Request for Information and Comments on Research That Involves Adult Individuals With Impaired Decision-making Capacity, 50966-50970 [E7-17490]
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Federal Register / Vol. 72, No. 171 / Wednesday, September 5, 2007 / Notices
a. Fiscal Year 2007 Results.
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Dated: August 31, 2007.
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[FR Doc. 07–4350 Filed 8–31–07; 11:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Request for Information and
Comments on Research That Involves
Adult Individuals With Impaired
Decision-making Capacity
Office for Human Research
Protections, Office of Public Health and
Science, Office of the Secretary, HHS.
ACTION: Notice.
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AGENCY:
SUMMARY: The Office for Human
Research Protections (OHRP), Office of
Public Health and Science is seeking
information and comments about
whether guidance or additional
regulations are needed to adequately
protect adult individuals with impaired
decision-making capacity who are
potential subjects in research. This
request for information and comments
stems from the recommendation of an
HHS working group, generated in
response to the report published by the
National Bioethics Advisory
Commission (NBAC) entitled ‘‘Research
Involving Persons With Mental
Disorders That May Affect Decisionmaking Capacity’’ (December 1998), and
from subsequent recommendations by
the National Human Research
Protections Advisory Committee
(NHRPAC).a
In addition, as part of its charge to
provide expert advice and
recommendations to the Secretary of
Health and Human Services (the
Secretary) and the Assistant Secretary
for Health on issues and topics
pertaining to or associated with the
protection of human subjects, the
Secretary’s Advisory Committee on
Human Research Protections (SACHRP)
has formed a Subcommittee on
Inclusion of Individuals with Impaired
a The National Human Research Protections
Advisory Committee has been disbanded and
replaced by the Secretary’s Advisory Committee on
Human Research Protections.
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Decision-Making in Research. This
SACHRP subcommittee is currently
considering whether guidance or
additional regulations are needed for
research involving individuals with
impaired decision-making capacity. The
information and comments submitted in
response to this notice will be shared
with SACHRP to inform the
Committee’s recommendations to the
Secretary and Assistant Secretary for
Health.
DATES: Submit written or electronic
information and comments by December
4, 2007.
ADDRESSES: Submit written comments
to REQUEST FOR INFORMATION ON
RESEARCH THAT INVOLVES ADULT
INDIVIDUALS WITH IMPAIRED
DECISION-MAKING CAPACITY, Office
for Human Research Protections, The
Tower Building, 1101 Wootton
Parkway, Suite 200, Rockville, MD
20852. Comments also may be sent via
e-mail to
impairedcapacityohrp@hhs.gov, or via
facsimile at 301–402–2071. Comments
received within the comment period,
including any personal information
provided, will be made available to the
public upon request.
FOR FURTHER INFORMATION CONTACT: Julie
Kaneshiro, Office for Human Research
Protections, Department of Health and
Human Services, The Tower Building,
1101 Wootton Parkway, Suite 200,
Rockville, MD 20852; 240–453–6900;
e-mail julie.kaneshiro@hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The Department of Health and Human
Services (HHS) regulates research
involving human subjects conducted or
supported by HHS through regulations
codified at 45 CFR part 46 which are
administered by OHRP. The HHS
regulations stipulate that in order to
approve research covered by the
regulations, an institutional review
board (IRB) shall determine that when
some or all of the subjects are likely to
be vulnerable to coercion or undue
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. 45
CFR 46.111(b). Apart from this broad
requirement regarding vulnerable
populations, the HHS regulations do not
contain specific additional standards for
the participation of adults with
impaired decision-making capacity in
research, nor do they define who should
be considered as part of this population.
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In response to the recommendations by
the National Commission for the
Protection of Human Subjects of
Biomedical and Behavioral Research
(National Commission) that pertained to
research involving individuals who are
institutionalized as mentally infirm, in
1978, the Department of Health,
Education, and Welfare (now HHS),
issued proposed regulations on research
involving those institutionalized as
mentally disabled. However, these
proposed regulations were never
finalized or adopted due to a lack of
consensus on the proposed regulatory
provisions, and a judgment that the
general HHS regulations governing
human subjects’ participation in
research were sufficient to address the
National Commission’s
recommendations.
The impetus for this request for
information and comments stems from a
number of different sources. HHS is
aware that some research currently
conducted or supported by HHS
involves adults with impaired decisionmaking capacity. HHS believes that
research involving adults with impaired
decision-making capacity is important
and necessary in order to improve the
health and well-being of such
individuals. HHS and others have long
recognized the potential vulnerability of
these subjects, and that research
involving this population needs to be
conducted with adequate safeguards. At
this time HHS believes it is appropriate
to solicit the views of the public on
whether the current human subject
protection regulations are adequate in
safeguarding these individuals. This
request for information and comments
also stems from recommendations of an
HHS working group (HHS WG),
generated in response to the report
published by the former NBAC entitled
‘‘Research Involving Persons with
Mental Disorders That May Affect
Decision-making Capacity’’ (December
1998), and from subsequent
recommendations by the former
NHRPAC.
A. NBAC Report
In its December 1998 report, the full
text of which can be found on the
Internet at https://
bioethics.georgetown.edu/nbac, NBAC
defined decisional impairment as a
limitation or incapacity that is not part
of normal growth and development.
NBAC’s report contained
recommendations for helping to ensure
adequate protections for people with
decisional impairment who participate
in research, but referred only to research
involving persons with mental disorders
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that may affect decision-making
capacity.
NBAC’s recommendations called for a
new regulatory framework requiring
IRBs to classify into one of three
categories all proposed research that
involves people with impaired decisionmaking capacity due to mental
disorders, based on the level of risk and
potential for direct medical benefit to
the research subject. NBAC identified
three categories of research that pose: (1)
Minimal risk to subjects; (2) greater than
minimal risk to subjects and having the
prospect of direct medical benefit; and
(3) greater than minimal risk to subjects
but having no prospect of direct medical
benefit. NBAC recommended that the
legally authorized representative of a
subject with impaired decision-making
capacity be able to give permission for
the subject’s participation in research
protocols that fall into either of the first
two categories. However, NBAC
recommended that research in the third
category could not proceed unless one
of two conditions occurred: Either (1)
the research subject would have had to
give Prospective Authorization for the
particular class of research when
competent, or (2) a Special Standing
Panel (SSP), convened by the Secretary
of HHS, would need to review the
research and find it approvable or have
issued guidelines about the class of
research indicating that it was
approvable. In NBAC’s
recommendations, Prospective
Authorization would provide
individuals, when competent, with an
opportunity to express their preferences
(if they have them) regarding future
research participation, within certain
limits. NBAC recommended that a
Prospective Authorization should
specify the ‘‘particular class of
research,’’ and the degree of specificity
in the Prospective Authorization should
be correlated with the level of risk
posed by the research. For example, a
person with a diagnosis of early stage
Alzheimer’s Disease who is still
competent to make decisions could
express his or her preference to
participate in greater than minimal risk
clinical trials testing interventions for
moderate or severe Alzheimer’s Disease
in the future, when he or she may not
be competent to make decisions.
