CFR 2000 Title45 Vol1 Part46 PDF

Pt.
46 45 CFR Subtitle A (10100 Edition)
immediately notify the Department 46.116 General requirements for informed

that such an action is pending. consent.
(e) The employee may, thereafter, re- 46.117 Documentation of informed consent.
46.118 Applications and proposals lacking
quest either (1) indemnification to sat- definite plans for involvement of human
isfy a verdict, judgment or award en- subjects.
tered against the employee or (2) pay- 46.119 Research undertaken without the in-
ment to satisfy the requirements of a tention of involving human subjects.
settlement proposal. The employee 46.120 Evaluation and disposition of applica-
shall submit a written request, with tions and proposals for research to be
documentation including copies of the conducted or supported by a Federal De-
partment or Agency.
verdict, judgment, award or settlement 46.121 [Reserved]
proposal, as appropriate, to the head of 46.122 Use of Federal funds.
his employing component, who shall 46.123 Early termination of research sup-
thereupon submit to the General Coun- port: Evaluation of applications and pro-
sel, in a timely manner, a rec- posals.
ommended disposition of the request. 46.124 Conditions.
The General Counsel shall also seek
Subpart BAdditional Protections Per-
the views of the Department of Justice.
taining to Research, Development,
The General Counsel shall forward the
and Related Activities Involving
request, the employing components
Fetuses, Pregnant Women, and Human
recommendation and the General
In Vitro Fertilization
Counsels recommendation to the Sec-
retary for decision. 46.201 Applicability.
(f) Any payment under this section 46.202 Purpose.
either to indemnify a Department of 46.203 Definitions.
Health and Human Services employee 46.204 Ethical Advisory Boards.
46.205 Additional duties of the Institutional
or to settle a personal damage claim Review Boards in connection with activi-
shall be contingent upon the avail- ties involving fetuses, pregnant women,
ability of appropriated funds of the em- or human in vitro fertilization.
ploying component of the Department 46.206 General limitations.
of Health and Human Services. 46.207 Activities directed toward pregnant
women as subjects.
AUTHORITY: 5 U.S.C. 301.
46.208 Activities directed toward fetuses in
[53 FR 11280, Apr. 6, 1988] utero as subjects.
46.209 Activities directed toward fetuses ex
utero, including nonviable fetuses, as
PART 46PROTECTION OF HUMAN subjects.
SUBJECTS 46.210 Activities involving the dead fetus,
fetal material, or the placenta.
Subpart ABasic HHS Policy for Protection 46.211 Modification or waiver of specific re-
of Human Research Subjects quirements.
Sec. Subpart CAdditional Protections Per-

46.101 To what does this policy apply? taining to Biomedical and Behavioral
46.102 Definitions. Research Involving Prisoners as Sub-
46.103 Assuring compliance with this pol- jects
icyresearch conducted or supported by
any Federal Department or Agency. 46.301 Applicability.
46.10446.106 [Reserved] 46.302 Purpose.
46.107 IRB membership. 46.303 Definitions.
46.108 IRB functions and operations. 46.304 Composition of Institutional Review
46.109 IRB review of research. Boards where prisoners are involved.
46.305 Additional duties of the Institutional
46.110 Expedited review procedures for cer-
Review Boards where prisoners are in-
tain kinds of research involving no more
volved.
than minimal risk, and for minor
46.306 Permitted research involving pris-
changes in approved research.
oners.
46.111 Criteria for IRB approval of research.
46.112 Review by institution. Subpart DAdditional Protections for
46.113 Suspension or termination of IRB ap-
Children Involved as Subjects in Research
proval of research.
46.114 Cooperative research. 46.401 To what do these regulations apply?
46.115 IRB records. 46.402 Definitions.
46.403 IRB duties.
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Department of Health and Human Services 46.101
46.404 Research not involving greater than to regulation by the federal govern-
minimal risk. ment outside the United States.
46.405 Research involving greater than (1) Research that is conducted or sup-
minimal risk but presenting the prospect ported by a federal department or
of direct benefit to the individual sub-
jects.
agency, whether or not it is regulated
46.406 Research involving greater than as defined in 46.102(e), must comply
minimal risk and no prospect of direct with all sections of this policy.
benefit to individual subjects, but likely (2) Research that is neither con-
to yield generalizable knowledge about ducted nor supported by a federal de-
the subjects disorder or condition. partment or agency but is subject to
46.407 Research not otherwise approvable regulation as defined in 46.102(e) must
which presents an opportunity to under- be reviewed and approved, in compli-
stand, prevent, or alleviate a serious ance with 46.101, 46.102, and 46.107
problem affecting the health or welfare
through 46.117 of this policy, by an in-
of children.
46.408 Requirements for permission by par-
stitutional review board (IRB) that op-
ents or guardians and for assent by chil- erates in accordance with the pertinent
dren. requirements of this policy.
46.409 Wards. (b) Unless otherwise required by de-
partment or agency heads, research ac-
AUTHORITY: 5 U.S.C. 301; 42 U.S.C. 289.
tivities in which the only involvement
EDITORIAL NOTE: The Department of of human subjects will be in one or
Health and Human Services issued a notice more of the following categories are
of waiver regarding the requirements set exempt from this policy:
forth in part 46, relating to protection of (1) Research conducted in established
human subjects, as they pertain to dem-
onstration projects, approved under section
or commonly accepted educational set-
1115 of the Social Security Act, which test tings, involving normal educational
the use of costsharing, such as deductibles, practices, such as (i) research on reg-
copayment and coinsurance, in the Medicaid ular and special education instruc-
program. For further information see 47 FR tional strategies, or (ii) research on the
9208, Mar. 4, 1982. effectiveness of or the comparison
among instructional techniques, cur-
Subpart ABasic HHS Policy for ricula, or classroom management
Protection of Human Research methods.
Subjects (2) Research involving the use of edu-
cational tests (cognitive, diagnostic,
aptitude, achievement), survey proce-
AUTHORITY: 5 U.S.C. 301; 42 U.S.C. 289, 42 dures, interview procedures or observa-
U.S.C. 300v1(b).
tion of public behavior, unless:
SOURCE: 56 FR 28012, 28022, June 18, 1991, (i) Information obtained is recorded
unless otherwise noted. in such a manner that human subjects
can be identified, directly or through
46.101 To what does this policy identifiers linked to the subjects; and
apply? (ii) any disclosure of the human sub-
(a) Except as provided in paragraph jects responses outside the research
(b) of this section, this policy applies could reasonably place the subjects at
to all research involving human sub- risk of criminal or civil liability or be
jects conducted, supported or otherwise damaging to the subjects financial
subject to regulation by any federal de- standing, employability, or reputation.
partment or agency which takes appro- (3) Research involving the use of edu-
priate administrative action to make cational tests (cognitive, diagnostic,
the policy applicable to such research. aptitude, achievement), survey proce-
This includes research conducted by dures, interview procedures, or obser-
federal civilian employees or military vation of public behavior that is not
personnel, except that each department exempt under paragraph (b)(2) of this
or agency head may adopt such proce- section, if:
dural modifications as may be appro- (i) The human subjects are elected or
priate from an administrative stand- appointed public officials or candidates
point. It also includes research con- for public office; or (ii) federal stat-
ducted, supported, or otherwise subject ute(s) require(s) without exception that
107
46.101 45 CFR Subtitle A (10100 Edition)
the confidentiality of the personally (f) This policy does not affect any
identifiable information will be main- state or local laws or regulations which
tained throughout the research and may otherwise be applicable and which
thereafter. provide additional protections for
(4) Research, involving the collection human subjects.
or study of existing data, documents, (g) This policy does not affect any
records, pathological specimens, or di- foreign laws or regulations which may
agnostic specimens, if these sources are otherwise be applicable and which pro-
publicly available or if the information vide additional protections to human
is recorded by the investigator in such
subjects of research.
a manner that subjects cannot be iden-
(h) When research covered by this
tified, directly or through identifiers
linked to the subjects. policy takes place in foreign countries,
(5) Research and demonstration procedures normally followed in the
projects which are conducted by or sub- foreign countries to protect human
ject to the approval of department or subjects may differ from those set
agency heads, and which are designed forth in this policy. [An example is a
to study, evaluate, or otherwise exam- foreign institution which complies
ine: with guidelines consistent with the
(i) Public benefit or service pro- World Medical Assembly Declaration
grams; (ii) procedures for obtaining (Declaration of Helsinki amended 1989)
benefits or services under those pro- issued either by sovereign states or by
grams; (iii) possible changes in or al- an organization whose function for the
ternatives to those programs or proce- protection of human research subjects
dures; or (iv) possible changes in meth- is internationally recognized.] In these
ods or levels of payment for benefits or circumstances, if a department or
services under those programs. agency head determines that the proce-
(6) Taste and food quality evaluation dures prescribed by the institution af-
and consumer acceptance studies, (i) if ford protections that are at least
wholesome foods without additives are equivalent to those provided in this
consumed or (ii) if a food is consumed policy, the department or agency head
that contains a food ingredient at or
may approve the substitution of the
below the level and for a use found to
foreign procedures in lieu of the proce-
be safe, or agricultural chemical or en-
vironmental contaminant at or below dural requirements provided in this
the level found to be safe, by the Food policy. Except when otherwise required
and Drug Administration or approved by statute, Executive Order, or the de-
by the Environmental Protection partment or agency head, notices of
Agency or the Food Safety and Inspec- these actions as they occur will be pub-
tion Service of the U.S. Department of lished in the FEDERAL REGISTER or will
Agriculture. be otherwise published as provided in
(c) Department or agency heads re- department or agency procedures.
tain final judgment as to whether a (i) Unless otherwise required by law,
particular activity is covered by this department or agency heads may waive
policy. the applicability of some or all of the
(d) Department or agency heads may provisions of this policy to specific re-
require that specific research activities search activities or classes of research
or classes of research activities con- activities otherwise covered by this
ducted, supported, or otherwise subject policy. Except when otherwise required
to regulation by the department or by statute or Executive Order, the de-
agency but not otherwise covered by partment or agency head shall forward
this policy, comply with some or all of advance notices of these actions to the
the requirements of this policy. Office for Protection from Research
(e) Compliance with this policy re- Risks, Department of Health and
quires compliance with pertinent fed-
Human Services (HHS), and shall also
eral laws or regulations which provide
publish them in the FEDERAL REGISTER
additional protections for human sub-
jects.
108
or in such other manner as provided in ministration). It does not include re-

