Page^pproved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
45 CFR 44
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 these regulations at intervals
appropriate to the degree of risk, but
not iess than once per year, and shail
have authority to observe or have a
third party observe the consent
process and the research.
§46„ilQ
Expedited review
procedures for certain kinds of
research involving no more than
minimal risk, and for minor
changes in approved research.
(a) The Secretary has established,
and published 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, through periodic
republication in the Federal
Register.
lb) An IRB may review some or all
of the research appearing on the
list
through an expedited review
procedure,
if the research involves no
more than minimal risk. The }RB may
also use the expedited review
procedure to review minor changes in
previously approved research during
the period 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
ail of the authorities of
the IRB except that die 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 Secretary may restrict,
suspend, or terminate an institution's
or IRB's use of the expedited review
procedure when necessary to protect
the rights or welfare of subjects.
§46.119
Criteria for IRB
approval of research.
(a) In order to approve research
covered by these regulations the 1R3
shall determine that all of the
following requirements arc 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
(si) 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.
(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 .
! 16
.
(5) Informed consenf wiSI be
appropriately documented, in
accordance with, and to the extent
required by
§ 46.
1 17.
(6) Where appropriate, the research
plan makes adequate provision for
monitoring the data collected to
insure the safety of subjects.
(7) Where appropriate, there are
adequate provisions to protect the
privacy of subjects and to maintain
the confidentiality of data.
(b) Where some or all of the
^
subjects are likely to be vulnerable to
coercion or undue influence, such as
persons with acute or severe physical
or mental
illness, or persons who are
economically or educationally
disadvantaged, appropriate additional;
safeguards have been included in the
study to protect the rights and welfare
of these subjects.
I 46.112
Review by institution.
Research covered by these
regulations 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 authorityto ^
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 Secretary
.
1 Reports should be filed wish ihc Office
for Protection from Research Risks, National
Institutes of Health, Department of Health
and Human Services, Sethesda, Maryland
20205 .
c
Approved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
!!
:IppmveH .For. Release 2000/08/08
: CIA-RDP.96-00788R001 700250001 -7
§ 46,114
Cooperative research.
Cooper.! live research projects are
those projects, normally supported
through grants, contracts, or similar
arrangements, which involve
institutions in addition to the grantee
or prime contractor (such as a
contractor with the grantee, or a
subcontractor with the prime
contractor). In such instances, the
grantee or prime contractor remains
responsible to the Department for
safeguarding the rights and welfare of
human subjects. Also, when
cooperating institutions conduct some
or all of the research involving some
or all of these subjects, each
cooperating institution shall comply
with these regulations as though
it
received funds for its participation in
the project directly from the
Department, except that in complying
with these regulations institutions
may use joint review, reliance upon
the review of another qualified IRB,
or similar arrangements aimed at
avoidance of duplication of effort.
4 46.115
IRB records.
”
(a) An institution, or where
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 repons 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 as
required by
§ 46.103(b)(3).
(6) Written procedures for the IRB
as required by
§ 46. 103(b)(4).
(?) Statements of significant new
findings provided to subjects, as
required by
§ 46.116(b)(5).
(b) The records required by this
regulation shall be retained for at
least 3 years after completion of the
research, and the records shall be
accessible for inspection and copying
by authorised representatives of the
Department at reasonable times and
in a reasonable manner.
§46.116
General requirements
for informed consent.
Except as provided elsewhere in
this or other subparts, no investigator
may involve a human being as a
subject
in research covered by these
regulations 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
iniluence. The information that
is
given to the subject or the
representative shall be in language
understandable to fhe subject or the
representative. H^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 dements of informed
consent. Except as provided
in
paragraph (c) or (d) of this section, in
Page 9
seeking informed consent the
following information shall be
provided to each subject?
<I> A statement that the study
involves research, an explanation of
the purposes of the research and the
jj, expected duration of the subject’s
; participation, a description of the
1 procedures to be followed, and
| identification of any procedures
\ which are experimental;
'll
( 2) A description of any reasonably
1 foreseeable risks or discomforts to the
4 subject;
(3) A description of any benefits to
,jj the subject or to others which may
• reasonably be expected from she
A 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
/t? A
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;
(?) An explanation of whom to
contact for answers to pertinent
\
questions about die research and
research subjects’ rights, and whom
to contact in the event of a research-
related injury to the subject; and
,
-48) 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 toss of benefits to
.which the subject is otherwise
"entitled.
r
(b) Additional elements of
informed consent.- When appropriate,
one or more of the following elements
of information shall also be provided
to each subject:
Approved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
45CFR46
~
'( I ) A statement that the particular
• treatment or procedure may involve
’/isks to the subject (or to the embryo
tor fetus,
if the subject
is or may
£ become pregnant) which arc currently
^unforeseeable;
(2)
Anticipated circumstances
Sunder which the subject’s
i participation may be terminated by
* She investigator without regard to the
K subject's consent;
tj|
(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
j course of the research which may
i relate to the subject’s willingness to
i continue participation will be
f provided to the subject; and
(6) The approximate number of
“subjects involved in the study.