B. HHS Working Group
The Office of Science Policy, Office of
the Assistant Secretary for Planning and
Evaluation, convened an HHS WG to
analyze NBAC’s recommendations and
to develop a proposed HHS response to
the NBAC report. The HHS WG’s report
can be found on the Internet at https://
aspe.hhs.gov/sp/human.shtml. The HHS
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WG considered, among other things,
NBAC’s recommended framework
described above. The HHS WG was
concerned that this framework was not
practical because it would lead to the
use of either a Prospective
Authorization or a SSP for a large
number of research protocols involving
subjects with impaired decision-making
capacity. The HHS WG concluded that
the widespread use of Prospective
Authorizations is unlikely. Thus, unless
the research involved the prospect of
direct medical benefit to the
participants, an SSP would need to
review all research involving greater
than minimal risk.
The HHS WG compared NBAC’s
proposed regulatory framework to the
HHS regulations governing the
participation of children in research (45
CFR part 46 subpart D [hereafter
referred to as ‘‘subpart D regulations’’]).
The subpart D regulations allow an IRB
to consider a broad range of different
types of direct benefits to the subject,
not just direct medical benefits, when
weighing the risks posed by research
involving greater than minimal risk that
presents the prospect of direct benefit to
the individual child. NBAC, on the
other hand, recommended that benefits
be limited to direct medical benefits
only for research involving subjects
with impaired decision-making
capacity. The subpart D regulations also
create an intermediate risk category, not
included in NBAC’s framework, called a
‘‘minor increase over minimal risk.’’
The HHS WG noted that an alternative
regulatory framework modeled on
subpart D could provide appropriate
protection and also decrease the number
of studies needing SSP review and thus
may increase the feasibility of such
reviews.
The HHS WG decided that NBAC’s
recommended framework would limit
an IRB’s authority to approve research
involving an adult with impaired
decision-making capacity more than it
would an IRB’s authority to approve a
child’s participation in the same type of
research. The HHS WG further noted
that NBAC’s framework would alter IRB
authority in ways that could produce
different results. For example, the
subpart D regulations permit a child’s
parent or guardian to enroll the child in
research that has no prospect of direct
benefit and that poses a minor increase
over minimal risk if an IRB determines
the research, among other things, is
‘‘likely to yield generalizable knowledge
* * * of vital importance’’ about the
child’s disorder or condition (45 CFR
46.406). However, under NBAC’s
recommendations, the legally
authorized representative of an adult
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with impaired decision-making capacity
could not enroll the adult in the same
type of research, unless the adult had
signed a Prospective Authorization or
the SSP approved or issued guidelines
about the research. The HHS WG
recognized that safeguards for children
and adults with impaired decisionmaking capacity need not necessarily be
identical, but noted that two different
standards might be confusing to
investigators and IRBs.
In addition, in its 1998 report, NBAC
considered how ethically acceptable
research could be conducted with
human subjects who suffer from mental
disorders that may affect their decisionmaking capacity. The HHS WG
interpreted the intended scope of
NBAC’s recommendations as applying
to research involving ‘‘persons with
mental disorders that may affect
decision making capacity,’’ but
determined that the scope of NBAC’s
recommendations seem appropriately
applicable to research involving adults
with decisional impairment,
irrespective of the cause. The HHS WG
noted that some physical disorders or
conditions (e.g., cancer, sepsis, head
injury) also might result in impaired
capacity to make decisions, and
therefore, an inability to give voluntary
informed consent to participate in
research. In addition, the HHS WG was
concerned that limiting the scope of
protections to research subjects whose
decision-making capacity is impaired
because of a mental disorder may be
perceived to be stigmatizing to such
individuals. Thus, the HHS WG
concluded that adults with an impaired
capacity to make a decision as a result
of any disease or condition should
receive the same protections as those
individuals with an impaired decisionmaking capacity from a mental disorder.
The HHS WG proposed that OHRP
request public comment on the issues
raised by the NBAC framework and the
HHS WG’s analysis of those issues. This
request for information and comments is
designed to accomplish that goal.
C. NHRPAC Report
In response to NBAC’s
recommendations and the HHS WG’s
report, at OHRP’s request, NHRPAC
drafted a report entitled ‘‘Informed
Consent and the Decisionally
Impaired.’’ NHRPAC was an advisory
committee to the Secretary of HHS, the
Assistant Secretary for Health, the
Director of OHRP, and other
Departmental officials on a broad range
of issues and topics pertaining to or
associated with the protection of human
research subjects. NHRPAC’s draft
report is available on the Internet at
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https://www.hhs.gov/ohrp/nhrpac/
documents/nhrpac10.pdf. NHRPAC’s
report applies to ‘‘all potential subjects
in biomedical and social/behavioral
research who lack decisional capacity
for any reason and is not limited to
persons with mental disorders.’’ In its
report, NHRPAC recommended specific
protections at different levels of risk and
potential benefit for research with the
decisionally impaired population. These
risk-benefit categories included:
(1) Research that involves no more
than minimal risk,
(2) Research that involves greater than
minimal risk but presents the prospect
of direct benefit to the subjects,
(3) Research that involves a minor
increase over minimal risk that does not
present the prospect of direct benefit but
is likely to yield generalizable
knowledge about the subject’s condition
or disorder, and
(4) Research not otherwise approvable
which presents an opportunity to
understand, prevent, or alleviate a
serious problem affecting the health or
welfare of persons with impaired
decision-making capacity, provided the
Secretary of HHS makes specified
determinations after consulting with a
panel of experts and providing the
opportunity for public review and
comment.
