Code of Federal Regulations
TITLE 45 — PUBLIC WELFARE
Department of Health and Human Services
PROTECTION OF HUMAN SUBJECTS
Revised June 23, 2005
Effective June 23, 2005
SUBPART A— SUBPART B— SUBPART D—
Basic HHS Policy for Protec- Additional Protections for Additional Protections
tion of Human Research Pregnant Women, Human Fe- for Children Involved as Sub-
Subjects tuses and Neonates Involved jects in Research
46.101 To what does this policy apply? Sec. 46.401 To what do these regulations
46.102 Definitions. 46.201 To what do these regulations apply?
46.103 Assuring compliance with this apply? 46.402 Definitions.
policy—research conducted or 46.202 Definitions. 46.403 IRB duties.
supported by any Federal Depart- 46.203 Duties of IRBs in connection 46.404 Research not involving greater
ment or Agency. with research involving pregnant than minimal risk.
46.104-46.106 [Reserved] women, fetuses, and neonates. 46.405 Research involving greater than
46.107 IRB membership. 46.204 Research involving pregnant minimal risk but presenting the
46.108 IRB functions and operations. women or fetuses. prospect of direct benefit to the in-
46.109 IRB review of research. 46.205 Research involving neonates. dividual subjects.
46.110 Expedited review procedures for 46.206 Research involving, after deliv- 46.406 Research involving greater than
certain kinds of research involving ery, the placenta, the dead fetus or minimal risk and no prospect of
no more than minimal risk, and for fetal material. direct benefit to individual sub-
minor changes in approved re- 46.207 Research not otherwise approv- jects, but likely to yield generaliz-
search. able which presents an opportunity able knowledge about the subject’s
46.111 Criteria for IRB approval of to understand, prevent, or alleviate disorder or condition.
research. a serious problem affecting the 46.407 Research not otherwise approv-
46.112 Review by institution. health or welfare of pregnant able which presents an opportunity
46.113 Suspension or termination of women, fetuses, or neonates. to understand, prevent, or alleviate
IRB approval of research. a serious problem affecting the
46.114 Cooperative research. health or welfare of children.
46.115 IRB records. 46.408 Requirements for permission by
46.116 General requirements for in- SUBPART C— parents or guardians and for assent
formed consent. by children.
46.117 Documentation of informed
Additional Protections 46.409 Wards.
consent. Pertaining to Biomedical and
46.118 Applications and proposals lack- Behavioral Research Involving Authority: 5 U.S.C. 301; 42 U.S.C. 289(a).
ing definite plans for involvement Prisoners as Subjects
of human subjects. Editorial Note: The Department of
46.119 Research undertaken without Sec. Health and Human Services issued a
the intention of involving human 46.301 Applicability. notice of waiver regarding the require-
subjects. 46.302 Purpose. ments set forth in part 46, relating to
46.120 Evaluation and disposition of 46.303 Definitions. protection of human subjects, as they
applications and proposals for re- 46.304 Composition of Institutional pertain to demonstration projects, ap-
search to be conducted or sup- Review Boards where prisoners are proved under section 1115 of the Social
ported by a Federal Department or involved. Security Act, which test the use of cost-
Agency. 46.305 Additional duties of the Institu- sharing, such as deductibles, copayment
46.121 [Reserved] tional Review Boards where pris- and coinsurance, in the Medicaid pro-
46.122 Use of Federal funds. oners are involved. gram. For further information see 47
46.123 Early termination of research 46.306 Permitted research involving FR 9208, Mar. 4, 1982.
support: Evaluation of applications prisoners.
45 CFR 46 - page 2
Subpart A — Basic HHS Policy for (2) Research involving the use of educa- contaminant at or below the level found
Protection of Human Research tional tests (cognitive, diagnostic, aptitude, to be safe, by the Food and Drug Admini-
achievement), survey procedures, inter- stration or approved by the Environ-
Subjects view procedures or observation of public mental Protection Agency or the Food
behavior, unless: Safety and Inspection Service of the U.S.
Authority: 5 U.S.C. 301; 42 U.S.C. 289;
Department of Agriculture.
42 U.S.C. 300v-1(b). (i) Information obtained is recorded in
such manner that human subjects can (c) Department or agency heads retain final
Source: 56 FR 28012, 28022, June 18, 1991, be identified, directly or through identi- judgment as to whether a particular activity
unless otherwise noted.
fiers linked to the subjects; and (ii) any is covered by this policy.
§ 46.101 To what does this policy apply? disclosure of the human subjects’ re-
(d) Department or agency heads may require
sponses outside the research could rea-
(a) Except as provided in paragraph (b) of that specific research activities or classes of
sonably place the subjects at risk of research activities conducted, supported, or
this section, this policy applies to all research criminal or civil liability or be damaging
involving human subjects conducted, sup- otherwise subject to regulation by the de-
to the subjects’ financial standing, em-
ported or otherwise subject to regulation by partment or agency but not otherwise cov-
ployability, or reputation.
any federal department or agency which ered by this policy, comply with some or all
takes appropriate administrative action to (3) Research involving the use of educa- of the requirements of this policy.
make the policy applicable to such research. tional tests (cognitive, diagnostic, aptitude,
(e) Compliance with this policy requires
This includes research conducted by federal achievement), survey procedures, inter- compliance with pertinent federal laws or
civilian employees or military personnel, view procedures, or observation of public regulations which provide additional protec-
except that each department or agency head behavior that is not exempt under para-
tions for human subjects.
may adopt such procedural modifications as graph (b)(2) of this section, if:
(f) This policy does not affect any state or
may be appropriate from an administrative (i) The human subjects are elected or
local laws or regulations which may other-
standpoint. It also includes research con- appointed public officials or candidates
wise be applicable and which provide addi-
ducted, supported, or otherwise subject to for public office; or (ii) federal statute(s)
tional protections for human subjects.
regulation by the federal government outside require(s) without exception that the
the United States. confidentiality of the personally identifi- (g) This policy does not affect any foreign
able information will be maintained laws or regulations which may otherwise be
(1) Research that is conducted or sup-
throughout the research and thereafter. applicable and which provide additional
ported by a federal department or agency,
protections to human subjects of research.
whether or not it is regulated as defined in (4) Research, involving the collection or
§ 46.102(e), must comply with all sections study of existing data, documents, records, (h) When research covered by this policy
of this policy. pathological specimens, or diagnostic takes place in foreign countries, procedures
specimens, if these sources are publicly normally followed in the foreign countries
(2) Research that is neither conducted nor
available or if the information is recorded to protect human subjects may differ from
supported by a federal department or
by the investigator in such a manner that those set forth in this policy. [An example is
agency but is subject to regulation as de-
subjects cannot be identified, directly or a foreign institution which complies with
fined in § 46.102(e) must be reviewed and
through identifiers linked to the subjects. guidelines consistent with the World Medi-
approved, in compliance with § 46.101,
cal Assembly Declaration (Declaration of
§ 46.102, and § 46.107 through § 46.117 (5) Research and demonstration projects
Helsinki amended 1989) issued either by
of this policy, by an institutional review which are conducted by or subject to the sovereign states or by an organization whose
board (IRB) that operates in accordance approval of department or agency heads, function for the protection of human re-
with the pertinent requirements of this and which are designed to study, evaluate,
search subjects is internationally recognized.]
