Private information must
be individually identifiable (i.e., the identity of the subject is or may
readily be ascertained by the investigator or associated with the information)
in order for obtaining the information to constitute research involving human
subjects.(g) IRB means an Institutional Review Board established in
accord with and for the purposes expressed in this policy.(h) IRB approval means
the determination of the IRB that the research has been reviewed and may
be conducted at an institution within the constraints set forth by the IRB
and by other institutional and Federal requirements.(i) Minimal risk means
that 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.(j) Certification means the official notification
by the institution to the supporting Department or Agency, in accordance
with the requirements of this policy, that a research project or activity
involving human subjects has been reviewed and approved by an IRB in accordance
with an approved assurance.§46.103
Assuring compliance with this policy -- research conducted or supported by
any Federal Department or Agency.(a)
Each institution engaged in research which is covered by this policy and
which is conducted or supported by a Federal Department or Agency shall providewritten
assurance satisfactory to the Department or Agency head that it will comply
with the requirements set forth in this policy. In lieu of requiring submission
of an assurance, individual Department or Agency heads shall accept the existence
of a current assurance, appropriate for the research in question, on file
with the Office for Protection from Research Risks, National Institutes Health,
DHHS, and approved for Federalwide use by that office. When the existence
of an DHHS-approved assurance is accepted in lieu of requiring submission
of an assurance, reports (except certification) required by this policy to
be made to Department and Agency heads shall also be made to the Office for
Protection from Research Risks, National Institutes of Health, DHHS.(b) Departments
and agencies will conduct or support research covered by this policy only
if the institution has an assurance approved as provided in this section,
and only if the institution has certified to the Department or Agency head
that the research has been reviewed and approved by an IRB provided for in
the assurance, and will be subject to continuing review by the IRB. Assurances
applicable to federally supported or conducted research shall at a minimum
include:(1) A statement of principles governing the institution in the discharge
of its responsibilities for protecting the rights and welfare of human subjects
of research conducted at or sponsored by the institution, regardless of whether
the research is subject to Federal regulation. This may include an appropriate
existing code, declaration, or statement of ethical principles, or a statement
formulated by the institution itself. This requirement does not preempt provisions
of this policy applicable to Department- or Agency-supported or regulated
research and need not be applicable to any research exempted or waived under §46.101 (b) or (i).(2) Designation of one or
more IRBs established in accordance with the requirements of this policy,
and for which provisions are made for meeting space and sufficient staff
to support the IRB's review and recordkeeping duties.(3) A list of IRB members
identified by name; earned degrees; representative capacity; indications
of experience such as board certifications, licenses, etc., sufficient to
describe each member's chief anticipated contributions to IRB deliberations;
and any employment or other relationship between each member and the institution;
for example: full-time employee, part-time employee, member of governing
panel or board, stockholder, paid or unpaid consultant. Changes in IRB membership
shall be reported to the Department or Agency head, unless in accord with §46.103(a)
of this policy, the existence of a DHHS-approved assurance is accepted. In
this case, change in IRB membership shall be reported to the Office for Protection
from Research Risks, National Institutes of Health, DHHS.(4) Written procedures
which the IRB will follow (i) for conducting its initial and continuing review
of research and for reporting its findings and actions to the investigator
and the institution; (ii) for determining which projects require review more
often than annually and which projects need verification from sources other
than the investigators that no material changes have occurred since previous
IRB review; and (iii) for ensuring prompt reporting to the IRB of proposed
changes in a research activity, and for ensuring that such changes in approved
research, during the period for which IRB approval has already been given,
may not be initiated without IRB review and approval except when necessary
to eliminate apparent immediate hazards to the subject.(5) Written procedures
for ensuring prompt reporting to the IRB, appropriate institutional officials,
and the Department or Agency head of (i) any unanticipated problems involving
risks to subjects or others or any serious or continuing noncompliance with
this policy or the requirements or determinations of the IRB; and (ii) any
suspension or termination of IRB approval.(c) The assurance shall be executed
by an individual authorized to act for the institution and to assume on behalf
of the institution the obligations imposed by this policy and shall be filed
in such form and manner as the Department or Agency head prescribes.(d) The