These risk categories are similar to
those contained in the subpart D
regulations governing research with
children.
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D. SACHRP Activities
In October 2002, SACHRP was created
by the Secretary to replace NHRPAC.
SACHRP is charged to advise, consult
with, and make recommendations to the
Secretary and Assistant Secretary for
Health on matters pertaining to the
continuance and improvement of
functions within the authority of HHS
directed toward protections for human
subjects in research. In carrying out its
charge, SACHRP formed a
Subcommittee on Inclusion of
Individuals with Impaired DecisionMaking Capacity in Research.
Specifically, this SACHRP
subcommittee will develop
recommendations for consideration by
SACHRP about whether guidance or
additional regulations are needed for
research involving individuals with
impaired decision-making capacity. In
making its assessment, the
Subcommittee will review the relevant
provisions of subpart A, 45 CFR part 46,
including the provisions at 45 CFR
46.111(b), and will seek additional
information to formulate its decision as
it deems necessary.
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The information and comments
submitted in response to this notice will
be shared with SACHRP to inform the
Committee’s recommendations to the
Secretary and Assistant Secretary for
Health.
The reports of the National
Commission, NBAC, and NHRPAC
specifically address and endorse the
inclusion of decisionally incapacitated
subjects in clinical research with the
provision of adequate protections for
these subjects. Based on these
recommendations and reports over the
years, and SACHRP’s current work on
this issue, OHRP is seeking comment on
whether it is necessary to develop
additional safeguards to protect adult
individuals with impaired decisionmaking capacity because these
individuals may have diminished or no
capacity to provide informed consent to
their participation in research. The next
section contains the specific questions
of interest to HHS.
II. Request for Information and
Comments
OHRP is seeking information and
comments from the public about
whether guidance or additional
regulations are needed to adequately
protect adult individuals with impaired
decision-making capacity who are
potential subjects in research. The scope
of this request for information and
comments is limited to research
involving adult subjects because
additional protections for children
involved as subjects in research already
exists under the subpart D regulations.
In addition, this notice is not directed
toward consideration of emergency
research involving the decisionally
impaired that would be covered under
the HHS’s Secretarial waiver under 45
CFR 46.101(i) on the exception from
informed consent requirements for
emergency research (published in the
Federal Register in 1996 at 61 FR
51531). OHRP believes that this existing
provision already addresses the conduct
of emergency research without informed
consent that involves individuals with
impaired decision-making capacity.
OHRP specifically seeks information
and comments on the following issues.
Comments should also include a
reference to the specific numbered
question being addressed:
1. What are investigators’ and IRBs’
current practices in regard to the
conduct, review, and approval of
research involving decisionally
impaired adult individuals?
1a. Have investigators’ or IRBs’
practices changed as a result of NBAC’s
or NHRPAC’s recommendations? If not,
why not?
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1b. If an IRB regularly reviews
research proposals involving adult
individuals with impaired decisionmaking capacity, do such IRBs include
one or more members or consultants
who are familiar with conditions that
may affect decision-making capacity
and with the concerns of the population
being studied?
1c. Are investigators proposing
research targeting adult individuals
with impaired decision-making capacity
as subjects providing IRBs with a
thorough justification for their proposed
research design, including a description
of the procedures that are designed to
minimize risks to subjects?
1d. If research protocols targeting
adult individuals with impaired
decision-making capacity as subjects are
being approved by IRBs when the
research could be done with other
subjects, what are the reasons for IRBs
approving such studies?
1e. Are investigators proposing
research targeting adult individuals
with impaired decision-making capacity
as subjects providing IRBs with a
thorough evaluation of the risks and
potential benefits to the subjects
involved in the proposed research
study?
1f. For research involving adult
individuals with impaired decisionmaking capacity as subjects, how are
subjects’ potential or actual objections
to enrollment or continued participation
in research being addressed by
investigators and IRBs?
1g. Are IRBs requiring investigators to
have an assessment of a potential
subject’s capacity to consent, and if so,
under what circumstances? If IRBs are
requiring capacity assessments for some
research, is the degree of risk presented
by the research pertinent to the IRB’s
decision to require such assessments?
What concerns have arisen in regard to
capacity assessments?
1h. For studies that have included an
assessment of potential subjects’
capacity to consent, how has this
assessment been used in the informed
consent process? Are subjects notified
when they have been found to lack
capacity to consent? When informed
consent is sought from such a subject’s
legally authorized representative, are
potential subjects provided an
opportunity to assent or object to their
participation in the research?
1i. For research involving subjects
who are able to provide informed
consent, but are expected to have
fluctuating, limited, or diminishing
decision-making capacity during the
course of the research study, what
processes or procedures have
investigators implemented, or have IRBs
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required, in order to ensure that the
rights and welfare of such subjects
remains adequately protected?
2. What problems or concerns have
arisen for investigators, IRBs, or
research subjects in the conduct or
review of research involving
decisionally impaired individuals as
subjects?
2a. To what extent, if any, has the
absence of OHRP guidance or additional
regulatory requirements given rise to
unacceptable practices by IRBs or
investigators reviewing or conducting
research targeting adult individuals
with impaired decision-making capacity
as subjects, or created inappropriate
barriers to the conduct of research
involving individuals with impaired
decision-making capacity as subjects?
2b. Please describe the process used
when a legally authorized representative
is asked to consent on behalf of a
prospective research subject for research
involving adult individuals with
impaired decision-making capacity as
subjects. Do the legally authorized
representatives use substituted
judgment (decisions that reflect the
views of the individual expressed while
decisionally capable) or the best interest
standard? Which seems more ethically
justified?
2c. How are advance directives for
health care and for research used when
a legally authorized representative is
available?
2d. Have any problems or concerns
arisen in regard to seeking consent from
a legally authorized representative on
behalf of a prospective research subject
for research involving adult individuals
with impaired decision-making capacity
as subjects? If so, please describe the
issues that have arisen.
3. The current requirement for IRB
approval under the HHS regulations at
45 CFR 46.111(b), states:
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When some or all of the subjects are likely
to be vulnerable to coercion or undue
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.
Please describe the additional
safeguards you have included in studies
to protect the rights and welfare of
subjects with impaired decision-making
capacity.
