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CODE OF FECTZIRVAL REGULATIONS
T!T1 r fic,
PUBLIC WELFARE
DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
-OFFICE FOR PROTECTION FROM"i RESEARCH RISKS
I'm
PART 46-PROTECTION OF HUMAN SUBJECTS
REVISED AS OF MARCH 8, 1983
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PART 4@-- Z @ _00"!
HUMAN
SUBJECTS
-,@iubpart A-B-9sic HHS Policy ior
,rrotection Y jliomap@ Research
lubjec-ti ---
Sec.
46 101 To what do these regulations apply?
4t). 102 Definition%.
46.103 Assurances
46 104 Section reserved
46.105 Scown reserved.
46.106 Section reserved.
46 107 IRB membership.
46.108 IRS functions and opcr@,nons.
46,109 IRS review of research.
46.110 Expedited review procedures for
certain kinds of research involving no
more (hart minimal risk, and for minor
changes in approved research.
46 111 Criteria for IRS approval of
research.
4t). 112 Review by institution.
4b. 113 Su!.I)cnsion or termination of IRB
approval of research.
46.114 Cooperative research,
46. 115 IRS record%,
46 116 General requirements fo; informed
consent.
46.117 Documentation of informed
consent.
46, 118 Applications and proposals lacking
definite plans for involvement of human
subjects,
46. 11.19 Research under 'Aaken without the
Intention of involving human subjects.
46.120 Evalu ,stion and disposition of
applications and proposals.
46.121 Investigational new drug or device
30-day delay requirement.
46.122 Use of federal funds.
4f). 121 Early termination of research
fundinli@ evaluation of subsequent
applications and proposals.
4t, 124 Conditions.
Subpart B-Additional Protections
Pertaining to Research,
Development, and Related
Activities Involving Fetuses,
Pregnant Women, and Human
In Vitro Fertilization
Sec.	
46.201	Applicability.
46.202	Puirposc.,
46.203	Definitions.
46,204	Ethical Advisory Boards.
46 205	Additional duties of the In%toutional
Rev	iew Boardt in cotinection %ith
46.20,f Gencral lirmiaii,if!&
4o..j-, Acn@wc@ direciez! to-aro p:rgr-nt
women as subjects
4;3 V0 Activities directed to%ard tctu@cs it,
uterly &I. subjects.
46.209 Activities directed toward fetuses ex
_-reru. including nonviable Iciuscs. 3,
subjects,
46.210 Activities involving [tic dead fetus,
fcial material, or the placenta.
46.211 Modification or waiver of specific
requirements.
Subpart C-Additional Protections
Pertaining to BiomedicRI and
Behiilvioral Research Involving
Prisoners as Subjects
46.301 Applicability.
46. 102 Purpost.
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. I
46.306 Permitted activities involving
ptisoncra,
Subpart D-Additionall Protections
for ChIldnn Involved as Subjects In
Research
Sec.
46.401 To what do these regulations apply?
46.402 DerinitiOrill.
46-403 IRD clutim
46.404 Revinarch not involving greater than
minimal risk,
46-405 Resmirch involving greater than
minimal risk but prmnting the prospect
of direct benefit to the individual subjects.
46-406 Rcwuch involving greater than
minimal riLk and no prospect of direct
benefit to individual subjects, but likely to
yield generalizable knowledge about the
subiect'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 Requircincrits for pcrmiwon by
parents or guardians and for assent by
children.
46A09 Wards.
Auibority@ 5 U,S C 301, sec. 474(a), SR
Nc.@.;. 31@2 (42 V,S.C. Z891-30i@).
45 CFR 46
p,virt AL--L1;,.,sic MIS 1@011c) for
Pruiection of Human Research
11F
'-urt-c! 46 FR 63", January 26, 1991, 4a FFI
92b", March 4, 198).
46-101 To what do these
tv,@Uialions apply"
(a) Except as provided in
paragraph (b) of this section, this
subpan applies to all research
involving human subjects conducted
by the Department of Health and
Human Services or funded in whole
or in part by a Department grant,
contract. Cooperative agreement or
fellowship,
1) This includes research
conducted by Dcpanment employees,
except each Principal Operating
Component head may adopt such
nonsubstantive. procedural
modifications as may be appropriate
from art administrative standpoint.
(2) It also includes research
conducted or funded by the
Department of Health and Human
Services outside the United States,
but in appropriate circumstances, the
Secietary may, under paragraph (e) of
this section waive the applicability of
some or all of the requirements of
these regulations for research of this
type
(b) Research activities in which the
only involvement of human subjects
will be in Pne or more of the
following latcl;orics are exempt from
these regulations unless the research
is covered by other subparts of this
part:
1) Research conducted in
established or commonly accepted
educational settings. involving
nortrial educational practices, such as
0) 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,
dt.-nostic, aptitudc. achievement), if
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tak"':
is ic,-orded in such a nianne:,- that
suhiccis cannot be Identified. directiv
V@F or-ifrough iL@cnlifltrs linkcJ to it',
suhject%.
(3) Rescarch involving surve), or
interview procedures, except where
All of the folloNxing conditions exim:
6) responses are recorded in such a
manner that the human subjects can
be identified, directly or through
identifiers linked to the subjet:ts, (ii)
Ilic subject's responses, if t@ey
be,.ame known outside the research.
could reasonably place the subject at
rt4, (if criminal or civil liability or be
darnaging to the subject's financial
standing or employability, and (iii)
the research deals with sensitive
aspects of the subject's own behavior,
such as illegal conduct, drug use,
sexual behavior, or u5c of alcohol.
All research involving survey or
interview procedures is exempt.
without exception, when the
respondents are elected or appointed
public officials or candidates for
public office.
(4) Research involving the
observation (including observation by
participants) of public behavior.
except where all of the foliowint,
conditions exist: (i) observations are
recorded in such a manner that the
hunian subjects can be identified.
directly or through identifiers linked
to the subjects, 60 the observaiions
recorded about the individual. if the),
becarne known outside the research,
couid reasonably, place the subject at
risk of' criminal or civil liability or be
damaging to the subject's financial
standing or employability, and (iii)
the research deals with sensitive
aspects of' the subject's own behavior
Such as illegal conduct, drug use.
sexual behavior. or use of alcohol.
(5) Research involving the
colloction or study of existing data,
documents, records, pathological
specimens, or diagnostic specimens,
it these sources are publicly available
M if the information is recorded 1)),
thc Investigator in such a manner that
or through identifiers liri@t@o to th@-
sum s
-icct,.
