PROTECTION OF TITLE 45 CODE OF FEDERAL REGULATIONS PART 46
REVISED JUNE 18,
1991
REPRINTED MARCH 15,
1994
CODE OF FEDERAL
REGULATIONS
TITLE 45
PUBLIC WELFARE
DEPARTMENT OF HEALTH AND HUMAN
SERVICES NATIONAL INSTITUTES OF HEALTH OFFICE FOR PROTECTION FROM
RESEARCH RISKS
PART 46--PROTECTION OF HUMAN
SUBJECTS
Revised June 18, 1991
(Effective August 19,
1991)
THE PUBLIC HEALTH SERVICE ACT AS
AMENDED BY THE NATIONAL INSTITUTES OF HEALTH REVITALIZATION ACT OF
1993 PUBLIC LAW 103-43 JUNE 10, 1993
CERTAIN PROVISIONS REGARDING
REVIEW AND APPROVAL OF PROPOSALS FOR RESEARCH
Sec. 492A. (a) REVIEW AS
PRECONDITION TO RESEARCH.--
(1) PROTECTION OF HUMAN RESEARCH
SUBJECTS.--
"(A) In the case of any
application submitted to the Secretary for financial assistance to
conduct research, the Secretary may not approve or fund any
application that is subject to review under section 491(a) by an
Institutional Review Board unless the application has undergone
review in accordance with such section and has been recommended
for approval by a majority of the members of the Board conducting
such review.
(B) In the case of research that
is subject to review under procedures established by the Secretary
for the protection of human subjects in clinical research
conducted by the National Institutes of Health, the Secretary may
not authorize the conduct of the research unless the research has,
pursuant to such procedures, been recommended for
approval.
THE CODE OF FEDERAL REGULATIONS
TITLE 45 CFR PART 46 IMPLEMENTS THESE AMENDMENTS TO THE PUBLIC
HEALTH SERVICE ACT
CODE OF FEDERAL
REGULATIONS
TITLE 45
PUBLIC WELFARE
DEPARTMENT OF HEALTH AND HUMAN
SERVICES NATIONAL INSTITUTES OF HEALTH OFFICE FOR PROTECTION FROM
RESEARCH RISKS
PART 46--PROTECTION OF HUMAN
SUBJECTS
Revised June 18, 1991
(Effective August 19,
1991)
PART 46--PROTECTION OF HUMAN SUBJECTS
Subpart A--Federal Policy for the
Protection of Human Subjects (Basic DHHS Policy for Protection of
Human Research Subjects)
Sec.
46.101 To what does this
policy apply?
46.102 Definitions.
46.103 Assuring compliance with
this policy--research conducted or supported by any Federal
Department or Agency.
46.104-46.106
[Reserved]
46.107 IRB
membership.
46.108 IRB functions and
operations.
46.109 IRB review of
research.
46.110 Expedited review
procedures for certain kinds of research involving no more than
minimal risk, and for minor changes in approved
research.
46.111 Criteria for IRB
approval of research.
46.112 Review by
institution.
46.113 Suspension or
termination of IRB approval of research.
46.114 Cooperative
research.
46.115 IRB records.
46.116 General requirements for
informed consent.
46.117 Documentation of
informed consent.
46.118 Applications and
proposals lacking definite plans for involvement of human
subjects.
46.119 Research undertaken
without the intention of involving human subjects.
46.120 Evaluation and
disposition of applications and proposals for research to be
conducted or supported by a Federal Department or
Agency.
46.121
[Reserved]
46.122 Use of Federal
funds.
46.123 Early termination of
research support: Evaluation of applications and
proposals.
46.124 Conditions.
Subpart B--Additional DHHS Protections Pertaining to Research,
Development, and Related Activities Involving Fetuses, Pregnant
Women, and Human In Vitro Fertilization
Sec.
46.201
Applicability.
46.202 Purpose.
46.203 Definitions.
46.204 Ethical Advisory
Boards.
Sec.
46.205 Additional duties
of the Institutional Review Boards in connection with
activities involving fetuses, pregnant women, or human in vitro
fertilization.
46.206 General
limitations.
46.207 Activities directed
toward pregnant women as subjects.
46.208 Activities directed
toward fetuses in utero as subjects.
46.209 Activities directed
toward fetuses ex utero, including nonviable fetuses, as
subjects.
46.210 Activities involving the
dead fetus, fetal material, or the placenta.
46.211 Modification or waiver
of specific requirements.
Subpart C--Additional DHHS
Protections Pertaining to Biomedical and Behavioral Research
Involving Prisoners as Subjects
Sec.
46.301
Applicability.
46.302 Purpose.
46.303 Definitions.
46.304 Composition of
Institutional Review Boards where prisoners are
involved.