policy. or otherwise examine:
In these circumstances, if a department or
(b) Unless otherwise required by department (i) Public benefit or service programs; agency head determines that the procedures
or agency heads, research activities in which (ii) procedures for obtaining benefits or prescribed by the institution afford protec-
the only involvement of human subjects will services under those programs; (iii) pos- tions that are at least equivalent to those
be in one or more of the following catego- sible changes in or alternatives to those provided in this policy, the department or
ries are exempt from this policy: programs or procedures; or (iv) possible agency head may approve the substitution of
(1) Research conducted in established or changes in methods or levels of pay- the foreign procedures in lieu of the proce-
commonly accepted educational settings, ment for benefits or services under dural requirements provided in this policy.
involving normal educational practices, those programs. Except when otherwise required by statute,
such as Executive Order, or the department or
(6) Taste and food quality evaluation and
agency head, notices of these actions as they
(i) research on regular and special edu- consumer acceptance studies, (i) if whole-
occur will be published in the FEDERAL
cation instructional strategies, or (ii) some foods without additives are con-
sumed or (ii) if a food is consumed that REGISTER or will be otherwise published as
research on the effectiveness of or the provided in department or agency proce-
comparison among instructional tech- contains a food ingredient at or below the
niques, curricula, or classroom manage- level and for a use found to be safe, or
ment methods. agricultural chemical or environmental
45 CFR 46 - page 3
(i) Unless otherwise required by law, depart- § 46.102 Definitions. sonal contact between investigator and sub-
ment or agency heads may waive the appli- ject. Private information includes information
(a) Department or agency head means the head
cability of some or all of the provisions of about behavior that occurs in a context in
of any federal department or agency and any
this policy to specific research activities or which an individual can reasonably expect
other officer or employee of any department
classes or research activities otherwise cov- or agency to whom authority has been dele- that no observation or recording is taking
ered by this policy. Except when otherwise place, and information which has been pro-
required by statute or Executive Order, the vided for specific purposes by an individual
department or agency head shall forward (b) Institution means any public or private and which the individual can reasonably
advance notices of these actions to the Of- entity or agency (including federal, state, and expect will not be made public (for example,
fice for Human Research Protections, De- other agencies). a medical record). Private information must
partment of Health and Human Services (c) Legally authorized representative means an be individually identifiable (i.e., the identity
(HHS), or any successor office, and shall individual or judicial or other body author- of the subject is or may readily be ascer-
also publish them in the FEDERAL REGIS- ized under applicable law to consent on tained by the investigator or associated with
TER or in such other manner as provided in behalf of a prospective subject to the sub- the information) in order for obtaining the
department or agency procedures.1 ject’s participation in the procedure(s) in- information to constitute research involving
volved in the research. human subjects.
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June
28, 1991, as amended at 70 FR 36328, June 23, 2005] (d) Research means a systematic investigation, (g) IRB means an institutional review board
including research development, testing and established in accord with and for the pur-
1 Institutions with HHS-approved assurances on file
evaluation, designed to develop or contrib- poses expressed in this policy.
will abide by provisions of Title 45 CFR part 46 sub-
parts A-D. Some of the other departments and agencies ute to generalizable knowledge. Activities (h) IRB approval means the determination of
have incorporated all provisions of Title 45 CFR part which meet this definition constitute re- the IRB that the research has been reviewed
46 into their policies and procedures as well. However, search for purposes of this policy, whether and may be conducted at an institution
the exemptions at 45 CFR 46.101(b) do not apply to or not they are conducted or supported un-
research involving prisoners, subpart C. The exemption within the constraints set forth by the IRB
at 45 CFR 46.101(b)(2), for research involving survey or der a program which is considered research and by other institutional and federal re-
interview procedures or observation of public behavior, for other purposes. For example, some dem- quirements.
does not apply to research with children, subpart D, onstration and service programs may include
except for research involving observations of public (i) Minimal risk means that the probability
behavior when the investigator(s) do not participate in and magnitude of harm or discomfort antici-
the activities being observed (e) Research subject to regulation, and similar pated in the research are not greater in and
terms are intended to encompass those re- of themselves than those ordinarily encoun-
search activities for which a federal depart- tered in daily life or during the performance
ment or agency has specific responsibility of routine physical or psychological exami-
for regulating as a research activity, (for ex- nations or tests.
ample, Investigational New Drug require-
(j) Certification means the official notification
ments administered by the Food and Drug
by the institution to the supporting depart-
Administration). It does not include research
ment or agency, in accordance with the re-
activities which are incidentally regulated by
a federal department or agency solely as part quirements of this policy, that a research
project or activity involving human subjects
of the department’s or agency’s broader
has been reviewed and approved by an IRB
responsibility to regulate certain types of
in accordance with an approved assurance.
activities whether research or non-research
in nature (for example, Wage and Hour re-
quirements administered by the Department
(f) Human subject means a living individual
about whom an investigator (whether pro-
fessional or student) conducting research
(1) Data through intervention or interac-
tion with the individual, or
(2) Identifiable private information.
Intervention includes both physical procedures
by which data are gathered (for example,
venipuncture) and manipulations of the sub-
ject or the subject’s environment that are
performed for research purposes. Interac-
tion includes communication or interper-
45 CFR 46 - page 4
§ 46.103 Assuring compliance with this ficient staff to support the IRB's review evaluate all assurances submitted in accor-
policy — research conducted or sup- and recordkeeping duties. dance with this policy through such officers
ported by any Federal Department and employees of the department or agency
(3) A list of IRB members identified by
or Agency. and such experts or consultants engaged for
name; earned degrees; representative ca-
(a) Each institution engaged in research pacity; indications of experience such as this purpose as the department or agency
head determines to be appropriate. The de-
which is covered by this policy and which is board certifications, licenses, etc., suffi-
partment or agency head's evaluation will
conducted or supported by a federal depart- cient to describe each member's chief an-
take into consideration the adequacy of the
ment or agency shall provide written assur- ticipated contributions to IRB delibera-
ance satisfactory to the department or tions; and any employment or other rela- proposed IRB in light of the anticipated
scope of the institution's research activities
agency head that it will comply with the tionship between each member and the
and the types of subject populations likely to
requirements set forth in this policy. In lieu institution; for example: full-time em-
be involved, the appropriateness of the pro-
of requiring submission of an assurance, ployee, part-time employee, member of
individual department or agency heads shall governing panel or board, stockholder, posed initial and continuing review proce-
dures in light of the probable risks, and the
accept the existence of a current assurance, paid or unpaid consultant. Changes in IRB
size and complexity of the institution.
appropriate for the research in question, on membership shall be reported to the de-
file with the Office for Human Research partment or agency head, unless in accord (e) On the basis of this evaluation, the de-
Protections, HHS, or any successor office, with § 46.103(a) of this policy, the exis- partment or agency head may approve or
and approved for federalwide use by that tence of an HHS-approved assurance is disapprove the assurance, or enter into ne-
office. When the existence of an HHS- accepted. In this case, change in IRB gotiations to develop an approvable one.
approved assurance is accepted in lieu of membership shall be reported to the Of- The department or agency head may limit
requiring submission of an assurance, re- fice for Human Research Protections, the period during which any particular ap-
ports (except certification) required by this HHS, or any successor office. proved assurance or class of approved assur-
policy to be made to department and agency ances shall remain effective or otherwise
(4) Written procedures which the IRB will
heads shall also be made to the Office for follow (i) for conducting its initial and condition or restrict approval.
