Research with Adults with
Diminished Capacity to Provide
Consent
Susan Loess-Perez, MS, CIP, CCRC
Director, Office of Research Protections
DePaul University
1
Objectives
Explain the current regulatory
requirements and the background for the
requirements for conducting research
with persons with diminished capacity
 Summarize guidance and literature
 Discuss best practices for IRBs who
review research that involves persons
with diminished capacity
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Regulations-Membership
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45 CFR 46.107 (21 CFR 56.107)-IRB
Membership
If an IRB regularly reviews research that
involves a 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.
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Regulations-Approval Criteria
45 CFR 46.111(21 CFR 56.111)-Approval
criteria
 (3) Selection of subjects is equitable. In
making this assessment the IRB 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.
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Regulations: Consent Requirements
45 CFR 46.116 (21 CFR 50.20)
 The information that is given to the
subject or the representative shall be in
language understandable to the subject or
the representative
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Intent of regulations
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Common Rule:
◦ identifies “mentally disabled” persons as an
example of a group of subjects that are likely
to be vulnerable (i.e. subject to coercion or
undue influence).
◦ recognizes that additional safeguards for this
population may be necessary, but provides no
specific instructions on how to identify this
group of subjects nor on what possible
additional safeguards may be.
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Origins of Regulations
1974- National Research Act formed the
National Commission for the Protection
of Human Subjects of Biomedical and
Behavioral Research.
 In1978 the Commission created
Recommendations on the
Institutionalized and Mentally Infirm
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IRB Guidebook-1993
“The predominant ethical concern in research
involving individuals with psychiatric, cognitive, or
developmental disorders, or who are substance
abusers is that their disorders may compromise
their capacity to understand the information
presented and their ability to make a reasoned
decision about participation.”
 Persons who are institutionalized may have
impaired ability to make a free choice, for
example they may participate to appear rationale
or cooperative in order to obtain release.
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IRB Guidebook-Definitions
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Cognitively Impaired: Having either a psychiatric disorder (e.g., psychosis, neurosis,
personality or behavior disorders), an organic impairment (e.g., dementia) or a developmental
disorder (e.g., mental retardation) that affects cognitive or emotional functions to the extent
that capacity for judgment and reasoning is significantly diminished. Others, including persons
under the influence of or dependent on drugs or alcohol, those suffering from degenerative
diseases affecting the brain, terminally ill patients, and persons with severely disabling physical
handicaps, may also be compromised in their ability to make decisions in their best interests.
Competence: A legal term, used to denote capacity to act on one's own behalf; the ability to
understand information presented, to appreciate the consequences of acting (or not acting) on
that information, and to make a choice.
◦ Competence may fluctuate as a function of the natural course of a mental illness, response
to treatment, effects of medication, general physical health, and other factors. Therefore,
mental status should be re-evaluated periodically. As a designation of legal status,
competence or incompetence pertains to an adjudication in court proceedings that a
person's abilities are so diminished that his or her decisions or actions (e.g., writing a will)
should have no legal effect. Such adjudications are often determined by inability to manage
business or monetary affairs and do not necessarily reflect a person's ability to function in
other situations.
Incapacity: Refers to a person's mental status and means inability to understand information
presented, to appreciate the consequences of acting (or not acting) on that information, and to
make a choice. Often used as a synonym for incompetence.
Incompetence: A legal term meaning inability to manage one's own affairs. Often used as a
synonym for incapacity.
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IRB Guidebook-Recommendations
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Persons who are institutionalized, particularly if disabled, should not be
chosen for studies that bear no relation to their situation just because it
would be convenient for the researcher.
Cognitively impaired subjects should be involved in research only where:
(1) they comprise the only appropriate subject population; (2) the research
question focuses on an issue unique to subjects in this population; and (3)
the research involves no more than minimal risk
A minor increase over minimal risk may be permitted in research
involving those institutionalized as mentally disabled, but only where the
research is designed to evaluate an intervention of foreseeable benefit to
their care
Research involving greater than minimal risk may be acceptable where the
purpose of the research is therapeutic with respect to individual subjects
and where the risk is commensurate with the degree of expected benefit.
.For research that does not involve beneficial interventions and that
presents more than minimal risk, the anticipated knowledge sought should
be of vital importance for understanding or eventually alleviating the
subject's disorder or condition.
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Recommendations –Consent
Process

All adults, regardless of their diagnosis or condition, should be presumed competent
to consent unless there is evidence of serious mental disability that would impair
reasoning or judgment.
◦ Mental disability alone should not disqualify a person from consenting to participate in
research; rather, there should be specific evidence of individuals' incapacity to understand
and to make a choice before they are deemed unable to consent.
