[Federal Register Volume 70, Number 57 (Friday, March 25, 2005)]
[Notices]
[Pages 15322-15327]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5947]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


Protection of Human Subjects, Proposed Criteria for 
Determinations of Equivalent Protection

AGENCY: Department of Health and Human Services, Office of the 
Secretary.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Office of Public Health and Science, Department of Health 
and Human Services (HHS) solicits public comment on criteria that have 
been recommended to the Office for Human Research Protections (OHRP) 
for making determinations of whether procedures prescribed by 
institutions outside the United States afford protections that are at 
least equivalent to those provided in the Federal Policy for the 
Protection of Human Subjects (codified by HHS as 45 CFR part 46, 
subpart A, and equivalent regulations of 14 Departments and Agencies, 
collectively referred to as the Federal Policy or the Common Rule).

DATES: Submit written or electronic comments on the recommended 
criteria for making determinations of equivalent protection on or 
before May 24, 2005.

ADDRESSES: Submit written comments to Ms. Gail Carter, Division of 
Policy and Assurances, Office for Human Research Protections, 1101 
Wootton Parkway, Suite 200, The Tower Building, Rockville, MD 20852, 
telephone number (301) 402-4521 (not a toll-free number). Comments also 
may be sent via facsimile to (301) 402-0527 or by e-mail to: 
[email protected].

FOR FURTHER INFORMATION CONTACT: Glen Drew, Office for Human Research 
Protections, Office of Public Health and Science, The Tower Building, 
1101 Wootton Parkway, Suite 200, Rockville, MD 20852, (301) 402-4994, 
facsimile (301) 402-2071; e-mail: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    The HHS codification of the Federal Policy states at 45 CFR 
46.101(h):

    (h) When research covered by this policy takes place in foreign 
countries, procedures normally followed in the foreign countries to 
protect human subjects may differ from those set forth in this 
policy. [An example is a foreign institution which complies with 
guidelines consistent with the World Medical Assembly Declaration 
(Declaration of Helsinki amended 1989) issued either by sovereign 
states or by an organization whose function for the protection of 
human research subjects is internationally recognized.] In these 
circumstances, if a Department or Agency head determines that the 
procedures prescribed by the institution afford protections that are 
at least equivalent to those provided in this policy, the Department 
or Agency head may approve the substitution of the foreign 
procedures in lieu of the procedural requirements provided in this 
policy. Except when otherwise required by statute, Executive Order, 
or the Department or Agency head, notices of these actions as they 
occur will be published in the Federal Register or will be otherwise 
published as provided in Department or Agency procedures.

    No formal findings of equivalent protection have been published in 
the Federal Register since the Federal policy was finalized in June, 
1991. Use of the authority provided by 45 CFR 46.101(h) has been 
advocated by various parties, including the National Bioethics Advisory 
Commission in its April, 2001 report ``Ethical and Policy Issues in 
International Research: Clinical Trials in Developing Countries,'' and 
the HHS Inspector General in the September, 2001 Report ``The 
Globalization of Clinical Trials: A Growing Challenge in Protecting 
Human Subjects.'' The authority of the Secretary of Health and Human 
Services has been delegated to OHRP (68 FR 60392), and in considering 
use of the 45 CFR 46.101(h) authority, OHRP recognized a need for using 
consistent criteria as a basis for decisions regarding equivalent 
protections. During 2002, the OHRP Director established a working group 
of representatives from interested HHS agencies, with staff support 
from OHRP, to consider potential criteria for use in making such 
decisions. The working group delivered its report in July 2003. That 
report recommends a framework

[[Page 15323]]

for implementing the existing regulatory authority of 45 CFR 46.101(h). 
The full working group report recommends the approach and criteria 
described in this notice and is available at http://www.hhs.gov/ohrp/international/EPWGReport2003.pdf and the appendix table is available at 
http://www.hhs.gov/ohrp/international/FPGWFramework.pdf, or by request 
to either of the addresses given above.