Human Research Protections, HHS, or any
continuing review of research and for re- (f) Certification is required when the re-
porting its findings and actions to the in- search is supported by a federal department
(b) Departments and agencies will conduct or agency and not otherwise exempted or
vestigator and the institution; (ii) for deter-
or support research covered by this policy mining which projects require review more waived under § 46.101(b) or (i). An institu-
only if the institution has an assurance ap- often than annually and which projects tion with an approved assurance shall certify
proved as provided in this section, and only need verification from sources other than that each application or proposal for re-
if the institution has certified to the depart- the investigators that no material changes search covered by the assurance and by
ment or agency head that the research has have occurred since previous IRB review; § 46.103 of this Policy has been reviewed
been reviewed and approved by an IRB pro- and (iii) for ensuring prompt reporting to and approved by the IRB. Such certification
vided for in the assurance, and will be sub- the IRB of proposed changes in a research must be submitted with the application or
ject to continuing review by the IRB. Assur- activity, and for ensuring that such proposal or by such later date as may be
ances applicable to federally supported or changes in approved research, during the prescribed by the department or agency to
conducted research shall at a minimum in- period for which IRB approval has already which the application or proposal is submit-
clude: been given, may not be initiated without ted. Under no condition shall research cov-
(1) A statement of principles governing IRB review and approval except when ered by § 46.103 of the Policy be supported
necessary to eliminate apparent immediate prior to receipt of the certification that the
the institution in the discharge of its re-
hazards to the subject. research has been reviewed and approved by
sponsibilities for protecting the rights and
welfare of human subjects of research (5) Written procedures for ensuring the IRB. Institutions without an approved
conducted at or sponsored by the institu- prompt reporting to the IRB, appropriate assurance covering the research shall certify
within 30 days after receipt of a request for
tion, regardless of whether the research is institutional officials, and the department
such a certification from the department or
subject to federal regulation. This may or agency head of (i) any unanticipated
include an appropriate existing code, dec- problems involving risks to subjects or agency, that the application or proposal has
laration, or statement of ethical principles, others or any serious or continuing non- been approved by the IRB. If the certifica-
tion is not submitted within these time lim-
or a statement formulated by the institu- compliance with this policy or the require-
its, the application or proposal may be re-
tion itself. This requirement does not pre- ments or determinations of the IRB; and
empt provisions of this policy applicable the
(ii) any suspension or termination of IRB turned toby theinstitution.
(Approved Office of Management and Budget
to department- or agency-supported or approval. under Control Number 0990-0260.)
regulated research and need not be appli-
(c) The assurance shall be executed by an [56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June
cable to any research exempted or waived individual authorized to act for the institu- 28, 1991, as amended at 70 FR 36328, June 23, 2005]
under § 46.101(b) or (i).
tion and to assume on behalf of the institu- §§ 46.104--46.106 [Reserved]
(2) Designation of one or more IRBs es- tion the obligations imposed by this policy
tablished in accordance with the require- and shall be filed in such form and manner
ments of this policy, and for which provi- as the department or agency head prescribes.
sions are made for meeting space and suf-
(d) The department or agency head will
45 CFR 46 - page 5
§ 46.107 IRB membership. § 46.108 IRB functions and operations. § 46.110 Expedited review procedures for
certain kinds of research involving no
(a) Each IRB shall have at least five mem- In order to fulfill the requirements of this more than minimal risk, and for minor
bers, with varying backgrounds to promote policy each IRB shall: changes in approved research.
complete and adequate review of research (a) Follow written procedures in the same (a) The Secretary, HHS, has established, and
activities commonly conducted by the insti- published as a Notice in the FEDERAL REG-
detail as described in § 46.103(b)(4) and, to
tution. The IRB shall be sufficiently quali- ISTER, a list of categories of research that
the extent required by, § 46.103(b)(5).
fied through the experience and expertise of may be reviewed by the IRB through an
its members, and the diversity of the mem- (b) Except when an expedited review proce- expedited review procedure. The list will be
bers, including consideration of race, gender, dure is used (see § 46.110), review proposed amended, as appropriate, after consultation
and cultural backgrounds and sensitivity to research at convened meetings at which a with other departments and agencies,
such issues as community attitudes, to pro- majority of the members of the IRB are through periodic republication by the Secre-
mote respect for its advice and counsel in present, including at least one member tary, HHS, in the FEDERAL REGISTER. A
whose primary concerns are in nonscientific copy of the list is available from the Office
safeguarding the rights and welfare of hu- for Human Research Protections, HHS, or
man subjects. In addition to possessing the areas. In order for the research to be ap- any successor office.
professional competence necessary to review proved, it shall receive the approval of a
specific research activities, the IRB shall be majority of those members present at the (b) An IRB may use the expedited review
meeting. procedure to review either or both of the
able to ascertain the acceptability of pro- following:
posed research in terms of institutional com- § 46.109 IRB review of research.
mitments and regulations, applicable law, (1) Some or all of the research appearing
and standards of professional conduct and (a) An IRB shall review and have authority on the list and found by the reviewer(s) to
to approve, require modifications in (to se- involve no more than minimal risk,
practice. The IRB shall therefore include
persons knowledgeable in these areas. If an cure approval), or disapprove all research (2) Minor changes in previously approved
IRB regularly reviews research that involves activities covered by this policy. research during the period (of one year or
a vulnerable category of subjects, such as less) for which approval is authorized.
(b) An IRB shall require that information
children, prisoners, pregnant women, or given to subjects as part of informed con- Under an expedited review procedure, the
handicapped or mentally disabled persons, sent is in accordance with § 46.116. The IRB review may be carried out by the IRB chair-
consideration shall be given to the inclusion person or by one or more experienced re-
may require that information, in addition to viewers designated by the chairperson from
of one or more individuals who are knowl- that specifically mentioned in § 46.116, be among members of the IRB. In reviewing
edgeable about and experienced in working given to the subjects when in the IRB's judg- the research, the reviewers may exercise all
with these subjects. ment the information would meaningfully of the authorities of the IRB except that the
(b) Every nondiscriminatory effort will be add to the protection of the rights and wel- reviewers may not disapprove the research.
made to ensure that no IRB consists entirely fare of subjects. A research activity may be disapproved only
after review in accordance with the non-
of men or entirely of women, including the (c) An IRB shall require documentation of expedited procedure set forth in § 46.108(b).
institution's consideration of qualified per- informed consent or may waive documenta-
sons of both sexes, so long as no selection is (c) Each IRB which uses an expedited re-
tion in accordance with § 46.117. view procedure shall adopt a method for
made to the IRB on the basis of gender. No
IRB may consist entirely of members of one (d) An IRB shall notify investigators and the keeping all members advised of research
institution in writing of its decision to ap- proposals which have been approved under
prove or disapprove the proposed research the procedure.
(c) Each IRB shall include at least one mem- activity, or of modifications required to se- (d) The department or agency head may
ber whose primary concerns are in scientific cure IRB approval of the research activity. If restrict, suspend, terminate, or choose not to
areas and at least one member whose pri- the IRB decides to disapprove a research authorize an institution's or IRB's use of the
mary concerns are in nonscientific areas. activity, it shall include in its written notifica- expedited review procedure.