(6) Uniess spmtfically rectLilred by
SLAW! '10 the exLciii
specified in paragraph (i)), research
and demonstration projects which
are cond@lcted by 0'. s-';1- :@,O, 'o "!,-r
approval ofthe Department of
fleafth and Human Services, and
which are designed to study.
evaluate, or other-wise examine: 6)
programs under the Social Security
Act, or other public benefit or
SeTViCC PTOgTanIS-, (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 thr.,st programs.
(c) The Secretary has final
authority to determine whether a
particular activity is covered by these
regulations.
(d) The Secretary may require that
specific research activities or classes
of research activities conducted or
funded by the Department, but not
otherwise covered by these
regulations, comply with some or all
of these 'tegulations.
(e) The. Secretary may also waive
applicabiliiy of these regulations to
specific reseatch activities or classes
of research activities, otherwise
covered by these regulations. Notices
of these actions will be published in
the Federal Register as they occur.
(f) No individual may receive
Department funding for research
covered by these regulations unless
the individual is affiliated with or
sponsored by an institution which
assumes responsibility for the
research under an assumnce latisf ing
the requirements of this part, or Z
individual makes other arrangements
with the Department.
(g) Compliance with these
regulations will in no way render
in:ipplicable p:fmm:nt, feudcr@d, ,ilac,
or local laws or repidm ions.
S k'L"-, 01 O'L SC
r-,-Imons cLniain% a separate
wh.-! the Sul-pari
JpPlIC1,- kcscarch which is covered
b Y n io ih--mi one subp@;ri shall
Ccii-1-1 i W,' r
P1, 01 ah applicable subparts.
W I f, following review of
r'.-Irch act:_ .
. 4itk@s "&La(_a1L
exempt froin thew regulations under
paragraph (b)(6), the Secretary
determines that a research or
demonstration project presents a
danger to the physical, mental, or
emo tional well-being of a participant
or subject of the research or
demonS,11-1111011 project. then federal
funds may not be expended for such
a project without the written,
informed consent of each participant
or subject.
46.102 Definitions.
(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) "Department- or -HHS-
means the Department of Health and
Human Services.
tic
Ji VC101
ne U ng
___(d_)-Lcgally 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.
(e) "Research' ineans a
systematic investigation designed to
develop or contribute to generalizable
knowledge. Activities which meet
this definition constitute "res.-arch"
for purposes of these regulations,
whether or not they are supported or
funded under a program which is
considered research for other
purposes. For example. some
"dernonstraiion" and "service"
programs may include research
activities.
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A@prnypd Fnr Relea-se_2fiftWo_9L1a__a - nPq6-QQZBqRQQ3QOQQ20Q02-5
(F) "Hu"Ur suhje@:t" rn-cart% a
it%iiy iriji,.,Ju@; aWui who-in, an
1101 1 @,-Utcf Pi,,@(S%1011.f@ Id
@[uclcni) conducting re,varch obtains
1) dma t@rmq',h ii!tOrvc-0,@" 0!
interaction " ith the individual, o- (2)
ide116:1.1ble pti%alc information.
includes both
physical procedures by which data are
and manipulations of the sUbject or
the subject's environment that are
performed for research purposes.
"Interactiom, - include.,.
communication or interpersonal
contact between investigator and
sub-iect. -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
h,, an individual and which the
individual can reasonably expect will
not he made public (for example, a
inedical record). Private information
must be individually identifiable
We- 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)
cnA- W2T!FY11`TFM'XMrM9'W
,Vjuwsg:tn
#04#9@ @_,_
Aft-j§ft M
(h) "CertificationY means the
official notification by the institution
to the Department in accordance with
the requirements of this part that a
research project or activity involving
human subjects has been rev .iewed
and approved by thq Iral
4WS" (Cenification is requi7wedp7wit-en
the research is funded by the
Department and not otherwise exempt
in accordance with § 46.101(b)).
in Outit'n cr'TjVC,@ In
C'- Aj@
shall provide Ari!ten as,,urin cc
!k, r,,c -!_jr r
will complN, wt(h the requireincril,, se(
folLil I!) ("IL'IC NgUiatiOnS.
(b) The Department %ill conduct or
fund rescarch Covered by these
o.-il", if tlw liisilloliu', IM,
an assurance approved as provided in
this section. and only if the institution
has certified to the Secretary 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. This
'assurance shall at a minimum include:
11) 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 1hc in.titution.
regardless of source of funding. 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 these regulations
applicable to Department-funded
research and is not applicable to any
research in an exempt category listed
in § 46. 10 1.
(2) Designation of one or more
IRBs,cstablished in accordance with
the requirements of this subpart, and
for which provisions are made for
meeting space and sufficient staff to
support (tic IRB's review and
rccordkeeping duties.
(3) A list of the 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
o
ther relationship between each
member and the institution; for
example: full-time employee. part-
time employee, member of yoverning
panel or board, stockholder, paid or
L;rr%-;d cowultzrit MR
01;0I hr ft",(@r`c,j !n ll:,:
4) W iiiien pr(vccJuiLs which Vl_@
,:1! ;o, its
initial and continuine review c,,f
rc,,earch anti for rept,iiirip its findings
arid actions to the invcsugator and the
institution: (ii) for determining which
k1IL.j
than annually and which projects
need verification trom s-urcel. other
than the investigators that no matcrial
changes have occurred since previous
IRB review. (iii) for insuring prompt
reporting to the IRB of propo,,,ed
changes in a research activity. and for
insuring that 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 where
necessary to eliminate apparent
immediate hazards to the subject. and
Ov) for insuring prompt reporting to
the IRB and to the Secretary I of
unanticipated problems involving
risLs to subjects or others.
(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 these
regulations', and shall be filed in such
form and manner as the Secretary
may prescribe.
M The Secretary will evaluate all
assurances submitted in accordance
with these regulations through such
officers and employees of the
Depariment and such experts or
consultants engaged for this purpose
as the Secretary determines to be
appropriate. The Secretary'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
Reports should be filed with the Office
for Protection from Research Risks, National
institute% of Health. Department ofHemith
and Human Scmccs, Bczhe@da, M-tryland
1-01.05
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----
PosseNsin@, the nrofesswfi@ti
fit' C L'C I NI , T k' C %V
ht I the
re, iew procedure,,, in liv if specific research acti Ivitics, thc IP\B
probable alld the SI?P(- and %hall hr- @-hjc t(@
1., 1!,, L
compiexity of the institution. uk,,@cptabilitv ot proposed research in
(c) On the hasis of this evaluniion, term,% ol Itw,uti,1110nal COmmitments
thc Secretary may approve or
disapprove the assurance, or enter
inlo rcvoliatlons to dt@velor an
appro%ahle one. The Secretary may,
liniii the period during which any
particular approved assurance Or class
of approved assurances shall remain
effective or otherwise condition or
restrict approval.