II. Request for Comments

    OHRP has solicited and considered comments from the other agencies 
that have adopted the Federal Policy, and now solicits public comment 
on the working group's recommended criteria for making determinations 
whether procedures prescribed by institutions outside the United States 
provide protections that are at least equivalent to those provided by 
the Federal Policy. OHRP will consider all public comments in deciding 
whether, and if so how, to proceed with implementing the authority 
under 45 CFR 46.101(h). Draft guidance describing OHRP's proposed 
method of implementing this authority would be published for public 
comment before OHRP would issue final guidance on this topic.
    OHRP neither endorses nor rejects the content, conclusions, or 
recommendations in the working group's report, but particularly 
solicits public comment on several questions related to the approach 
and criteria recommended in the report:
    1. Is the recommended approach appropriate for implementing the 
authority under 45 CFR 46.101(h)?
    1.a. Is it preferable to make determinations of equivalent 
protections on the basis of submissions by individual institutions or 
on the basis of national or international procedural standards that may 
be relied upon by multiple institutions without repeated assessments?
    2. Could an alternative approach provide equal or greater 
effectiveness and efficiency for implementation of this authority?
    2.a. If so, what approach and why would effectiveness or efficiency 
be improved?
    3. Do the recommended criteria appropriately and adequately 
describe the protections provided to human subjects by the Federal 
Policy?
    3.a. Do the regulatory provisions the working group cited as 
contributing to particular protections provided by the Federal Policy 
relate directly to those protections? (See Table 1.)
    3.b. Should other regulatory provisions be cited as relating to 
particular protections?
    3.c. What, if any, alterations or additions to the proposed 
criteria would be helpful in assessing whether procedures followed in 
foreign countries provide protections at least equivalent to those 
provided by the Federal Policy?
    4. Is the procedure recommended by the working group for seeking a 
finding of equivalent protections under 45 CFR 46.101(h) appropriate?

III. Framework Proposed in Working Group Report

    The working group report concluded that

    The primary focus of the U.S. policy is the accountability of 
the research institution for the welfare and rights of human 
subjects. The overarching goal of the specific accountability 
mechanisms and procedures described in the policy is to establish 
expectations of ethical conduct within the research institution. The 
responsibility for achieving these aims is shared by the 
institution, the Institutional Review Board (IRB), or Research 
Ethics Committee (REC), and the relevant U.S. Agency or Department 
head. Although investigators are critical actors in achieving these 
goals, the policy provides very little explicit guidance to 
investigators and therefore suggests that the protection of human 
subjects depends largely on the proper promotion and conscientious 
execution of standard practices and procedures, including those 
related to research ethics review, within the institution.

    The working group proposed an approach to equivalent protections 
that involves five separate steps, the first of which is to identify 
the specific protections provided by 45 CFR part 46 subpart A, followed 
by three steps of determining the equivalence of the protections 
offered by the set of procedures employed in foreign research 
institutions, and the fifth step is to provide an assurance that these 
procedures will be followed within the institution.
    Steps in determining equivalence.
    (1) Articulation of the specific protections embodied in 45 CFR 
part 46 subpart A.
    (2) Assessment of the protections provided by the institution's 
procedures.
    (3) Comparison of the protections provided by the institution's 
procedures with those provided by 45 CFR part 46 subpart A and 
determination whether or not the institution's procedures provide at 
least equivalent protections.
    (4) Approval of the relevant department or agency head for the 
substitution of the institutional procedures in lieu of the procedures 
of 45 CFR part 46 subpart A.
    Mechanism of assurance with OHRP.
    (5) Assurance from the institution that the substituted procedures 
will be followed in the conduct of human subjects research funded by 
HHS. The assurance will be completed and filed with OHRP.
    The working group identified 7 specific protections afforded by 45 
CFR part 46 subpart A that it recommended be included in the 
determination of equivalence:
    Establish norms of ethical conduct and due diligence in review and 
performance of research within the institution;
    Ensure adequate authority and independence of the IRB/Research 
Ethics Committee;
    Protect against biased decision making and arbitrary decisions in 
research ethics review;
    Ensure sufficient quality and comprehensiveness of research ethics 
review;
    Ensure research ethics review and oversight are commensurate with 
risks to research subjects and vulnerability of the study population;
    Protect against unnecessary or unjustified risk throughout the 
course of the study; and
    Ensure voluntary participation after adequate disclosure of 
information related to the study.
    The working group concluded that each of these protections is 
necessary for a determination of equivalent protections. It also 
concluded that each protection may be achieved in a number of different 
ways, including the use of procedures that differ from those provided 
in 45 CFR part 46 subpart A. In making determinations of equivalence, 
the working group recommended that OHRP assess whether the procedures 
employed by the foreign institution are able to satisfy each of these 
protections individually and in the aggregate.
    The working group also recommended that, based on a recommendation 
from OHRP following a comparison of the protections provided by the 
institution's procedures and 45 CFR part 46 subpart A, the Secretary of 
HHS may find that the institution's procedures provide at least 
equivalent protections and approve the substitution of these procedures 
in lieu of those of 45 CFR part 46 subpart A. The working group 
concluded that a determination of equivalent protections does not 
affect OHRP's oversight authority for HHS funded research conducted 
within the institution. The working group considered the authority of 
OHRP to conduct on-going assessment of the equivalence of the 
institution's procedures and protections to be a protection implied in 
45 CFR part 46 subpart A, though not part of the