(d) Each IRB shall include at least one mem- tion a statement of the reasons for its deci- [56 FR 28012, 28022, June 18, 1991, as amended at 70
ber who is not otherwise affiliated with the sion and give the investigator an opportunity FR 36328, June 23, 2005]
institution and who is not part of the imme- to respond in person or in writing. § 46.111 Criteria for IRB approval of re-
diate family of a person who is affiliated (e) An IRB shall conduct continuing review search.
with the institution. of research covered by this policy at inter- (a) In order to approve research covered by
(e) No IRB may have a member participate vals appropriate to the degree of risk, but this policy the IRB shall determine that all of
not less than once per year, and shall have the following requirements are satisfied:
in the IRB's initial or continuing review of
any project in which the member has a con- authority to observe or have a third party (1) Risks to subjects are minimized: (i) By
flicting interest, except to provide informa- observe the consent process and the re- using procedures which are consistent
tion requested by the IRB. search. with sound research design and which do
(Approved by the Office of Management and Budget not unnecessarily expose subjects to risk,
(f) An IRB may, in its discretion, invite indi- under Control Number 0990-0260.) and (ii) whenever appropriate, by using
viduals with competence in special areas to
[56 FR 28012, 28022, June 18, 1991, as amended at 70 procedures already being performed on
assist in the review of issues which require
FR 36328, June 23, 2005] the subjects for diagnostic or treatment
expertise beyond or in addition to that avail-
able on the IRB. These individuals may not
vote with the IRB
45 CFR 46 - page 6
§ 46.113 Suspension or termination of provided to subjects, as required by
(2) Risks to subjects are reasonable in rela- IRB approval of research. § 46.116(b)(5).
tion to anticipated benefits, if any, to sub-
jects, and the importance of the knowl- An IRB shall have authority to suspend or (b) The records required by this policy shall
edge that may reasonably be expected to terminate approval of research that is not be retained for at least 3 years, and records
result. In evaluating risks and benefits, the being conducted in accordance with the relating to research which is conducted shall
IRB should consider only those risks and IRB's requirements or that has been associ- be retained for at least 3 years after comple-
benefits that may result from the research tion of the research. All records shall be
(as distinguished from risks and benefits of ated with unexpected serious harm to sub- accessible for inspection and copying by
therapies subjects would receive even if jects. Any suspension or termination of ap- authorized representatives of the depart-
not participating in the research). The IRB proval shall include a statement of the rea- ment or agency at reasonable times and in a
should not consider possible long-range sons for the IRB's action and shall be re- reasonable manner.
effects of applying knowledge gained in ported promptly to the investigator, appro- (Approved by the Office of Management and Budget
the research (for example, the possible priate institutional officials, and the depart- under Control Number 0990-0260.)
effects of the research on public policy) as ment or agency head.
among those research risks that fall within [56 FR 28012, 28022, June 18, 1991, as amended at 70
the purview of its responsibility. (Approved by the Office of Management and Budget FR 36328, June 23, 2005]
under Control Number 0990-0260.)
(3) Selection of subjects is equitable. In § 46.116 General requirements for in-
[56 FR 28012, 28022, June 18, 1991, as amended at 70
making this assessment the IRB should FR 36328, June 23, 2005]
take into account the purposes of the re-
§ 46.114 Cooperative research. Except as provided elsewhere in this policy,
search and the setting in which the re- no investigator may involve a human being
search will be conducted and should be Cooperative research projects are those pro-
particularly cognizant of the special prob- as a subject in research covered by this pol-
jects covered by this policy which involve icy unless the investigator has obtained the
lems of research involving vulnerable more than one institution. In the conduct of legally effective informed consent of the
populations, such as children, prisoners, cooperative research projects, each institu-
pregnant women, mentally disabled per- subject or the subject's legally authorized
tion is responsible for safeguarding the representative. An investigator shall seek
sons, or economically or educationally rights and welfare of human subjects and for such consent only under circumstances that
disadvantaged persons. complying with this policy. With the ap- provide the prospective subject or the repre-
(4) Informed consent will be sought from proval of the department or agency head, an sentative sufficient opportunity to consider
each prospective subject or the subject's institution participating in a cooperative whether or not to participate and that mini-
legally authorized representative, in accor- project may enter into a joint review ar- mize the possibility of coercion or undue
dance with, and to the extent required by rangement, rely upon the review of another influence. The information that is given to
§ 46.116. qualified IRB, or make similar arrangements the subject or the representative shall be in
for avoiding duplication of effort. language understandable to the subject or
(5) Informed consent will be appropriately the representative. No informed consent,
documented, in accordance with, and to § 46.115 IRB records.
whether oral or written, may include any
the extent required by § 46.117. (a) An institution, or when appropriate an exculpatory language through which the
(6) When appropriate, the research plan IRB, shall prepare and maintain adequate subject or the representative is made to
makes adequate provision for monitoring documentation of IRB activities, including waive or appear to waive any of the subject's
the data collected to ensure the safety of the following: legal rights, or releases or appears to release
subjects. (1) Copies of all research proposals re- the investigator, the sponsor, the institution
viewed, scientific evaluations, if any, that or its agents from liability for negligence.
(7) When appropriate, there are adequate
provisions to protect the privacy of sub- accompany the proposals, approved sam- (a) Basic elements of informed consent.
jects and to maintain the confidentiality of ple consent documents, progress reports Except as provided in paragraph (c) or (d) of
data. submitted by investigators, and reports of this section, in seeking informed consent the
injuries to subjects. following information shall be provided to
(b) When some or all of the subjects are
likely to be vulnerable to coercion or undue (2) Minutes of IRB meetings which shall each subject:
influence, such as children, prisoners, preg- be in sufficient detail to show attendance (1) A statement that the study involves
nant women, mentally disabled persons, or at the meetings; actions taken by the IRB; research, an explanation of the purposes
economically or educationally disadvantaged the vote on these actions including the of the research and the expected duration
persons, additional safeguards have been number of members voting for, against, of the subject's participation, a description
included in the study to protect the rights and abstaining; the basis for requiring of the procedures to be followed, and
and welfare of these subjects. changes in or disapproving research; and a identification of any procedures which are
written summary of the discussion of con- experimental;
§ 46.112 Review by institution. troverted issues and their resolution.
(2) A description of any reasonably fore-
Research covered by this policy that has (3) Records of continuing review activities. seeable risks or discomforts to the subject;
been approved by an IRB may be subject to
further appropriate review and approval or (4) Copies of all correspondence between (3) A description of any benefits to the
disapproval by officials of the institution. the IRB and the investigators. subject or to others which may reasonably
However, those officials may not approve (5) A list of IRB members in the same be expected from the research;
the research if it has not been approved by detail as described in § 46.103(b)(3).
an IRB. (4) A disclosure of appropriate alternative
(6) Written procedures for the IRB in the procedures or courses of treatment, if any,
same detail as described in § 46.103(b)(4) that might be advantageous to the subject;
and § 46.103(b)(5). (5) A statement describing the extent, if
(7) Statements of significant new findings any, to which confidentiality of records
identifying the subject will be maintained;
45 CFR 46 - page 7
(6) For research involving more than mini- (2) The research could not practicably be witness to the oral presentation. Also, the
mal risk, an explanation as to whether any carried out without the waiver or altera- IRB shall approve a written summary of
compensation and an explanation as to tion. what is to be said to the subject or the
whether any medical treatments are avail- representative. Only the short form itself
able if injury occurs and, if so, what they (d) An IRB may approve a consent proce- is to be signed by the subject or the repre-
dure which does not include, or which alters,
consist of, or where further information some or all of the elements of informed sentative. However, the witness shall sign
may be obtained; both the short form and a copy of the
consent set forth in this section, or waive summary, and the person actually obtain-
(7) An explanation of whom to contact for the requirements to obtain informed con-
answers to pertinent questions about the sent provided the IRB finds and documents ing consent shall sign a copy of the sum-
mary. A copy of the summary shall be
research and research subjects' rights, and that: given to the subject or the representative,
whom to contact in the event of a re-
search-related injury to the subject; and (1) The research involves no more than in addition to a copy of the short form.