46.305 Additional duties of the
Institutional Review Boards where prisoners are
involved.
46.306 Permitted research
involving prisoners.
Subpart D--Additional DHHS Protections for Children Involved as
Subjects in Research
Sec.
46.401 To what do these
regulations apply?
46.402 Definitions.
46.403 IRB duties.
46.404 Research not involving
greater than minimal risk.
46.405 Research involving
greater than minimal risk but presenting the prospect of direct
benefit to the individual subjects.
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.
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.
46.408 Requirements for
permission by parents or guardians and for assent by
children.
46.409 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
PART 46--PROTECTION OF HUMAN SUBJECTS
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 United
States.
(1) Research that is conducted or
supported by a Federal Department or Agency, whether or not it is
regulated as defined in 46.102(e), must comply with all sections
of this policy.
(2) Research that is neither
conducted nor supported by a Federal Department or Agency but is
subject to regulation as defined in 46.102(e) must be reviewed and
approved, in compliance with 46.101, 46.102, and 46.107 through
46.117 of this policy, by an Institutional Review Board (IRB) that
operates in accordance with the pertinent requirements of this
policy.
(b) Unless otherwise required by
Department or Agency heads, research activities in which the only
involvement of human subjects will be in one or more of the
following categories are exempt from this policy:
(1) Research conducted in
established or commonly accepted educational settings, involving
normal educational practices, such as (i) research on regular and
special education instructional strategies, or (ii) research on
the effectiveness of or the comparison among instructional
techniques, curricula, or classroom management methods.
(2) Research involving the use of
educational tests (cognitive, diagnostic, aptitude, achievement),
survey procedures, interview procedures or observation of public
behavior, unless:
(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 is consumed 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 Agency head 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.[1]
[1] 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 incidentally regulated 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 provide written
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 consents 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.
Subpart B--Additional DHHS
Protections Pertaining to Research, Development, and Related
Activities Involving Fetuses, Pregnant Women, and Human In Vitro
Fertilization
Source: 40 FR 33528, Aug. 8, 1975,
43 FR 1758, January 11, 1978; 43 FR. 51559, November 3,
1978.
46.201
Applicability.
(a) The regulations in this
subpart are applicable to all Department of Health and Human
Services grants and contracts supporting research, development,
and related activities involving: (1) the fetus, (2) pregnant
women, and (3) human in vitro fertilization.
(b) Nothing in this subpart shall
be construed as indicating that compliance with the procedures set
forth herein will in any way render inapplicable pertinent State
or local laws bearing upon activities covered by this
subpart.
(c) The requirements of this
subpart are in addition to those imposed under the other subparts
of this part.
46.202 Purpose.
It is the purpose of this subpart
to provide additional safeguards in reviewing activities to which
this subpart is applicable to assure that they conform to
appropriate ethical standards and relate to important societal
needs.
46.203
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 (DHHS) to
whom authority has been delegated.
(b) "Pregnancy" encompasses the
period of time from confirmation of implantation (through any of
the presumptive signs of pregnancy, such as missed menses, or by a
medically acceptable pregnancy test), until expulsion or
extraction of the fetus.
(c) "Fetus" means the product of
conception from the time of implantation (as evidenced by any of
the presumptive signs of pregnancy, such as missed menses, or a
medically acceptable pregnancy test), until a determination is
made, following expulsion or extraction of the fetus, that it is
viable.
(d) "Viable" as it pertains to the
fetus means being able, after either spontaneous or induced
delivery, to survive (given the benefit of available medical
therapy) to the point of independently maintaining heart beat 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 fetus is viable for
purposes of this subpart. If a fetus is viable after delivery, it
is a premature infant.
(e) "Nonviable fetus" means a
fetus ex utero which, although living, is not viable.
(f) "Dead fetus" means a fetus ex
utero which exhibits neither heartbeat, spontaneous respiratory
activity, spontaneous movement of voluntary muscles, nor pulsation
of the umbilical cord (if still attached).
(g) "In vitro fertilization" means
any fertilization of human ova which occurs outside the body of a
female, either through admixture of donor human sperm and ova or
by any other means.
46.204 Ethical Advisory Boards.
(a) One or more Ethical Advisory
Boards shall be established by the Secretary. Members of these
Board(s) shall be so selected that the Board(s) will be competent
to deal with medical, legal, social, ethical, and related issues
and may include, for example, research scientists, physicians
physiologists, sociologists, educators, lawyers, and ethicists, as
well as representatives of the general public. No Board member may
be a regular, full-time employee of the Department of Health and
Human Services.
(b) At the request of the
Secretary, the Ethical Advisory Board shall render advice
consistent with the policies and requirements of this part as to
ethical issues, involving activities covered by this subpart,
raised by individual applications or proposals. In addition, upon
request by the Secretary, the Board shall render advice as to
classes of applications or proposals and general policies,
guidelines, and procedures.