[[Page 15324]]

assessment of the protections provided by an institution's procedures.
    Similarly, the substitution of the institution's procedures in lieu 
of those of 45 CFR part 46 subpart A does not obviate the need for the 
institution to enter into an assurance with OHRP that the procedures 
will be followed by the institution in the conduct of HHS funded 
research. An assurance is a legal promise to comply with certain 
conditions attached to the provision of U.S. federal research funding.
    To show the relationship between the Federal Policy and each of the 
seven protections the working group discerned in the Federal Policy, it 
developed a table matching the protections with provisions of 45 CFR 
part 46 subpart A that contribute to each of the protections. The 
center column of the table provides examples of procedures that the 
working group thought institutions might use to provide the protection 
related to those regulatory provisions. The table appears below.

Appendix

             Table 1.--Framework for Equivalent Protections
------------------------------------------------------------------------
                                     Example           45 CFR part 46
      Specific protection           procedures      subpart A authority
------------------------------------------------------------------------
                     INSTITUTIONAL RESPONSIBILITIES
------------------------------------------------------------------------
Establish norms of ethical      --Institutional    46.103(a); 46.103 (f)
 conduct and due diligence in    statement of       Establish and
 review and performance of       principles.        satisfy terms of
 research within the            --Procedures for    assurance.
 institution.                    review.           46.103(b)(1) Develop
                                --Procedures for    or adopt statement
                                 reporting to       of principles
                                 Research Ethics    governing
                                 Committee (REC).   institution's human
                                --Procedures for    subjects protections
                                 REC record         responsibilities.
                                 keeping.          46.103(b)(4) Ensure
                                                    initial and
                                                    continuing review of
                                                    research; determine
                                                    necessary frequency
                                                    of review for each
                                                    study; determine
                                                    where external
                                                    verification is
                                                    necessary that no
                                                    material changes
                                                    have occurred since
                                                    last IRB review;
                                                    establish procedures
                                                    for IRB reporting of
                                                    findings and actions
                                                    to institution and
                                                    investigator(s).
                                --Statement of     46.103(b)(5)
                                 investigator       Establish and 46.108
                                 responsibilities.  (a) follow written
                                --Effective         procedures for
                                 dissemination of   prompt reporting to
                                 REC submission     IRB and
                                 procedures.        Institutional
                                --Investigator      officials of:
                                 training.         --Unanticipated
                                                    problems involving
                                                    risk to subjects or
                                                    others, or non-
                                                    compliance with the
                                                    policy;
                                                   --Suspension or
                                                    termination of IRB
                                                    approval.
                                                   46.103(b)(4) Ensuring
                                                    prompt reporting to
                                                    the IRB of proposed
                                                    changes in a
                                                    research activity,
                                                    and for ensuring
                                                    that such changes in
                                                    approved research,
                                                    during the period
                                                    for which IRB
                                                    approval has already
                                                    been given, may not
                                                    be initiated without
                                                    IRB review and
                                                    approval except when
                                                    necessary to
                                                    eliminate apparent
                                                    immediate hazards to
                                                    the subject.
                                                   46.103(b)(5) Written
                                                    procedures for
                                                    ensuring prompt
                                                    reporting to the
                                                    IRB, appropriate
                                                    institutional
                                                    officials, and the
                                                    Department or Agency
                                                    head of (i) any
                                                    unanticipated
                                                    problems involving
                                                    risks to subjects or
                                                    others or any
                                                    serious or
                                                    continuing
                                                    noncompliance with
                                                    this policy or the
                                                    requirements or
                                                    determinations of
                                                    the IRB; and (ii)
                                                    any suspension or
                                                    termination of IRB
                                                    approval.
                                                   46.115 An
                                                    institution, or when
