Ethical Issues in Research with “Vulnerable” and “Hard‐to‐Reach” Populations
Emily E. Anderson, PhD, MPH
Assistant Professor
Neiswanger Institute for Bioethics
L l U i
Loyola University Chicago
it Chi
May 15, 2014
UIC Institute for Health Research and Policy Talk
UIC Institute for Health Research and Policy Talk
“Bioethical
Bioethical Trump Card
Trump Card”??
• “The
The concept of vulnerability appears to have concept of vulnerability appears to have
been grandfathered into the lexicon, lore, and literature of research ethics without undergoing g g
stringent certification. And yet the need for some such notion has long been appreciated.”
‐Ken
Ken Kipnis, 2001
Kipnis, 2001
“Vulnerability in Research Subjects: A Bioethical Taxonomy
Taxonomy”
Definitions/Interpretations
• Vulnerable means Vulnerable means “subject
subject to exploitation
to exploitation”
• Unequal power relationships between potential subjects and investigators/sponsors create the potential for exploitation
• Exploitation is wrong, and therefore we want t
to prevent/avoid it in research
t/ id it i
h
Or… are we all at risk?
Or… are we all at risk?
• We
We are all vulnerable although some may be are all vulnerable although some may be
more “predisposed” to additional harm than others
• Vulnerability is inevitable because people are interdependent interdependent
• One can be vulnerable w/o being harmed or wronged (and vice versa)
d( d i
)
2 Ways of Looking at Vulnerability
2 Ways of Looking at Vulnerability
• A
A characteristic inherent to an individual or characteristic inherent to an individual or
group
• A characteristic inherent in a situation
KEY RESEARCH ETHICS GUIDANCE KEY
RESEARCH ETHICS GUIDANCE
DOCUMENTS
Belmont Report
Belmont Report
• A
A reaction to historical abuses perpetrated reaction to historical abuses perpetrated
against certain groups in certain settings
• Principle of JUSTICE, fair selection of subjects
Principle of JUSTICE fair selection of subjects
• Presumption: Certain categories of people are presumed more likely to be mistreated, d
lik l
b
i
d
misled, or otherwise taken advantage of
• Vulnerability generates a duty for “special protections” (for researchers, regulators, IRBs)
Belmont Report
Belmont Report
• Vulnerability results from Vulnerability results from
– “dependent status and frequently compromised capacity for free consent” capacity for free consent
combined with
combined with – “ready
ready availability in settings where research is availability in settings where research is
conducted”
CIOMS (2002)
CIOMS (2002)
• Vulnerable
Vulnerable persons defined as persons defined as “those
those who are who are
relatively (or absolutely) incapable of protecting their own interests because they
protecting their own interests because they may have insufficient power, intelligence, education resources strength or other
education, resources, strength or other needed attributes to protect their own interests
interests”
Kipnis
“A
A MOTLEY COLLECTION OF MOTLEY COLLECTION OF
VULNERABLE SUBPOPULATIONS”
Belmont Report (1979)
Belmont Report (1979)
•
•
•
•
racial minorities
racial
minorities
economically disadvantaged
very sick
i k
institutionalized
45 CFR 46
45 CFR 46
“vulnerable category of subjects”
g y
j
“special problems of research involving vulnerable populations”
“vulnerable to coercion or undue influence”
ADD’L PROTECTIONS CODIFIED
• Pregnant women (Subpart B)
• Prisoners (Subpart C)
• Children (Subpart D)
ADDITIONAL SAFEGUARDS?
• handicapped persons • mentally disabled persons
• economically disadvantaged persons
• educationally disadvantaged persons
OHRP Guidance (Website)
OHRP Guidance (Website)
• “Vulnerable
Vulnerable populations
populations” has its own heading
has its own heading
– Children
– People with HIV/AIDS
People with HIV/AIDS
– Prisoners
– Privacy protections/ Certificates of Confidentiality
Pi
t ti / C tifi t
f C fid ti lit
– A video that I could not bring myself to watch
OHRP IRB Guidebook (2001)
OHRP IRB Guidebook (2001)
•
•
•
•
•
•
•
•
•
•
Cognitively impaired
Traumatized
Comatose
T
Terminally ill
i ll ill
Elderly/aged
Minorities
Students
Employees
“normal” volunteers
Participants in international research (anyone not American?)
CIOMS (2002)
CIOMS (2002)
• Residents of nursing es de s o u s g
homes
• People receiving welfare benefits & social assistance
• Unemployed
U
l d
• Other poor people
• People in emergency People in emergency
rooms
• Homeless
• Nomads, refugees, o ads, e ugees,
displaced persons
• Prisoners
• Patients with incurable disease
• Individuals who are politically powerless
• Members of communities Members of communities
unfamiliar with modern medical concepts
p
Does the concept help us protect participants?
• “So many groups are now considered to be So a y g oups a e o co s de ed to be
vulnerable in the context of research, particularly international research, that the concept has lost f
force.” (Levine, et al)
”(
l)
• Obsession with adding groups to the list
• Little talk of appropriate protections
• Stereotyping versus actually protecting? (doesn’t distinguish between individuals in a group)
RECOMMENDED SAFEGUARDS, RECOMMENDED
SAFEGUARDS,
“EXTRA” & “SPECIAL” PROTECTIONS
Declaration of Helsinki (2013)
Declaration of Helsinki (2013)
19. Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or of incurring additional harm.