department or agency procedures.1 search activities which are inciden-
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756,
tally regulated by a federal department
June 28, 1991] or agency solely as part of the depart-
ments or agencys broader responsi-
46.102 Definitions. bility to regulate certain types of ac-
(a) Department or agency head means tivities whether research or non-re-
the head of any federal department or search in nature (for example, Wage
agency and any other officer or em- and Hour requirements administered
ployee of any department or agency to by the Department of Labor).
whom authority has been delegated. (f) Human subject means a living indi-
(b) Institution means any public or vidual about whom an investigator
private entity or agency (including fed- (whether professional or student) con-
eral, state, and other agencies). ducting research obtains
(c) Legally authorized representative (1) Data through intervention or
means an individual or judicial or interaction with the individual, or
other body authorized under applicable (2) Identifiable private information.
law to consent on behalf of a prospec- Intervention includes both physical pro-
tive subject to the subjects participa- cedures by which data are gathered (for
tion in the procedure(s) involved in the example, venipuncture) and manipula-
research. tions of the subject or the subjects en-
(d) Research means a systematic in- vironment that are performed for re-
vestigation, including research devel- search purposes. Interaction includes
opment, testing and evaluation, de- communication or interpersonal con-
signed to develop or contribute to gen- tact between investigator and subject.
eralizable knowledge. Activities which Private information includes informa-
meet this definition constitute re- tion about behavior that occurs in a
search for purposes of this policy, context in which an individual can rea-
whether or not they are conducted or sonably expect that no observation or
supported under a program which is recording is taking place, and informa-
considered research for other purposes. tion which has been provided for spe-
For example, some demonstration and cific purposes by an individual and
service programs may include research which the individual can reasonably
activities. expect will not be made public (for ex-
(e) Research subject to regulation, and ample, a medical record). Private infor-
similar terms are intended to encom- mation must be individually identifi-
pass those research activities for which able (i.e., the identity of the subject is
a federal department or agency has or may readily be ascertained by the
specific responsibility for regulating as investigator or associated with the in-
a research activity, (for example, In- formation) in order for obtaining the
vestigational New Drug requirements information to constitute research in-
administered by the Food and Drug Ad- volving human subjects.
(g) IRB means an institutional review
1 Institutions with HHS-approved assur- board established in accord with and
ances on file will abide by provisions of title for the purposes expressed in this pol-
45 CFR part 46 subparts AD. Some of the icy.
other Departments and Agencies have incor-
porated all provisions of title 45 CFR part 46
(h) IRB approval means the deter-
into their policies and procedures as well. mination of the IRB that the research
However, the exemptions at 45 CFR 46.101(b) has been reviewed and may be con-
do not apply to research involving prisoners, ducted at an institution within the
fetuses, pregnant women, or human in vitro constraints set forth by the IRB and by
fertilization, subparts B and C. The exemp- other institutional and federal require-
tion at 45 CFR 46.101(b)(2), for research in- ments.
volving survey or interview procedures or ob-
servation of public behavior, does not apply
(i) Minimal risk means that the prob-
to research with children, subpart D, except ability and magnitude of harm or dis-
for research involving observations of public comfort anticipated in the research are
behavior when the investigator(s) do not par- not greater in and of themselves than
ticipate in the activities being observed. those ordinarily encountered in daily
109
life or during the performance of rou- lation. This may include an appro-
tine physical or psychological exami- priate existing code, declaration, or
nations or tests. statement of ethical principles, or a
(j) Certification means the official no- statement formulated by the institu-
tification by the institution to the sup- tion itself. This requirement does not
porting department or agency, in ac- preempt provisions of this policy appli-
cordance with the requirements of this cable to department- or agency-sup-
policy, that a research project or activ- ported or regulated research and need
ity involving human subjects has been not be applicable to any research ex-
reviewed and approved by an IRB in ac- empted or waived under 46.101 (b) or
cordance with an approved assurance. (i).
(2) Designation of one or more IRBs
46.103 Assuring compliance with this
policyresearch conducted or sup- established in accordance with the re-
ported by any Federal Department quirements of this policy, and for
or Agency. which provisions are made for meeting
space and sufficient staff to support
(a) Each institution engaged in re-
the IRBs review and recordkeeping du-
search which is covered by this policy
ties.
and which is conducted or supported by
a federal department or agency shall (3) A list of IRB members identified
provide written assurance satisfactory by name; earned degrees; representa-
to the department or agency head that tive capacity; indications of experience
it will comply with the requirements such as board certifications, licenses,
set forth in this policy. In lieu of re- etc., sufficient to describe each mem-
quiring submission of an assurance, in- bers chief anticipated contributions to
dividual department or agency heads IRB deliberations; and any employ-
shall accept the existence of a current ment or other relationship between
assurance, appropriate for the research each member and the institution; for
in question, on file with the Office for example: full-time employee, part-time
Protection from Research Risks, HHS, employee, member of governing panel
and approved for federalwide use by or board, stockholder, paid or unpaid
that office. When the existence of an consultant. Changes in IRB member-
HHS-approved assurance is accepted in ship shall be reported to the depart-
lieu of requiring submission of an as- ment or agency head, unless in accord
surance, reports (except certification) with 46.103(a) of this policy, the exist-
required by this policy to be made to ence of an HHS-approved assurance is
department and agency heads shall accepted. In this case, change in IRB
also be made to the Office for Protec- membership shall be reported to the
tion from Research Risks, HHS. Office for Protection from Research
(b) Departments and agencies will Risks, HHS.
conduct or support research covered by (4) Written procedures which the IRB
this policy only if the institution has will follow (i) for conducting its initial
an assurance approved as provided in and continuing review of research and
this section, and only if the institution for reporting its findings and actions to
has certified to the department or the investigator and the institution;
agency head that the research has been (ii) for determining which projects re-
reviewed and approved by an IRB pro- quire review more often than annually
vided for in the assurance, and will be and which projects need verification
subject to continuing review by the from sources other than the investiga-
IRB. Assurances applicable to federally tors that no material changes have oc-
supported or conducted research shall curred since previous IRB review; and
at a minimum include: (iii) for ensuring prompt reporting to
(1) A statement of principles gov- the IRB of proposed changes in a re-
erning the institution in the discharge search activity, and for ensuring that
of its responsibilities for protecting the such changes in approved research,
rights and welfare of human subjects of during the period for which IRB ap-
research conducted at or sponsored by proval has already been given, may not
the institution, regardless of whether be initiated without IRB review and
the research is subject to federal regu- approval except when necessary to
110
eliminate apparent immediate hazards posal or by such later date as may be