                                                    appropriate an IRB,
                                                    shall prepare and
                                                    maintain adequate
                                                    documentation of IRB
                                                    activities. The
                                                    records required by
                                                    this policy shall be
                                                    retained for at
                                                    least 3 years, and
                                                    records relating to
                                                    research which is
                                                    conducted shall be
                                                    retained for at
                                                    least 3 years after
                                                    completion of the
                                                    research. All
                                                    records shall be
                                                    accessible for
                                                    inspection and
                                                    copying by
                                                    authorized
                                                    representatives of
                                                    the Department or
                                                    Agency at reasonable
                                                    times and in a
                                                    reasonable manner.
-------------------------------
Ensure adequate authority, and  --Documentation    46.109(a); 46.109 (e)
 independence of IRB.            of REC authority.  grant and ensure
                                                    necessary authority
                                                    for IRB, including:
                                                    discretion to
                                                    review, approve,
                                                    require
                                                    modifications, or
                                                    disapprove research
                                                    activities; increase
                                                    information for
                                                    informed consent,
                                                    observe, or have
                                                    third party observe
                                                    consent process and
                                                    research.
                                                   46.112 Research
                                                    covered by this
                                                    policy that has been
                                                    approved by an IRB
                                                    may be subject to
                                                    further appropriate
                                                    review and approval
                                                    or disapproval by
                                                    officials of the
                                                    institution.
                                                    However, those
                                                    officials may not
                                                    approve the research
                                                    if it has not been
                                                    approved by an IRB.
                                                   46.113 An IRB shall
                                                    have authority to
                                                    suspend or terminate
                                                    approval of research
                                                    that is not being
                                                    conducted in
                                                    accordance with the
                                                    IRB's requirements
                                                    or that has been
                                                    associated with
                                                    unexpected serious
                                                    harm to subjects.
                                                   46.110(b) Under an
                                                    expedited review
                                                    procedure, the
                                                    review may be
                                                    carried out by the
                                                    IRB chairperson or
                                                    by one or more
                                                    experienced
                                                    reviewers designated
                                                    by the chairperson
                                                    from among members
                                                    of the IRB. In
                                                    reviewing the
                                                    research, the
                                                    reviewers may
                                                    exercise all of the
                                                    authorities of the
                                                    IRB except that the
                                                    reviewers may not
                                                    disapprove the
                                                    research. A research
                                                    activity may be
                                                    disapproved only
                                                    after review in
                                                    accordance with the
                                                    non-expedited
                                                    procedure set forth
                                                    in Sec.   46.108(b).

[[Page 15325]]

 
                                --REC member(s)    46.107(d) Each IRB
                                 unaffiliated       shall include at
                                 with the           least one member who
                                 institution.       is not otherwise
                                                    affiliated with the
                                                    institution and who
                                                    is not part of the
                                                    immediate family of
                                                    a person who is
                                                    affiliated with the
                                                    institution.
-------------------------------
            Research Ethics Committee (REC) Responsibilities
 