Department or Agency head will evaluate all assurances submitted in accordance
with this policy through such officers and employees of the Department or
Agency and such experts or consultants engaged for this purpose as the Department
or Agency head determines to be appropriate. The Department or Agency head's
evaluation will take into consideration the adequacy of the proposed IRB
in light of the anticipated scope of the institution's research activities
and the types of subject populations likely to be involved, the appropriateness
of the proposed initial and continuing review procedures in light of the
probable risks, and the size and complexity of the institution.(e) On the
basis of this evaluation, the Department or Agency head may approve or disapprove
the assurance, or enter into negotiations to develop an approvable one. The
Department or Agency head may limit the period during which any particular
approved assurance or class of approved assurances shall remain effective
or otherwise condition or restrict approval.(f) Certification is required
when the research is supported by a Federal Department or Agency and not
otherwise exempted or waived under §46.101 (b) or (i). An institution with an approved
assurance shall certify that each application or proposal for research covered
by the assurance and by §46.103 of this policy has been reviewed and
approved by the IRB. Such certification must be submitted with the application
or proposal or by such later date as may be prescribed by the Department
or Agency to which the application or proposal is submitted. Under no condition
shall research covered by §46.103 of the policy be supported prior to receipt
of the certification that the research has been reviewed and approved by
the IRB. Institutions without an approved assurance covering the research
shall certify within 30 days after receipt of a request for such a certification
from the Department or Agency, that the application or proposal has been
approved by the IRB. If the certification is not submitted within these time
limits, the application or proposal may be returned to the institution.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§§46.104--46.106
[Reserved]§46.107
IRB membership.(a) Each IRB shall
have at least five members, with varying backgrounds to promote complete
and adequate review of research activities commonly conducted by the institution.
The IRB shall be sufficiently qualified through the experience and expertise
of its members, and the diversity of the members, including consideration
of race, gender, and cultural backgrounds and sensitivity to such issues
as community attitudes, to promote respect for its advice and counsel in
safeguarding the rights and welfare of human subjects. In addition to possessing
the professional competence necessary to review specific research activities,
the IRB shall be able to ascertain the acceptability of proposed research
in terms of institutional commitments and regulations, applicable law, and
standards of professional conduct and practice. The IRB shall therefore include
persons knowledgeable in these areas. If an IRB regularly reviews research
that involves a vulnerable category of subjects, such as children, prisoners,
pregnant women, or handicapped or mentally disabled persons, consideration
shall be given to the inclusion of one or more individuals who are knowledgeable
about and experienced in working with these subjects.(b) Every nondiscriminatory
effort will be made to ensure that no IRB consists entirely of men or entirely
of women, including the institution's consideration of qualified persons
of both sexes, so long as no selection is made to the IRB on the basis of
gender. No IRB may consist entirely of members of one profession.(c) Each
IRB shall include at least one member whose primary concerns are in scientific
areas and at least one member whose primary concerns are in nonscientific
areas.(d) Each IRB shall include at least one member who is not otherwise
affiliated with the institution and who is not part of the immediate family
of a person who is affiliated with the institution.(e) No IRB may have a
member participate in the IRB's initial or continuing review of any project
in which the member has a conflicting interest, except to provide information
requested by the IRB.(f) An IRB may, in its discretion, invite individuals
with competence in special areas to assist in the review of issues which
require expertise beyond or in addition to that available on the IRB. These
individuals may not vote with the IRB§46.108
IRB functions and operations.In
order to fulfill the requirements of this policy each IRB shall:(a) Follow
written procedures in the same detail as described in §46.103(b)(4) and to the extent required by §46.103(b)(5).(b) Except when an expedited review
procedure is used (see §46.110), review proposed research at convened
meetings at which a majority of the members of the IRB are present, including
at least one member whose primary concerns are in nonscientific areas. In
order for the research to be approved, it shall receive the approval of a
majority of those members present at the meeting§46.109
IRB review of research.(a) An IRB
shall review and have authority to approve, require modifications in (to
secure approval), or disapprove all research activities covered by this policy.(b)
An IRB shall require that information given to subjects as part of informed
consent is in accordance with §46.116. The IRB may require that information,
