45 CFR46
Page 8
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a statement of the reasons for its
decision #nd ptvc the
in' cMtgclor an
oppomum>
to icspoi.d
in person or
in
writing.
(e) An fRB shall conduct
continuing review of research covered
hy these regulations
at intervals
appropriate to the degree of risk, hut
not less thtn once per year, and shall
have authority
tu oOncivc ui have
a
third party observe the consent
process and the research.
$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 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
rcpublicalton in the Federal
Register.
(b) 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 IRB 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 the reviewers may
not disapprove the research. A
research activity may be disapproved
only after review in accordance with
the non-expedited procedure set forth
in
§ 46.108(b).
(c) Each IRB which uses an
expedited review procedure shall
adopt a method for keeping all
members advised of research
proposals which have been appowed
under
li e procedure
(d) The Secretary may
rest net,
suspend, or terminate an institution's
or IRB
s use ol the cxpcuiUo review
procedure when necessary to protect
the rights or welfare of subjects.
§46. 1 1 !
Criteria for IRB
approval of research.
(a) In order to approve research
covered by these regulations the IRB
shall determine that all of the
following requirements are satisfied:
( 1) Risks to subjects are
minimized:
(i) By using procedures
which arc 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.
(4) Informed consent will be
sought from each prospective subject
or the subject’s legally authorized
representative, in accordance with,
and to the extent required by
§ 46.116.
(5) informed consent will be
h ^rvropri z tr
1 y dr
me
it d
. m
accordance with, and
to the extent
required by
§ 46
| 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 arc
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 arc
economically or educationally
disadvantaged, appropriate additional
safeguard* 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 authority, to
suspend or terminate approval of J
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 actiop and shall be reported
promptly to the investigator,
appropriate institutional officials, and
the Secretary.
1 Report* thotiid be filed with the Office
for Protection from Research Risk*, National
Institutes of Health, Department of Health
and Human Services, Bcthcsda. Maryland
20205.
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4^ .fFR 46*
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5 46.114
Cooperative research.
Cooperative research
protect', arc
liiusc piojecis.
nortiuiif) supported
through grants, contracts, or similar
-rrangc merits, which involve
institutions
in addition to the grantee
or prime contractor (such as a
contractor with the grantee, or a
subcontractor with the prime
com rac tor)
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 ot 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
rnav use
joint review, reliance upon
the review of another qualified IRR,
or similar arrangements aimed at
avoidance of duplication of effort.
6 46. 1 15
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 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
ihr JPP. and the
investigator?..
(5) A
list of IRB members as
icquircu by
46.103(b)(3).
(6) Written procedures for the IRB
as required by
§ 46.103(b)(4).
(7) 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 authorized representatives of the
Department at reasonable times and
in a reasonable manner.
scU mg informed consent the
;
-•••<-
r
i
. liii-
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= *»
-
.
...
/ provided to each subject:
'*• (1> A statement that the study
involves research, an explanation of
the purposes of the research and the
t expected duration of the subject's
;
participation, a description of the
* procedures to be followed, and
h identification of any procedures
^
which arc experimental;
i'
A description of any reasonably
.foreseeable risks or discomforts to the
i subject;
,
A description of any benefits to
.»
subject or to others which may
' reasonably be expected from the
5 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
reg ulations unless the investigator has
^snossnitericgally effccfiv*
Bforrn^
orfite
fUbjc£fTTegaliy authorizedT
JHHfflWative. 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 shajl be in language
understandable to
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
j
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
«r«)“A disclosure of appropriate
alternative procedures or courses of
treatment, if any, that might be
•, advantageous to the subject;
A statement describing the
extent,
if any, to which
confidentiality of records identifying
the subject will be maintained;
‘ J0 For research involving more
than minimal risk, an explanation as
; lo whether any compensation and an
/t7
> explanation as to whether any
medical treatments are available if
injury occurs and,
if so, what they
consist of, or where further
in^pation may be obtained;
4^7
explanation of whom to
'~j
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
,
A statement that participation is
voluntary, relusal 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:
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r
iff*
4'
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,*r
iilri
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"^u, wmc or
sit of the
.»! uv'orrrrd co:i vmf
*-?i
ft-'ovr, or waive the
iiirnis to obtain informed
-
[tiovidcu Uic IRB finds and
•~iu% that:
Mir research involves no more
minimal
risk to the subjects;
Hie waiver or alteration will
* rifely aiiect the rights and
•r o i the subjects;
* The research could not
c»My be carried out without the
vs
oi
alteration; and
Whenever appropriate r the
i*> will be provided with
•oimi pertinent information after
-ipation.
t he informed consent
cements in these regulations are
^tended to preempt any
cable federal, state, or local laws
n squire additional information
disclosed
in order for informed
at to be legally effective.