                Appropriate Scope and Quality of Review:
------------------------------------------------------------------------
Protect against biased          --Public           46.103(b)3 A list of
 decision making and arbitrary   accessibility of   IRB members
 decisions in research ethics    REC membership     identified by name;
 review.                         and affiliation    earned degrees;
                                 within             representative
                                 institution.       capacity;
                                                    indications of
                                                    experience such as
                                                    board
                                                    certifications,
                                                    licenses, etc.,
                                                    sufficient to
                                                    describe each
                                                    member's chief
                                                    anticipated
                                                    contributions to IRB
                                                    deliberations.
                                                    Disclosure of any
                                                    employment or other
                                                    relationship between
                                                    each [IRB] member
                                                    and the institution.
                                                   46.107(a) IRB
                                                    membership. (see 45
                                                    CFR 46 for specific
                                                    criteria).
                                                   46.107(b) Gender
                                                    balance.
                                --Institutional    46.107(c) Each IRB
                                 policy on REC      shall include at
                                 conflict of        least one member
                                 interest.          whose primary
                                                    concerns are in
                                                    scientific areas and
                                                    at least one member
                                                    whose primary
                                                    concerns are in
                                                    nonscientific areas.
                                --REC membership   46.107(d) Each IRB
                                 to reflect:        shall include at
                                 independence,      least one member who
                                 unaffiliated       is not otherwise
                                 member(s).         affiliated with the
                                                    institution and who
                                                    is not part of the
                                                    immediate family of
                                                    a person who is
                                                    affiliated with the
                                                    institution.
                                                   46.107(e) No IRB may
                                                    have a member
                                                    participate in the
                                                    IRB's initial or
                                                    continuing review of
                                                    any project in which
                                                    the member has a
                                                    conflicting
                                                    interest, except to
                                                    provide information
                                                    requested by the
                                                    IRB.
-------------------------------
Ensure sufficient quality and   --REC membership   46.107(b) Gender
 comprehensiveness of review.    to reflect         balance.
                                 competence,       46.107(c) Each IRB
                                 comprehensivenes   shall include at
                                 s of review;       least one member
                                 adequate           whose primary
                                 expertise for      concerns are in
                                 study              scientific areas and
                                 population;        at least one member
                                 diversity of       whose primary
                                 representation;    concerns are in
                                 gender balance.    nonscientific areas.
                                                   46.107(d) Each IRB
                                                    shall include at
                                                    least one member who
                                                    is not otherwise
                                                    affiliated with the
                                                    institution and who
                                                    is not part of the
                                                    immediate family of
                                                    a person who is
                                                    affiliated with the
                                                    institution.
                                                   46.107(f) An IRB may,
                                                    in its discretion,
                                                    invite individuals
                                                    with competence in
                                                    special areas to
                                                    assist in the review
                                                    of issues which
                                                    require expertise
                                                    beyond or in
                                                    addition to that
                                                    available on the
                                                    IRB. These
                                                    individuals may not
                                                    vote with the IRB.
                                                   46.108(b) Except when
                                                    an expedited review
                                                    procedure is used
                                                    (see Sec.   46.110),
                                                    review proposed
                                                    research at convened
                                                    meetings at which a
                                                    majority of the
                                                    members of the IRB
                                                    are present,
                                                    including at least
                                                    one member whose
                                                    primary concerns are
                                                    in nonscientific
                                                    areas. In order for
                                                    the research to be
                                                    approved, it shall
                                                    receive the approval
                                                    of a majority of
                                                    those members
                                                    present at the
                                                    meeting.
Ensure research ethics review   --Procedures for   46.109(e) An IRB
 and oversight are               continuing         shall conduct
 commensurate with risks to      review and         continuing review of
 research subjects and           monitoring         research covered by
 vulnerability of the study      commensurate       this policy at
 population.                     with risk.         intervals
                                --Procedures for    appropriate to the
                                 evaluating risk    degree of risk, but
                                 and benefit.       not less than once
                                Procedures for      per year, and shall
                                 reviewing          have authority to
                                 selection of       observe or have a
                                 subjects and       third party observe
                                 safeguards         the consent process
                                 provided.          and the research.
                                --Procedures for   46.110(b) Expedited
                                 IRB reporting to   Review.
                                 investigators.    46.111(a)(2) In
                                                    evaluating risks and
                                                    benefits, the IRB
                                                    should consider only
                                                    those risks and
                                                    benefits that may
                                                    result from the
                                                    research (as
                                                    distinguished from
                                                    risks and benefits
                                                    of therapies
                                                    subjects would
                                                    receive even if not
                                                    participating in the
                                                    research). The IRB
                                                    should not consider
                                                    possible long-range
                                                    effects of applying
                                                    knowledge gained in
                                                    the research (for
                                                    example, the
                                                    possible effects of
                                                    the research on
                                                    public policy) as
                                                    among those research
                                                    risks that fall
                                                    within the purview
                                                    of its
                                                    responsibility.
                                                   46.111(a)(3)
                                                    Selection of
                                                    subjects as
                                                    equitable. In making
                                                    this assessment the
                                                    IRB should take into
                                                    account the purposes
                                                    of the research and
                                                    the setting in which
                                                    the research will be
                                                    conducted and should
                                                    be particularly
                                                    cognizant of the
                                                    special problems of
                                                    research involving
                                                    vulnerable
                                                    populations, such as
                                                    children, prisoners,
                                                    pregnant women,
                                                    mentally disabled
                                                    persons, or
                                                    economically or
                                                    educationally
                                                    disadvantaged
                                                    persons.
                                                   46.113 Any suspension
                                                    or termination or
                                                    approval shall
                                                    include a statement
                                                    of the reasons for
                                                    the IRB's action and
                                                    shall be reported
                                                    promptly to the
                                                    investigator,
                                                    appropriate
                                                    institutional
                                                    officials, and the
                                                    Department or Agency
                                                    head.
-------------------------------