3a. Does the regulatory provision
cited above provide sufficient
protections for adult subjects with
impaired decision-making capacity or
are additional regulatory safeguards
needed? If additional safeguards are
needed, what should these additional
protections be? Below please find a
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compendium of possible additional
protections for subjects with impaired
decision-making capacity. Please feel
free to comment on any or all of them,
and to suggest others. In your
comments, please indicate if your
comments are directed towards the
issuance of either guidance or
additional regulations:
• Consent auditor/independent
consent monitor.
• Sliding scale of capacity, (i.e.,
protections should be proportional to
the severity of capacity impairment, or
to the magnitude of experimental risk,
or both).
• Description of specific tasks to
assess capacity (these may be studyspecific).
• Independent assessment of
decision-making capacity.
• Enhancement of IRB expertise such
that the IRB includes members or
consultants familiar with conditions
that may affect decision-making
capacity and with the concerns of the
population being studied.
• Obtaining consent from legally
authorized representative.
• Obtaining assent from subjects with
impaired decision-making capacity
(may be limited to objecting to inclusion
in the research study). This would be in
addition to consent from the legally
authorized representative.
• Use of advance directive for
research where permitted by state/local
law.
• Use of appropriate waiting periods
(after research presented to the subject)
before obtaining assent or consent as
possible.
• Consent enhancements:
Interventions to increase the subject’s
decision-making capacity.
• Other suggestions.
3b. If the regulations at 45 CFR part
46 are sufficient, should OHRP issue
additional guidance on how the
regulations should be applied to protect
adult subjects with impaired decisionmaking capacity?
3c. If additional regulations are
needed would a risk-based model, such
as a model based on the subpart D
regulations be appropriate? If not, what
type of regulatory model would be
appropriate?
3d. If additional regulations are
needed, would it be appropriate to
develop additional regulations that
would only apply to a subset of the
population of adult subjects with
impaired decision-making capacity? For
example, would it be appropriate to
develop additional regulations that
would apply only to adult individuals
who have no capacity to provide legally
effective informed consent (e.g.
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50969
comatose individuals or individuals in
a persistent vegetative state)?
4. How should the population of
adults with impaired decision-making
be defined for the purposes of guidance
or regulation? Note that the subpart D
regulations contain a definition of the
term ‘‘children,’’ who are defined as ‘‘
* * * persons who have not attained
the legal age for consent to treatments or
procedures involved in the research,
under the applicable law of the
jurisdiction in which the research will
be conducted.’’ See 45 CFR 46.402(a).
Does the definition of the term
‘‘children’’ in the subpart D regulations
provide a helpful model for developing
a definition of ‘‘adults with impaired
decision-making capacity,’’ or would a
definition modeled on the definition of
‘‘children’’ inappropriately exclude
adult individuals who are at risk of
decisional impairment, and those who
suffer from some form of persistent,
fluctuating, or progressive decisional
impairment, but who nevertheless retain
the capacity to give legally effective
informed consent under the applicable
law of the jurisdiction in which the
research will be conducted? If a
comparable definition of adults with
impaired decision-making capacity was
to be developed, such a definition could
read: ‘‘Adults with impaired decisionmaking capacity are persons who do not
have the capacity to give legally
effective informed consent to treatments
or procedures involved in research/
clinical investigation, under the
applicable law of the jurisdiction in
which the research/clinical
investigation will be conducted.’’
5. In some circumstances, certain
adult subjects may develop impaired
decision-making capacity (e.g.
persistent, fluctuating, or progressive
decisional impairment) after consenting
and enrolling in research. In such cases,
is guidance needed, or are additional
regulations necessary, in order to
adequately protect adult subjects who
become decisionally impaired during
their participation in research? For
example, should guidance or additional
regulations address when it would be
appropriate for investigators to seek the
consent of the subject’s legally
authorized representative to enable the
subject’s continued participation?
6. If guidance or additional
regulations are needed to adequately
protect the rights and welfare of subjects
with impaired decision-making
capacity, should such guidance or
regulations address the issue of assent?
Note that the subpart D regulations
generally require that IRBs determine
that adequate provisions are made for
soliciting the assent of children when in
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the judgment of the IRB the children are
capable of providing assent. (See 45 CFR
46.408.)
6a. If an adult with impaired decisionmaking capacity is capable of providing
assent to participation in research,
should the guidance or regulation
indicate that the adult subject’s assent
should always be a condition for
proceeding with the research? If there
are circumstances when an adult
subject’s assent should not be necessary,
what are those circumstances?
Melody Lin,
Deputy Director, Office for Human Research
Protections.
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Health/Agency for Toxic Substances
and Disease Registry; the Program
Peer Review Subcommittee (PPRS) of
the Board of Scientific Counselors
(BSC), Centers for Disease Control and
Prevention (CDC), National Center for
Environmental Health/Agency for Toxic
Substances and Disease Registry
(NCEH/ATSDR): Teleconference
In accordance with section 10(a)(2) of
the Federal Advisory Committee Act
(Pub. L. 92–463), the Centers for Disease
Control and Prevention (CDC)
announces the aforementioned meeting.
In accordance with section 10(a)(2) of
the Federal Advisory Committee Act
(Pub. L. 92–463), CDC, NCEH/ATSDR
announces the aforementioned
subcommittee meeting:
Time and Date:
8:30 a.m.–5 p.m., October 22, 2007
(Closed).
8 a.m.–2 p.m., October 23, 2007 (Closed).
Place: Sheraton Gateway Atlanta Airport
Hotel, 1900 Sullivan Road, Atlanta, Georgia
30337, Telephone (770) 997–1100.
Status: The meeting will be closed to the
public in accordance with provisions set
forth in section 552b(c)(4) and (6), Title 5
U.S.C., and the Determination of the Director,
Management Analysis and Services Office,
CDC, pursuant to Public Law 92–463.
Matters to be Discussed: The meeting will
include the review, discussion, and
evaluation of ‘‘National HIV Behavioral
Surveillance System,’’ FOA Number PS 07–
001.
Contact Person for More Information:
Shoukat Qari, D.V.M., Ph.D., Scientific
Review Administrator, Strategic Science and
Program Unit, Office of the Director,
Coordinating Center for Infectious Diseases,
CDC, 1600 Clifton Road, NE., MS E05,
Time and Date: 3 p.m.–5 p.m., September
24, 2007.