Nothing
in these regulations
is
ded to limit the authority of a
iciiin
to provide emergency
cal care, to the extent the
>ician
is permitted to do so under
ph/
.cable federal, state, or local law.
Hit
^ *117
Documentation of
•
I
J rmtd consent.
I* 1
c. ; Except as provided
in
*
/raph (c) of this section,
t
4 *1 *
fmed consent shall be
h*-
yincntcd by the use of a written
ent form approved by the IRB
*
Mgned by the subject or the
'ct's legally authorized
tentative.
P f* } Except as provided in
!
^raph (c) of this section, the
M
‘cpi form may be either of the
.-y vying;
^ If } A Written consent document
v £/nbodies the elements of
{^f j}}WJ consent required by
^
}/- TI6* This form may be read to
I
; wbject or the subject’s legally
jj
;
i?riwd representative, but in any
f.
the investigator shall give
'
* dir subject or the representative
iM
adequate opportunity to read
it before
it
i
r
. signed; o:
(2> A
“short form** written
consent document stating that the
elements of informed consent
required by
5 46,
1 16 have beer
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 nummary, and the
person actually ocuuning 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
for<§hsr^
iff**
totflTslgnc<fconsemformforsAuc
eit
(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
mmm**
MfljMO
cresearc#
where the documentation
requirement
is waived, the IRB may
require the investigator to provide
subjects with a written statement
regarding the research.
9 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
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II
*4
» u iid mj:
, hut del in he plan*
=
i
-J
he
sel f;v-th
:r,
[};e
£«
-Priuaaon or proposal. These
include activities such as institutional
‘.M'-
(including bloc grams)
^iiere selection of specific projects
j
tiK
institution *s responsibility;
research training grants where the
activities involving subjects remain n
he ^elected; and projects
in which
human subjects’ involvement will
depend upon completion of
m«aruments, prior animal studies, or
purification of compounds. These
applications need not be reviewed by
an IRQ 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
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
in 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.
5 46.120
Evaluation and
disposition of applications and
proposals.
(a) The Secretary will evaluate
all
applications and proposals involving
human subjects submitted to the
Department through such officers and
employees of the Department and
such expens and consultants as the
Secretary determines to be
appropriate. This evaluation will take
info consideration the risks to the
subjects,
the adequacy of protection
against these risks,
the potential
oe n cut:, o I the proposed
re s ea r c h
(
o
the subjects and others, and the
important-.
<•;
ih:
k nou irdg,c
l-j K
gained.
(b) On the basis of this evnluafion.
the Secretary may approve or
disapprove the application or
proposal, or enter into negotiations
to
develop an approvablr one.
I 46.121
Investigational new drug
or device 33-day delay requirement.
When an institution
is required to
prepare or to submit a certification
with an application or proposal under
these regulations,
arid the application
or proposal involves an
investigational new drug (within the
meaning of 21 U.S.C. 355(i) or
357(d)) or a significant risk device (as
defined in 21 CFR 8l2.3(m)), the
institution shall identify the drug or
device in the certification. The
institution shall also state whether the
30-day interval required for
investigational new drugs by 21 CFR
312.1(a) and for significant
risk
devices by 21 CFR 812.30 has
elapsed, or whether the Food and
Drug Administration has waived that
requirement.
If 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 a 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.
§ 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
regulations, including
ail sufp--,.
th.-M regulations, have been satislicd.
5 46.123 Early termination of
.
research funding; evaluation of
subsequent applications and
proposals.
(a) 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.
(b) 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).
5 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 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 13528. Aug.
8.
1975. 47 FR
1758. January
I I,
1978, 43 FR
51559, November 3.
197K
S 46.201 Applicability.
(a) 1 he regulations
in
this subpart
arc applicable to
all Department of
Health, Education, and Welfare
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