< c
:> An IRB may approve a.conceal
- procedure jmgft d«ce..a*K. jGduder or
which liifaekfc;some or all of.the,
efeincau^qf informed, consent set
fonh above, or waive the requirement
to obtam 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) programs
under the Social Security Act, or
other 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 aUsra.someor ail of the
dements of informed consent set
forth above, 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 these regulations 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 these regulations
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.
§ 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.
1 16
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 "jborl.fonn” written
consent document stating that the
elements of informed consent
required by $ 46. 1 16 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 die summary, and the
person actually oouuning 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 ail 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 (he f^arch presents go
more than iwiTmiE risk of harm to
subjects ana involves m procedures
for which written
jf horrishlly
required outside 6f the research
context.
In cases where the documentation
requirement
is waived, the IRB may
require the investigator to provide
subjects with a written statement
regarding the research.
$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 the
Department with the knowledge that
subjects may be involved within the
Approved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
submitted to the Department.
§ 46.119
Research undertaken
without the intention of involving
human subjects.
In the event research (conducted or
funded by the Department)
is
undertaken without the intention of
involving human subjects, but
it
is
later proposed to use human subjects
its the research, the research shall
first
be reviewed and approved by an IRB,
as provided
in these regulations, a
certification submitted to the
Department, and
final approval given
to the proposed change by the
Department.
§ 46.120
Evaluation and
disposition of applications and
proposals.
(a) The Secretary will evaluate
ail
applications and proposals involving
human subjects submitted to the
Department through such officers and
employees of the Department and
such experts and consultants as the
Secretary 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 proposed research to
investigational new drugs by 21 CFR
312. 1(a) and lor significant risk
devices by 21 CFR 8(2.30 has
elapsed, or whether the Food and
Drug Administration has waived that
requirement.
It the 30-day interval
has expired, the institution shall state
whether the Food and Drug
Administration has requested that the
sponsor continue to withhold or
restrict the use of the drug or device
in human subjects,
if the 30 day
interval has not expired, and a waiver
has not been received,
the institution
shall send a statement to the
Department upon expiration of the
interval. The Department will not
consider 3 certification acceptable
until the institution has submitted
a
statement that the 30-day interval has
elapsed, and the Food and Drug
Administration has not requested
it to
limit the use of the drug or device, or
that the Food and Drug
Administration has waived the 30 day
interval.
5 46,122
Use of Federal funds.
Federal funds administered by the
Department may not be expended
for
research involving human subjects
unless the requirement of these
i*age 11
regulations, including all subparts of
these regulations, have been satisfied.
§ 46.123 Early termination of
research funding; evaluation of
subsequent applications arid
proposals.
fa) The Secretary may require that
Department funding for any project
be terminated or suspended in the
manner prescribed in applicable
program requirements, when the
Secretary finds an institution has
materially failed to comply with the
terms of these regulations.
fb) In making decisions about
funding applications or proposals
covered by these regulations the
Secretary 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 who would direct the
scientific and technical aspects of an
activity has in the judgment of the
Secretary materially failed to
discharge responsibility for the
protection of the rights and welfare of
human subjects (whether or not
Department funds were involved).
8 46.124 Conditions.
With respect to any research
project or any class of research
projects the Secretary may impose
additional conditions prior to or at the
time of funding when in the
Secretary ’s judgment additional
conditions arc 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’
i
. 40 FR. M528, Aug.
X.
1975. 45 FR
i 758, January
!
.
1978, 44 FR
51559, November 3.
1 97s
8 46.201 Applicability,
(a)
} fie regulations
in
this subpart
are applicable to ail Department of
Health, Education, and Welfare
45 cfm>ved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7
period of funding, but definite pians
would not normally be set forth in the
application or proposal. These
include activities such as institutional
type grams (including bloc grants)
where selection of specific projects
is
the institution's responsibility;
research training grants where 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
described in
§ 46.101(b), 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 these regulations, and certification
the subjects and others, and the
importance of the knowledge to be
gained.
(b) On the basis of this evaluation,
she Secretary may approve or
disapprove the application or
proposal, or enter into negotiations to
develop an approvable one.
§46.121
Investigational new drug
or device 34May delay requirement.
When an institution
is required to
prepare or to submit a certification
with an application or proposal under
these regulations, and the application
or proposal involves an
investigational new drug (within the
meaning of 21 U.S.C. 355(i) or
357(d)} or a signif icant risk device (as
defined in 21 CFR 812. 3(m)), she
institution shall identify the drug or
device in the certification. The
institution shall also state whether the
30-day interval required for
Approved For Release 2000/08/08
: CIA-RDP96-00788R001 700250001 -7