to the subject. prescribed by the department or agen-
(5) Written procedures for ensuring cy to which the application or proposal
prompt reporting to the IRB, appro- is submitted. Under no condition shall
priate institutional officials, and the research covered by 46.103 of the Pol-
department or agency head of (i) any icy be supported prior to receipt of the
unanticipated problems involving risks certification that the research has been
to subjects or others or any serious or reviewed and approved by the IRB. In-
continuing noncompliance with this stitutions without an approved assur-
policy or the requirements or deter- ance covering the research shall certify
minations of the IRB and (ii) any sus- within 30 days after receipt of a request
pension or termination of IRB ap- for such a certification from the de-
proval. partment or agency, that the applica-
(c) The assurance shall be executed tion or proposal has been approved by
by an individual authorized to act for the IRB. If the certification is not sub-
the institution and to assume on behalf mitted within these time limits, the
of the institution the obligations im- application or proposal may be re-
posed by this policy and shall be filed turned to the institution.
in such form and manner as the depart-
(Approved by the Office of Management and
ment or agency head prescribes. Budget under control number 99990020)
(d) The department or agency head
will evaluate all assurances submitted [56 FR 28012, 28022, June 18, 1991; 56 FR 29756,
June 28, 1991]
in accordance with this policy through
such officers and employees of the de- 46.10446.106 [Reserved]
partment or agency and such experts
or consultants engaged for this purpose 46.107 IRB membership.
as the department or agency head de- (a) Each IRB shall have at least five
termines to be appropriate. The depart- members, with varying backgrounds to
ment or agency heads evaluation will promote complete and adequate review
take into consideration the adequacy of research activities commonly con-
of the proposed IRB in light of the an- ducted by the institution. The IRB
ticipated scope of the institutions re- shall be sufficiently qualified through
search activities and the types of sub- the experience and expertise of its
ject populations likely to be involved, members, and the diversity of the
the appropriateness of the proposed ini- members, including consideration of
tial and continuing review procedures race, gender, and cultural backgrounds
in light of the probable risks, and the and sensitivity to such issues as com-
size and complexity of the institution. munity attitudes, to promote respect
(e) On the basis of this evaluation, for its advice and counsel in safe-
the department or agency head may guarding the rights and welfare of
approve or disapprove the assurance, or human subjects. In addition to pos-
enter into negotiations to develop an sessing the professional competence
approvable one. The department or necessary to review specific research
agency head may limit the period dur- activities, the IRB shall be able to as-
ing which any particular approved as- certain the acceptability of proposed
surance or class of approved assurances research in terms of institutional com-
shall remain effective or otherwise mitments and regulations, applicable
condition or restrict approval. law, and standards of professional con-
(f) Certification is required when the duct and practice. The IRB shall there-
research is supported by a federal de- fore include persons knowledgeable in
partment or agency and not otherwise these areas. If an IRB regularly reviews
exempted or waived under 46.101 (b) or research that involves a vulnerable
(i). An institution with an approved as- category of subjects, such as children,
surance shall certify that each applica- prisoners, pregnant women, or handi-
tion or proposal for research covered capped or mentally disabled persons,
by the assurance and by 46.103 of this consideration shall be given to the in-
Policy has been reviewed and approved clusion of one or more individuals who
by the IRB. Such certification must be are knowledgeable about and experi-
submitted with the application or pro- enced in working with these subjects.
111
(b) Every nondiscriminatory effort (b) An IRB shall require that infor-
will be made to ensure that no IRB mation given to subjects as part of in-
consists entirely of men or entirely of formed consent is in accordance with
women, including the institutions con- 46.116. The IRB may require that in-
sideration of qualified persons of both formation, in addition to that specifi-
sexes, so long as no selection is made cally mentioned in 46.116, be given to
to the IRB on the basis of gender. No the subjects when in the IRBs judg-
IRB may consist entirely of members ment the information would meaning-
of one profession. fully add to the protection of the rights
(c) Each IRB shall include at least and welfare of subjects.
one member whose primary concerns (c) An IRB shall require documenta-
are in scientific areas and at least one tion of informed consent or may waive
member whose primary concerns are in documentation in accordance with
nonscientific areas. 46.117.
(d) Each IRB shall include at least (d) An IRB shall notify investigators
one member who is not otherwise affili- and the institution in writing of its de-
ated with the institution and who is cision to approve or disapprove the pro-
not part of the immediate family of a posed research activity, or of modifica-
person who is affiliated with the insti- tions required to secure IRB approval
tution. of the research activity. If the IRB de-
(e) No IRB may have a member par- cides to disapprove a research activity,
ticipate in the IRBs initial or con- it shall include in its written notifica-
tinuing review of any project in which tion a statement of the reasons for its
the member has a conflicting interest, decision and give the investigator an
except to provide information re- opportunity to respond in person or in
quested by the IRB. writing.
(f) An IRB may, in its discretion, in- (e) An IRB shall conduct continuing
vite individuals with competence in review of research covered by this pol-
special areas to assist in the review of icy at intervals appropriate to the de-
issues which require expertise beyond gree of risk, but not less than once per
or in addition to that available on the year, and shall have authority to ob-
IRB. These individuals may not vote serve or have a third party observe the
with the IRB. consent process and the research.
46.108 IRB functions and operations. (Approved by the Office of Management and
Budget under control number 99990020)
In order to fulfill the requirements of
this policy each IRB shall: 46.110 Expedited review procedures
(a) Follow written procedures in the for certain kinds of research involv-
same detail as described in 46.103(b)(4) ing no more than minimal risk, and
and, to the extent required by, for minor changes in approved re-
46.103(b)(5). search.
(b) Except when an expedited review (a) The Secretary, HHS, has estab-
procedure is used (see 46.110), review lished, and published as a Notice in the
proposed research at convened meet- FEDERAL REGISTER, a list of categories
ings at which a majority of the mem- of research that may be reviewed by
bers of the IRB are present, including the IRB through an expedited review
at least one member whose primary procedure. The list will be amended, as
concerns are in nonscientific areas. In appropriate after consultation with
order for the research to be approved, other departments and agencies,
it shall receive the approval of a ma- through periodic republication by the
jority of those members present at the Secretary, HHS, in the FEDERAL REG-
meeting. ISTER. A copy of the list is available
from the Office for Protection from Re-
46.109 IRB review of research. search Risks, National Institutes of
(a) An IRB shall review and have au- Health, HHS, Bethesda, Maryland
thority to approve, require modifica- 20892.
tions in (to secure approval), or dis- (b) An IRB may use the expedited re-
approve all research activities covered view procedure to review either or both
by this policy. of the following:
112
(1) Some or all of the research ap- gained in the research (for example,
pearing on the list and found by the re- the possible effects of the research on
viewer(s) to involve no more than mini- public policy) as among those research
mal risk, risks that fall within the purview of its
(2) Minor changes in previously ap- responsibility.
proved research during the period (of (3) Selection of subjects is equitable.
one year or less) for which approval is In making this assessment the IRB
authorized. should take into account the purposes
Under an expedited review procedure, of the research and the setting in
the review may be carried out by the which the research will be conducted
IRB chairperson or by one or more ex- and should be particularly cognizant of
perienced reviewers designated by the the special problems of research in-
chairperson from among members of volving vulnerable populations, such as
the IRB. In reviewing the research, the children, prisoners, pregnant women,
reviewers may exercise all of the au- mentally disabled persons, or economi-
thorities of the IRB except that the re- cally or educationally disadvantaged
viewers may not disapprove the re- persons.
search. A research activity may be dis- (4) Informed consent will be sought
approved only after review in accord- from each prospective subject or the
ance with the non-expedited procedure subjects legally authorized representa-
set forth in 46.108(b). tive, in accordance with, and to the ex-
(c) Each IRB which uses an expedited tent required by 46.116.
review procedure shall adopt a method (5) Informed consent will be appro-
for keeping all members advised of re- priately documented, in accordance
search proposals which have been ap- with, and to the extent required by
proved under the procedure. 46.117.
(d) The department or agency head (6) When appropriate, the research
may restrict, suspend, terminate, or plan makes adequate provision for
choose not to authorize an institu- monitoring the data collected to en-
tions or IRBs use of the expedited re- sure the safety of subjects.
view procedure. (7) When appropriate, there are ade-
quate provisions to protect the privacy
46.111 Criteria for IRB approval of of subjects and to maintain the con-
research. fidentiality of data.
(a) In order to approve research cov- (b) When some or all of the subjects
ered by this policy the IRB shall deter- are likely to be vulnerable to coercion
mine that all of the following require- or undue influence, such as children,
ments are satisfied: prisoners, pregnant women, mentally
(1) Risks to subjects are minimized: disabled persons, or economically or
(i) By using procedures which are con- educationally disadvantaged persons,
sistent with sound research design and additional safeguards have been in-
which do not unnecessarily expose sub- cluded in the study to protect the
jects to risk, and (ii) whenever appro- rights and welfare of these subjects.
priate, by using procedures already
being performed on the subjects for di- 46.112 Review by institution.
agnostic or treatment purposes. Research covered by this policy that
(2) Risks to subjects are reasonable has been approved by an IRB may be
in relation to anticipated benefits, if subject to further appropriate review
any, to subjects, and the importance of and approval or disapproval by officials
the knowledge that may reasonably be of the institution. However, those offi-
expected to result. In evaluating risks cials may not approve the research if it
and benefits, the IRB should consider has not been approved by an IRB.
only those risks and benefits that may
result from the research (as distin- 46.113 Suspension or termination of
guished from risks and benefits of IRB approval of research.
therapies subjects would receive even if An IRB shall have authority to sus-
not participating in the research). The pend or terminate approval of research
IRB should not consider possible long- that is not being conducted in accord-
range effects of applying knowledge ance with the IRBs requirements or
113
that has been associated with unex- (7) Statements of significant new
pected serious harm to subjects. Any findings provided to subjects, as re-
suspension or termination of approval quired by 46.116(b)(5).
shall include a statement of the rea- (b) The records required by this pol-
sons for the IRBs action and shall be icy shall be retained for at least 3
reported promptly to the investigator, years, and records relating to research
appropriate institutional officials, and which is conducted shall be retained
the department or agency head. for at least 3 years after completion of
(Approved by the Office of Management and the research. All records shall be acces-
Budget under control number 99990020) sible for inspection and copying by au-
thorized representatives of the depart-
46.114 Cooperative research. ment or agency at reasonable times
Cooperative research projects are and in a reasonable manner.
those projects covered by this policy
(Approved by the Office of Management and
which involve more than one institu- Budget under control number 99990020)
tion. In the conduct of cooperative re-
search projects, each institution is re- 46.116 General requirements for in-
sponsible for safeguarding the rights formed consent.
and welfare of human subjects and for
complying with this policy. With the Except as provided elsewhere in this
approval of the department or agency policy, no investigator may involve a
head, an institution participating in a human being as a subject in research
cooperative project may enter into a covered by this policy unless the inves-
joint review arrangement, rely upon tigator has obtained the legally effec-
the review of another qualified IRB, or tive informed consent of the subject or
make similar arrangements for avoid- the subjects legally authorized rep-
ing duplication of effort. resentative. An investigator shall seek
such consent only under circumstances
46.115 IRB records. that provide the prospective subject or
(a) An institution, or when appro- the representative sufficient oppor-
priate an IRB, shall prepare and main- tunity to consider whether or not to
tain adequate documentation of IRB participate and that minimize the pos-
activities, including the following: sibility of coercion or undue influence.
(1) Copies of all research proposals re- The information that is given to the
viewed, scientific evaluations, if any, subject or the representative shall be
that accompany the proposals, ap- in language understandable to the sub-
proved sample consent documents, ject or the representative. No informed
progress reports submitted by inves- consent, whether oral or written, may
tigators, and reports of injuries to sub- include any exculpatory language
jects. through which the subject or the rep-
(2) Minutes of IRB meetings which resentative is made to waive or appear
shall be in sufficient detail to show at- to waive any of the subjects legal
tendance at the meetings; actions rights, or releases or appears to release
taken by the IRB; the vote on these ac- the investigator, the sponsor, the insti-
tions including the number of members tution or its agents from liability for
voting for, against, and abstaining; the negligence.
basis for requiring changes in or dis- (a) Basic elements of informed con-
approving research; and a written sum- sent. Except as provided in paragraph
mary of the discussion of controverted (c) or (d) of this section, in seeking in-
issues and their resolution. formed consent the following informa-
(3) Records of continuing review action shall be provided to each subject:
tivities. (1) A statement that the study in-
(4) Copies of all correspondence be- volves research, an explanation of the
tween the IRB and the investigators. purposes of the research and the ex-
(5) A list of IRB members in the same pected duration of the subjects partici-
detail as described is 46.103(b)(3). pation, a description of the procedures
(6) Written procedures for the IRB in to be followed, and identification of
the same detail as described in any procedures which are experi-
46.103(b)(4) and 46.103(b)(5). mental;
114
(2) A description of any reasonably (5) A statement that significant new