in addition to that specifically mentioned in §46.116, be given to the subjects when in the
IRB's judgment the information would meaningfully add to the protection of
the rights and welfare of subjects.(c) An IRB shall require documentation
of informed consent or may waive documentation in accordance with §46.117.(d) An IRB shall notify investigators
and the institution in writing of its decision to approve or disapprove the
proposed research activity, or of modifications required to secure IRB approval
of the research activity. If the IRB decides to disapprove a research activity,
it shall include in its written notification a statement of the reasons for
its decision and give the investigator an opportunity to respond in person
or in writing.(e) An IRB shall conduct continuing review of research covered
by this policy at intervals appropriate to the degree of risk, but not less
than once per year, and shall have authority to observe or have a third party
observe the consent process and the research.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§46.110
Expedited review procedures for certain kinds of research involving no more
than minimal risk, and for minor changes in approved research.(a)
The Secretary, HHS, has established, and published as a Notice in the Federal
Register, a list
of categories of research that may be reviewed by the IRB through an
expedited review procedure. The list will be amended, as appropriate, after
consultation with other departments and agencies, through periodic republication
by the Secretary, HHS, in the Federal Register. A copy of the list is available
from the Office for Protection from Research Risks, National Institutes of
Health, DHHS, Bethesda, Maryland 20892.(b) An IRB may use the expedited review
procedure to review either or both of the following:(1) some or all of the
research appearing on the list and found by the reviewer(s) to involve no
more than minimal risk,(2) minor changes in previously approved research
during the period (of one year or less) for which approval is authorized.Under
an expedited review procedure, the review may be carried out by the IRB chairperson
or by one or more experienced reviewers designated by the chairperson from
among members of the IRB. In reviewing the research, the reviewers may exercise
all of the authorities of the IRB except that the reviewers may not disapprove
the research. A research activity may be disapproved only after review in
accordance with the non-expedited procedure set forth in §46.108(b).(c) Each IRB which uses an expedited
review procedure shall adopt a method for keeping all members advised of
research proposals which have been approved under the procedure.(d) The Department
or Agency head may restrict, suspend, terminate, or choose not to authorize
an institution's or IRB's use of the expedited review procedure.§46.111
Criteria for IRB approval of research.(a)
In order to approve research covered by this policy the IRB shall determine
that all of the following requirements are satisfied:(1) Risks to subjects
are minimized: (i) by using procedures which are consistent with sound research
design and which do not unnecessarily expose subjects to risk, and (ii) whenever
appropriate, by using procedures already being performed on the subjects
for diagnostic or treatment purposes.(2) Risks to subjects are reasonable
in relation to anticipated benefits, if any, to subjects, and the importance
of the knowledge that may reasonably be expected to result. In evaluating
risks and benefits, the IRB should consider only those risks and benefits
that may result from the research (as distinguished from risks and benefits
of therapies subjects would receive even if not participating in the research).
The IRB should not consider possible long-range effects of applying knowledge
gained in the research (for example, the possible effects of the research
on public policy) as among those research risks that fall within the purview
of its responsibility.(3) Selection of subjects is equitable. In making this
assessment the IRB should take into account the purposes of the research
and the setting in which the research will be conducted and should be particularly
cognizant of the special problems of research involving vulnerable populations,
such as children, prisoners, pregnant women, mentally disable persons, or
economically or educationally disadvantaged persons.(4) Informed consent
will be sought from each prospective subject or the subject's legally authorized
representative, in accordance with, and to the extent required by §46.116.(5) Informed consent will be appropriately
documented, in accordance with, and to the extent required by §46.117.(6) When appropriate, the research plan
makes adequate provision for monitoring the data collected to ensure the
safety of subjects.(7) When appropriate, there are adequate provisions to
protect the privacy of subjects and to maintain the confidentiality of data.(b)
When some or all of the subjects are likely to be vulnerable to coercion
or undue influence, such as children, prisoners, pregnant women, mentally
disabled persons, or economically or educationally disadvantaged persons,
additional safeguards have been included in the study to protect the rights
and welfare of these subjects.§46.112
Review by institution.Research
covered by this policy that has been approved by an IRB may be subject to
further appropriate review and approval or disapproval by officials of the