(0 Within 60 days after the date of
submission to I-IHS of an application
or proposal, an institution with an
approved assurance covering the
proposed research shall certify that
the application or proposal has been
reviewed and approved by the IRB.
Other institutions shall certify that the
application or proposal has been
approved by the IRB within 30 days
after receipt of a request for such a
certification from the Department. If
ihe certification is not submitted
within these time limits, the
application or proposal may be
returned to the institution.
§ 46.104 [Reserved)
46.105 [Reserved]
46.106 [Reserved)
146.107 IRB membership.
(a) Each IRB shall have at least
five members, with varying
backgrounds to promete complete and
adequate review of research activities
commonly conducted by the
institmion. The IRB shall be
sufficiently qualified Wough the
exp@nence and expertise of its
membiirs, and the diversity of the
members' backgrounds including
consideration of the racial and
cultural backgrounds of members and
sensitivity to such issues as
community attitudes. to promote
respect for its advice and counsel in
safeguarding the rights and welfare of
human suhjcct%. In addition to
and regulations, applicable law, and
standards of professional conduct and
pracucz. 'I'llm 11RIB 014H Giciefore
include persons knowledgeable in
these areas. If an IR9 regularly
review-, research that involves a
vulnerable category of subjects,
including but not limited to subjects
covered by other subparts of this part,
the IRB shall include one or more
individuals who are primarily
concerned with the welfare of these
subjects.
(b) No IRB may consist entirely of
men or entirely of,women, or entirely
of members'of one .. profession.
(c) Each IRB shall include at Icubt
one member whose primary concerns
I ntific areas; for
are in nonscie
exampie: lawyers, ethicists, members
of the 'Clergy.
(d) Each IRB shall include at least
one -membcrwho is.not otherwise
affiliated with the institution and who
is not pan of the immediate family of
a person who is affiliated with the
institution.
(e) No IRB may have a member
participating in the IRB's initial or
continuing review of any project in
whichthe member has a conflicting
interest, except to provide
information requested by the IRB.
(f) An IRD may, in its discretion,
invite individuals with competence in
special areas to assist in the review of
complex issues which require
expertise beyond or in addition to that
available on the IRB. These
individuals may not vote with the
IRB.
46.108 IRB functions and
operations.
In order to fulfill the requirements
of these regulations each IRD shall:
(a) Follow written procedures as
provided in § 46.103(b)(4).
Page 7
fh@ Fxccr, vAn-r. @,iz
TCN )CM, pr,kcdurc is uscd t!,Cc
review propo%cd research
§ 46.110),
Lonvened mectirigs at whicr; a
majority of the members of the IPB
ale,present, including a( 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.
(c) Be responsible for repor-ting it;
the appropriate institutional officifls
and the Secretary I any serious or
continuing, noncompliance by
investigators with the requirements
and determinations of the IRB.
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 these regulations.
(b) An IRB shall require that
information given to subjects " Part'
of informed consent is in accordance
with § 46.116. The IRB may require
that, information, in addition to that
specifically mentioned in § 46.116,
be given to the subjects when in the
IRB's judgment the information
would meaningfully add to the
protection of the rights and welfare of
subjects.
(c) An IRB shall require
documentation of informed consent or
may waive documentation in
accordance with § 46.117.
(d) An IRB shall notify
investigators and the institution in 4
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
Repons should be filed with the Office
for Pro(emon from Research Risks, National
I
In%inutes ot i1calth, Department (if licallh
and Hunnan Sc-vtk;cs. bethesda. Maryland
20211
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a statcment of the rczwn- f,,r it:,
Oerliiori vild give Oic imrslip--tor ar
10 It, Pcrsoh Of lis
wrid .rig.
I
,c) An IRB %hLl! conduct
cont@nuing review of rercarch covered
by thest-, regulations at intervals
appropriate to the degree of risk, but
ntx less than once per year, and shall
fla'vu authWily lo ubscivu 0i havc a
thifd party observe the consent
process and the research.
§46.110 Expedited rewlew
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
rese.arch that may be revicwe by the
IRB through an expedited review
procedure, The list will be amended.
as appropriate, through periodic
rcpublication in the Federal
Register.
N 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. 71c IRS 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 b the IRB chairperson or
y
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
ity may bc disap
research activ proved
only after review in accordance with
the non-expeditcd procedure set fonh
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 uhich have bccn
UndCr 0 c pr(wedurc
(d) I lic Nmrctar% may
suspend, or terminate an inswunon's
'B'S , CXpC 1;;k -4 re,, je,k@
0, lp USC Of 1C
procedure when necessary to protect
[he rights or welfare of subjects.
§46. 111 Criteria for IRR
approval or research.
(a) In order to approvc 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 are consistent with sound
research design and which do not
unnecessarily expQse subjects to risk.
and (ii) wliencvcr 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 IRS should
cotisider o its
@nly@ those risics and better
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 IRS should not
-. '@ie
consider possible long-ra 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 o .f subjects Is
equitable.'In making this assessment
the IRS 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.
(511 InfOr-InCd COnwnt will be
witl@, and iti thc exicrit
ircquired by § 46-117.
(6) Wilcic dppiopitate, the rcsca,-ct,
plan makes odequatc provision fof
monitoring the data collected to
insure the safety of sub*ts.
(7) Where., appropriate, therc are
adequate provisions ' to Protect the
privacy of subjects and to maintain
the confidemiality of data.
(b) Where some or all of the
subjects are likely to be vulncrablc-i@'
coercion or unduc influence. such as
persons with acute or severe physical
mcntal illness, or persons who arc
or
economically or educationally
disadvantaged. spVopriatc II44itional-
ssifeguards have been included in the
study to protect the rights and welfare
of thesw subjects.
146.112 Review by institution.
Research covered by these
regulations that has been approved by
an IRS 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 IRS.
146-113 Suspension or
terminuflon of IRS approval of
research. to
An IRB shall have 4uthQ_rAY,;1
suspend or terminate appro ... va'I of
research that is not being conducted
in accordance with the IRS '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
-IRS's -acoop AW "I. be reported,
promptly to the investigator,
appropriate institutional officials, and
the Secretary.
Repons should be filed with the Office
for Protection from Research Risks, National
Institutes of Health. Dcpanment of Health
and Human Smices, Bethesda, MMIand
20205.
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t, 46.114 Coopet-ative rvsi@arch.