foreseeable risks or discomforts to the findings developed during the course of
subject; the research which may relate to the
(3) A description of any benefits to subjects willingness to continue par-
the subject or to others which may rea- ticipation will be provided to the sub-
sonably be expected from the research; ject; and
(4) A disclosure of appropriate alter- (6) The approximate number of sub-
native procedures or courses of treat- jects involved in the study.
ment, if any, that might be advan- (c) An IRB may approve a consent
tageous to the subject; procedure which does not include, or
(5) A statement describing the ex- which alters, some or all of the ele-
tent, if any, to which confidentiality of ments of informed consent set forth
records identifying the subject will be above, or waive the requirement to ob-
maintained; tain informed consent provided the IRB
(6) For research involving more than finds and documents that:
minimal risk, an explanation as to (1) The research or demonstration
whether any compensation and an ex- project is to be conducted by or subject
planation as to whether any medical to the approval of state or local gov-
treatments are available if injury oc- ernment officials and is designed to
curs and, if so, what they consist of, or study, evaluate, or otherwise examine:
where further information may be ob- (i) Public benefit of service programs;
tained; (ii) procedures for obtaining benefits or
(7) An explanation of whom to con- services under those programs; (iii)
tact for answers to pertinent questions possible changes in or alternatives to
about the research and research sub- those programs or procedures; or (iv)
jects rights, and whom to contact in possible changes in methods or levels
the event of a research-related injury of payment for benefits or services
to the subject; and under those programs; and
(8) A statement that participation is (2) The research could not prac-
voluntary, refusal to participate will ticably be carried out without the
involve no penalty or loss of benefits to waiver or alteration.
which the subject is otherwise entitled, (d) An IRB may approve a consent
and the subject may discontinue par- procedure which does not include, or
ticipation at any time without penalty which alters, some or all of the ele-
or loss of benefits to which the subject ments of informed consent set forth in
is otherwise entitled. this section, or waive the requirements
(b) Additional elements of informed to obtain informed consent provided
consent. When appropriate, one or the IRB finds and documents that:
more of the following elements of in- (1) The research involves no more
formation shall also be provided to than minimal risk to the subjects;
each subject: (2) The waiver or alteration will not
(1) A statement that the particular adversely affect the rights and welfare
treatment or procedure may involve of the subjects;
risks to the subject (or to the embryo (3) The research could not prac-
or fetus, if the subject is or may be- ticably be carried out without the
come pregnant) which are currently waiver or alteration; and
unforeseeable; (4) Whenever appropriate, the sub-
(2) Anticipated circumstances under jects will be provided with additional
which the subjects participation may pertinent information after participa-
be terminated by the investigator tion.
without regard to the subjects con- (e) The informed consent require-
sent; ments in this policy are not intended
(3) Any additional costs to the sub- to preempt any applicable federal,
ject that may result from participation state, or local laws which require addi-
in the research; tional information to be disclosed in
(4) The consequences of a subjects order for informed consent to be le-
decision to withdraw from the research gally effective.
and procedures for orderly termination (f) Nothing in this policy is intended
of participation by the subject; to limit the authority of a physician to
115
provide emergency medical care, to the subject will be asked whether the sub-
extent the physician is permitted to do ject wants documentation linking the
so under applicable federal, state, or subject with the research, and the sub-
local law. jects wishes will govern; or
(Approved by the Office of Management and (2) That the research presents no
Budget under control number 99990020) more than minimal risk of harm to
subjects and involves no procedures for
46.117 Documentation of informed which written consent is normally re-
consent. quired outside of the research context.
(a) Except as provided in paragraph In cases in which the documentation
(c) of this section, informed consent requirement is waived, the IRB may re-
shall be documented by the use of a quire the investigator to provide sub-
written consent form approved by the jects with a written statement regard-
IRB and signed by the subject or the ing the research.
subjects legally authorized representa-
tive. A copy shall be given to the per- (Approved by the Office of Management and
son signing the form. Budget under control number 99990020)
(b) Except as provided in paragraph
(c) of this section, the consent form 46.118 Applications and proposals
lacking definite plans for involve-
may be either of the following: ment of human subjects.
(1) A written consent document that
embodies the elements of informed Certain types of applications for
consent required by 46.116. This form grants, cooperative agreements, or con-
may be read to the subject or the sub- tracts are submitted to departments or
jects legally authorized representa- agencies with the knowledge that sub-
tive, but in any event, the investigator jects may be involved within the period
shall give either the subject or the rep- of support, but definite plans would not
resentative adequate opportunity to normally be set forth in the applica-
read it before it is signed; or tion or proposal. These include activi-
(2) A short form written consent doc- ties such as institutional type grants
ument stating that the elements of in- when selection of specific projects is
formed consent required by 46.116 the institutions responsibility; re-
have been presented orally to the sub- search training grants in which the ac-
ject or the subjects legally authorized tivities involving subjects remain to be
representative. When this method is selected; and projects in which human
used, there shall be a witness to the subjects involvement will depend upon
oral presentation. Also, the IRB shall completion of instruments, prior ani-
approve a written summary of what is mal studies, or purification of com-
to be said to the subject or the rep- pounds. These applications need not be
resentative. Only the short form itself
reviewed by an IRB before an award
is to be signed by the subject or the
may be made. However, except for re-
representative. However, the witness
search exempted or waived under
shall sign both the short form and a
copy of the summary, and the person 46.101 (b) or (i), no human subjects
actually obtaining consent shall sign a may be involved in any project sup-
copy of the summary. A copy of the ported by these awards until the
summary shall be given to the subject project has been reviewed and approved
or the representative, in addition to a by the IRB, as provided in this policy,
copy of the short form. and certification submitted, by the in-
(c) An IRB may waive the require- stitution, to the department or agency.
ment for the investigator to obtain a
signed consent form for some or all 46.119 Research undertaken without
subjects if it finds either: the intention of involving human
subjects.
(1) That the only record linking the
subject and the research would be the In the event research is undertaken
consent document and the principal without the intention of involving
risk would be potential harm resulting human subjects, but it is later pro-
from a breach of confidentiality. Each posed to involve human subjects in the
116
research, the research shall first be re- into account, in addition to all other
viewed and approved by an IRB, as pro- eligibility requirements and program
vided in this policy, a certification sub- criteria, factors such as whether the
mitted, by the institution, to the de- applicant has been subject to a termi-
partment or agency, and final approval nation or suspension under paragarph
given to the proposed change by the de- (a) of this section and whether the ap-
partment or agency. plicant or the person or persons who
would direct or has have directed the
46.120 Evaluation and disposition of
applications and proposals for re- scientific and technical aspects of an
search to be conducted or sup- activity has have, in the judgment of
ported by a Federal Department or the department or agency head, mate-
Agency. rially failed to discharge responsibility
(a) The department or agency head for the protection of the rights and
will evaluate all applications and pro- welfare of human subjects (whether or
posals involving human subjects sub- not the research was subject to federal
mitted to the department or agency regulation).
through such officers and employees of
the department or agency and such ex- 46.124 Conditions.
perts and consultants as the depart- With respect to any research project
ment or agency head determines to be or any class of research projects the de-
appropriate. This evaluation will take partment or agency head may impose
into consideration the risks to the sub- additional conditions prior to or at the
jects, the adequacy of protection time of approval when in the judgment
against these risks, the potential bene- of the department or agency head addi-
fits of the research to the subjects and
tional conditions are necessary for the
others, and the importance of the
protection of human subjects.
knowledge gained or to be gained.
(b) On the basis of this evaluation,
the department or agency head may Subpart BAdditional Protections
approve or disapprove the application Pertaining to Research, Devel-
or proposal, or enter into negotiations opment, and Related Activi-
to develop an approvable one. ties Involving Fetuses, Preg-
46.121 [Reserved] nant Women, and Human In
Vitro Fertilization
46.122 Use of Federal funds.
Federal funds administered by a de- SOURCE: 40 FR 33528, Aug. 8, 1975, unless
partment or agency may not be ex- otherwise noted.
pended for research involving human
subjects unless the requirements of 46.201 Applicability.
this policy have been satisfied. (a) The regulations in this subpart
are applicable to all Department of
46.123 Early termination of research
support: Evaluation of applications Health and Human Services grants and
and proposals. contracts supporting research, develop-
ment, and related activities involving:
(a) The department or agency head
(1) The fetus, (2) pregnant women, and
may require that department or agency
(3) human in vitro fertilization.
support for any project be terminated
or suspended in the manner prescribed (b) Nothing in this subpart shall be
in applicable program requirements, construed as indicating that compli-
when the department or agency head ance with the procedures set forth
finds an institution has materially herein will in any way render inappli-
failed to comply with the terms of this cable pertinent State or local laws
policy. bearing upon activities covered by this
(b) In making decisions about sup- subpart.
porting or approving applications or (c) The requirements of this subpart
proposals covered by this policy the de- are in addition to those imposed under
partment or agency head may take the other subparts of this part.
117
46.202 Purpose. through admixture of donor human