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Persons may have court appointed guardians, who may have conflicting interests:
◦ Institutional officials- conflicting interests and loyalties
◦ Family members- financial, and emotional, issues, or be ambivalent
IRBs should be cautious about recommending legal proceedings to establish
guardianship for the purpose of obtaining consent for research participation.
 Consent may be obtained from a legally authorized representative or guardian, but
the feelings and expressed wishes of an incompetent person should still be
respected.
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◦ Consider obtaining assent from the subject.
◦ Should incompetent subjects refusal to participate override the consent of the legal
guardian.
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In some cases, a consent auditor should be appointed by the IRB to determine
whether the subjects actually consent, assent, or object to participation in research,
especially if the research involves more than minimal risk and no foreseeable
direct benefit.
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National Bioethics Advisory
Commission (NBAC)
Research Involving Persons with Mental
Disorders That May Affect
Decisionmaking Capacity, 1998
 Conditions include: Dementia, delirium,
Schizophrenia, depression, mental
retardation, bipolar disorder, substance
abuse disorders
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NBAC Recommendations
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IRBs should have at least 2 members familiar with
the disorders or concerns of the population
IRBs should not approve protocols targeting
persons with mental disorders if other types of
subjects can be used
IRBs should use heightened scrutiny and
investigators should justify the research design
Protocols should include evaluation of risks and
benefits and clearly distinguish between direct
and other benefits.
No person with capacity to consent should be
enrolled without his or her informed consent.
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NBAC Recommendations (cont.)
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The potential subject’s objection should be
heeded.
If greater than minimal risk research, an
independent professional should assess the
subject’s capacity to consent.
A person who has been deemed to lack
capacity must be told of that determination
before the LAR is approached. If the subject
objects after LAR permission is obtained, it
must be heeded.
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NBAC recommendations (cont.)
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If Minimal Risk
◦ Consent can be waived
◦ Subject gives consent
◦ Prospective authorization (advance directive) of
the subject in the event they lose the capacity
with LAR permission
◦ LAR provides permission
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If Greater than Minimal Risk, but direct
benefit
◦ Subject gives consent
◦ Prospective authorization with LAR permission
◦ LAR permission
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NBAC Recommendations (cont.)

If Greater than Minimal Risk, but no
prospect of direct medical benefit
◦ Subjects gives consent
◦ Prospective Authorization and LAR
permission
◦ Protocol approved by federal panel
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NBAC Recommendationssurrogate consent

Potential subjects provides Prospective
Authorization to a class of research while they
have capacity giving an LAR the ability to enroll
them in research after they lose capacity to
consent
◦ LAR must be available to monitor the subject during
the research
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LAR may give permission:
◦ The LAR bases decision on best estimate of what the
subject would want
◦ LAR available to monitor subject on research
◦ LAR chosen by subject or is a relative or friend
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NBAC recommendations-Surrogate
consent (cont.)
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Investigators should accept LAR as per state law
for clinical decisions
◦ States should confirm LAR for clinical decisions =
LAR for research
◦ Friends may serve as LAR if they are actively involved
in care of the person
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State law should allow for persons to choose
LAR for research
For protocols involving subjects whose capacity
may fluctuate, the IRBs should ensure protocols
have provisions for ongoing communication (reconsent, consent when the subject regains
capacity)
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Literature References
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Research Consent for Cognitively Impaired Adults: Recommendations for
Institutional Review Boards and Investigators, Alzheimer’s Association,
Alzheimer’s Disease & Associated Disorders,Vol. 18, No. 3, July/September
2004, pp 171-175
Research Involving Persons with Cognitive Impairments: Results of a
Survey of Alzheimer disease Research Centers in the United States, Cahill,
Maura; Wichman, Alison, Alzheimer Disease & Associated Disorders,Vol. 14,
January/March 2000, pp 20-27
Protecting Subjects with Decisional Impairment in Research : The Need for
a Multi Faceted Approach, Silverman, Henry; Luce, John; and Schwartz, Jack,
American Journal of Respiratory Care Medicine, Vol. 169, 2004, pp 10-14
Obtaining Informed Consent for Research : A Model for Use with
Participants Who are Mentally Ill, Poythress, Norman, Journal of Law,
Medicine & Ethics, 30: 3, Fall 2002 , pp 1-8
Ethical Issues Surrounding the Conduct of Research with Decisionally
Impaired Adults, O’Mathuna, Donal, Research Practitioner, Vol. 4, No.2,
pp42-50.