[[Page 15326]]

 
Protect against unnecessary or  --REC membership   46.107(a) If an IRB
 unjustified risk throughout     policy reflects    regularly reviews
 the course of the study.        adequate           research that
                                 expertise and      involves a
                                 experience.        vulnerable category
                                                    of subjects, such as
                                                    children, prisoners,
                                                    pregnant women, or
                                                    handicapped or
                                                    mentally disabled
                                                    persons,
                                                    consideration shall
                                                    be given to the
                                                    inclusion of one or
                                                    more individuals who
                                                    are knowledgeable
                                                    about and
                                                    experienced in
                                                    working with these
                                                    subjects.
                                --Policy has       46.111(a)(1) Risks to
                                 provisions for     subjects are
                                 supplementing      minimized: (i) by
                                 expertise,         using procedures
                                 experience and     which are consistent
                                 disciplinary       with sound research
                                 perspective as     design and which do
                                 required.          not unnecessarily
                                                    expose subjects to
                                                    risks, and (ii)
                                                    whenever
                                                    appropriate, by
                                                    using procedures
                                                    already being
                                                    performed on the
                                                    subjects for
                                                    diagnostic or
                                                    treatment purposes.
                                                   46.111(a)(2) Risks to
                                                    subjects are
                                                    reasonable in
                                                    relation to
                                                    anticipated
                                                    benefits, if any, to
                                                    subjects, and the
                                                    importance of the
                                                    knowledge that may
                                                    reasonably be
                                                    expected to result.
                                --Procedures for   46.111(a)(3)
                                 review of          Selection of
                                 minimization of    subjects is
                                 risk.              equitable. In making
                                                    this assessment the
                                                    IRB should take into
                                                    account the purposes
                                                    of the research and
                                                    the setting in which
                                                    the research will be
                                                    conducted and should
                                                    be particularly
                                                    cognizant of the
                                                    special problems of
                                                    research involving
                                                    vulnerable
                                                    populations, such as
                                                    children, prisoners,
                                                    pregnant women,
                                                    mentally disabled
                                                    persons, or
                                                    economically or
                                                    educationally
                                                    disadvantaged
                                                    persons.
                                --Procedures for   46.111(b) When some
                                 reviewing          or all of the
                                 selection of       subjects are likely
                                 subjects and       to be vulnerable to
                                 safeguards         coercion or undue
                                 provided.          influence, such as
                                                    children, prisoners,
                                                    pregnant women,
                                                    mentally disabled
                                                    persons, or
                                                    economically or
                                                    educationally
                                                    disadvantaged
                                                    persons, additional
                                                    safeguards have been
                                                    included in the
                                                    study to protect the
                                                    rights and welfare
                                                    of these subjects.
                                                   46.111(a)(6) When
                                                    appropriate, the
                                                    research plan makes
                                                    adequate provision
                                                    for monitoring the
                                                    data collected to
                                                    ensure the safety of
                                                    subjects.
                                --Procedures for   46.109(e) An IRB
                                 continued          shall conduct
                                 oversight and      continuing review of
                                 monitoring.        research covered by
                                                    this policy at
                                                    intervals
                                                    appropriate to the
                                                    degree of risk, but
                                                    not less than once
                                                    per year, and shall
                                                    have authority to
                                                    observe or have a
                                                    third party observe
                                                    the consent process
                                                    and the research.
-------------------------------
Ensure voluntary participation  --Policies on      46.116 Except as
 after adequate disclosure of    obtaining          provided elsewhere
 information related to the      verifiable         in this policy, no
 study.                          informed consent.  investigator may
                                                    involve a human
                                                    being as a subject
                                                    in research covered
                                                    by this policy
                                                    unless the
                                                    investigator has
                                                    obtained the legally
                                                    effective informed
                                                    consent of the
                                                    subject or the
                                                    subject's legally