(c) A Board may establish, with
the approval of the Secretary, classes of applications or
proposals which: (1) must be submitted to the Board, or (2) need
not be submitted to the Board. Where the Board so establishes a
class of applications or proposals which must be submitted, no
application or proposal within the class may be funded by the
Department or any component thereof until the application or
proposal has been reviewed by the Board and the Board has rendered
advice as to its acceptability from an ethical
standpoint.
Nullified June 10, 1993 (Public
Law 103-43)
46.205 Additional duties of the
Institutional Review Boards in connection with activities
involving fetuses, pregnant women, or human in vitro
fertilization.
(a) In addition to the
responsibilities prescribed for Institutional Review Boards under
Subpart A of this part, the applicant's or offeror's Board shall,
with respect to activities covered by this subpart, carry out the
following additional duties:
(1) determine that all aspects of
the activity meet the requirements of this subpart;
(2) determine that adequate
consideration has been given to the manner in which potential
subjects will be selected, and adequate provision has been made by
the applicant or offeror for monitoring the actual informed
consent process (e.g., through such mechanisms, when appropriate,
as participation by the Institutional Review Board or subject
advocates in: (i) overseeing the actual process by which
individual consents required by this subpart are secured either by
approving induction of each individual into the activity or
verifying, perhaps through sampling, that approved procedures for
induction of individuals into the activity are being followed, and
(ii) monitoring the progress of the activity and intervening as
necessary through such steps as visits to the activity site and
continuing evaluation to determine if any unanticipated risks have
arisen);
(3) carry out such other
responsibilities as may be assigned by the Secretary.
(b) No award may be issued until
the applicant or offeror has certified to the Secretary that the
Institutional Review Board has made the determinations required
under paragraph (a) of this section and the Secretary has approved
these determinations, as provided in 46.120 of Subpart A of this
part.
(c) Applicants or offerors seeking
support for activities covered by this subpart must provide for
the designation of an Institutional Review Board, subject to
approval by the Secretary, where no such Board has been
established under Subpart A of this part.
46.206 General limitations.
(a) No activity to which this
subpart is applicable may be undertaken unless:
(1) appropriate studies on animals
and nonpregnant individuals have been completed;
(2) except where the purpose of
the activity is to meet the health needs of the mother or the
particular fetus, the risk to the fetus is minimal and, in all
cases, is the least possible risk for achieving the objectives of
the activity;
(3) individuals engaged in the
activity will have no part in: (i) any decisions as to the timing,
method, and procedures used to terminate the pregnancy, and (ii)
determining the viability of the fetus at the termination of the
pregnancy; and
(4) no procedural changes which
may cause greater than minimal risk to the fetus or the pregnant
woman will be introduced into the procedure for terminating the
pregnancy solely in the interest of the activity.
(b) No inducements, monetary or
otherwise, may be offered to terminate pregnancy for purposes of
the activity.
Source: 40 FR 33528, Aug. 8, 1975,
as amended at 40 FR 51638, Nov. 6, 1975.
46.207 Activities directed
toward pregnant women as subjects.
(a) No pregnant woman may be
involved as a subject in an activity covered by this subpart
unless: (1) the purpose of the activity is to meet the health
needs of the mother and the fetus will be placed at risk only to
the minimum extent necessary to meet such needs, or (2) the risk
to the fetus is minimal.
(b) An activity permitted under
paragraph (a) of this section may be conducted only if the mother
and father are legally competent and have given their informed
consent after having been fully informed regarding possible impact
on the fetus, except that the father's informed consent need not
be secured if: (1) the purpose of the activity is to meet the
health needs of the mother; (2) his identity or whereabouts cannot
reasonably be ascertained; (3) he is not reasonably available; or
(4) the pregnancy resulted from rape.
46.208 Activities directed
toward fetuses in utero as subjects.
(a) No fetus in utero may be
involved as a subject in any activity covered by this subpart
unless: (1) the purpose of the activity is to meet the health
needs of the particular fetus and the fetus will be placed at risk
only to the minimum extent necessary to meet such needs, or (2)
the risk to the fetus imposed by the research is minimal and the
purpose of the activity is the development of important biomedical
knowledge which cannot be obtained by other means.
(b) An activity permitted under
paragraph (a) of this section may be conducted only if the mother
and father are legally competent and have given their informed
consent, except that the father's consent need not be secured if:
(1) his identity or whereabouts cannot reasonably be ascertained,
(2) he is not reasonably available, or (3) the pregnancy resulted
from rape.
46.209 Activities directed toward fetuses ex utero, including
nonviable fetuses, as subjects.