Place: The teleconference will originate at
NCEH/ATSDR in Atlanta, Georgia. To
participate, dial (877)315–6535 and enter
conference code 383520.
Purpose: Under the charge of the BSC,
NCEH/ATSDR, the PPRS will provide the
BSC, NCEH/ATSDR with advice and
recommendations on NCEH/ATSDR program
peer review. They will serve the function of
organizing, facilitating, and providing a longterm perspective to the conduct of NCEH/
ATSDR program peer review.
Matters To Be Discussed: A discussion of
Preparedness and Emergency Response Peer
Review, and review and approve previous
meeting minutes.
Agenda items are subject to change as
priorities dictate.
Supplementary Information: This meeting
is scheduled to begin at 3 p.m. Eastern Time.
To participate, please dial (877)315–6535 and
enter conference code 383520. Public
comment period is scheduled for 4–4:15 p.m.
rfrederick on PROD1PC67 with NOTICES
Centers for Disease Control and
Prevention
Dated: August 29, 2007.
Diane C. Allen,
Acting Director, Management Analysis and
Services Office, Centers for Disease Control
and Prevention.
[FR Doc. E7–17522 Filed 9–4–07; 8:45 am]
BILLING CODE 4163–18–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Disease Control and
Prevention
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Contact Person for More Information:
Sandra Malcom, Committee Management
Specialist, Office of Science, NCEH/ATSDR,
M/S E–28, 1600 Clifton Road, NE., Atlanta,
Georgia 30333, Telephone (404)498–0622.
The Director, Management Analysis and
Services Office, has been delegated the
authority to sign Federal Register notices
pertaining to announcements of meetings and
other committee management activities for
both CDC and NCEH/ATSDR.
Administration for Children and
Families
Proposed Information Collection
Activity; Comment Request; Proposed
Projects
Title: Child Care and Development
Fund Tribal Annual Report (ACF–700
Report).
OMB No.: 0980–0241.
Description: The Child Care and
Development Fund (CCDF) report
requests annual Tribal aggregate
information on services provided
through the CCDF, which is required by
the CCDF Final Rule (45 CFR parts 98
and 99). Tribal Lead Agencies (TLAs)
are required to submit annual aggregate
data appropriate to Tribal programs on
children and families receiving CCDFfunded child care services.
The CCDF statute and regulations also
require TLAs to submit a supplemental
narrative as part of the ACF–700 report.
This narrative describes general child
care activities and actions in the TLA’s
service area and is not restricted to
CCDF-funded child care activities.
Instead, this description is intended to
address all child care available in the
TLA’s service area. The ACF–700 and
supplemental narrative report will be
included in the Secretary’s report to
Congress, as appropriate, and will be
shared with all TLA’s to inform them of
CCDF-funded activities in other Tribal
programs.
Respondents: Tribal Governments.
ANNUAL BURDEN ESTIMATES
Number of respondents
Instrument
Number of responses per
respondent
Average burden hours per
response
260
1
38
ACF–700 Report ..............................................................................................
VerDate Aug<31>2005
13:51 Sep 04, 2007
Jkt 211001
PO 00000
Frm 00040
Fmt 4703
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hours
9,880
]]>Agencies
[Federal Register Volume 72, Number 171 (Wednesday, September 5, 2007)]
[Notices]
[Pages 50966-50970]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-17490]
=======================================================================
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Request for Information and Comments on Research That Involves
Adult Individuals With Impaired Decision-making Capacity
AGENCY: Office for Human Research Protections, Office of Public Health
and Science, Office of the Secretary, HHS.
ACTION: Notice.
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SUMMARY: The Office for Human Research Protections (OHRP), Office of
Public Health and Science is seeking information and comments about
whether guidance or additional regulations are needed to adequately
protect adult individuals with impaired decision-making capacity who
are potential subjects in research. This request for information and
comments stems from the recommendation of an HHS working group,
generated in response to the report published by the National Bioethics
Advisory Commission (NBAC) entitled ``Research Involving Persons With
Mental Disorders That May Affect Decision-making Capacity'' (December
1998), and from subsequent recommendations by the National Human
Research Protections Advisory Committee (NHRPAC).\a\
---------------------------------------------------------------------------
\a\ The National Human Research Protections Advisory Committee
has been disbanded and replaced by the Secretary's Advisory
Committee on Human Research Protections.
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In addition, as part of its charge to provide expert advice and
recommendations to the Secretary of Health and Human Services (the
Secretary) and the Assistant Secretary for Health on issues and topics
pertaining to or associated with the protection of human subjects, the
Secretary's Advisory Committee on Human Research Protections (SACHRP)
has formed a Subcommittee on Inclusion of Individuals with Impaired
Decision-Making in Research. This SACHRP subcommittee is currently
considering whether guidance or additional regulations are needed for
research involving individuals with impaired decision-making capacity.
The information and comments submitted in response to this notice will
be shared with SACHRP to inform the Committee's recommendations to the
Secretary and Assistant Secretary for Health.
DATES: Submit written or electronic information and comments by
December 4, 2007.
ADDRESSES: Submit written comments to REQUEST FOR INFORMATION ON
RESEARCH THAT INVOLVES ADULT INDIVIDUALS WITH IMPAIRED DECISION-MAKING
CAPACITY, Office for Human Research Protections, The Tower Building,
1101 Wootton Parkway, Suite 200, Rockville, MD 20852. Comments also may
be sent via e-mail to impairedcapacityohrp@hhs.gov, or via facsimile at
301-402-2071. Comments received within the comment period, including
any personal information provided, will be made available to the public
upon request.
FOR FURTHER INFORMATION CONTACT: Julie Kaneshiro, Office for Human
Research Protections, Department of Health and Human Services, The
Tower Building, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852;
240-453-6900; e-mail julie.kaneshiro@hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The Department of Health and Human Services (HHS) regulates
research involving human subjects conducted or supported by HHS through
regulations codified at 45 CFR part 46 which are administered by OHRP.