Coopetonvc rvsearch proiccf@- OT('
PtOjccls, n0ruw@,i@ @wpporlvd
through grants, contracts, or simdar
Z., ,gciricra.;, imol\,c
inNtitutions in addition to thc gmntce
or prinie contractor (such as a
Con,ractor with the grantee, or a
subcontractor with [he Prime
c4poiracior) in such instance@,, the
grantee or prome contractor remains
responsible to the Department for
safeguardijig the rights and welfare of
human subjects, Also, when
Coopera!!r!@ institutions conduct some
or all of the research involving some
or 311 of !hose subjects, each
cooperating institution shall comply
%viEh these regulations as though it
received funds for its participation in
the project directly from the
Department, except that in complying
with t1licsc regulations institutions
rjia@ use -joint review, reliance upon
the review of another qualified IRB,
or sin-611af arrangements aimed at
avoidance of duplication of effort.
46.115 IRB records.
(a) An institution. or where
app itopriate 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
invdstigators, and reports of injuries
to subjects.
(2) Minutes of IRB meetings which
shall be in sufficient detail to s . how
attendance a[ 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 tesolution.
(3) Records of continuing review
activities.
(4) Celpic% oI fll
t@- IPP .,nJ thc
LII'@C@nga!or@_
(5) A list (if IlZB mcmbers a%
1c4uircj hv § 4(). W3(bwi),
(6) Writtell PrOcedures for the I R B
a,, requircd by § 46, 101(b)(4).
(7) Statements of significant new
finding% provided to subjtct,@, 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 bt,
accessible for inspection and copying
by authorized representatives of the
Department at reasonable times and
in a reasonable manner.
146.116 General requirements
ror 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
JUIMEMcftally- effftfiAr"
Ac@@Va*e
.4uthwilbW
11WOMative. An investigator shall
seek s,uch consent only under
circums .tances that provide the
prospective subject or the
representative sufficient opportunity
to consider whether or not to
participate and that minimize the
ossibility of coercion or undue
influence. The information that Is
given to the subject or the
representative $haq!,@e. in language
understandablc t0_0c,,subject or the
representative.,.kinformcd consent,
whether oral or. w@tiei. 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
sc,iliny inforined conscril tt@c
provided to each subjecu
A statement that the siudv
invcIves rcscai,ti, act explanation of
the purposes of the rest-!%:h and the
exNcted duration of the subject's
participation, a description of the
pr(wcdures t-o he followed! and
identification of any procedures
which are experimental,
411 gV A description of any reasonably
i foreseeable risks or discomforts to the
Isubject;
A description of any benefits to
the subject or to others which may
reasonably be expected from the
6escalch;
AW-A disclosure of appropriate
alternative procedures or courses of
treatment, if any, that might be
advantageous to the subject,
4W A statement describine the
extent. if any, to which
confidentiality of records identifying
the subject will be maintained;
-40 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
info ation may be obtained;
WAn 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
AOA statement that participation is
voluntary, refusal to participate will
involve no penalty or loss of benefits
.6 which the subject is otherwise
intitled, and the subject may
discontinue participation at any time
without penalty or loss of benefits to
which the subject is otherwise
entitled.
I(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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"W
I
ow
04,
$,k
0 o1i J!v 11A%V
i'I @@ f,
%@xyic CT &11 of the
cv@i!@.rnr iiri
.-JVt" 0, Walve the
al-its to obtain informed
piovLdej the IRB i-linds and
.-,)I& that:
r' tic research involves no more
"Iminial risk to the subjects;
1 tic, waiver or Atcration will
affect the rights and
W the subjects,
Tht rcsearch could not
t 1114Y be carried out without the
Of alteration; and
Whenever appropriate, [tie
A', will be provided with
."1114@. pertinent information after
_,ipalion.
The informed consent
irements in these regulations are
I @litended to preempt any
-,,Able federal, state, or local laws
rquire additional information
dl%closed in order for informed
it 14) be legally effective,
Nothing in these regulations is
Aed to limit the authority of a
-clan to Provide emergency
-c-41 Care, to the extent the
nor ,iciaft is permitted to do so under
!@cbhle federal, state. or local law.
/P J 17 Documentation of
oned consent.
Except as provided in
yraph (c) of this section,
consent shall be
Meliled by the use of a written
ent form approved by the IRB
,-igned by the subject or the
_cWh legally authorized
xentative. IVA
lql
@Fxccpt as pro
vided in
-par)h (c) of this section, the
it 1 01 form may be either of the
Wing.,
i A written consent document
9111kWics the elements of
it I ,
,,J1Pe consent required by
it 116, This form may be read to
I " "object or the subject's legally
i-06IN representative, but in any
I. the investigator shall give
Ille mbiect or the representative
adequate opp,:)rturity to rcad it kfore
it i" 0,
(2) A ', '&hort form- written
consent document stating that the
c1cments of informed consent
rei4uired by J 46,116 have beer
presented orally to the subject or the
subject's legally authorized
representative. When this method is
used. there shall be & Witness tG the
oral presentation. Also, the IRB shall
approve a written summary of what is
to he 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 slimmary, and the
person actually ootaining 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
WhIRB MAY waiVe IF
Ar
-W --R-7il A0
JIM rinien or einvestigato
0@rm
Tar:
(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
subjSLtLs wishes will govern; or
-Mearch oresentSA0
(21M&ML,
y
111111110TIftes 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
Invoivement or 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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611 laii Jirir , but JL I in'te plans (he SUIM L 1N imd o0irr@. and' the
or proposal. TheNc
InClude activities such as institutional
@,,jjno- (including bloc grants)
ulle-re sclection of spceific projects is
th, institution's responsibility;
re@earch training grants where the
aciivitles involving subiocts rema;v to
1w ,Occied-, and projects in which
hunian subjects' involvement will
depend upon completion of
in-oruments, prior animal studics, yr
r-orification of compounds. These
applications need not be revtf!wt:,-' by
in iRB before an award may be
Made. However, except for rcscaich
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 Dep4riment,
§ 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
Dcpjrtrnent.
§ 46.120 Evaluation and
disposition of applications and
proposals.
(u) The Secretary will evaluate all
applications and Proposals involving
hurnin subjects submitted to the
Department through such officers and
employees of the Department and
such experts and consultants as the
Secretary determines to be
appr,ipriale. This evaluation will take
into consideration the risks to the
%UbiC,71S, the adCOUICY Of PrOteCtiOn
iramst thew risk5, the potential
of &.c proposed research to
gained.
N Orl 111C basis of this evdilarioll.
the Secretafy may approve or
disapprove ,,lie app)ltatlon (it
proposal, or enter into negotiations to
develop an approvable one,
46.121 Investigutiunal new drug
or device 33-day delay rtqWrement.