minimal risk to the subjects;
(c) An IRB may waive the requirement for
(8) A statement that participation is volun- (2) The waiver or alteration will not ad- the investigator to obtain a signed consent
tary, refusal to participate will involve no versely affect the rights and welfare of the form for some or all subjects if it finds ei-
penalty or loss of benefits to which the
subject is otherwise entitled, and the sub- subjects; ther:
ject may discontinue participation at any (3) The research could not practicably be (1) That the only record linking the sub-
time without penalty or loss of benefits to carried out without the waiver or altera- ject and the research would be the con-
which the subject is otherwise entitled. tion; and sent document and the principal risk
would be potential harm resulting from a
(b) Additional elements of informed con- (4) Whenever appropriate, the subjects breach of confidentiality. Each subject will
sent. When appropriate, one or more of the will be provided with additional pertinent be asked whether the subject wants docu-
following elements of information shall also information after participation.
be provided to each subject: mentation linking the subject with the
(e) The informed consent requirements in research, and the subject's wishes will
(1) A statement that the particular treat- this policy are not intended to preempt any govern; or
ment or procedure may involve risks to applicable federal, state, or local laws which
the subject (or to the embryo or fetus, if require additional information to be dis- (2) That the research presents no more
the subject is or may become pregnant) closed in order for informed consent to be than minimal risk of harm to subjects and
involves no procedures for which written
which are currently unforeseeable; legally effective. consent is normally required outside of
(2) Anticipated circumstances under which (f) Nothing in this policy is intended to limit the research context.
the subject's participation may be termi- the authority of a physician to provide emer-
nated by the investigator without regard to gency medical care, to the extent the physi- In cases in which the documentation re-
quirement is waived, the IRB may require
the subject's consent; cian is permitted to do so under applicable the investigator to provide subjects with a
federal, state, or local law.
(3) Any additional costs to the subject that written statement regarding the research.
may result from participation in the re- (Approved by the Office of Management and Budget
(Approved by the Office of Management and Budget
search; under Control Number 0990-0260.)
under Control Number 0990-0260.)
(4) The consequences of a subject's deci- [56 FR 28012, 28022, June 18, 1991, as amended at 70
[56 FR 28012, 28022, June 18, 1991, as amended at 70
sion to withdraw from the research and FR 36328, June 23, 2005]
FR 36328, June 23, 2005]
procedures for orderly termination of par-
ticipation by the subject; § 46.117 Documentation of informed
consent. § 46.118 Applications and proposals lack-
ing definite plans for involvement of
(5) A statement that significant new find- (a) Except as provided in paragraph (c) of human subjects.
ings developed during the course of the this section, informed consent shall be docu-
research which may relate to the subject's Certain types of applications for grants, co-
willingness to continue participation will mented by the use of a written consent form operative agreements, or contracts are sub-
approved by the IRB and signed by the sub-
be provided to the subject; and ject or the subject's legally authorized repre- mitted to departments or agencies with the
knowledge that subjects may be involved
(6) The approximate number of subjects sentative. A copy shall be given to the per- within the period of support, but definite
involved in the study. son signing the form.
plans would not normally be set forth in the
(c) An IRB may approve a consent proce- (b) Except as provided in paragraph (c) of application or proposal. These include ac-
dure which does not include, or which alters, this section, the consent form may be either tivities such as institutional type grants when
some or all of the elements of informed of the following: selection of specific projects is the institu-
consent set forth above, or waive the re- tion's responsibility; research training grants
quirement to obtain informed consent pro- (1) A written consent document that em- in which the activities involving subjects
bodies the elements of informed consent
vided the IRB finds and documents that: required by § 46.116. This form may be remain to be selected; and projects in which
human subjects' involvement will depend
(1) The research or demonstration project read to the subject or the subject's legally upon completion of instruments, prior ani-
is to be conducted by or subject to the authorized representative, but in any
approval of state or local government offi- event, the investigator shall give either the mal studies, or purification of compounds.
These applications need not be reviewed by
cials and is designed to study, evaluate, or subject or the representative adequate an IRB before an award may be made. How-
otherwise examine: (i) public benefit or opportunity to read it before it is signed;
service programs; (ii) procedures for ob- or ever, except for research exempted or
waived under § 46.101(b) or (i), no human
taining benefits or services under those subjects may be involved in any project sup-
programs; (iii) possible changes in or alter- (2) A short form written consent docu-
natives to those programs or procedures; ment stating that the elements of in- ported by these awards until the project has
formed consent required by § 46.116 have been reviewed and approved by the IRB, as
or (iv) possible changes in methods or been presented orally to the subject or the provided in this policy, and certification
levels of payment for benefits or services
under those programs; and subject's legally authorized representative. submitted, by the institution, to the depart-
When this method is used, there shall be a ment or agency.
45 CFR 46 - page 8
of an activity has have, in the judgment of (c) Fetus means the product of conception
§ 46.119 Research undertaken without the department or agency head, materially
the intention of involving human from implantation until delivery.
subjects. failed to discharge responsibility for the pro-
tection of the rights and welfare of human (d) Neonate means a newborn.
In the event research is undertaken without subjects (whether or not the research was (e) Nonviable neonate means a neonate after
the intention of involving human subjects, subject to federal regulation).
but it is later proposed to involve human delivery that, although living, is not viable.
subjects in the research, the research shall § 46.124 Conditions.
(f) Pregnancy encompasses the period of
first be reviewed and approved by an IRB, With respect to any research project or any time from implantation until delivery. A
as provided in this policy, a certification class of research projects the department or woman shall be assumed to be pregnant if
submitted, by the institution, to the depart- agency head may impose additional condi-
ment or agency, and final approval given to tions prior to or at the time of approval she exhibits any of the pertinent presump-
the proposed change by the department or when in the judgment of the department or tive signs of pregnancy, such as missed men-
agency. agency head additional conditions are neces- ses, until the results of a pregnancy test are
sary for the protection of human subjects. negative or until delivery.
§ 46.120 Evaluation and disposition of
applications and proposals for re- (g) Secretary means the Secretary of Health
search to be conducted or supported and Human Services and any other officer
by a Federal Department or Agency. Subpart B — Additional Protections
for Pregnant Women, Human or employee of the Department of Health
(a) The department or agency head will Fetuses and Neonates Involved in and Human Services to whom authority has
evaluate all applications and proposals in- Research been delegated.
volving human subjects submitted to the
Source: 66 FR 56778, Nov. 13, 2001, unless otherwise
(h) Viable, as it pertains to the neonate,
department or agency through such officers
noted. means being able, after delivery, to survive
and employees of the department or agency
and such experts and consultants as the de- § 46.201 To what do these regulations (given the benefit of available medical ther-
partment or agency head determines to be apply? apy) to the point of independently maintain-
appropriate. This evaluation will take into ing heartbeat and respiration. The Secretary
consideration the risks to the subjects, the (a) Except as provided in paragraph (b) of
this section, this subpart applies to all re- may from time to time, taking into account
adequacy of protection against these risks, medical advances, publish in the FEDERAL
the potential benefits of the research to the search involving pregnant women, human
subjects and others, and the importance of fetuses, neonates of uncertain viability, or REGISTER guidelines to assist in determining
the knowledge gained or to be gained. nonviable neonates conducted or supported whether a neonate is viable for purposes of
by the Department of Health and Human this subpart. If a neonate is viable then it
(b) On the basis of this evaluation, the de-
partment or agency head may approve or Services (DHHS). This includes all research may be included in research only to the ex-
disapprove the application or proposal, or conducted in DHHS facilities by any person tent permitted and in accordance with the
enter into negotiations to develop an ap- and all research conducted in any facility by requirements of subparts A and D of this
provable one. DHHS employees. part.
§ 46.121 [Reserved] (b) The exemptions at § 46.101(b)(1) § 46.203 Duties of IRBs in connection
§ 46.122 Use of Federal funds. through (6) are applicable to this subpart. with research involving pregnant
women, fetuses, and neonates.