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NIH Guidance
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Research Involving Individuals with Questionable Capacity to
Consent: Points to Consider (first issued 1999, current
version November 2009)
◦ Must have a process for evaluating consent capacity
 May be multi-step plan
◦ IRBs evaluate what additional safeguards are appropriate on a
protocol per protocol basis
◦ Consent ongoing process
 Disorders with progressive or fluctuating capacity
◦ IRB membership:
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professionals with appropriate background, knowledge, and experience;
patient advocacy groups;
experts in consent capacity;
experts in ethical issues with vulnerable populations
Ad hoc consultants
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NIH Guidance (cont.)
Therapeutic Misconception and the consent
process
 Additional safeguards
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◦ Independent consent monitor
◦ Method of assessing capacity to consent
◦ Use of educational techniques to enhance the
consent process
 multi-media presentations, combination of oral and written
 Step-wise consent, interactive questioning, additional
education, and repetition
 Continuous dissemination and communication
 Supplemental materials
 Waiting periods- allow for family conference or consultation
 Use of LAR and Advance Directives
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NIH OHSR Information Sheet 7
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Research Involving Cognitively Impaired
Subjects: A Review of Some Ethical
Considerations (11/21/2006)
http://ohsr.od.nih.gov/info/sheet7.html
Assent of the cognitively impaired subject is
necessary, but not sufficient. Must do more
to verify this is what the subject would do if
they were making the decision
Promotes use of advanced directives
(Durable Power of Attorney)and
appointment of a representative
Presents 8 cases or categories
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OHRP FAQs
if an adult lacks capacity to consent, for example, as a result
of trauma, mental retardation, some forms of mental illness,
or dementia - whether temporary, progressive, or permanent
- only a LAR for that adult can give consent for participation
in the research, unless the requirement to obtain informed
consent is waived
 In longitudinal studies involving progressive disorders or
aging populations, enrolled subjects may be competent to
consent on their own behalf at the outset, yet may
experience effects of progressive or intermittent disorders
that lead to decisional impairment during the course of the
study. In these situations IRBs and investigators should
consider the need to discuss with the prospective subjects
whether they should designate someone to serve as a LAR
at the outset of the study
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SACHRP
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Subcommittee on Inclusion of Individuals
with Impaired Decision-Making in Research
◦ The Subcommittee will develop either one or both of
the following products, depending on its conclusions:
(1) recommendations on the interpretation of specific
Subpart A provisions that will enhance protections for
this population; and (2) recommendations for a new
subpart under 45 CFR part 46 (and FDA's human
subject protection regulations) that would provide
additional regulatory protections for this population.
◦ http://www.hhs.gov/ohrp/sachrp/20090715lettertohhs
secretary.html
 new guidance and/or additional regulations are necessary to
provide appropriate research protections for individuals who
have impaired consent capacity
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SACHRP Recommendations
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Understanding capacity to consent
IRB review and membership
Consent autonomy and LAR role
Value self determination even when capacity is
limited; assent, dissent
Guidance should define role of LAR and limitations
Guidance to better define applicable law
Create new subpart that describes hierarchy for LAR
Encourage states to create research specific laws for
third party consent
http://www.hhs.gov/ohrp/sachrp/mtgings/mtg0309/present.html
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Best Practices for IRBs
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Evaluate your state laws and obtain legal
counsel guidance on interpretation and
applicability to research
◦ Medical Patient Rights Act (IL410 50/3.1)
 No physician may conduct any research program or experimental procedure on a
patient without the prior informed consent of the patient or, if the patient is unable
to consent, the patient's guardian, spouse, parent, or authorized agent.
◦ Illinois Power of Attorney Act (755 ILCS 45)
 Rules for appointing a person for property, personal, or healthcare decisions
◦ Illinois Health Care Surrogate Act (IL755 40)
 Describes who can be a surrogate for healthcare decisions and the order of
priority
◦ Illinois Living Will Act (IL 755 CS 35)
 Limits some of 755-40
◦ Mental Health Treatment Preference Declaration Act (755 ILCS 43/10)
 Allows for advanced directives related to mental health treatment
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IRB Best Practices
Review NBAC guidance and SACHRP
recommendations
 Benchmark other institutions
 Create guidance specific to your
organization
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◦ Utilize the guidance from legal counsel
◦ Consult expertise in decisionally impaired
populations
◦ Incorporate levels of review and anticipate
the type of populations at your institution
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Best Practices for IRBs
Consider consent templates with surrogate consent
or advanced directive language
 Make decisions regarding additional protections and
consent processes on a protocol per protocol basis
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Consider the population
When to require an independent assessment of capacity
Consider the use of consent monitors
When should advance directives be included
Risk level: minimal, minor increase over minimal, greater
than minimal
◦ Benefit
 Direct or indirect
 No benefit
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Q &A
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Contact Information:
Susan Loess-Perez, MS, CIP, CCRC
Director, Office of Research Protections
DePaul University
(312) 362-7593
sloesspe@depaul.edu
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