institution. However, those officials may not approve the research if it
has not been approved by an IRB.§46.113
Suspension or termination of IRB approval of research.An IRB shall have authority to suspend or terminate
approval of research that is not being conducted in accordance with the IRB's
requirements or that has been associated with unexpected serious harm to
subjects. Any suspension or termination or approval shall include a statement
of the reasons for the IRB's action and shall be reported promptly to the
investigator, appropriate institutional officials, and the Department or
Agency head.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§46.114
Cooperative research.Cooperative
research projects are those projects covered by this policy which involve
more than one institution. In the conduct of cooperative research projects,
each institution is responsible for safeguarding the rights and welfare of
human subjects and for complying with this policy. With the approval of the
Department or Agency head, an institution participating in a cooperative
project may enter into a joint review arrangement, rely upon the review of
another qualified IRB, or make similar arrangements for avoiding duplication
of effort.§46.115
IRB records.(a) An institution,
or when appropriate an IRB, shall prepare and maintain adequate documentation
of IRB activities, including the following:(1) Copies of all research proposals
reviewed, scientific evaluations, if any, that accompany the proposals, approved
sample consent documents, progress reports submitted by investigators, and
reports of injuries to subjects.(2) Minutes of IRB meetings which shall be
in sufficient detail to show attendance at the meetings; actions taken by
the IRB; the vote on these actions including the number of members voting
for, against, and abstaining; the basis for requiring changes in or disapproving
research; and a written summary of the discussion of controverted issues
and their resolution.(3) Records of continuing review activities.(4) Copies
of all correspondence between the IRB and the investigators.(5) A list of
IRB members in the same detail as described in §46.103(b)(3).(6) Written procedures for the
IRB in the same detail as described in §46.103(b)(4) and §46.103(b)(5).(7) Statements of significant new
findings provided to subjects, as required by §46.116(b)(5).(b) The records required by this
policy shall be retained for at least 3 years, and records relating to research
which is conducted shall be retained for at least 3 years after completion
of the research. All records shall be accessible for inspection and copying
by authorized representatives of the Department or Agency at reasonable times
and in a reasonable manner.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§46.116
General requirements for informed consent.Except
as provided elsewhere in this policy, no investigator may involve a human
being as a subject in research covered by this policy unless the investigator
has obtained the legally effective informed consent of the subject or the
subject's legally authorized representative. An investigator shall seek such
consent only under circumstances that provide the prospective subject or
the representative sufficient opportunity to consider whether or not to participate
and that minimize the possibility of coercion or undue influence. The information
that is given to the subject or the representative shall be in language understandable
to the subject or the representative. No informed consent, whether oral or
written, may include any exculpatory language through which the subject or
the representative is made to waive or appear to waive any of the subject's
legal rights, or releases or appears to release the investigator, the sponsor,
the institution or its agents from liability for negligence.(a) Basic elements
of informed consent. Except as provided in paragraph (c) or (d) of this section,
in seeking informed consent the following information shall be provided to
each subject:(1) a statement that the study involves research, an explanation
of the purposes of the research and the expected duration of the subject's
participation, a description of the procedures to be followed, and identification
of any procedures which are experimental;(2) a description of any reasonably
foreseeable risks or discomforts to the subject;(3) a description of any
benefits to the subject or to others which may reasonably be expected from
the research;(4) a disclosure of appropriate alternative procedures or courses
of treatment, if any, that might be advantageous to the subject;(5) a statement
describing the extent, if any, to which confidentiality of records identifying
the subject will be maintained;(6) for research involving more than minimal
risk, an explanation as to whether any compensation and an explanation as
to whether any medical treatments are available if injury occurs and, if
so, what they consist of, or where further information may be obtained;(7)
an explanation of whom to contact for answers to pertinent questions about
the research and research subjects' rights, and whom to contact in the event
of a research-related injury to the subject; and(8) a statement that participation
is voluntary, refusal to participate will involve no penalty or loss of benefits
to which the subject is otherwise entitled, and the subject may discontinue
participation at any time without penalty or loss of benefits to which the
subject is otherwise entitled.(b) additional elements of informed consent.