Federal funds administered by a department (c) The provisions of § 46.101(c) through (i)
or agency may not be expended for research are applicable to this subpart. Reference to In addition to other responsibilities assigned
involving human subjects unless the require- State or local laws in this subpart and in to IRBs under this part, each IRB shall re-
ments of this policy have been satisfied. § 46.101(f) is intended to include the laws of view research covered by this subpart and
§ 46.123 Early termination of research federally recognized American Indian and approve only research which satisfies the
support: Evaluation of applications and Alaska Native Tribal Governments. conditions of all applicable sections of this
proposals. subpart and the other subparts of this part.
(d) The requirements of this subpart are in
(a) The department or agency head may addition to those imposed under the other § 46.204 Research involving pregnant
require that department or agency support women or fetuses.
for any project be terminated or suspended subparts of this part.
in the manner prescribed in applicable pro- § 46.202 Definitions. Pregnant women or fetuses may be involved
gram requirements, when the department or in research if all of the following conditions
agency head finds an institution has materi- The definitions in § 46.102 shall be applica- are met:
ally failed to comply with the terms of this ble to this subpart as well. In addition, as
policy. used in this subpart: (a) Where scientifically appropriate, preclini-
cal studies, including studies on pregnant
(b) In making decisions about supporting or (a) Dead fetus means a fetus that exhibits animals, and clinical studies, including stud-
approving applications or proposals covered neither heartbeat, spontaneous respiratory
by this policy the department or agency head ies on nonpregnant women, have been con-
activity, spontaneous movement of volun- ducted and provide data for assessing poten-
may take into account, in addition to all
other eligibility requirements and program tary muscles, nor pulsation of the umbilical tial risks to pregnant women and fetuses;
criteria, factors such as whether the appli- cord.
(b) The risk to the fetus is caused solely by
cant has been subject to a termination or (b) Delivery means complete separation of
suspension under paragraph (a) of this sec- interventions or procedures that hold out
the fetus from the woman by expulsion or the prospect of direct benefit for the woman
tion and whether the applicant or the person
or persons who would direct or has have extraction or any other means. or the fetus; or, if there is no such prospect
directed the scientific and technical aspects of benefit, the risk to the fetus is not greater
45 CFR 46 - page 9
than minimal and the purpose of the re- der paragraph (b)(2) or (c)(5) of this sec- of both parents of the neonate is obtained
search is the development of important bio- tion is fully informed regarding the rea- in accord with subpart A of this part, ex-
medical knowledge which cannot be ob- sonably foreseeable impact of the research cept that the waiver and alteration provi-
tained by any other means; on the neonate. sions of § 46.116(c) and (d) do not apply.
(c) Any risk is the least possible for achiev- (3) Individuals engaged in the research will However, if either parent is unable to con-
sent because of unavailability, incompe-
ing the objectives of the research; have no part in determining the viability of
tence, or temporary incapacity, the in-
(d) If the research holds out the prospect of formed consent of one parent of a nonvi-
direct benefit to the pregnant woman, the (4) The requirements of paragraph (b) or able neonate will suffice to meet the re-
prospect of a direct benefit both to the preg- (c) of this section have been met as appli- quirements of this paragraph (c)(5), except
nant woman and the fetus, or no prospect of cable. that the consent of the father need not be
benefit for the woman nor the fetus when (b) Neonates of uncertain viability. Until it obtained if the pregnancy resulted from
risk to the fetus is not greater than minimal rape or incest. The consent of a legally
has been ascertained whether or not a neo-
and the purpose of the research is the devel- authorized representative of either or both
nate is viable, a neonate may not be involved
opment of important biomedical knowledge in research covered by this subpart unless of the parents of a nonviable neonate will
that cannot be obtained by any other means, the following additional conditions have not suffice to meet the requirements of
her consent is obtained in accord with the this paragraph (c)(5).
informed consent provisions of subpart A
(1) The IRB determines that: (d) Viable neonates. A neonate, after deliv-
of this part;
ery, that has been determined to be viable
(e) If the research holds out the prospect of (i) The research holds out the prospect may be included in research only to the ex-
direct benefit solely to the fetus then the of enhancing the probability of survival tent permitted by and in accord with the
consent of the pregnant woman and the of the neonate to the point of viability, requirements of subparts A and D of this
father is obtained in accord with the in- and any risk is the least possible for part.
formed consent provisions of subpart A of achieving that objective, or
§ 46.206 Research involving, after deliv-
this part, except that the father's consent (ii) The purpose of the research is the ery, the placenta, the dead fetus or
need not be obtained if he is unable to con- development of important biomedical
sent because of unavailability, incompetence, fetal material.
knowledge which cannot be obtained by
or temporary incapacity or the pregnancy other means and there will be no added (a) Research involving, after delivery, the
resulted from rape or incest. risk to the neonate resulting from the placenta; the dead fetus; macerated fetal
(f) Each individual providing consent under research; and material; or cells, tissue, or organs excised
from a dead fetus, shall be conducted only
paragraph (d) or (e) of this section is fully (2) The legally effective informed consent in accord with any applicable Federal, State,
informed regarding the reasonably foresee- of either parent of the neonate or, if nei- or local laws and regulations regarding such
able impact of the research on the fetus or ther parent is able to consent because of
unavailability, incompetence, or temporary
incapacity, the legally effective informed (b) If information associated with material
(g) For children as defined in § 46.402(a)
consent of either parent's legally author- described in paragraph (a) of this section is
who are pregnant, assent and permission are
obtained in accord with the provisions of ized representative is obtained in accord recorded for research purposes in a manner
subpart D of this part; with subpart A of this part, except that the that living individuals can be identified, di-
consent of the father or his legally author- rectly or through identifiers linked to those
(h) No inducements, monetary or otherwise,
ized representative need not be obtained if individuals, those individuals are research
will be offered to terminate a pregnancy;
the pregnancy resulted from rape or incest. subjects and all pertinent subparts of this
(i) Individuals engaged in the research will part are applicable.
(c) Nonviable neonates. After delivery non-
have no part in any decisions as to the tim- § 46.207 Research not otherwise approv-
viable neonate may not be involved in re-
ing, method, or procedures used to termi- able which presents an opportunity
search covered by this subpart unless all of
nate a pregnancy; and to understand, prevent, or alleviate a
the following additional conditions are met:
(j) Individuals engaged in the research will serious problem affecting the health
(1) Vital functions of the neonate will not or welfare of pregnant women, fe-
have no part in determining the viability of a
be artificially maintained; tuses, or neonates.
