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Greg A. Sachs, MD primary author
*Last Updated in 2007*
Background
Over the last fifty years, informed consent has
been seen as the most critical element in the ethical conduct of
research involving human subjects. For the last fifteen years, ethicists,
legal scholars, policy makers, researchers, and affected patients
and families have debated how research on dementia can proceed in
an ethical fashion when potential subjects are either in the process
of losing or have lost the capacity to provide informed consent.
This debate focuses on addressing the tension between providing
adequate protection for subjects who are vulnerable due to diminished
capacity and allowing promising research to go forward. Informed
consent for dementia research has become a growing concern for the
American Geriatrics Society due to the following: 1) previous national
commissions and federal regulations have not adequately addressed
this topic; 2) advances in the scientific study of dementia have
increased the need to be able to conduct human subjects research;
3) courts and policy makers in various states have begun addressing
these issues, often in dramatically different ways, raising the
possibility that considerable confusion may result and that multi-center
clinical trials may become very difficult, if not impossible, to
conduct.
Position 1
Enrolling subjects with dementia in research must
be justified on scientific, clinical, and ethical grounds. Research
using demented subjects to study conditions other than the dementia
itself can be justified.
Rationale
In general, people who cannot provide their own
informed consent deserve protection from exploitation. Research
on the causes and treatments of dementia, management of the complications
of dementia, or health services research related to problems experienced
by people with dementia certainly warrant conducting research on
subjects with dementia. Examples of research on conditions commonly
associated with dementia include studies on pressure sores and urinary
incontinence. People with dementia living in long term care settings
are appropriate subjects for research and should be selected on
scientific and clinical grounds.
Position 2
Because decision making capacity is task specific,
some cognitively impaired individuals remain capable of making informed
decisions for themselves regarding research participation. The capacity
to obtain informed consent should be assessed in each individual,
for each research protocol being considered.
Rationale
The diagnosis of dementia does not automatically
confer decisional incapacity on affected individuals. Especially
in the earliest stages of dementia, many people with dementia remain
capable of making a wide variety of decisions, including deciding
whether or not to participate in research. Identification of these
individuals is important both because they should be the highest
priority subjects for enrolling in studies (if they meet other inclusion
criteria), and because they may be able to provide guidance for
research decision making for projects in the future when they may
no longer retain decision making capacity.
Position 3
Advance consent, including formal advance directives
for research purposes, is an appropriate mechanism for allowing
individuals with decision making capacity to express their preferences
regarding research participation that should, in general, be respected
when making decisions about research enrollment at points in the
future when those individuals have lost decisional capacity.
Rationale
As we look to individuals’ previous expressed
values and preferences and written advance directives to guide clinical
decision making in the event of incapacity, even decisions to forgo
life-sustaining treatment, so too should we respect prior statements
and advance directives for research decision making. Incorporating
instructions or guidance for a proxy for research decision making
into a standard advance directive, or creating research-specific
advance directives, should be seen as an aid to research decision
making, but not as required documents (except for the special circumstances
discussed below in Position 6).
Position 4
In the absence of advance directives speaking
directly to research decision making, health professionals offering
research enrollment to people with dementia should be able to turn
to traditional surrogates, most often next of kin, or another person
who has been identified as the most appropriate surrogate because
that person "has loving and intimate knowledge of the subject’s
wishes or values system." (from AGS position statement on "Making
Treatment Decisions for Incapacitated Elderly Without Advance Directives;
"subject’s" substituted for "patient’s.")
Rationale
As the disease progresses, people with dementia
come to rely on others for all kinds of decisions, from decisions
about the use of life-sustaining medical treatment to decisions
about where they should live and what they can do for themselves.
Families and other surrogates should be trusted to make research
participation decisions as well. (See Position 6 for exception to
surrogate consent.)
Position 5
Federal and state authorities should clarify existing
laws and regulations as they relate to research on dementia, especially
regarding the use of advance directives for research and the status
of proxy consent for research in the absence of advance directives.
If necessary, pertinent laws and regulations should be amended to
facilitate important research on dementia in accord with the other
positions made in this paper.
Rationale
Federal research regulations indicate that consent
for research participation may be given only by a competent individual
for him or herself or that person’s legally authorized representative.