The HHS regulations stipulate that in order to approve research covered
by the regulations, an institutional review board (IRB) shall determine
that when some or all of the subjects are likely to be vulnerable to
coercion or undue 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. 45 CFR
46.111(b). Apart from this broad requirement regarding vulnerable
populations, the HHS regulations do not contain specific additional
standards for the participation of adults with impaired decision-making
capacity in research, nor do they define who should be considered as
part of this population. In response to the recommendations by the
National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research (National Commission) that pertained to
research involving individuals who are institutionalized as mentally
infirm, in 1978, the Department of Health, Education, and Welfare (now
HHS), issued proposed regulations on research involving those
institutionalized as mentally disabled. However, these proposed
regulations were never finalized or adopted due to a lack of consensus
on the proposed regulatory provisions, and a judgment that the general
HHS regulations governing human subjects' participation in research
were sufficient to address the National Commission's recommendations.
The impetus for this request for information and comments stems
from a number of different sources. HHS is aware that some research
currently conducted or supported by HHS involves adults with impaired
decision-making capacity. HHS believes that research involving adults
with impaired decision-making capacity is important and necessary in
order to improve the health and well-being of such individuals. HHS and
others have long recognized the potential vulnerability of these
subjects, and that research involving this population needs to be
conducted with adequate safeguards. At this time HHS believes it is
appropriate to solicit the views of the public on whether the current
human subject protection regulations are adequate in safeguarding these
individuals. This request for information and comments also stems from
recommendations of an HHS working group (HHS WG), generated in response
to the report published by the former NBAC entitled ``Research
Involving Persons with Mental Disorders That May Affect Decision-making
Capacity'' (December 1998), and from subsequent recommendations by the
former NHRPAC.
A. NBAC Report
In its December 1998 report, the full text of which can be found on
the Internet at https://bioethics.georgetown.edu/nbac, NBAC defined
decisional impairment as a limitation or incapacity that is not part of
normal growth and development. NBAC's report contained recommendations
for helping to ensure adequate protections for people with decisional
impairment who participate in research, but referred only to research
involving persons with mental disorders
[[Page 50967]]
that may affect decision-making capacity.
NBAC's recommendations called for a new regulatory framework
requiring IRBs to classify into one of three categories all proposed
research that involves people with impaired decision-making capacity
due to mental disorders, based on the level of risk and potential for
direct medical benefit to the research subject. NBAC identified three
categories of research that pose: (1) Minimal risk to subjects; (2)
greater than minimal risk to subjects and having the prospect of direct
medical benefit; and (3) greater than minimal risk to subjects but
having no prospect of direct medical benefit. NBAC recommended that the
legally authorized representative of a subject with impaired decision-
making capacity be able to give permission for the subject's
participation in research protocols that fall into either of the first
two categories. However, NBAC recommended that research in the third
category could not proceed unless one of two conditions occurred:
Either (1) the research subject would have had to give Prospective
Authorization for the particular class of research when competent, or
(2) a Special Standing Panel (SSP), convened by the Secretary of HHS,
would need to review the research and find it approvable or have issued
guidelines about the class of research indicating that it was
approvable. In NBAC's recommendations, Prospective Authorization would
provide individuals, when competent, with an opportunity to express
their preferences (if they have them) regarding future research
participation, within certain limits. NBAC recommended that a
Prospective Authorization should specify the ``particular class of
research,'' and the degree of specificity in the Prospective
Authorization should be correlated with the level of risk posed by the
research. For example, a person with a diagnosis of early stage
Alzheimer's Disease who is still competent to make decisions could
express his or her preference to participate in greater than minimal
risk clinical trials testing interventions for moderate or severe
Alzheimer's Disease in the future, when he or she may not be competent
to make decisions.
B. HHS Working Group
The Office of Science Policy, Office of the Assistant Secretary for
Planning and Evaluation, convened an HHS WG to analyze NBAC's
recommendations and to develop a proposed HHS response to the NBAC
report. The HHS WG's report can be found on the Internet at https://
aspe.hhs.gov/sp/human.shtml. The HHS WG considered, among other things,
NBAC's recommended framework described above. The HHS WG was concerned
that this framework was not practical because it would lead to the use
of either a Prospective Authorization or a SSP for a large number of
research protocols involving subjects with impaired decision-making
capacity. The HHS WG concluded that the widespread use of Prospective
Authorizations is unlikely. Thus, unless the research involved the
prospect of direct medical benefit to the participants, an SSP would
need to review all research involving greater than minimal risk.
The HHS WG compared NBAC's proposed regulatory framework to the HHS
regulations governing the participation of children in research (45 CFR
part 46 subpart D [hereafter referred to as ``subpart D
regulations'']). The subpart D regulations allow an IRB to consider a
broad range of different types of direct benefits to the subject, not
just direct medical benefits, when weighing the risks posed by research
involving greater than minimal risk that presents the prospect of
direct benefit to the individual child. NBAC, on the other hand,
recommended that benefits be limited to direct medical benefits only
for research involving subjects with impaired decision-making capacity.
The subpart D regulations also create an intermediate risk category,
not included in NBAC's framework, called a ``minor increase over
minimal risk.'' The HHS WG noted that an alternative regulatory
framework modeled on subpart D could provide appropriate protection and
also decrease the number of studies needing SSP review and thus may
increase the feasibility of such reviews.
The HHS WG decided that NBAC's recommended framework would limit an
IRB's authority to approve research involving an adult with impaired
decision-making capacity more than it would an IRB's authority to
approve a child's participation in the same type of research. The HHS
WG further noted that NBAC's framework would alter IRB authority in
ways that could produce different results. For example, the subpart D
regulations permit a child's parent or guardian to enroll the child in
research that has no prospect of direct benefit and that poses a minor
increase over minimal risk if an IRB determines the research, among
other things, is ``likely to yield generalizable knowledge * * * of
vital importance'' about the child's disorder or condition (45 CFR
46.406). However, under NBAC's recommendations, the legally authorized
representative of an adult with impaired decision-making capacity could
not enroll the adult in the same type of research, unless the adult had
signed a Prospective Authorization or the SSP approved or issued
guidelines about the research. The HHS WG recognized that safeguards
for children and adults with impaired decision-making capacity need not
necessarily be identical, but noted that two different standards might
be confusing to investigators and IRBs.
In addition, in its 1998 report, NBAC considered how ethically
acceptable research could be conducted with human subjects who suffer
from mental disorders that may affect their decision-making capacity.
The HHS WG interpreted the intended scope of NBAC's recommendations as
applying to research involving ``persons with mental disorders that may
affect decision making capacity,'' but determined that the scope of
NBAC's recommendations seem appropriately applicable to research
involving adults with decisional impairment, irrespective of the cause.