sperm and ova or by any other means.
It is the purpose of this subpart to
provide additional safeguards in re- [40 FR 33528, Aug. 8, 1975, as amended at 43
viewing activities to which this sub- FR 1759, Jan. 11, 1978]
part is applicable to assure that they
46.204 Ethical Advisory Boards.
conform to appropriate ethical stand-
ards and relate to important societal (a) One or more Ethical Advisory
needs. Boards shall be established by the Sec-
retary. Members of these board(s) shall
46.203 Definitions. be so selected that the board(s) will be
As used in this subpart: competent to deal with medical, legal,
(a) Secretary means the Secretary of social, ethical, and related issues and
may include, for example, research sci-
Health and Human Services and any
entists, physicians, psychologists, soci-
other officer or employee of the De-
ologists, educators, lawyers, and
partment of Health and Human Serv-
ethicists, as well as representatives of
ices to whom authority has been dele-
the general public. No board member
gated.
may be a regular, full-time employee of
(b) Pregnancy encompasses the period the Department of Health and Human
of time from confirmation of implanta- Services.
tion (through any of the presumptive (b) At the request of the Secretary,
signs of pregnancy, such as missed the Ethical Advisory Board shall
menses, or by a medically acceptable render advice consistent with the poli-
pregnancy test), until expulsion or ex- cies and requirements of this part as to
traction of the fetus. ethical issues, involving activities cov-
(c) Fetus means the product of con- ered by this subpart, raised by indi-
ception from the time of implantation vidual applications or proposals. In ad-
(as evidenced by any of the presump- dition, upon request by the Secretary,
tive signs of pregnancy, such as missed the Board shall render advice as to
menses, or a medically acceptable classes of applications or proposals and
pregnancy test), until a determination general policies, guidelines, and proce-
is made, following expulsion or extrac- dures.
tion of the fetus, that it is viable. (c) A Board may establish, with the
(d) Viable as it pertains to the fetus approval of the Secretary, classes of
means being able, after either sponta- applications or proposals which: (1)
neous or induced delivery, to survive Must be submitted to the Board, or (2)
(given the benefit of available medical need not be submitted to the Board.
therapy) to the point of independently Where the Board so establishes a class
maintaining heart beat and respira- of applications or proposals which
tion. The Secretary may from time to must be submitted, no application or
time, taking into account medical ad- proposal within the class may be fund-
vances, publish in the FEDERAL REG- ed by the Department or any compo-
ISTER guidelines to assist in deter- nent thereof until the application or
mining whether a fetus is viable for proposal has been reviewed by the
purposes of this subpart. If a fetus is Board and the Board has rendered ad-
viable after delivery, it is a premature vice as to its acceptability from an eth-
infant. ical standpoint.
(e) Nonviable fetus means a fetus ex
utero which, although living, is not via- [40 FR 33528, Aug. 8, 1975, as amended at 43
FR 1759, Jan. 11, 1978; 59 FR 28276, June 1,
ble.
1994]
(f) Dead fetus means a fetus ex utero
which exhibits neither heartbeat, spon- 46.205 Additional duties of the Insti-
taneous respiratory activity, sponta- tutional Review Boards in connec-
neous movement of voluntary muscles, tion with activities involving
nor pulsation of the umbilical cord (if fetuses, pregnant women, or human
still attached). in vitro fertilization.
(g) In vitro fertilization means any fer- (a) In addition to the responsibilities
tilization of human ova which occurs prescribed for Institutional Review
outside the body of a female, either Boards under Subpart A of this part,
118
the applicants or offerors Board shall, (2) Except where the purpose of the
with respect to activities covered by activity is to meet the health needs of
this subpart, carry out the following the mother or the particular fetus, the
additional duties: risk to the fetus is minimal and, in all
(1) Determine that all aspects of the cases, is the least possible risk for
activity meet the requirements of this achieving the objectives of the activ-
subpart; ity.
(2) Determine that adequate consid- (3) Individuals engaged in the activ-
eration has been given to the manner ity will have no part in: (i) Any deci-
in which potential subjects will be se- sions as to the timing, method, and
lected, and adequate provision has been procedures used to terminate the preg-
made by the applicant or offeror for nancy, and (ii) determining the viabil-
monitoring the actual informed con- ity of the fetus at the termination of
sent process (e.g., through such mecha- the pregnancy; and
nisms, when appropriate, as participa- (4) No procedural changes which may
tion by the Institutional Review Board cause greater than minimal risk to the
or subject advocates in: (i) Overseeing fetus or the pregnant woman will be in-
the actual process by which individual troduced into the procedure for termi-
consents required by this subpart are nating the pregnancy solely in the in-
secured either by approving induction terest of the activity.
of each individual into the activity or (b) No inducements, monetary or oth-
verifying, perhaps through sampling, erwise, may be offered to terminate
that approved procedures for induction pregnancy for purposes of the activity.
of individuals into the activity are
[40 FR 33528, Aug. 8, 1975, as amended at 40
being followed, and (ii) monitoring the FR 51638, Nov. 6, 1975]
progress of the activity and inter-
vening as necessary through such steps 46.207 Activities directed toward
as visits to the activity site and con- pregnant women as subjects.
tinuing evaluation to determine if any (a) No pregnant woman may be in-
unanticipated risks have arisen); volved as a subject in an activity cov-
(3) Carry out such other responsibil- ered by this subpart unless: (1) The
ities as may be assigned by the Sec- purpose of the activity is to meet the
retary. health needs of the mother and the
(b) No award may be issued until the fetus will be placed at risk only to the
applicant or offeror has certified to the minimum extent necessary to meet
Secretary that the Institutional Re- such needs, or (2) the risk to the fetus
view Board has made the determina- is minimal.
tions required under paragraph (a) of (b) An activity permitted under para-
this section and the Secretary has ap- graph (a) of this section may be con-
proved these determinations, as pro- ducted only if the mother and father
vided in 46.120 of Subpart A of this are legally competent and have given
part. their informed consent after having
(c) Applicants or offerors seeking been fully informed regarding possible
support for activities covered by this impact on the fetus, except that the fa-
subpart must provide for the designa- thers informed consent need not be se-
tion of an Institutional Review Board, cured if: (1) The purpose of the activity
subject to approval by the Secretary, is to meet the health needs of the
where no such Board has been estab- mother; (2) his identity or whereabouts
lished under Subpart A of this part. cannot reasonably be ascertained; (3)
[40 FR 33528, Aug. 8, 1975, as amended at 46 he is not reasonably available; or (4)
FR 8386, Jan. 26, 1981] the pregnancy resulted from rape.
46.206 General limitations. 46.208 Activities directed toward
(a) No activity to which this subpart fetuses in utero as subjects.
is applicable may be undertaken un- (a) No fetus in utero may be involved
less: as a subject in any activity covered by
(1) Appropriate studies on animals this subpart unless: (1) The purpose of
and nonpregnant individuals have been the activity is to meet the health needs
completed; of the particular fetus and the fetus
119
will be placed at risk only to the min- ther are legally competent and have
imum extent necessary to meet such given their informed consent, except
needs, or (2) the risk to the fetus im- that the fathers informed consent need
posed by the research is minimal and not be secured if: (1) His identity or
the purpose of the activity is the devel- whereabouts cannot reasonably be
opment of important biomedical ascertained, (2) he is not reasonably
knowledge which cannot be obtained available, or (3) the pregnancy resulted
by other means. from rape.
(b) An activity permitted under para-
[40 FR 33528, Aug. 8, 1975, as amended at 43
graph (a) of this section may be con-
FR 1759, Jan. 11, 1978]
ducted only if the mother and father
are legally competent and have given 46.210 Activities involving the dead
their informed consent, except that the fetus, fetal material, or the pla-
fathers consent need not be secured if: centa.
(1) His identity or whereabouts cannot
reasonably be ascertained, (2) he is not Activities involving the dead fetus,
reasonably available, or (3) the preg- mascerated fetal material, or cells, tis-
nancy resulted from rape. sue, or organs excised from a dead fetus
shall be conducted only in accordance
46.209 Activities directed toward with any applicable State or local laws