Who is someone’s legally authorized representative varies from
state to state and may not be clear in some states. Advance directives
for clinical decision making exist in all states, but advance directives
for research purposes may not have a clear legal status or may not
be allowed in some states. Proxy consent for research in the absence
of formal guardian designation or advance directives may also not
have clear status under some states’ laws.
Position 6
Research protocols that do not hold out a reasonable
prospect of direct benefit to the participating subjects, and that
expose subjects to more than a minor increment above minimal risk,
should be offered only to those subjects who either retain decision
making capacity or those who have indicated in an advance directive
that they would be willing to be enrolled in such studies. A national
mechanism should be established for considering, on a case-by-case
basis, potential research projects that might allow some especially
promising studies to be done with subjects lacking decision making
capacity who have not executed research advance directives.
Rationale
The circumstances described in Position 6 are
the special circumstances referred to in Positions 3 and 4 above
regarding advance consent and surrogate consent. In general, advance
directives should be looked on to guide research decision making,
but should not be required for research enrollment, and turning
to family or other surrogates is generally acceptable, as it is
in other medical treatment decision making. However, research studies
that involve more than a minor increment above minimal risk and
no reasonable prospect of direct benefit to subjects with dementia
can be appropriately limited to those situations where it is clear
that the subject indicated a desire to enroll in such studies at
a time when he or she had (or has) decision making capacity. Because
some studies in this category may be especially promising for the
class of people with dementia, a national mechanism that is open
and public is the appropriate means for reviewing and approving
the enrollment of incompetent subjects who do not have research
advance directives.
Position 7
Local Institutional Review Boards (IRBs) remain
the proper bodies for weighing of issues for particular research
projects, such as categorizing projects by level of risk, balancing
risks and benefits, and deciding what additional safeguards a project
might require, such as a consent monitor or an independent monitor
for the project.
Rationale
Regulations, guidelines and position papers can
only provide the ethical and procedural framework for evaluating
protocols that involve subjects with dementia. Weighing particular
studies’ potential benefits, potential risks, methods for assessing
decision making capacity, methods for obtaining consent, and the
need for special safeguards is best left to IRBs as the local deliberative
bodies that have experience making such assessments.
Position 8
Surrogates should be allowed to refuse to enroll
potential subjects or to withdraw a subject from an ongoing trial
on the basis that the surrogate believes that the research protocol
is not in the best interests of the subject or is not what the subject
intended, even if that decision would conflict with the subject’s
advance directive.
Rationale
Instructions in advance directives for research
are like to be imperfect at best as they will be based on knowledge
at one point in time, but will be applied perhaps several years
in the future. The individual’s condition, available treatments,
and other factors may change in the intervening years, making it
safer to allow surrogates to decline enrollment or withdraw the
subject from a trial if the surrogate determines that enrollment
would either not be in the subject’s best interests or would
not be consistent with what the subject intended.
Position 9
In general, the refusal of a (potential) subject,
even if that subject has lost decision making capacity, should be
followed. The only exception should be protocols that meeting the
following four conditions: 1) a very high potential benefit to risk
ratio; 2) where access to this benefit is available only through
the research study (e.g.., a promising experimental drug for severe
agitation in patients with dementia, being tried on subjects who
have not benefited from standard treatments); 3) proxy consent is
obtained; and 4) any additional safeguards selected by an IRB are
in place.
Rationale
As participation in research is essentially an
optional activity, as opposed to clinical care directed solely at
the benefit of the individual patient, even an uninformed or uncomprehending
refusal should be respected. The exception outlined above illustrates
the very rare case in which enrollment in a research trial against
the spoken or demonstrated preferences of a subject might be acceptable.
Position 10
Continued efforts should be made to broaden community
involvement in the research enterprise.
Rationale
Increased community involvement should both ensure
that the community’s values and interests are incorporated
more directly into the design and conduct of research, and will
facilitate education and recruitment efforts by investigators. The
involvement of patients and families affected by dementia is especially
important.
Developed by the AGS Ethics Committee, Greg A. Sachs, MD primary author, and approved by the AGS Board of Directors in May 1998. Reviewed and updated in May 2007. This statement will next be reviewed in 2010. The American Geriatrics Society, The Empire State Building, 350 Fifth Avenue, Suite 801, New York, NY 10118, 212-308-1414, Fax: 212-832-8646, info.amger@americangeriatrics.org.
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