When appropriate, one or more of the following elements of information shall
also be provided to each subject:(1) a statement that the particular treatment
or procedure may involve risks to the subject (or to the embryo or fetus,
if the subject is or may become pregnant) which are currently unforeseeable;(2)
anticipated circumstances under which the subject's participation may be
terminated by the investigator without regard to the subject's consent;(3)
any additional costs to the subject that may result from participation in
the research;(4) the consequences of a subject's decision to withdraw from
the research and procedures for orderly termination of participation by the
subject;(5) A statement that significant new findings developed during the
course of the research which may relate to the subject's willingness to continue
participation will be provided to the subject; and(6) the approximate number
of subjects involved in the study.(c) An IRB may approve a consent procedure
which does not include, or which alters, some or all of the elements of informed
consent set forth above, or waive the requirement to obtain informed consent
provided the IRB finds and documents that:(1) the research or demonstration
project is to be conducted by or subject to the approval of state or local
government officials and is designed to study, evaluate, or otherwise examine:
(i) public benefit or service programs; (ii) procedures for obtaining benefits
or services under those programs; (iii) possible changes in or alternatives
to those programs or procedures; or (iv) possible changes in methods or levels
of payment for benefits or services under those programs; and(2) the research
could not practicably be carried out without the waiver or alteration.(d)
An IRB may approve a consent procedure which does not include, or which alters,
some or all of the elements of informed consent set forth in this section,
or waive the requirements to obtain informed consent provided the IRB finds
and documents that:(1) the research involves no more than minimal risk to
the subjects;(2) the waiver or alteration will not adversely affect the rights
and welfare of the subjects;(3) the research could not practicably be carried
out without the waiver or alteration; and(4) whenever appropriate, the subjects
will be provided with additional pertinent information after participation.(e)
The informed consent requirements in this policy are not intended to preempt
any applicable Federal, State, or local laws which require additional information
to be disclosed in order for informed consent to be legally effective.(f)
Nothing in this policy is intended to limit the authority of a physician
to provide emergency medical care, to the extent the physician is permitted
to do so under applicable Federal, State, or local law.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§46.117
Documentation of informed consent.(a)
Except as provided in paragraph (c) of this section, informed consent shall
be documented by the use of a written consent form approved by the IRB and
signed by the subject or the subject's legally authorized representative.
A copy shall be given to the person signing the form.(b) Except as provided
in paragraph (c) of this section, the consent form may be either of the following:(1)
A written consent document that embodies the elements of informed consent
required by §46.116. This form may be read to the subject or the subject's
legally authorized representative, but in any event, the investigator shall
give either the subject or the representative adequate opportunity to read
it before it is signed; or(2) A short form written consent document stating
that the elements of informed consent required by §46.116 have been
presented orally to the subject or the subject's legally authorized representative.
When this method is used, there shall be a witness to the oral presentation.
Also, the IRB shall approve a written summary of what is to be said to the
subject or the representative. Only the short form itself is to be signed
by the subject or the representative. However, the witness shall sign both
the short form and a copy of the summary, and the person actually obtaining
consent shall sign a copy of the summary. A copy of the summary shall be
given to the subject or the representative, in addition to a copy of the
short form.(c) An IRB may waive the requirement for the investigator to obtain
a signed consent form for some or all subjects if it finds either:(1) That
the only record linking the subject and the research would be the consent
document and the principal risk would be potential harm resulting from a
breach of confidentiality. Each subject will be asked whether the subject
wants documentation linking the subject with the research, and the subject's
wishes will govern; or(2) That the research presents no more than minimal
risk of harm to subjects and involves no procedures for which written consent
is normally required outside of the research context.In cases in which the
documentation requirement is waived, the IRB may require the investigator
to provide subjects with a written statement regarding the research.
(Approved by the Office of Management and Budget under Control Number 9999-0020.)§46.118
Applications and proposals lacking definite plans for involvement of human
subjects.Certain types of applications
for grants, cooperative agreements, or contracts are submitted to departments
or agencies with the knowledge that subjects may be involved within the period
of support, but definite plans would not normally be set forth in the application
or proposal. These include activities such as institutional type grants when
selection of specific projects is the institution's responsibility; research
training grants in which the activities involving subjects remain to be selected;
and projects in which human subjects' involvement will depend upon completion
of instruments, prior animal studies, or purification of compounds. These
applications need not be reviewed by an IRB before an award may be made.