The HHS WG noted that some physical disorders or conditions (e.g.,
cancer, sepsis, head injury) also might result in impaired capacity to
make decisions, and therefore, an inability to give voluntary informed
consent to participate in research. In addition, the HHS WG was
concerned that limiting the scope of protections to research subjects
whose decision-making capacity is impaired because of a mental disorder
may be perceived to be stigmatizing to such individuals. Thus, the HHS
WG concluded that adults with an impaired capacity to make a decision
as a result of any disease or condition should receive the same
protections as those individuals with an impaired decision-making
capacity from a mental disorder.
The HHS WG proposed that OHRP request public comment on the issues
raised by the NBAC framework and the HHS WG's analysis of those issues.
This request for information and comments is designed to accomplish
that goal.
C. NHRPAC Report
In response to NBAC's recommendations and the HHS WG's report, at
OHRP's request, NHRPAC drafted a report entitled ``Informed Consent and
the Decisionally Impaired.'' NHRPAC was an advisory committee to the
Secretary of HHS, the Assistant Secretary for Health, the Director of
OHRP, and other Departmental officials on a broad range of issues and
topics pertaining to or associated with the protection of human
research subjects. NHRPAC's draft report is available on the Internet
at
[[Page 50968]]
https://www.hhs.gov/ohrp/nhrpac/documents/nhrpac10.pdf. NHRPAC's report
applies to ``all potential subjects in biomedical and social/behavioral
research who lack decisional capacity for any reason and is not limited
to persons with mental disorders.'' In its report, NHRPAC recommended
specific protections at different levels of risk and potential benefit
for research with the decisionally impaired population. These risk-
benefit categories included:
(1) Research that involves no more than minimal risk,
(2) Research that involves greater than minimal risk but presents
the prospect of direct benefit to the subjects,
(3) Research that involves a minor increase over minimal risk that
does not present the prospect of direct benefit but is likely to yield
generalizable knowledge about the subject's condition or disorder, and
(4) Research not otherwise approvable which presents an opportunity
to understand, prevent, or alleviate a serious problem affecting the
health or welfare of persons with impaired decision-making capacity,
provided the Secretary of HHS makes specified determinations after
consulting with a panel of experts and providing the opportunity for
public review and comment.
These risk categories are similar to those contained in the subpart
D regulations governing research with children.
D. SACHRP Activities
In October 2002, SACHRP was created by the Secretary to replace
NHRPAC. SACHRP is charged to advise, consult with, and make
recommendations to the Secretary and Assistant Secretary for Health on
matters pertaining to the continuance and improvement of functions
within the authority of HHS directed toward protections for human
subjects in research. In carrying out its charge, SACHRP formed a
Subcommittee on Inclusion of Individuals with Impaired Decision-Making
Capacity in Research. Specifically, this SACHRP subcommittee will
develop recommendations for consideration by SACHRP about whether
guidance or additional regulations are needed for research involving
individuals with impaired decision-making capacity. In making its
assessment, the Subcommittee will review the relevant provisions of
subpart A, 45 CFR part 46, including the provisions at 45 CFR
46.111(b), and will seek additional information to formulate its
decision as it deems necessary.
The information and comments submitted in response to this notice
will be shared with SACHRP to inform the Committee's recommendations to
the Secretary and Assistant Secretary for Health.
The reports of the National Commission, NBAC, and NHRPAC
specifically address and endorse the inclusion of decisionally
incapacitated subjects in clinical research with the provision of
adequate protections for these subjects. Based on these recommendations
and reports over the years, and SACHRP's current work on this issue,
OHRP is seeking comment on whether it is necessary to develop
additional safeguards to protect adult individuals with impaired
decision-making capacity because these individuals may have diminished
or no capacity to provide informed consent to their participation in
research. The next section contains the specific questions of interest
to HHS.
II. Request for Information and Comments
OHRP is seeking information and comments from the public about
whether guidance or additional regulations are needed to adequately
protect adult individuals with impaired decision-making capacity who
are potential subjects in research. The scope of this request for
information and comments is limited to research involving adult
subjects because additional protections for children involved as
subjects in research already exists under the subpart D regulations. In
addition, this notice is not directed toward consideration of emergency
research involving the decisionally impaired that would be covered
under the HHS's Secretarial waiver under 45 CFR 46.101(i) on the
exception from informed consent requirements for emergency research
(published in the Federal Register in 1996 at 61 FR 51531). OHRP
believes that this existing provision already addresses the conduct of
emergency research without informed consent that involves individuals
with impaired decision-making capacity.
OHRP specifically seeks information and comments on the following
issues. Comments should also include a reference to the specific
numbered question being addressed:
1. What are investigators' and IRBs' current practices in regard to
the conduct, review, and approval of research involving decisionally
impaired adult individuals?
1a. Have investigators' or IRBs' practices changed as a result of
NBAC's or NHRPAC's recommendations? If not, why not?
1b. If an IRB regularly reviews research proposals involving adult
individuals with impaired decision-making capacity, do such IRBs
include one or more members or consultants who are familiar with
conditions that may affect decision-making capacity and with the
concerns of the population being studied?
1c. Are investigators proposing research targeting adult
individuals with impaired decision-making capacity as subjects
providing IRBs with a thorough justification for their proposed
research design, including a description of the procedures that are
designed to minimize risks to subjects?
1d. If research protocols targeting adult individuals with impaired
decision-making capacity as subjects are being approved by IRBs when
the research could be done with other subjects, what are the reasons
for IRBs approving such studies?
1e. Are investigators proposing research targeting adult
individuals with impaired decision-making capacity as subjects
providing IRBs with a thorough evaluation of the risks and potential
benefits to the subjects involved in the proposed research study?
1f. For research involving adult individuals with impaired
decision-making capacity as subjects, how are subjects' potential or
actual objections to enrollment or continued participation in research
being addressed by investigators and IRBs?
1g. Are IRBs requiring investigators to have an assessment of a
potential subject's capacity to consent, and if so, under what
circumstances? If IRBs are requiring capacity assessments for some
research, is the degree of risk presented by the research pertinent to
the IRB's decision to require such assessments? What concerns have
arisen in regard to capacity assessments?