fetuses ex utero, including non- regarding such activities.
viable fetuses, as subjects.
(a) Until it has been ascertained 46.211 Modification or waiver of spe-
cific requirements.
whether or not a fetus ex utero is via-
ble, a fetus ex utero may not be in- Upon the request of an applicant or
volved as a subject in an activity cov- offeror (with the approval of its Insti-
ered by this subpart unless: tutional Review Board), the Secretary
(1) There will be no added risk to the may modify or waive specific require-
fetus resulting from the activity, and ments of this subpart, with the ap-
the purpose of the activity is the devel- proval of the Ethical Advisory Board
opment of important biomedical after such opportunity for public com-
knowledge which cannot be obtained ment as the Ethical Advisory Board
by other means, or considers appropriate in the particular
(2) The purpose of the activity is to instance. In making such decisions, the
enhance the possibility of survival of Secretary will consider whether the
the particular fetus to the point of via- risks to the subject are so outweighed
bility. by the sum of the benefit to the subject
(b) No nonviable fetus may be in- and the importance of the knowledge
volved as a subject in an activity cov- to be gained as to warrant such modi-
ered by this subpart unless: fication or waiver and that such bene-
(1) Vital functions of the fetus will fits cannot be gained except through a
not be artificially maintained, modification or waiver. Any such modi-
(2) Experimental activities which of fications or waivers will be published
themselves would terminate the heart- as notices in the FEDERAL REGISTER.
beat or respiration of the fetus will not
be employed, and Subpart CAdditional Protections
(3) The purpose of the activity is the Pertaining to Biomedical and
development of important biomedical Behavioral Research Involving
knowledge which cannot be obtained
by other means.
Prisoners as Subjects
(c) In the event the fetus ex utero is
found to be viable, it may be included SOURCE: 43 FR 53655, Nov. l6, l978, unless
as a subject in the activity only to the otherwise noted.
extent permitted by and in accordance
with the requirements of other sub- 46.301 Applicability.
parts of this part. (a) The regulations in this subpart
(d) An activity permitted under para- are applicable to all biomedical and be-
graph (a) or (b) of this section may be havioral research conducted or sup-
conducted only if the mother and fa- ported by the Department of Health
120
and Human Services involving pris- tutional Review Board, carrying out
oners as subjects. responsibilities under this part with re-
(b) Nothing in this subpart shall be spect to research covered by this sub-
construed as indicating that compli- part, shall also meet the following spe-
ance with the procedures set forth cific requirements:
herein will authorize research involv- (a) A majority of the Board (exclu-
ing prisoners as subjects, to the extent sive of prisoner members) shall have no
such research is limited or barred by association with the prison(s) involved,
applicable State or local law. apart from their membership on the
(c) The requirements of this subpart Board.
are in addition to those imposed under (b) At least one member of the Board
the other subparts of this part. shall be a prisoner, or a prisoner rep-
resentative with appropriate back-
46.302 Purpose. ground and experience to serve in that
Inasmuch as prisoners may be under capacity, except that where a par-
constraints because of their incarcer- ticular research project is reviewed by
ation which could affect their ability more than one Board only one Board
to make a truly voluntary and need satisfy this requirement.
uncoerced decision whether or not to [43 FR 53655, Nov. 16, 1978, as amended at 46
participate as subjects in research, it is FR 8386, Jan. 26, 1981]
the purpose of this subpart to provide
additional safeguards for the protec- 46.305 Additional duties of the Insti-
tion of prisoners involved in activities tutional Review Boards where pris-
to which this subpart is applicable. oners are involved.
(a) In addition to all other respon-
46.303 Definitions. sibilities prescribed for Institutional
As used in this subpart: Review Boards under this part, the
(a) Secretary means the Secretary of Board shall review research covered by
Health and Human Services and any this subpart and approve such research
other officer or employee of the De- only if it finds that:
partment of Health and Human Serv- (1) The research under review rep-
ices to whom authority has been dele- resents one of the categories of re-
gated. search permissible under 46.306(a)(2);
(b) DHHS means the Department of (2) Any possible advantages accruing
Health and Human Services. to the prisoner through his or her par-
(c) Prisoner means any individual in- ticipation in the research, when com-
voluntarily confined or detained in a pared to the general living conditions,
penal institution. The term is intended medical care, quality of food, amen-
to encompass individuals sentenced to ities and opportunity for earnings in
such an institution under a criminal or the prison, are not of such a magnitude
civil statute, individuals detained in that his or her ability to weigh the
other facilities by virtue of statutes or risks of the research against the value
commitment procedures which provide of such advantages in the limited
alternatives to criminal prosecution or choice environment of the prison is im-
incarceration in a penal institution, paired;
and individuals detained pending ar- (3) The risks involved in the research
raignment, trial, or sentencing. are commensurate with risks that
(d) Minimal risk is the probability and would be accepted by nonprisoner vol-
magnitude of physical or psychological unteers;
harm that is normally encountered in (4) Procedures for the selection of
the daily lives, or in the routine med- subjects within the prison are fair to
ical, dental, or psychological examina- all prisoners and immune from arbi-
tion of healthy persons. trary intervention by prison authori-
ties or prisoners. Unless the principal
46.304 Composition of Institutional investigator provides to the Board jus-
Review Boards where prisoners are tification in writing for following some
involved. other procedures, control subjects
In addition to satisfying the require- must be selected randomly from the
ments in 46.107 of this part, an Insti- group of available prisoners who meet
121
the characteristics needed for that par- example, vaccine trials and other re-
ticular research project; search on hepatitis which is much
(5) The information is presented in more prevalent in prisons than else-
language which is understandable to where; and research on social and psy-
the subject population; chological problems such as alco-
(6) Adequate assurance exists that holism, drug addiction and sexual as-
parole boards will not take into ac- saults) provided that the study may
count a prisoners participation in the proceed only after the Secretary has
research in making decisions regarding consulted with appropriate experts in-
parole, and each prisoner is clearly including experts in penology medicine
formed in advance that participation in and ethics, and published notice, in the
the research will have no effect on his FEDERAL REGISTER, of his intent to ap-
or her parole; and prove such research; or
(7) Where the Board finds there may (iv) Research on practices, both inno-
be a need for follow-up examination or vative and accepted, which have the in-
care of participants after the end of tent and reasonable probability of im-
their participation, adequate provision proving the health or well-being of the
has been made for such examination or subject. In cases in which those studies
care, taking into account the varying require the assignment of prisoners in
lengths of individual prisoners sen- a manner consistent with protocols ap-
tences, and for informing participants proved by the IRB to control groups
of this fact. which may not benefit from the re-
(b) The Board shall carry out such search, the study may proceed only
other duties as may be assigned by the after the Secretary has consulted with
Secretary. appropriate experts, including experts
(c) The institution shall certify to in penology medicine and ethics, and
the Secretary, in such form and man- published notice, in the FEDERAL REG-
ner as the Secretary may require, that ISTER, of his intent to approve such re-
the duties of the Board under this sec- search.
tion have been fulfilled. (b) Except as provided in paragraph
(a) of this section, biomedical or behav-
46.306 Permitted research involving ioral research conducted or supported
prisoners. by DHHS shall not involve prisoners as
(a) Biomedical or behavioral research subjects.
conducted or supported by DHHS may
involve prisoners as subjects only if: Subpart DAdditional Protections
(1) The institution responsible for the for Children Involved as Sub-
conduct of the research has certified to jects in Research
the Secretary that the Institutional
Review Board has approved the re- SOURCE: 48 FR 9818, Mar. 8, 1983, unless oth-
search under 46.305 of this subpart; erwise noted.
and
(2) In the judgment of the Secretary 46.401 To what do these regulations
