[Code of Federal Regulations]
[Title 45]
[Revised as of 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)
Sections:
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 and Human in
vitro Fertilization
Sections:
46.201 Applicability.
46.202 Purpose.
46.203 Definitions.
46.204 Ethical Advisory Boards.
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
Sections:
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 Protections for Children Involved as Subjects in Research
Sections:
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.
ADDENDUM:
46 FR 8392 RESEARCH ACTIVITIES WHICH MAY BE
REVIEWED THROUGH EXPEDITED REVIEW PROCEDURES
[AUTHORITY: 5 U.S.C. 301; Section
474(a) 88 Stat. 352 (42 U.S.C. 2891-3(a))]
[EDITORIAL Note: The Department of Health and
Human Services issued a notice of waiver regarding
the requirements set forth in part 46, relating
to protection of human subjects, as they pertain
to demonstration projects approved under section
1115 of the Social Security Act, which test
the use of cost-sharing, such as deductibles
copayment and coinsurance, in the Medicaid
program. For further information see 47 FR
9208, March 4, 1982.]
Subpart
A--PROTECTION OF HUMAN SUBJECTS
[AUTHORITY: 5 U.S.C. 301; 42 U.S.C. 289, 42
U.S.C. 300v- l(b).]
[SOURCE: 58 FR 28012, 28022, June 18, 1991,
unless otherwise noted.]
§ 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
of 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, Department of Health and
Human Services (HHS), and shall also publish
them in the FEDERAL REGISTER or in such other
manner, as provided in department or agency
procedures.
[56 FR 28012, 28022, June 18, 1991; 56 FR
29756, June 28, 1991]
§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, HHS, and approved for
federal-wide use by that office. When the existence
of an 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, HHS.
b. Departments and agencies will conduct or
support research covered by this policy, only
if the institution has 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 IRBs' review and record-keeping 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 an HHS-approved assurance is accepted. In
this case, change in IRB membership shall be
reported to the Office for Protection from
Research Risks, HHS.
4. Written procedures, which the IRB will follow
(i) for conducting its initial and continuing
review of research, and for reporting its findings
andactions 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.)
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756,
June 28, 1991]
§§ 46.104-106 [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, HHS, Bethesda, Maryland
20892.
[Editor: See Addendum 46 FR 8392 at the end
of this document.]
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 disabled 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 of 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 should give
either the subject or the representative adequate
opportunity to read it before it is signed.
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 application 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 or have directed the scientific
and technical aspects of an activity, has or
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 Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Human in vitro Fertilization
[SOURCE: 40 FR 33528, August 8,
1975, unless otherwise noted.]
§ 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, 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.
[40 FR 33528, August 8, 1975, as amended at
43 FR 1759, January 11,1978]
§ 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,
psychologists, 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.
[40 FR 33528, August 8, 1975, as amended at 43
FR 1759, January 11, 1978; 59 FR 28276, June
1, 1994]
§ 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.
[40 FR 33628, August 8, 1975, as amended at 46
FR 8386, January 26, 1981]
§ 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.
[40 FR 33628, August 8, 1975, as amended at
40 FR 51638, November 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.
[40 FR 33528, August 8, l975, as amended at 43
FR 1759, January 11, 1978]
§ 46.210 Activities involving the
dead fetus, fetal material, or the placenta.
Activities involving the dead fetus, macerated
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 Protections Pertaining
to Biomedical and Behavioral Research Involving
Prisoners as Subjects
[SOURCE: 43 FR 53655, November 16, 1978, unless
otherwise noted.]
§ 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.
[43 FR 53655, November 16, 1978, as amended at
46 FR 8386, January 26, 1981]
§ 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 prisoner's 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: (i) 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; (ii) 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; (iii) 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 (iv)
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 his 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
Protections for Children involved as Subjects in Research
[SOURCE: 48 FR 9818, March 8, 1983,unless otherwise
noted.]
§ 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
(e) 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.
[48 FR 9818, March 8, 1983; 56 FR 28032, June
18, 1991; 56 FR 29757, June 28, 1991]
§ 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.
HHS 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.
HHS 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.
HHS 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.
HHS 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, providedan 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.
ADDENDUM: 46 FR 8392
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 sub-gingival
dental plaque and calculus, provided the procedure
is not more invasive than routine prophylactic
sealing 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 FR 8392; January 26, 1981.]
back
to top |