1h. For studies that have included an assessment of potential
subjects' capacity to consent, how has this assessment been used in the
informed consent process? Are subjects notified when they have been
found to lack capacity to consent? When informed consent is sought from
such a subject's legally authorized representative, are potential
subjects provided an opportunity to assent or object to their
participation in the research?
1i. For research involving subjects who are able to provide
informed consent, but are expected to have fluctuating, limited, or
diminishing decision-making capacity during the course of the research
study, what processes or procedures have investigators implemented, or
have IRBs
[[Page 50969]]
required, in order to ensure that the rights and welfare of such
subjects remains adequately protected?
2. What problems or concerns have arisen for investigators, IRBs,
or research subjects in the conduct or review of research involving
decisionally impaired individuals as subjects?
2a. To what extent, if any, has the absence of OHRP guidance or
additional regulatory requirements given rise to unacceptable practices
by IRBs or investigators reviewing or conducting research targeting
adult individuals with impaired decision-making capacity as subjects,
or created inappropriate barriers to the conduct of research involving
individuals with impaired decision-making capacity as subjects?
2b. Please describe the process used when a legally authorized
representative is asked to consent on behalf of a prospective research
subject for research involving adult individuals with impaired
decision-making capacity as subjects. Do the legally authorized
representatives use substituted judgment (decisions that reflect the
views of the individual expressed while decisionally capable) or the
best interest standard? Which seems more ethically justified?
2c. How are advance directives for health care and for research
used when a legally authorized representative is available?
2d. Have any problems or concerns arisen in regard to seeking
consent from a legally authorized representative on behalf of a
prospective research subject for research involving adult individuals
with impaired decision-making capacity as subjects? If so, please
describe the issues that have arisen.
3. The current requirement for IRB approval under the HHS
regulations at 45 CFR 46.111(b), states:
When some or all of the subjects are likely to be vulnerable to
coercion or undue 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.
Please describe the additional safeguards you have included in
studies to protect the rights and welfare of subjects with impaired
decision-making capacity.
3a. Does the regulatory provision cited above provide sufficient
protections for adult subjects with impaired decision-making capacity
or are additional regulatory safeguards needed? If additional
safeguards are needed, what should these additional protections be?
Below please find a compendium of possible additional protections for
subjects with impaired decision-making capacity. Please feel free to
comment on any or all of them, and to suggest others. In your comments,
please indicate if your comments are directed towards the issuance of
either guidance or additional regulations:
Consent auditor/independent consent monitor.
Sliding scale of capacity, (i.e., protections should be
proportional to the severity of capacity impairment, or to the
magnitude of experimental risk, or both).
Description of specific tasks to assess capacity (these
may be study-specific).
Independent assessment of decision-making capacity.
Enhancement of IRB expertise such that the IRB includes
members or consultants familiar with conditions that may affect
decision-making capacity and with the concerns of the population being
studied.
Obtaining consent from legally authorized representative.
Obtaining assent from subjects with impaired decision-
making capacity (may be limited to objecting to inclusion in the
research study). This would be in addition to consent from the legally
authorized representative.
Use of advance directive for research where permitted by
state/local law.
Use of appropriate waiting periods (after research
presented to the subject) before obtaining assent or consent as
possible.
Consent enhancements: Interventions to increase the
subject's decision-making capacity.
Other suggestions.
3b. If the regulations at 45 CFR part 46 are sufficient, should
OHRP issue additional guidance on how the regulations should be applied
to protect adult subjects with impaired decision-making capacity?
3c. If additional regulations are needed would a risk-based model,
such as a model based on the subpart D regulations be appropriate? If
not, what type of regulatory model would be appropriate?
3d. If additional regulations are needed, would it be appropriate
to develop additional regulations that would only apply to a subset of
the population of adult subjects with impaired decision-making
capacity? For example, would it be appropriate to develop additional
regulations that would apply only to adult individuals who have no
capacity to provide legally effective informed consent (e.g. comatose
individuals or individuals in a persistent vegetative state)?
4. How should the population of adults with impaired decision-
making be defined for the purposes of guidance or regulation? Note that
the subpart D regulations contain a definition of the term
``children,'' who are defined as `` * * * persons who have not attained
the legal age for consent to treatments or procedures involved in the
research, under the applicable law of the jurisdiction in which the
research will be conducted.'' See 45 CFR 46.402(a). Does the definition
of the term ``children'' in the subpart D regulations provide a helpful
model for developing a definition of ``adults with impaired decision-
making capacity,'' or would a definition modeled on the definition of
``children'' inappropriately exclude adult individuals who are at risk
of decisional impairment, and those who suffer from some form of
persistent, fluctuating, or progressive decisional impairment, but who
nevertheless retain the capacity to give legally effective informed
consent under the applicable law of the jurisdiction in which the
research will be conducted? If a comparable definition of adults with
impaired decision-making capacity was to be developed, such a
definition could read: ``Adults with impaired decision-making capacity
are persons who do not have the capacity to give legally effective
informed consent to treatments or procedures involved in research/
clinical investigation, under the applicable law of the jurisdiction in
which the research/clinical investigation will be conducted.''
5. In some circumstances, certain adult subjects may develop
impaired decision-making capacity (e.g. persistent, fluctuating, or
progressive decisional impairment) after consenting and enrolling in
research. In such cases, is guidance needed, or are additional
regulations necessary, in order to adequately protect adult subjects
who become decisionally impaired during their participation in
research? For example, should guidance or additional regulations
address when it would be appropriate for investigators to seek the
consent of the subject's legally authorized representative to enable
the subject's continued participation?
6. If guidance or additional regulations are needed to adequately
protect the rights and welfare of subjects with impaired decision-
making capacity, should such guidance or regulations address the issue
of assent? Note that the subpart D regulations generally require that
IRBs determine that adequate provisions are made for soliciting the
assent of children when in
[[Page 50970]]
the judgment of the IRB the children are capable of providing assent.
(See 45 CFR 46.408.)
6a. If an adult with impaired decision-making capacity is capable
of providing assent to participation in research, should the guidance
or regulation indicate that the adult subject's assent should always be
a condition for proceeding with the research? If there are
circumstances when an adult subject's assent should not be necessary,
what are those circumstances?
Melody Lin,
Deputy Director, Office for Human Research Protections.
[FR Doc. E7-17490 Filed 9-4-07; 8:45 am]
BILLING CODE 4150-36-P