(a) Until it has been ascertained
whether or not a fetus ex utero is viable, a fetus ex utero may
not be involved as a subject in an activity covered by this
subpart unless:
(1) there will be no added risk to
the fetus resulting from the activity, and the purpose of the
activity is the development of important biomedical knowledge
which cannot be obtained by other means, or
(2) the purpose of the activity is
to enhance the possibility of survival of the particular fetus to
the point of viability.
(b) No nonviable fetus may be
involved as a subject in an activity covered by this subpart
unless:
(1) vital functions of the fetus
will not be artificially maintained,
(2) experimental activities which
of themselves would terminate the heartbeat or respiration of the
fetus will not be employed, and
(3) the purpose of the activity is
the development of important biomedical knowledge which cannot be
obtained by other means.
(c) In the event the fetus ex
utero is found to be viable, it may be included as a subject in
the activity only to the extent permitted by and in accordance
with the requirements of other subparts of this part.
(d) An activity permitted under
paragraph (a) or (b) of this section may be conducted only if the
mother and father are legally competent and have given their
informed consent, except that the father's informed consent need
not be secured if: (1) his identity or whereabouts cannot
reasonably be ascertained, (2) he is not reasonably available, or
(3) the pregnancy resulted from rape.
46.210 Activities involving the
dead fetus, fetal material, or the placenta.
Activities involving the dead
fetus, mascerated fetal material, or cells, tissue, or organs
excised from a dead fetus shall be conducted only in accordance
with any applicable State or local laws regarding such
activities.
46.211 Modification or waiver
of specific requirements.
Upon the request of an applicant
or offeror (with the approval of its Institutional Review Board),
the Secretary may modify or waive specific requirements of this
subpart, with the approval of the Ethical Advisory Board after
such opportunity for public comment as the Ethical Advisory Board
considers appropriate in the particular instance. In making such
decisions, the Secretary will consider whether the risks to the
subject are so outweighed by the sum of the benefit to the subject
and the importance of the knowledge to be gained as to warrant
such modification or waiver and that such benefits cannot be
gained except through a modification or waiver. Any such
modifications or waivers will be published as notices in the
Federal Register.
Subpart C--Additional DHHS
Protections Pertaining to Biomedical and Behavioral Research
Involving Prisoners as Subjects
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 provide alternatives 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 act, 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 as incarcerated 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.
Subpart D--Additional DHHS
Protections for Children Involved as Subjects in
Research.
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 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 provisions 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 an
appropriate 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.
RESEARCH ACTIVITIES WHICH MAY BE REVIEWED THROUGH EXPEDITED
REVIEW PROCEDURES
Research activities involving no
more than minimal risk and in which the only involvement of human
subjects will be in one or more of the following categories
(carried out through standard methods) may be reviewed by the
Institutional Review Board through the expedited review procedure
authorized in
46.110 of 45 CFR Part
46.
(1) Collection of: hair and nail
clippings, in a nondisfiguring manner; deciduous teeth; and
permanent teeth if patient care indicates a need for
extraction.
(2) Collection of excreta and
external secretions including sweat, uncannulated saliva, placenta
removed at delivery, and amniotic fluid at the time of rupture of
the membrane prior to or during labor.
(3) Recording of data from
subjects 18 years of age or older using noninvasive procedures
routinely employed in clinical practice. This includes the use of
physical sensors that are applied either to the surface of the
body or at a distance and do not involve input of matter or
significant amounts of energy into the subject or an invasion of
the subject's privacy. It also includes such procedures as
weighing, testing sensory acuity, electrocardiography,
electroencephalography, thermography, detection of naturally
occurring radioactivity, diagnostic echography, and
electroretinography. It does not include exposure to
electromagnetic radiation outside the visible range (for example,
x-rays, microwaves).
(4) Collection of blood samples by
venipuncture, in amounts not exceeding 450 milliliters in an
eight-week period and no more often than two times per week, from
subjects 18 years of age or older and who are in good health and
not pregnant.
(5) Collection of both supra- and
subgingival dental plaque and calculus, provided the procedure is
not more invasive than routine prophylactic scaling of the teeth
and the process is accomplished in accordance with accepted
prophylactic techniques.
(6) Voice recordings made for
research purposes such as investigations of speech
defects.
(7) Moderate exercise by healthy
volunteers.
(8) The study of existing data,
documents, records, pathological specimens, or diagnostic
specimens.
(9) Research on individual or
group behavior or characteristics of individuals, such as studies
of perception, cognition, game theory, or test development, where
the investigator does not manipulate subjects' behavior and the
research will not involve stress to subjects.
(10) Research on drugs or devices
for which an investigational new drug exemption or an
investigational device exemption is not required.
Source: 46 CFR 8392; January 26,
1981.
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