However, except for research exempted or waived under §46.101 (b) or (i), no human subjects may be
involved in any project supported by these awards until the project has been
reviewed and approved by the IRB, as provided in this policy, and certification
submitted, by the institution, to the Department or Agency.§46.119
Research undertaken without the intention of involving human subjects.In
the event research is undertaken without the intention of involving human
subjects, but it is later proposed to involve human subjects in the research,
the research shall first be reviewed and approved by an IRB, as provided
in this policy, a certification submitted, by the institution, to the Department
or Agency, and final approval given to the proposed change by the Department
or Agency.§46.120
Evaluation and disposition of applications and proposals for research to
be conducted or supported by a Federal Department or Agency.(a)
The Department or Agency head will evaluate all applications and proposals
involving human subjects submitted to the Department or Agency through such
officers and employees of the Department or Agency and such experts and consultants
as the Department or Agency head determines to be appropriate. This evaluation
will take into consideration the risks to the subjects, the adequacy of protection
against these risks, the potential benefits of the research to the subjects
and others, and the importance of the knowledge gained or to be gained.(b)
On the basis of this evaluation, the Department or Agency head may approve
or disapprove the application or proposal, or enter into negotiations to
develop an approvable one.§46.121
[Reserved]§46.122
Use of Federal funds.Federal funds
administered by a Department or Agency may not be expended for research involving
human subjects unless the requirements of this policy have been satisfied.§46.123
Early termination of research support: Evaluation of applications and proposals.(a)
The Department or Agency head may require that Department or Agency support
for any project be terminated or suspended in the manner prescribed in applicable
program requirements, when the Department or Agency head finds an institution
has materially failed to comply with the terms of this policy.(b) In making
decisions about supporting or approving applications or proposals covered
by this policy the Department or Agency head may take into account, in addition
to all other eligibility requirements and program criteria, factors such
as whether the applicant has been subject to a termination or suspension
under paragraph (a) of this section and whether the applicant or the person
or persons who would direct or has/have directed the scientific and technical
aspects of an activity has/have, in the judgment of the Department or Agency
head, materially failed to discharge responsibility for the protection of
the rights and welfare of human subjects (whether or not the research was
subject to Federal regulation).§46.124
Conditions.With respect to any
research project or any class of research projects the Department or Agency
head may impose additional conditions prior to or at the time of approval
when in the judgment of the Department or Agency head additional conditions
are necessary for the protection of human subjects.
Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research |
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Source: Federal Register: November 13, 2001 (Volume 66, Number 219), Rules and Regulations, Page 56775-56780, from the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr13no01-9]. |
§46.201 To what do these regulations apply?(a) Except as provided in paragraph (b) of this section, this subpart applies to all research involving pregnant women, human fetuses, neonates of uncertain viability, or nonviable neonates conducted or supported by the Department of Health and Human Services (DHHS). This includes all research conducted in DHHS facilities by any person and all research conducted in any facility by DHHS employees.(b) The exemptions at Sec. 46.101(b)(1) through (6) are applicable to this subpart.(c) The provisions of Sec. 46.101(c) through (i) are applicable to this subpart. Reference to State or local laws in this subpart and in Sec. 46.101(f) is intended to include the laws of federally recognized American Indian and Alaska Native Tribal Governments.(d) The requirements of this subpart are in addition to those imposed under the other subparts of this part.§46.202 Definitions.The definitions in Sec. 46.102 shall be applicable to this subpart as well. In addition, as used in this subpart:(a) Dead fetus means a fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord.(b) Delivery means complete separation of the fetus from the woman by expulsion or extraction or any other means.(c) Fetus means the product of conception from implantation until delivery.(d) Neonate means a newborn.(e) Nonviable neonate means a neonate after delivery that, although living, is not viable.(f) Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.(g) Secretary means the Secretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.(h) Viable, as it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. The Secretary may from time to time, taking into account medical advances, publish in the Federal Register guidelines to assist in determining whether a neonate is viable for purposes of this subpart. If a neonate is viable then it may be included in research only to the extent permitted and in accordance with the requirements of subparts A and D of this part.§46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.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 and the other subparts of this part.§46.204 Research involving pregnant women or fetuses.Pregnant women or fetuses may be involved in research if all of the following conditions are met:(a) Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;(b) The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;(c) Any risk is the least possible for achieving the objectives of the research;(d) If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with the informed consent provisions of subpart A of this part;(e) If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the informed consent provisions of subpart A of this part, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.(f) Each individual providing consent under paragraph (d) or (e) of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;(g) For children as defined in Sec. 46.402(a) who are pregnant, assent and permission are obtained in accord with the provisions of subpart D of this part;(h) No inducements, monetary or otherwise, will be offered to terminate a pregnancy;(i) Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and(j) Individuals engaged in the research will have no part in determining the viability of a neonate§46.205 Research involving neonates.(a) Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:(1) Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.(2) Each individual providing consent under paragraph (b)(2) or (c)(5) of this section is fully informed regarding the reasonably foreseeable impact of the research on the neonate.