When an institution is required to
prepare or to submit a certification
with an application or proposal undex
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 significant risk device (as
defini:d in 21 CFR 812.3(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. l(a) and for significant risk
devices by 21 CFIZ 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
Adminisirmion 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 bv the
Department may not he expended for
rescarch involving hunian subjects
unle,;s the requirement of the@c
rt vL 'aoons, inchid n,- I! ,ut
regulations, lii@vc
0 46.123 Early termination of
reseal
-ch funding; evaluation of
subsequent applications and
proposals.
(a) The Secrctary may require that
Dcparcmcnt fundirm for :,ny projcei
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.
M In making decisions about
funding applications or proposal@@
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
suspensiun 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).
146.124 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
"AdIvitles ffii4A vi ng Fetuses.
Pregnant Wornen, and Human Iii
Vitro Fertilization'
souptc,L: 40 FR 135@18. Avg@ 8. 1973. 43 FR
1738. Januarv 11, 1978, 43 FR
51559, November 3. 1978
§ 46.201 Applicability.
(it) The regulations in this subpart
are applicable to all Department of
Health, Education, and Wvfflir,
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I
I
		0 tw su'-riiiltrd to the board,
	ill (mle to time. taking intu	
OF (4) necd not be submitted to the
	niedi%:Al aci@allce,@, pubh%h in	Ro.,rd Whcre the Boar@ so
	''A RAi_ R i:co@l ER guidelines	establishes a class of applicaiions or
	in deterinininy whe(hcr a	proposals which must be submitted,
	'liable for purposes of this	no appi cation or proposal within the
	If a fetus is viable after	class may be funded by the
	it is a irifan!	Dckpartmer., or any companci-st theicof
	Nonviable fetus" means a	until the application or proposal has
	t utero which, although living,	been reviewed by the Board and the
14-	viable.	Board has rendered advice as to its
it,	Dead fetus" means a fetus ex	acceptability from an ethical
	1-ehich exhibits neither	standpoint.
	at, spontaneous respiratory	(d) No application or proposal
	spontancous movement of	involving human in vitro fertilization
	.tiy muscles, nor pulsation of	may he funded by the Department or
aii@	bilical cord (if still attached).	any component thereof until the
	In vitro fertilization" means	application or proposal has been
C@i,k	-filization of human ova which	reviewed by the Ethical Advisory
hv@@	outside the body of a female,	Board and the Board has rendered
	1hrough admixture ofdonor	advice as to its acceptability from an
	perm and ova or by any other	ethical standpoint.
b		
		46.205 Additionall duties ot tAte
	.4 Ethical Advisory	1nsdtutI6Q'keiiiii_w'B@*rds In
	1.	connection with activities
Sc	'ne or more Ethical Advisory	Involving fetuses, pregnant
sh_	shall be established by the	wome
n, or human In vitro
wilt' "A @	'P -y. Members of these board(s)	'
fertilization.
m;%',	so selected that the board(s)	(a) In addition to the
rclit	competent to deal with	responsibilities prescribed for
exla_	1, legal. social, ethical. and	Institutional Review Boards under
plij,	issues and may include, for	Subpart A of this part, the applicant's
i $04@ t\ _	i@v, research- scientists,	or offeror's Board shall. with respect
ethi,,,_,	lvas, psychologists,	to activities covered by this su@@,
the	
,ists, educators, lawyers, and	
carry out the following additional
ma N
'	as well as representatives of	duties:
\
of th,	, -nal public. No board member	(1) Determine that all aspects of
Edt,,	a regular, full-time employee	the activity meet the requirements of
(6@	IN-partment of Health,	this subpart;
the	@ti, and Welfare,	(2) Determine that adequate
reni,,	!, the request of the Secretary,	consideration has been given to the
Nh,	-at Advisory Board shall	
manner in which potential subjects
As	dvice consistent with the	will be selected, and adequate
iWil..	and requirements of this Part	
provision has been made by the
	1: cal issues, involving	applicant or offeror for monitoring
	ill. Covered by this subpart,	the actual informed consent process
by th.,	individual applications or	(e.g., through such mechanisms,
rrnd;@	-,is. In addition. upon request	when appropriate, as participation by
apo i,	twretary, the Board shall	the Institutional Review Board or
J_A I,,	@Vice as to classes of	subject advocates in: (i) Overseeing
	ons or proposals and general	the actual process by which
	r!jidefines, and procedures.	individual consents required by this
	'lard may establish, with	subpart are secured either by
	.?I of the Secretary, classes	approving induction of each
	-Its or proposal,; " hich:	iidiv dual into thr activ Iity or
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mrouim siniplim-.
of In diviuiuais into 1he
are beinc tollowed, ;knd 6i)
nionitoying the progress of tiv:
.1clivitv and intcn,cning as ricce%sary
through such stcp% as vi%11- in the
acttvify site and continuing evaluation
to delerinine if any uri.,tnticip.ated
ri4s have ariscri).
(3) Carry out such othcr
responsibilities as may be assigned by
the Secretary.
(b) No award mav be issued until
the applicant or offtror has certified
to the Secretary that the Institutional
Review Board has rnau`c the
determinations required under
aragraph (a) of this section and the
,
P
Secretary has approved these
de term i nations, as provided in
§ 46.120 of Subpart A of this part.
(c) Applicants or offerurs seeking
sopport for activities covered by this
subpart must provide I-or Eric
A
ciesignation of an Institutional Review
Board, subject to approval by the
Secretary, where no such Board has
becn established under Subpart A of
this part,
46.206 General limitations.
(a) No activity to which this
subpart is applicable may be
undertaken unless:
( 1) Appropriate studies on animals
and nonpregnant individuals have
been completed-.
(21) Except where the purpose of
the activity is to meet the health
needs of the mother or the parricular
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 0i) determining the
viability of the fetus at the
termination of the pregnancy; and
(4) No procedural chances whic.h
may cause greater f1l.--in inininial risk
to thw fetus or the pregnant wornar.
UM 1,e introduced into ihi@ prc-cedurc
r terinmative th.- pri-mancN
ini.- -@ of 111C tlvjl@.
(b) No inducements, monetary or
ot@erwisc. may bt: offetud to
terminate pregnancy for purposes of'
the activity.
140 FR 33528, Aug. 8. 1975, as amerKled at
40 FR 51638. Nov. 6, 1975)
-
46.207 Acti*,"Ies directed
toward preognan! women as
subjects.
.(a) No pregnant woman may be
involved as a subject in an activity
covered by this sulwart unless: ( 1)
The purpose of the activity is to meet
the healLh itecds ofthe mother and the
fetus will be placed at risk only to the
rainintunt extent necessary to meet
such needs, or (2) the risk to the fetus
is minimal.
