[Code of Federal Regulations]
[Title 45, Volume 1, Parts 1 to 199]
[Revised as of October 1, 1997]
From the U.S. Government Printing Office via GPO Access
[CITE: 45CFR46]
[Page 106-125]
TITLE 45--PUBLIC WELFARE
SUBTITLE A--DEPARTMENT OF HEALTH AND HUMAN SERVICES
PART 46--PROTECTION OF HUMAN SUBJECTS
Subpart A--Basic HHS 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 Protections Pertaining to Research, Development,
and Related Activities Involving Fetuses, Pregnant Women, and Human In
Vitro Fertilization
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 Protections Pertaining to Biomedical and
Behavioral Research Involving Prisoners as Subjects
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
46.401 To what do these regulations apply?
46.402 Definitions.
46.403 IRB duties.
46.404 Research not involving greater than minimal risk.
[[Page 107]]
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; 42 U.S.C. 289.
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, Mar. 4, 1982.
Subpart A--Basic HHS Policy for Protection of Human Research Subjects
Authority: 5 U.S.C. 301; 42 U.S.C. 289, 42 U.S.C. 300v-1(b).
Source: 56 FR 28012, 28022, June 18, 1991, unless otherwise noted.
Sec. 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 Sec. 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
Sec. 46.102(e) must be reviewed and approved, in compliance with
Sec. 46.101, Sec. 46.102, and Sec. 46.107 through Sec. 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
[[Page 108]]
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.\1\
---------------------------------------------------------------------------
\1\ Institutions with HHS-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.
---------------------------------------------------------------------------
[[Page 109]]
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June 28, 1991]
Sec. 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
[[Page 110]]
policy, that a research project or activity involving human subjects has
been reviewed and approved by an IRB in accordance with an approved
assurance.
Sec. 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
federalwide use by that office. When the existence of an HHS-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 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 Sec. 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 Sec. 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 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
[[Page 111]]
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
Sec. 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 Sec. 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 Sec. 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]
Secs. 46.104--46.106 [Reserved]
Sec. 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
[[Page 112]]
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.
Sec. 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
Sec. 46.103(b)(4) and, to the extent required by, Sec. 46.103(b)(5).
(b) Except when an expedited review procedure is used (see
Sec. 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.
Sec. 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 Sec. 46.116. The IRB may
require that information, in addition to that specifically mentioned in
Sec. 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 Sec. 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)
Sec. 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.
(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
[[Page 113]]
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 Sec. 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.
Sec. 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 Sec. 46.116.
(5) Informed consent will be appropriately documented, in accordance
with, and to the extent required by Sec. 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.
Sec. 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.
Sec. 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
[[Page 114]]
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)
Sec. 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.
Sec. 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 is
Sec. 46.103(b)(3).
(6) Written procedures for the IRB in the same detail as described
in Sec. 46.103(b)(4) and Sec. 46.103(b)(5).
(7) Statements of significant new findings provided to subjects, as
required by Sec. 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)
Sec. 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;
[[Page 115]]
(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 of
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
[[Page 116]]
so under applicable federal, state, or local law.
(Approved by the Office of Management and Budget under control number
9999-0020)
Sec. 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 Sec. 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 Sec. 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)
Sec. 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 Sec. 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.
Sec. 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
[[Page 117]]
given to the proposed change by the department or agency.
Sec. 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.
Sec. 46.121 [Reserved]
Sec. 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.
Sec. 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 paragarph (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).
Sec. 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, Aug. 8, 1975, unless otherwise noted.
Sec. 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.
Sec. 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.
[[Page 118]]
Sec. 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, Aug. 8, 1975, as amended at 43 FR 1759, Jan. 11, 1978]
Sec. 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, Aug. 8, 1975, as amended at 43 FR 1759, Jan. 11, 1978; 59
FR 28276, June 1, 1994]
Sec. 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
[[Page 119]]
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 Sec. 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 33528, Aug. 8, 1975, as amended at 46 FR 8386, Jan. 26, 1981]
Sec. 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 33528, Aug. 8, 1975, as amended at 40 FR 51638, Nov. 6, 1975]
Sec. 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.
Sec. 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.
[[Page 120]]
(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.
Sec. 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, Aug. 8, 1975, as amended at 43 FR 1759, Jan. 11, 1978]
Sec. 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.
Sec. 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, Nov. l6, l978, unless otherwise noted.
Sec. 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
[[Page 121]]
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.
Sec. 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.
Sec. 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.
Sec. 46.304 Composition of Institutional Review Boards where prisoners
are involved.
In addition to satisfying the requirements in Sec. 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, Nov. 16, 1978, as amended at 46 FR 8386, Jan. 26, 1981]
Sec. 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 Sec. 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;
[[Page 122]]
(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.
Sec. 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 Sec. 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, Mar. 8, 1983, unless otherwise noted.
Sec. 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
Sec. 46.101 of Subpart A, waive the applicability of some or all of the
requirements of these regulations for research of this type.
[[Page 123]]
(b) Exemptions at Sec. 46.101(b)(1) and (b)(3) through (b)(6) are
applicable to this subpart. The exemption at Sec. 46.101(b)(2) regarding
educational tests is also applicable to this subpart. However, the
exemption at Sec. 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 Sec. 46.101 of Subpart A are
applicable to this subpart.
[48 FR 9818, Mar. 8, 1983; 56 FR 28032, June 18, 1991; 56 FR 29757, June
28, 1991]
Sec. 46.402 Definitions.
The definitions in Sec. 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.
Sec. 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.
Sec. 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 Sec. 46.408.
Sec. 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
Sec. 46.408.
Sec. 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;
[[Page 124]]
(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
Sec. 46.408.
Sec. 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 Sec. 46.404, Sec. 46.405, or Sec. 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
Sec. 46.404, Sec. 46.405, or Sec. 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 Sec. 46.408.
Sec. 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 Sec. 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
Sec. 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 Sec. 46.404 or Sec. 46.405. Where research is covered by
Secs. 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
Sec. 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
[[Page 125]]
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 Sec. 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.
Sec. 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
Sec. 46.406 or Sec. 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.