(2) The research will not terminate the The Secretary will conduct or fund research
§ 46.205 Research involving neonates.
heartbeat or respiration of the neonate; that the IRB does not believe meets the
(a) Neonates of uncertain viability and non- (3) There will be no added risk to the neo- requirements of § 46.204 or § 46.205 only if:
viable neonates may be involved in research
nate resulting from the research; (a) The IRB finds that the research presents
if all of the following conditions are met:
(4) The purpose of the research is the de- a reasonable opportunity to further the un-
(1) Where scientifically appropriate, pre- velopment of important biomedical derstanding, prevention, or alleviation of a
clinical and clinical studies have been con- serious problem affecting the health or wel-
knowledge that cannot be obtained by
ducted and provide data for assessing po- fare of pregnant women, fetuses or neo-
other means; and
tential risks to neonates. nates; and
(5) The legally effective informed consent
(2) Each individual providing consent un- (b) The Secretary, after consultation with a
45 CFR 46 - page 10
panel of experts in pertinent disciplines (for subpart is applicable. under this part, the Board shall review re-
example: science, medicine, ethics, law) and search covered by this subpart and approve
§ 46.303 Definitions.
following opportunity for public review and such research only if it finds that:
comment, including a public meeting an- As used in this subpart:
(1) The research under review represents
nounced in the FEDERAL REGISTER, has (a) Secretary means the Secretary of Health one of the categories of research permissi-
determined either: and Human Services and any other officer ble under § 46.306(a)(2);
(1) That the research in fact satisfies the or employee of the Department of Health
and Human Services to whom authority has (2) Any possible advantages accruing to
conditions of § 46.204, as applicable; or the prisoner through his or her participa-
(2) The following: tion in the research, when compared to the
(b) DHHS means the Department of Health general living conditions, medical care,
(i) The research presents a reasonable
and Human Services. quality of food, amenities and opportunity
opportunity to further the understand-
(c) Prisoner means any individual involuntar- for earnings in the prison, are not of such
ing, prevention, or alleviation of a seri-
ily confined or detained in a penal institu- a magnitude that his or her ability to weigh
ous problem affecting the health or
welfare of pregnant women, fetuses or tion. The term is intended to encompass the risks of the research against the value
neonates; individuals sentenced to such an institution of such advantages in the limited choice
under a criminal or civil statute, individuals environment of the prison is impaired;
(ii) The research will be conducted in detained in other facilities by virtue of stat-
accord with sound ethical principles; (3) The risks involved in the research are
utes or commitment procedures which pro- commensurate with risks that would be
vide alternatives to criminal prosecution or accepted by nonprisoner volunteers;
(iii) Informed consent will be obtained incarceration in a penal institution, and indi-
in accord with the informed consent viduals detained pending arraignment, trial, (4) Procedures for the selection of subjects
within the prison are fair to all prisoners
provisions of subpart A and other appli- or sentencing.
and immune from arbitrary intervention
cable subparts of this part. (d) Minimal risk is the probability and magni- by prison authorities or prisoners. Unless
tude of physical or psychological harm that the principal investigator provides to the
is normally encountered in the daily lives, or Board justification in writing for following
Subpart C — Additional Protections in the routine medical, dental, or psychologi- some other procedures, control subjects
Pertaining to Biomedical and cal examination of healthy persons. must be selected randomly from the group
Behavioral Research Involving § 46.304 Composition of Institutional of available prisoners who meet the char-
Prisoners as Subjects Review Boards where prisoners are acteristics needed for that particular re-
involved. search project;
Source: 43 FR 53655, Nov. 16, 1978, unless otherwise
In addition to satisfying the requirements in (5) The information is presented in lan-
§ 46.301 Applicability. § 46.107 of this part, an Institutional Review guage which is understandable to the sub-
Board, carrying out responsibilities under ject population;
(a) The regulations in this subpart are appli-
cable to all biomedical and behavioral re- this part with respect to research covered by (6) Adequate assurance exists that parole
search conducted or supported by the De- this subpart, shall also meet the following boards will not take into account a pris-
partment of Health and Human Services specific requirements: oner's participation in the research in mak-
involving prisoners as subjects. (a) A majority of the Board (exclusive of ing decisions regarding parole, and each
prisoner members) shall have no association prisoner is clearly informed in advance
(b) Nothing in this subpart shall be con- that participation in the research will have
strued as indicating that compliance with the with the prison(s) involved, apart from their no effect on his or her parole; and
procedures set forth herein will authorize membership on the Board.
research involving prisoners as subjects, to (b) At least one member of the Board shall (7) Where the Board finds there may be a
the extent such research is limited or barred be a prisoner, or a prisoner representative need for follow-up examination or care of
by applicable State or local law. with appropriate background and experience participants after the end of their partici-
to serve in that capacity, except that where a pation, adequate provision has been made
(c) The requirements of this subpart are in for such examination or care, taking into
addition to those imposed under the other particular research project is reviewed by
more than one Board only one Board need account the varying lengths of individual
subparts of this part. prisoners' sentences, and for informing
satisfy this requirement.
§ 46.302 Purpose. participants of this fact.
[43 FR 53655, Nov. 16, 1978, as amended at 46 FR
Inasmuch as prisoners may be under con- 8366, Jan. 26, 1981] (b) The Board shall carry out such other
straints because of their incarceration which duties as may be assigned by the Secretary.
could affect their ability to make a truly vol- (c) The institution shall certify to the Secre-
untary and uncoerced decision whether or § 46.305 Additional duties of the Institu- tary, in such form and manner as the Secre-
not to participate as subjects in research, it is tional Review Boards where prison- tary may require, that the duties of the
the purpose of this subpart to provide addi- ers are involved. Board under this section have been fulfilled.
tional safeguards for the protection of pris- (a) In addition to all other responsibilities
oners involved in activities to which this prescribed for Institutional Review Boards
45 CFR 46 - page 11
§ 46.306 Permitted research involving Subpart D — Additional Protections to object should not, absent affirmative
prisoners. for Children Involved as Sub- agreement, be construed as assent.
(a) Biomedical or behavioral research con- jects in Research (c) Permission means the agreement of
ducted or supported by DHHS may involve parent(s) or guardian to the participation of
Source: 48 FR 9818, March 8, 1983, unless otherwise
prisoners as subjects only if: noted. their child or ward in research.
(1) The institution responsible for the con- § 46.401 To what do these regulations (d) Parent means a child's biological or adop-
duct of the research has certified to the apply? tive parent.
Secretary that the Institutional Review
(a) This subpart applies to all research in- (e) Guardian means an individual who is au-
Board has approved the research under
volving children as subjects, conducted or thorized under applicable State or local law
§ 46.305 of this subpart; and to consent on behalf of a child to general
supported by the Department of Health and
(2) In the judgment of the Secretary the Human Services. medical care.
proposed research involves solely the fol-
(1) This includes research conducted by § 46.403 IRB duties.
Department employees, except that each In addition to other responsibilities assigned
(i) Study of the possible causes, effects, head of an Operating Division of the De- to IRBs under this part, each IRB shall re-
and processes of incarceration, and of partment may adopt such nonsubstantive, view research covered by this subpart and
criminal behavior, provided that the procedural modifications as may be appro- approve only research which satisfies the
study presents no more than minimal priate from an administrative standpoint. conditions of all applicable sections of this
risk and no more than inconvenience to
(2) It also includes research conducted or subpart.
supported by the Department of Health § 46.404 Research not involving greater
(ii) Study of prisons as institutional struc- and Human Services outside the United
than minimal risk.
tures or of prisoners as incarcerated per- States, but in appropriate circumstances,
sons, provided that the study presents no the Secretary may, under paragraph (e) of HHS will conduct or fund research in which
more than minimal risk and no more § 46.101 of Subpart A, waive the applica- the IRB finds that no greater than minimal
than inconvenience to the subjects; bility of some or all of the requirements of risk to children is presented, only if the IRB
these regulations for research of this type. finds that adequate provisions are made for
(iii) Research on conditions particularly soliciting the assent of the children and the
affecting prisoners as a class (for exam- (b) Exemptions at § 46.101(b)(1) and (b)(3)
permission of their parents or guardians, as
ple, vaccine trials and other research on through (b)(6) are applicable to this subpart.
set forth in § 46.408.
hepatitis which is much more prevalent The exemption at § 46.101(b)(2) regarding
in prisons than elsewhere; and research educational tests is also applicable to this § 46.405 Research involving greater than
on social and psychological problems subpart. However, the exemption at minimal risk but presenting the
such as alcoholism, drug addiction, and § 46.101(b)(2) for research involving survey prospect of direct benefit to the indi-
sexual assaults) provided that the study or interview procedures or observations of vidual subjects.