(b) An acfivivY permitted under
paragraph (a) of this section may be
conducted onfl- if the mother and
father are legally competent and have
.en their infortned consent after
91v
having been fully informed regarding
ossible impact on the fetus, except
p
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
no( reasonably available: or (4) the
pregnancy resulted from rape.
46.208 Activities directed
toward fetuses in utero as
subjects.
(a) -No fetus in "Iero 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
impoEtant biomedical knowledge
which cannot be obtained by other
means.
(b) An activity permitted under
paragraph (a) of this section may be
covid'acled only if the mother and
(.@thc@ are Iccally c,"mripctent arw haNe
lritorlll@d CXCCPI
that the father's conscrit need not be
secured if- (1) His identi(N, or
whereabouts cann(x reas-onahl) bc
a,@(:riained. (2) he is not reasonably
available, or (3) the pregnancy
resulted from rape.
46.209 Activities directed
toward fetusts ex uttro,
including nonviable fetuses, as
subjects.
(a) Until it has been ascertained
whether or not a fetus cx utero is
viable, a fetus cx 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
portant biomedical
development of im
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 pcrmittcd by and in
accordance with the requirements of
ot er 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 arc legally competent and
have given their informed consent,
except that the father's informed
consent need not be secured if: M his
identitv or whereabouts cannot
reasonably be ascertained, (2) he is
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nor rci,@Onahly ;1vallahle, C), ON th
'C
l)rCJ!n2nCN ,(:,U!tt:J froM uii-@L
46,210 Activities invollrit'i
ficad felus, fetal nuafvrir', q,, ihe
placenta.
A,_-tivities involting 0!e dcad fctus,
mascerated f"etal iralcr;al. -,@ cclk,
tissue, or organs excised from a dead
fviw@ %hall hz- condm-i-I --f-
accordance with any applicable State
or local laws regarding such
activities.
146.211 Modification or waiver
of specific requirements.
Upon the request of an applicant or
offeror twit -h the approval of' I .is
Institutional Review Board'i, the
Secretary may modify or waive
specific requirement; of this subpart,
with the approval of the Ethical
Advisory Board after such
opportunity for public comment as
the Ethical AdvisoCw Board considers
appropriate in the particular .nstance.
In making such decisions, the
SecTetaTy 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 inothfication or waiver and that
such benefits cannot be gained except
iver.,
through a modification or wai
Any such modifications or waivers
will be published as notices in the
F FA*KAi. R EGIST@k
Subpart C-Additionai Protections;
Pertaining to Biomedical and
Behavioral Research involving
Prisonen as Subjects
Source: 43 FR 53655, Nov 16. 1978
§ 46.301 Applicability.
(a) The regulations in this subpart
are applicable to all biomedical and
behavioral research conducted or
supported by the Department of
Health, Education, and Welfare
involving prisoners as subjects.
(b) Nothing in this subpart shall he
construed as indicating that
C0111pliance with the procedures set
forth herein will authorize research
iri@(,Mn- nrisonet@@ as io lic
CNIert "Uch rescarch is limited or
barTCd 11Y At rlicabic Stair or lo,-,i)
(L; I Ov it quiTci:icr3s oi this
subpart are in addition to those
@mrn,@.-J @llc oPhei SUbJ)arLS 01
this part.
46.302 Purposc.
Inasinuch as prisoners may he
1_-J-Z.1r co'nstraIIIII.N t)ccduse ol their
incarceration which could affect their
ability to make a truly voluntary and
uncoerced decision whether or not to
participate as sub ects in research it
J I
is the purpose of this subpart
provide additional safeguards for the
protection of prisoncrs invollicd in
activities to which this subpart is
applicable.
46.303 Definitions.
As used in this subpart:
(a) "Secretary" means th c
Secretary of Health, Education, and
Welfare and any other officer or
employee of the Departrncai of
Health, I-Iducation, and Welfare to
whom authority has been delegated.
(b) -DHEW- means the
Department of Health, Education,
and Welfare.
(c) "Prisoner" means any
zifidividual invol unta'ri ly -confined of
I
d@tii n-Gd-In ii penal institutioii .The
I .,V-@@ ' ""
lierm is intended to c-n'co inpass"'
i@dividuals'scntcniidio such in
ii@stitution under a criminal or civil
.,@;tute, 1@4&1d@ails"'Jciia'in'ed in-6ibe'r
1@!cilities_by yirtue.of sta4utes or
Commitm, e" procedures. which.
provide-afteruat' ives:to 7cdm inal.
pro .s-ec tfo@.'r i' 'iic-r ation in4a
u o nc -c
i'insti6iion,.4xn4,individuaIs
Pena
detained pepding affaignment, trial,
Wsentencing'. I'
(d) "Minimal risk" is the
probability and magnitude of physical
or psychojogical harm that is
normally encountered in the daily
lives, or in the routine medica.1,
dental, or psychological examination
of healthy persons.
§ 46.304 Composition of
Institutional Review Boards
@,-Iivirv ptisoners are involved.
In addition to sati4,@ing the
requirements in § 46-107 of this, pan,
an Inkiinoton3f K@@vjcw P1ty,,,J,
carrying out responsibilities under
this part with respect to research
covered by this subpart, shall also
meet the following specific
requirements:
(a) A majority bf ft BoQ.
(ex .. 11 1
clusivc ot prt!@,ner rnernb-crs) shall,
L "' * "' ' - at
nave no Jtssoci ion with the prison(&@
involved, apar .t from -g.heir
membership on the Board."
(b) At)east one member of the-4
I @ .k. I - ; ag" & _; 4
Board,;hall boc apsp@er or a -
e@i@ectrevrtscntative with
SW'Watc 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.
146.305 Addllt;ansill duties of the
Institutional Review Boards
where prisoners are involved.
(a) In addition to all other
responsibilities prescribed for
Institutional Review Boards under
this part. the Board shall review
research covered by this subpart and
apprOve such research only if it finds
that:
(1) The research under review
represents one of the categories of
research permissible under
§ 46.306(a)(2);
(2) Any possible advantages
accruing to the prisoner through his
or her participation in the research,
when compared to the general living
conditions. medical care, quality of
food, amenities and opportunity for
earnings in the prisoo, -are. not of such
a magnitude that. bis or her ability to.
weigh the-risks, of the research against..,
the value of such'-idvantages 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
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@01 ri@:-icri, znd ir,.rnL@ric ir.-i:
aull',i)iri(ics of prisoners. urlics , L111C
Val investigator provides to the
princl
11 --1 Justifica I
- J_ I tion in writing, for
fC01O1A'inf' SO.Mr Other PrCtCC@dUFCS,
control suhjcct& mutt be selected
randomly from the group of available
posoricn- who ineet the charact,@risnl_s
necded for that particular research
PTOjC(:I'.