(3) Individuals engaged in the research will have no part in determining the viability of a neonate.(4) The requirements of paragraph (b) or (c) of this section have been met as applicable.(b)Neonates of uncertain viability. Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the following additional conditions have been met:(1) The IRB determines that:(i) The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or(ii) The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research; and(2) The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with subpart A of this part, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.(c) Nonviable neonates. After delivery nonviable neonate may not be involved in research covered by this subpart unless all of the following additional conditions are met:(1) Vital functions of the neonate will not be artificially maintained;(2) The research will not terminate the heartbeat or respiration of the neonate;(3) There will be no added risk to the neonate resulting from the research;(4) The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and(5) The legally effective informed consent of both parents of the neonate is obtained in accord with subpart A of this part, except that the waiver and alteration provisions of Sec. 46.116(c) and (d) do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements of this paragraph (c)(5), except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements of this paragraph (c)(5).(d) Viable neonates. A neonate, after delivery, that has been determined to be viable may be included in research only to the extent permitted by and in accord with the requirements of subparts A and D of this part.§46.206 Research involving, after delivery, the placenta, the dead fetus or fetal material.(a) Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.(b) If information associated with material described in paragraph (a) of this section is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent subparts of this part are applicable.§46.207 Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women, fetuses, or neonates.The Secretary will conduct or fund research that the IRB does not believe meets the requirements of Sec. 46.204 or Sec. 46.205 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 pregnant women, fetuses or neonates; and(b) The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law) and following opportunity for public review and comment, including a public meeting announced in the Federal Register, has determined either:(1) That the research in fact satisfies the conditions of Sec. 46.204, 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 pregnant women, fetuses or neonates;(ii) The research will be conducted in accord with sound ethical principles; and(iii) Informed consent will be obtained in accord with the informed consent provisions of subpart A and other applicable subparts of this part.
Additional DHHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects |
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Source: 43 FR 53655, Nov. 16, 1978. |
§46.301 Applicability.(a) The regulations in this subpart are applicable to all biomedical and behavioral research conducted or supported by the Department of Health and Human Services involving prisoners as subjects.(b) Nothing in this subpart shall be construed as indicating that compliance with the procedures set forth herein will authorize research involving prisoners as subjects, to the extent such research is limited or barred by applicable State or local law.(c) The requirements of this subpart are in addition to those imposed under the other subparts of this part.§46.302 Purpose.Inasmuch as prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, it is the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in activities to which this subpart is applicable.§46.303 Definitions.As used in this subpart:(a) "Secretary" means the Secretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.(b) "DHHS" means the Department of Health and Human Services.(c) "Prisoner" means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which providealternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.(d) "Minimal risk" is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.§46.304 Composition of Institutional Review Boards where prisoners are involved.In addition to satisfying the requirements in §46.107 of this part, an Institutional Review Board, carrying out responsibilities under this part with respect to research covered by this subpart, shall also meet the following specific requirements:(a) A majority of the Board (exclusive of prisoner members) shall have no association with the prison(s) involved, apart from their membership on the Board.(b) At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board only one Board need satisfy this requirement.§46.305 Additional duties of the Institutional Review Boards where prisoners are involved.(a) In addition to all other responsibilities prescribed for Institutional Review Boards under this part, the Board shall review research covered by this subpart and approve such research only if it finds that:(1) the research under review represents one of the categories of research permissible under §46.306(a)(2);(2) any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;(3) the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers;(4) procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;(5) the information is presented in language which is understandable to the subject population;(6) adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and(7) where the Board finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.(b) The Board shall carry out such other duties as may be assigned by the Secretary.(c) The institution shall certify to the Secretary, in such form and manner as the Secretary may require, that the duties of the Board under this section have been fulfilled.§46.306 Permitted research involving prisoners.(a) Biomedical or behavioral research conducted or supported by DHHS may involve prisoners as subjects only if:(1) the institution responsible for the conduct of the research has certified to the Secretary that the Institutional Review Board has approved the research under §46.305 of this subpart; and(2) in the judgment of the Secretary the proposed research involves solely the following:(A) study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;(B) study of prisons as institutional structures or of prisoners asincarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;(C) research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of his intent to approve such research; or(D) research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research.(b) Except as provided in paragraph (a) of this section, biomedical or behavioral research conducted or supported by DHHS shall not involve prisoners as subjects.
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.§46.402
Definitions.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.§46.403
IRB duties.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.§46.409
Wards.(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.
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