                                                    authorized
                                                    representative. An
                                                    investigator shall
                                                    seek such consent
                                                    only under
                                                    circumstances that
                                                    provide the
                                                    prospective subject
                                                    or the
                                                    representative
                                                    sufficient
                                                    opportunity to
                                                    consider whether or
                                                    not to participate
                                                    and that minimize
                                                    the possibility of
                                                    coercion or undue
                                                    influence.
                                                   46.111(a)(4) Informed
                                                    consent will be
                                                    sought from each
                                                    prospective subject
                                                    or the subject's
                                                    legally authorized
                                                    representative, in
                                                    accordance with, and
                                                    to the extent
                                                    required by Sec.
                                                    46.116.
                                                   46.111(a)(5) Informed
                                                    consent process will
                                                    be appropriately
                                                    documented, in
                                                    accordance with, and
                                                    to the extent
                                                    required by Sec.
                                                    46.117.
                                                   46.116 The
                                                    information that is
                                                    given to the subject
                                                    or the
                                                    representative shall
                                                    be in language
                                                    understandable to
                                                    the subject or the
                                                    representative.
                                                   46.117(a) Except as
                                                    provided in
                                                    paragraph (c) of
                                                    this section,
                                                    informed consent
                                                    shall be documented
                                                    by the use of a
                                                    written consent form
                                                    approved by the IRB
                                                    and signed by the
                                                    subject or the
                                                    subject's legally
                                                    authorized
                                                    representative.
                                --Policies on      46.109(b) An IRB
                                 types of           shall require that
                                 information to     information given to
                                 be disclosed in    subjects as part of
                                 the informed       informed consent is
                                 consent process.   in accordance with
                                                    Sec.   46.116. The
                                                    IRB may require that
                                                    information, in
                                                    addition to that
                                                    specifically
                                                    mentioned in Sec.
                                                    46.116, be given to
                                                    the subjects when in
                                                    the IRB's judgment
                                                    the information
                                                    would meaningfully
                                                    add to the
                                                    protection of the
                                                    rights and welfare
                                                    of subjects.
                                                   46.109(c) An IRB
                                                    shall require
                                                    documentation of
                                                    informed consent or
                                                    may waive
                                                    documentation in
                                                    accordance with Sec.
                                                      46.117.
                                                   46.109(e) An IRB
                                                    shall conduct
                                                    continuing review of
                                                    research covered by
                                                    this policy at
                                                    intervals
                                                    appropriate to the
                                                    degree of risk, but
                                                    not less than once
                                                    per year, and shall
                                                    have authority to
                                                    observe or have a
                                                    third party observe
                                                    the consent process
                                                    and the research.

[[Page 15327]]

 
                                                   46.111(a)(4) Informed
                                                    consent will be
                                                    sought from each
                                                    prospective subject
                                                    or the subject's
                                                    legally authorized
                                                    representative, in
                                                    accordance with, and
                                                    to the extent
                                                    required by Sec.
                                                    46.116.
                                                   46.116(a)(1-8)
                                                    Necessary elements
                                                    of disclosure.
                                                   46.116(b)(1-6)
                                                    Necessary elements
                                                    of disclosure.
                                                   46.116(c)(1-2) Waiver
                                                    of informed consent.
                                                   46.116(d)(1-4)
                                                    Approval of
                                                    alternate consent
                                                    procedures or
                                                    waiver.
                                                   46.117(a) Written
                                                    informed consent.
------------------------------------------------------------------------


Bernard A. Schwetz,
Director, Office for Human Research Protections.
[FR Doc. 05-5947 Filed 3-24-05; 8:45 am]
BILLING CODE 4150-36-P