(5) The information is presented in
language which is understandahle to
the subject population,
W Adequate assurance exists that
pie bowd; wt, J"Jqw,
account a prisomf's participation In
the research in making decisions
regarding parole, and each prisoner is
clearly infonned in advance that
I
participation in the research will have
no effect on his or her parole; and
(7) Where the Board finds there
ma) 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 caffy out such
other duties as may be assigned by
the Secretary.
(c) The institution shall certify to
the Secretary, in such form and
mariner as the Secretary may requite,
that the duties of the Board under this
section have been fulfilled.
146.306 Pemlitted rmarch
involving pirt".ners.
(a) Biomedical or behavioral
research conducted or supporied by
DHEW may involve prisoners 39
subjects only it:
(1) The institution responsible for
the-conduct of the research has
certified to the Secretary that the
Institutional Review Board has
approved he research under § 46.305
Of tili% subpart and
1.1 dric judgment of the
Sck@ic-.ery tht prot-fosed rcscarkti
1 r f ,:! 1
(A) Study or the possible caus.-s.
ar"! procf-@-,C. Off
incarceratior, and of criminal
bch;z%-Jor. privided that the study
Picsents no more than minimal risk
and no more than inconvenience to
k@;S;
(B) Study of prisons as institutional
structures or of prisoners as
incarcerated persons, provided that
the study presents no more than
minimal risk and no more than
inconvenience to the subjects,
ic) Kcscari:h tin Condilions
particularly affecting pni Isoner% as a
class (for 'example, vaccine trials and
other research on hepatitis which is
n
much more prevalent in prisons tha
elsewhere. and research on social and
psychological problems such as
alcoholisin, 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 REGIS"TER,
of his intent to approve such research;
or
(D) Research on practices, both
Innovativc 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 mariner
consistent with protocols approved by
the IRB to control groups which may
not benefit frown the research, the
study may proceed only after the
Sccretary 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,
biomedicil or behavioral research
conducted or -4upportud by DIfEW
shall not imolye plisoners as
suhjects -
SuLps.t D--Ad6tiv.rrJ ProtecLior-.s
LXVwYee- IL:i Subject* ik
Reoearc*4
Source; 48 M 91 It March 9, 19A3
46.401 To what do theme
reg"Istions APPINY?
(z) nis subpart applim to all
rcsseaurch involving children as
subj=ts, conducted or supported by
the Department of Health and
Human Services.
01@f nis includes resmch
conducted by Department
c, -!oym, except that each licad of
an Opefuling Division of lilt
Department may adopt such
nonsubstantive, procedural
modifications as may be appropriate
firom an administrative standpoint.
(2) It also includes research
conducted or supported by the
Department of Health and Human
Services outside the United States,
but in appropriate circumstances, the
Secretary may, under paragraph (e)
of §46-101 of Subpart A, waive the
applicability of some or all of the
requirements of these regulations for
research of this type.
(b) Exemptions (1), (2), (5) and (6)
as listed in Subpart A at §46.101(b)
are applicable to this subpart.
Exemption (4), research involving
the observation of public behavior,
listed at §46.101(b), is applicable to
this subpart where the investigator(s)
does not participate in the activities
being observed. Exemption (3),
research involving survey or
interview proicedurm listed at
§46.101(b)does not apply to research
covered by this subpart.
(c) 'The exceptions., additions, and
provisions for waiver as they appear
I
.n paragraphs (c) through (i) of
§ 46. 101 of Subpart A arc applicable
to this subpart.
§".402 Definitions.
The definitions in § 46.102 of
Subpart A shall be applicable to this
subpart as well. In addition, as used
in this subpart:
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(.0 -Clildf ell" arc, lk"r-Orls A ho
cow,,enl to treatments oi plocedufrs
involved in the re@iearch, tinder the
apr 11"-a@)!C L'A' JU-1 L'Sldict;On III
%A+lch thr re-&-qrrh w-:0!
conducted.
N "Ass@WV means a child's
affirri-intive agrccnici-it to nartizipaw
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) "Parct:tt- meaus a child's
biological or adoptive parent.
(c) "Guardian". means an
individual who is authorized under
applicable state or local law to
consent on behalf of a child to
general medical care.
§46.403 IRB duties.
In addition to other responsibilities
assigned to IRDs under this part,
each IRB shall review research
covered by this subpart and approve
only research which satisfies the
conditions of all applicable sections
of this subpart.
§ 46.404 Jtewmch. n .ot,Iinvolviag
7 -
greater than minimal risL
HHS will conduct or fund
research in which the IRB finds that
no greater than minimal risk to
children is presented, only ifthe IRB
finds that adequate provisions are
made for soliciting the assent of the
children and the permission or their
parents or guardians, as set forth in
§ 46.406.
§ 46-405 Research involving greater
tbm minimal risk bid Pr mizift the
prospect at directlenefit to the
Inidividual 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 sut icci, or by a
I
lllooito@a,j@, pr(%:vdurc Ehist i, likely to
c 6 S. I I - 0@ i 11, W
oilly if the IYV finds that.
i. bN.
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
prescniccl by available alternative
approaches; and
(c) Adequate provisions are made
for soliciting the assent of the
children and permission of their
parents or guardians, as set forth in
§ 46.408.
§ 46-406 Research Irvolving greater
than minimal risk and no proopectof
direct benefit to individual subjects,
but likely to yield generalizable
knowledge about the subject's disorder
or condition.
HHS will conduct or fund
research it) 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 benerit 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;
N T1c intervention or procedure
Presents experiences to subjects that
are reasonably commensurate with
those inherent in their actual or
expected medical, dental,
psychological. social, or educational
situations;
(c) The intervention or procedure
is likely to yield generalizable
knowledge about the subjects'
disorder or condition which is of
vital importance for the
understanding or amelioration of the
subjects' disorder or condition; and
(d) Adeqviate provisions are made
for soliciting ;,swra of the childrcn
and permission of their parents or
Suardiant., _-s @@C@ forth itt § 46.408@
§ 446.40 7 Re,4@earch not atherwiv
%isprcf@ablc which prese"is an
OPP(wtunity to understand, prevent,'or4
r@criouz problem aff"ng
the health or welfare of children.