the proposed research involves solely apply?
the following: (a) This subpart applies to all re-
(i) Study of the possible causes, ef- search involving children as subjects,
fects, and processes of incarceration, conducted or supported by the Depart-
and of criminal behavior, provided that ment of Health and Human Services.
the study presents no more than mini- (1) This includes research conducted
mal risk and no more than inconven- by Department employees, except that
ience to the subjects; each head of an Operating Division of
(ii) Study of prisons as institutional the Department may adopt such non-
structures or of prisoners as incarcer- substantive, procedural modifications
ated persons, provided that the study as may be appropriate from an admin-
presents no more than minimal risk istrative standpoint.
and no more than inconvenience to the (2) It also includes research con-
subjects; ducted or supported by the Department
(iii) Research on conditions particu- of Health and Human Services outside
larly affecting prisoners as a class (for the United States, but in appropriate
122
circumstances, the Secretary may, which satisfies the conditions of all ap-
under paragraph (e) of 46.101 of Sub- plicable sections of this subpart.
part A, waive the applicability of some
or all of the requirements of these reg- 46.404 Research not involving great-
ulations for research of this type. er than minimal risk.
(b) Exemptions at 46.101(b)(1) and HHS will conduct or fund research in
(b)(3) through (b)(6) are applicable to which the IRB finds that no greater
this subpart. The exemption at than minimal risk to children is pre-
46.101(b)(2) regarding educational tests sented, only if the IRB finds that ade-
is also applicable to this subpart. How- quate provisions are made for solic-
ever, the exemption at 46.101(b)(2) for iting the assent of the children and the
research involving survey or interview permission of their parents or guard-
procedures or observations of public be- ians, as set forth in 46.408.
havior does not apply to research cov-
ered by this subpart, except for re- 46.405 Research involving greater
than minimal risk but presenting
search involving observation of public the prospect of direct benefit to the
behavior when the investigator(s) do individual subjects.
not participate in the activities being
observed. HHS will conduct or fund research in
which the IRB finds that more than
(c) The exceptions, additions, and
minimal risk to children is presented
provisions for waiver as they appear in
by an intervention or procedure that
paragraphs (c) through (i) of 46.101 of
holds out the prospect of direct benefit
Subpart A are applicable to this sub-
for the individual subject, or by a mon-
part.
itoring procedure that is likely to con-
[48 FR 9818, Mar. 8, 1983; 56 FR 28032, June 18, tribute to the subjects well-being, only
1991; 56 FR 29757, June 28, 1991] if the IRB finds that:
(a) The risk is justified by the antici-
46.402 Definitions. pated benefit to the subjects;
The definitions in 46.102 of Subpart (b) The relation of the anticipated
A shall be applicable to this subpart as benefit to the risk is at least as favor-
well. In addition, as used in this sub- able to the subjects as that presented
part: by available alternative approaches;
(a) Children are persons who have not and
attained the legal age for consent to (c) Adequate provisions are made for
treatments or procedures involved in soliciting the assent of the children
the research, under the applicable law and permission of their parents or
of the jurisdiction in which the re- guardians, as set forth in 46.408.
search will be conducted.
(b) Assent means a childs affirmative 46.406 Research involving greater
than minimal risk and no prospect
agreement to participate in research. of direct benefit to individual sub-
Mere failure to object should not, ab- jects, but likely to yield generaliz-
sent affirmative agreement, be con- able knowledge about the subjects
strued as assent. disorder or condition.
(c) Permission means the agreement of HHS will conduct or fund research in
parent(s) or guardian to the participa- which the IRB finds that more than
tion of their child or ward in research. minimal risk to children is presented
(d) Parent means a childs biological by an intervention or procedure that
or adoptive parent. does not hold out the prospect of direct
(e) Guardian means an individual who benefit for the individual subject, or by
is authorized under applicable State or a monitoring procedure which is not
local law to consent on behalf of a likely to contribute to the well-being
child to general medical care. of the subject, only if the IRB finds
that:
46.403 IRB duties. (a) The risk represents a minor in-
In addition to other responsibilities crease over minimal risk;
assigned to IRBs under this part, each (b) The intervention or procedure
IRB shall review research covered by presents experiences to subjects that
this subpart and approve only research are reasonably commensurate with
123
those inherent in their actual or ex- children, when in the judgment of the
pected medical, dental, psychological, IRB the children are capable of pro-
social, or educational situations; viding assent. In determining whether
(c) The intervention or procedure is children are capable of assenting, the
likely to yield generalizable knowledge IRB shall take into account the ages,
about the subjects disorder or condi- maturity, and psychological state of
tion which is of vital importance for the children involved. This judgment
the understanding or amelioration of may be made for all children to be in-
the subjects disorder or condition; and volved in research under a particular
(d) Adequate provisions are made for protocol, or for each child, as the IRB
soliciting assent of the children and deems appropriate. If the IRB deter-
permission of their parents or guard- mines that the capability of some or
ians, as set forth in 46.408. all of the children is so limited that
46.407 Research not otherwise ap- they cannot reasonably be consulted or
provable which presents an oppor- that the intervention or procedure in-
tunity to understand, prevent, or al- volved in the research holds out a pros-
leviate a serious problem affecting pect of direct benefit that is important
the health or welfare of children. to the health or well-being of the chil-
HHS will conduct or fund research dren and is available only in the con-
that the IRB does not believe meets text of the research, the assent of the
the requirements of 46.404, 46.405, or children is not a necessary condition
46.406 only if: for proceeding with the research. Even
(a) The IRB finds that the research where the IRB determines that the sub-
presents a reasonable opportunity to jects are capable of assenting, the IRB
further the understanding, prevention, may still waive the assent requirement
or alleviation of a serious problem af- under circumstances in which consent
fecting the health or welfare of chil- may be waived in accord with 46.116 of
dren; and Subpart A.
(b) The Secretary, after consultation (b) In addition to the determinations
with a panel of experts in pertinent dis- required under other applicable sec-
ciplines (for example: science, medi- tions of this subpart, the IRB shall de-
cine, education, ethics, law) and fol- termine, in accordance with and to the
lowing opportunity for public review extent that consent is required by
and comment, has determined either: 46.116 of Subpart A, that adequate pro-
(1) That the research in fact satisfies visions are made for soliciting the per-
the conditions of 46.404, 46.405, or mission of each childs parents or
46.406, as applicable, or
guardian. Where parental permission is
(2) The following:
to be obtained, the IRB may find that
(i) The research presents a reasonable
the permission of one parent is suffi-
opportunity to further the under-
cient for research to be conducted
standing, prevention, or alleviation of
under 46.404 or 46.405. Where research
a serious problem affecting the health
is covered by 46.406 and 46.407 and
or welfare of children;
(ii) The research will be conducted in permission is to be obtained from par-
accordance with sound ethical prin- ents, both parents must give their per-
ciples; mission unless one parent is deceased,
(iii) Adequate provisions are made unknown, incompetent, or not reason-
for soliciting the assent of children and ably available, or when only one parent
the permission of their parents or has legal responsibility for the care
guardians, as set forth in 46.408. and custody of the child.
(c) In addition to the provisions for
46.408 Requirements for permission waiver contained in 46.116 of Subpart
by parents or guardians and for as- A, if the IRB determines that a re-
sent by children. search protocol is designed for condi-
(a) In addition to the determinations tions or for a subject population for
required under other applicable sec- which parental or guardian permission
tions of this subpart, the IRB shall de- is not a reasonable requirement to pro-
termine that adequate provisions are tect the subjects (for example, ne-
made for soliciting the assent of the glected or abused children), it may
124
waive the consent requirements in Sub- PART 50U.S. EXCHANGE VISITOR