may proceed only after the Secretary has public behavior does not apply to research HHS will conduct or fund research in which
consulted with appropriate experts in- covered by this subpart, except for research the IRB finds that more than minimal risk to
cluding experts in penology, medicine, involving observation of public behavior children is presented by an intervention or
and ethics, and published notice, in the when the investigator(s) do not participate in procedure that holds out the prospect of
FEDERAL REGISTER, of his intent to the activities being observed. direct benefit for the individual subject, or
approve such research; or by a monitoring procedure that is likely to
(c) The exceptions, additions, and provisions
(iv) Research on practices, both innova- for waiver as they appear in paragraphs (c) contribute to the subject's well-being, only if
tive and accepted, which have the intent through (i) of § 46.101 of Subpart A are the IRB finds that:
and reasonable probability of improving applicable to this subpart. (a) The risk is justified by the anticipated
the health or well-being of the subject. In benefit to the subjects;
cases in which those studies require the [48FR 29757, Mar.8, 1983; 56 FR 28032, June 18, 1991;
56 June 28, 1991.]
assignment of prisoners in a manner (b) The relation of the anticipated benefit to
consistent with protocols approved by § 46.402 Definitions. the risk is at least as favorable to the subjects
the IRB to control groups which may The definitions in § 46.102 of Subpart A as that presented by available alternative
not benefit from the research, the study shall be applicable to this subpart as well. In approaches; and
may proceed only after the Secretary has addition, as used in this subpart: (c) Adequate provisions are made for solicit-
consulted with appropriate experts, in- ing the assent of the children and permission
cluding experts in penology, medicine, (a) Children are persons who have not at-
tained the legal age for consent to treat- of their parents or guardians, as set forth in
and ethics, and published notice, in the § 46.408.
FEDERAL REGISTER, of the intent to ments or procedures involved in the re-
approve such research. search, under the applicable law of the juris-
diction in which the research will be con-
(b) Except as provided in paragraph (a) of ducted.
this section, biomedical or behavioral re-
search conducted or supported by DHHS (b) Assent means a child's affirmative agree-
shall not involve prisoners as subjects. ment to participate in research. Mere failure
45 CFR 46 - page 12
§ 46.406 Research involving greater than opportunity to further the understand- reasonably available, or when only one par-
minimal risk and no prospect of di- ing, prevention, or alleviation of a seri- ent has legal responsibility for the care and
rect benefit to individual subjects, ous problem affecting the health or custody of the child.
but likely to yield generalizable welfare of children;
(c) In addition to the provisions for waiver
knowledge about the subject's disor- (ii) The research will be conducted in contained in § 46.116 of Subpart A, if the
der or condition. accordance with sound ethical princi- IRB determines that a research protocol is
HHS will conduct or fund research in which ples; designed for conditions or for a subject
the IRB finds that more than minimal risk to (iii) Adequate provisions are made for population for which parental or guardian
children is presented by an intervention or permission is not a reasonable requirement
soliciting the assent of children and the
procedure that does not hold out the pros- to protect the subjects (for example, ne-
permission of their parents or guardi-
pect of direct benefit for the individual sub- glected or abused children), it may waive the
ans, as set forth in § 46.408.
ject, or by a monitoring procedure which is consent requirements in Subpart A of this
not likely to contribute to the well-being of § 46.408 Requirements for permission by part and paragraph (b) of this section, pro-
the subject, only if the IRB finds that: parents or guardians and for assent vided an appropriate mechanism for pro-
by children. tecting the children who will participate as
(a) The risk represents a minor increase over
(a) In addition to the determinations re- subjects in the research is substituted, and
quired under other applicable sections of provided further that the waiver is not in-
(b) The intervention or procedure presents this subpart, the IRB shall determine that consistent with Federal, state, or local law.
experiences to subjects that are reasonably
adequate provisions are made for soliciting The choice of an appropriate mechanism
commensurate with those inherent in their
the assent of the children, when in the judg- would depend upon the nature and purpose
actual or expected medical, dental, psycho-
ment of the IRB the children are capable of of the activities described in the protocol,
logical, social, or educational situations; providing assent. In determining whether the risk and anticipated benefit to the re-
(c) The intervention or procedure is likely to children are capable of assenting, the IRB search subjects, and their age, maturity,
yield generalizable knowledge about the shall take into account the ages, maturity, status, and condition.
subjects’ disorder or condition which is of and psychological state of the children in- (d) Permission by parents or guardians shall
vital importance for the understanding or volved. This judgment may be made for all be documented in accordance with and to
amelioration of the subjects' disorder or children to be involved in research under a the extent required by § 46.117 of Subpart
condition; and particular protocol, or for each child, as the A.
(d) Adequate provisions are made for solicit- IRB deems appropriate. If the IRB deter- (e) When the IRB determines that assent is
mines that the capability of some or all of
ing assent of the children and permission of required, it shall also determine whether and
the children is so limited that they cannot
their parents or guardians, as set forth in how assent must be documented.
reasonably be consulted or that the interven-
tion or procedure involved in the research § 46.409 Wards.
§ 46.407 Research not otherwise approv- holds out a prospect of direct benefit that is
(a) Children who are wards of the state or
able which presents an opportunity important to the health or well-being of the
to understand, prevent, or alleviate a children and is available only in the context any other agency, institution, or entity can
serious problem affecting the health of the research, the assent of the children is be included in research approved under
or welfare of children. § 46.406 or § 46.407 only if such research is:
not a necessary condition for proceeding
HHS will conduct or fund research that the with the research. Even where the IRB de- (1) Related to their status as wards; or
IRB does not believe meets the require- termines that the subjects are capable of (2) Conducted in schools, camps, hospi-
ments of § 46.404, § 46.405, or § 46.406 only assenting, the IRB may still waive the assent tals, institutions, or similar settings in
if: requirement under circumstances in which which the majority of children involved as
consent may be waived in accord with subjects are not wards.
(a) The IRB finds that the research presents § 46.116 of Subpart A.
a reasonable opportunity to further the un- (b) If the research is approved under para-
derstanding, prevention, or alleviation of a (b) In addition to the determinations re- graph (a) of this section, the IRB shall re-
serious problem affecting the health or wel- quired under other applicable sections of quire appointment of an advocate for each
fare of children; and this subpart, the IRB shall determine, in child who is a ward, in addition to any other
accordance with and to the extent that con- individual acting on behalf of the child as
(b) The Secretary, after consultation with a sent is required by § 46.116 of Subpart A,
panel of experts in pertinent disciplines (for that adequate provisions are made for solic- guardian or in loco parentis. One individual
may serve as advocate for more than one
example: science, medicine, education, eth- iting the permission of each child's parents
child. The advocate shall be an individual
ics, law) and following opportunity for pub- or guardian. Where parental permission is to
lic review and comment, has determined who has the background and experience to
be obtained, the IRB may find that the per- act in, and agrees to act in, the best interests
either: mission of one parent is sufficient for re- of the child for the duration of the child's
(1) That the research in fact satisfies the search to be conducted under § 46.404 or participation in the research and who is not
conditions of § 46.404, § 46.405, or § 46.405. Where research is covered by associated in any way (except in the role as
§ 46.406, as applicable, or §§ 46.406 and 46.407 and permission is to be advocate or member of the IRB) with the
obtained from parents, both parents must research, the investigator(s), or the guardian
(2) The following: give their permission unless one parent is organization.
(i) The research presents a reasonable deceased, unknown, incompetent, or not