HHS will conduct or fund
research that the IRID does not
believe meets the requirements of
1, z AN. 46.4M, ow 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
detcrmined el'Ehcr. (1) That the
research in fact satisfics the
cond i tions of § I 46AD4, 46.405, or
46-406, as applicable, or (2) the
following:
(i) The research presents a
reasonable opportunity to further the
understanding, prevention. or
alleviation of a serious problem
affecting the health or welfare of
children;
(ii) The research will be conducted
in accordance with sound ethical
principles;
(iii) Adequate provisions arc made
for soliciting the ament of children
and the permission of their parents or
guardians, as set forth in 146.408.
146-408 Requiremexits for
Permission by parents or guardians
and for aneint 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
cMdren are'cap ible of .providing .
Ailsent. In determining whether
children are capable of assenting, the,
IR11 shall take intO account the age&,.;
Inaturity, and Psychological sta4c of
the cluldren involved. '17his judgment
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nlad-@ for all ch';!i1rcr. to be
-ilar protocol, or for eacii child,
IRB deems appropriate. ir the
1clerminez tbnt the C=nbilil@-y of
I V
or all of the children is ui
@-d that they cannot reasonably
-onsulted or that the intervention
c-ccdurc involved in the
i ch holds out a prospect of
ct benefit that is importwit to the
i!lh or well-being of the children
i-@ available only in the context or
research, the assent of the
Jrcri is not a necemry condition
procceding with the restuch.
where the IRB ditermincs that
subjects are capable of mentin&
rt I RD may *tM waive tbz =,crit
Witernent under circuitristances in
"ch consent may be waived in
A,-,NYJ With 1446.116 of Subpart A.
I I @) In addition to the
i,munations required under other
licable sections of this subpart,
IRB shall determine, in
th- "'idasice with and to the extent
S` consent is required byl 46.116of
8,1@ ),Part A, that adequate provisions
of _ lade for soliciting the permission
Wl@,juch child's parents or'Suardiam
Ob- 4 -re parental permission is to be
pci M%cd, the IRB may.find that the
fol @iission of one parent is sufficient
I I it-scarch to be conducted under
is c @ 6.404 or 46.405. Where research
'-wered by J ".406 and 46.407
is to be obtained from
pd,-t-nts, hot!. m@rei;u, ri-.L;,,@ Five oiv-ii
decca", wc:omJ-rtCn!, or
nat rcasonably or whtn
only one purent he!, legal
resport-tibility for the@ cair- and
custody of the child.
(c) In addition to the provisions for
waiver containM in 0 46.116 of
Subpart A, if the IRD determine5 that
a research protocol is desigricd 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 abuscd
children), it may waivc the coriscrit
requirements in Subpart A of this
part and paragraph (b) of this section,
provided an appropriate mechanism
for protecting the children who will
participate as subjects in the rescarch
is substituted, and provided further
that the waiver is not inconsistent
with federal state or local law. Tle
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 J 46.117 of Subpart A.
(e) When the IRB determines that
assent is required, it shall also
detc-rmittc NAht-tlier iind how assent
@ ".409 War*%
(a) Children who are %vards of the
atate or any other agency, institution,
or entity can be included in research
undcr 46ACK6 ot 46.407
only if such research is:
or (1) Related to their status as wards;
(2) Conducted in schools, "mps,
hospitals, institutions, or smilar
settings in which the majofity of
children involved as subjw3i arc 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 locc. 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.
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NOTICES
HUMAN SUBJECTS
Minimum Criteria ldcraif)Lisi; il,c
Viable Fetus
On March 13, 1975, regulations
were published in the FE!)LRkI
k L(;isi E K (4o FR 11 K54) relating to the
protection of human subjects in
research. development, and reLted
activities supported by Departmert of
Ifealth, Education, and Wclfare
grants and contracts. These
regulations are codified at 45 CFR
Part 46.
Elm-whrre it) this is-iut-of th,-
FEULkAl. R F(IISTEP, the SCL-l`Ctd!`V
zmv-n"';ng,!5 CFR Nit .40 hs,,
aniong other things. adding it ncw
Subpart B to provide additional
prntf-,-iiors ;--rt:@;ning to r-sT=, h,
developmeist, and related activities
involving fetuses. pregnant worricri.
and in vitro fertilization.
Section 46.203(d) of Subpart B
provides inter alia as follows:
The Secretary may from time to time.
taking into account medical advances.
publish in the rEDERAL R LGIST1,11
Rui-lincs to ai%,%, in &icrrnininr %,hcthz,-r a
letus is viable for purpose, of this subpart.
This no;icc is published in
wxordanze with § 46.20.3(d). For
purposes of Subpart 0. the guidelines
ind.catirir that P fetus other than a
dead fetus within the meaning of
§ 46.203(t) is viable include the
following-
an csitmated gestational age of 20 weeks or
mote and a body weight of 5OU gram-, or
more -
FEDERAL Rr-GISTER, VOL 40,
AUGUST 4, 1975
U.S. GOVERNMENT PRINTING orFicE : 2983 0 - 406-756
Sri
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PROCEDURE 13. EXPERIMENTATION ON HUMAN SUBJECTS FOR
INTELLIGENCE PUR?0S'ES
A. APPLICABILITY
This procedure applies to experimentation on human sub-
jects if such experimentati-on is conducted by or on behalf of
a DoD intelligence component, This procedure does not apply
to experimentation on animal subjects.
B. EXPLANATION OF UNDEFINED TERMS
1. Exp(@rimentation in this context means any research or
testing activity involving human subjects that may,expose such
subjects to the possibility '@of permanent or temporary injury
(including physical or psychological damage and damage to the
reputation of such persons) beyond the risks of injury to
wn
lich such subjects are ordinarily exposed in their daily
lives.
2. Experimentation is conducted on behalf of a DoD
intelligence component if it is conducted under contract to
that component or to another DoD component for the benefit of
the intelligence component or at the request of such a com-
ponent regardless of the existence of a contractual rela-
tionship.
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C4
3. Human subjeccs in this context includes any petson
-'T'he?-her or not such person ic. .-a U-k4i#lcd S@"-atcs Person.
C. PROCEDURES
1. Experimentation an human subjects conducted by or on
behalf of a DoD intelligence component may be undertaken only
with the informed consent of the subject, and in accordance
with guidelines issued by the Department of Health and Human
Services, setting out conditions that safeguard the welfare of
such subjects.
2. DoD intellige nce components may not engage in or
contract for experimentation on human subjects without appro-
val of the Secretary or Deputy Secretary of Defense, or the
Secretary or Under Secretary of a Military Department, as
appropriate. [Requests for such approval submitted by Army
intelligence components will be addressed through command
channels to HQDA (DAMI-CIC), WASH DC 20310.]
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