part A of this part and paragraph (b) of PROGRAMREQUEST FOR WAIV-
this section, provided an appropriate ER OF THE TWO-YEAR FOREIGN
mechanism for protecting the children RESIDENCE REQUIREMENT
who will participate as subjects in the
research is substituted, and provided Sec.
further that the waiver is not incon- 50.1 Authority.
sistent with Federal, state or local law. 50.2 Exchange Visitor Waiver Review Board.
The choice of an appropriate mecha- 50.3 Policy.
50.4 Procedures for submission of applica-
nism would depend upon the nature
tion to HHS.
and purpose of the activities described 50.5 Personal hardship, persecution and visa
in the protocol, the risk and antici- extension considerations.
pated benefit to the research subjects, 50.6 Release from foreign government.
and their age, maturity, status, and AUTHORITY: 75 Stat. 527 (22 U.S.C. 2451 et
condition. seq.); 84 Stat. 116 (8 U.S.C. 1182(e)).
(d) Permission by parents or guard- SOURCE: 49 FR 9900, Mar. 16, 1984, unless
ians shall be documented in accordance otherwise noted.
with and to the extent required by
46.117 of Subpart A. 50.1 Authority.
(e) When the IRB determines that as- Under the authority of Mutual Edu-
sent is required, it shall also determine cational and Cultural Exchange Act of
whether and how assent must be docu- 1961 (75 Stat. 527) and the Immigration
mented. and Nationality Act as amended (84
Stat. 116), the Department of Health
46.409 Wards. and Human Services is an interested
United States Government agency
(a) Children who are wards of the
with the authority to request the
state or any other agency, institution, United States Information Agency to
or entity can be included in research recommend to the Attorney General
approved under 46.406 or 46.407 only if waiver of the two-year foreign resi-
such research is: dence requirement for exchange visi-
(1) Related to their status as wards; tors under the Mutual Educational and
or Cultural Exchange Program.
(2) Conducted in schools, camps, hos-
pitals, institutions, or similar settings 50.2 Exchange Visitor Waiver Review
in which the majority of children in- Board.
volved as subjects are not wards. (a) Establishment. The Exchange Vis-
(b) If the research is approved under itor Waiver Review Board is estab-
paragraph (a) of this section, the IRB lished to carry out the Departments
shall require appointment of an advo- responsibilities under the Exchange
cate for each child who is a ward, in ad- Visitor Program.
dition to any other individual acting (b) Functions. The Exchange Visitor
on behalf of the child as guardian or in Waiver Review Board is responsible for
making thorough and equitable evalua-
loco parentis. One individual may serve
tions of applications submitted by in-
as advocate for more than one child.
stitutions, acting on behalf of exchange
The advocate shall be an individual visitors, to the Department of HHS for
who has the background and experience a favorable recommendation to the
to act in, and agrees to act in, the best United States Information Agency that
interests of the child for the duration the two-year foreign residence require-
of the childs participation in the re- ment for exchange visitors under the
search and who is not associated in any Exchanges Visitor Program be waived.
way (except in the role as advocate or (c) Membership. The Exchange Visitor
member of the IRB) with the research, Waiver Review Board consists of no
the investigator(s), or the guardian or- fewer than three members and two al-
ganization. ternates, of whom no fewer than three
125

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Pt.

46 45 CFR Subtitle A (10100 Edition)

immediately notify the Department 46.116 General requirements for informed

Sec. Subpart CAdditional Protections Per-

or in such other manner as provided in ministration). It does not include re-

eliminate apparent immediate hazards posal or by such later date as may be

(2) A description of any reasonably (5) A statement that significant new

46.202 Purpose. through admixture of donor human

waive the consent requirements in Sub- PART 50U.S. EXCHANGE VISITOR

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