• All vulnerable groups and individuals should receive specifically considered protection.
20. Medical research with a vulnerable group is only justified if the research is responsive to the health needs or priorities of this group and the research cannot be carried out in a non‐
of this group and the research cannot be carried out in a non
vulnerable group. In addition, this group should stand to benefit from the knowledge, practices or interventions that result from the research.
45 CFR 46.111(a)(3) ‐ approval
45 CFR 46.111(a)(3) • Selection
Selection of subjects is equitable. In making of subjects is equitable. In making
this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research i
f h
i l
bl
f
h
involving vulnerable populations, such as children prisoners pregnant women
children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons
educationally disadvantaged persons.
45 CFR 46.111(7)(b)‐approval
45 CFR 46.111(7)(b)
approval
• When
When some or all of the subjects are likely to some or all of the subjects are likely to
be vulnerable to coercion or undue influence, such as children prisoners pregnant women
such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons
educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of
the study to protect the rights and welfare of these subjects.
Types of Safeguards
Types of Safeguards
• IRB
IRB membership/representation in ethics membership/representation in ethics
review • Specific regulations
Specific regulations
• Restrictions/limitations on participation prisoners (prisoners)
i
( i
)
• “Add‐ons” to or replacements for individual informed consent (children) y p (
)
• Processes for community input (EFIC)
45 CFR 46.107a – IRB membership
45 CFR 46.107a IRB membership
• If
If an IRB regularly reviews research that an IRB regularly reviews research that
involves a vulnerable category of subjects, such as children prisoners pregnant women
such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of
consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in
knowledgeable about and experienced in working with these subjects.
Specific Subparts
Specific Subparts
• 45 CFR 46 45 CFR 46
– Subpart A) prisoners
– Subpart B) children
Subpart B) children
– Subpart C) pregnant women
• 21 CFR 50.24 (FDA)
– Exception from informed consent requirements for emergency research
Prisoners 46.304 (representation)
Prisoners 46.304 (representation)
• ((a) A majority of the Board (exclusive of prisoner )
j y
(
p
members) shall have no association with the prison(s) involved, apart from their membership on the Board
on the Board.
• (b) At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one
research project is reviewed by more than one Board only one Board need satisfy this requirement.
Restrictions on Participation: Prisoners
Restrictions on Participation: Prisoners
• Studies
Studies of causes/effects/processes of of causes/effects/processes of
incarceration or of prisons as institutions that are < minimal risk
are < minimal risk
• Research on conditions that particularly affect prisoners as a class
prisoners as a class
• Research with strong possibility of direct b
benefit
fi
Children (Subpart D) 46.408
Children (Subpart D) 46.408
• Parental consent a e ta co se t
– 1 or both parents – depends on risk, benefit, and reasonableness
– Waivers of parental consent allowable provided “an appropriate mechanism for protected the children who will participate” is in place….
p
p
p
• Child assent
– Rule of 7s
– When to require assent/take dissent seriously
– Always inform
EFIC
A different way of looking at vulnerability?
A
different way of looking at vulnerability?
Consultation
Public disclosure
bli di l
Independent data monitoring
LAR or contact within “therapeutic window” y
with a family member
• Inform subject as soon as possible
•
•
•
•
•
“RECONNOITERING
RECONNOITERING THE TERRAIN THE TERRAIN
OF VULNERABILITY”
Kipnis (2001)
• Analyzed
Analyzed categories of vulnerability, not categories of vulnerability not
subpopulations
• Defined vulnerability as limit on ability to Defined vulnerability as limit on ability to
provide informed consent
• What characteristics are common among Wh h
i i
disparate groups?
• What should researchers do?
Cognitive Vulnerability
Cognitive Vulnerability
• Does the individual have the capacity to oes t e d dua a e t e capac ty to
deliberate about and decide whether or not to participate in the study?
– Immaturity, dementia, mental illness, mental retardation
– Education, language
Education language
– Individuals in situations where there’s not enough time
• Plain language forms, advance directives, supplementary education, surrogates/advocates
Juridic Vulnerability
• Is the person liable to the authority of others who may p
y
y
have an independent interest in that participation?
• Formal authority relationships
–
–
–
–
–
–
Prison
Military
Children/parents
Students
Institutionalized Women subjected to husbands’ authority
• How to devise a consent procedure that adequately protects the individual from the hierarchical system
protects the individual from the hierarchical system
Deferential Vulnerability
Deferential Vulnerability
• Is
Is the individual given to patterns of the individual given to patterns of
deferential behavior that may mask an underlying unwillingness to participate?
underlying unwillingness to participate?
• Informal relationships (as opposed to juridic)
I f
l l i hi (
d j idi )
• IC process should eliminate pressure
Medical Vulnerability
Medical Vulnerability
• Has
Has the individual been selected, in part, the individual been selected in part
because she has a serious health‐related condition for which there are no satisfactory
condition for which there are no satisfactory remedies?
Allocational Vulnerability Vulnerability
• Is
Is the person seriously lacking in important the person seriously lacking in important
social goods that will be provided as a consequence of his or her participation in
consequence of his or her participation in research?
Infrastructural Vulnerability
Infrastructural Vulnerability
• Does
Does the political, organizational, economic, the political organizational economic
and social context of the research setting possess the integrity and resources to manage
possess the integrity and resources to manage the study?
Social Vulnerability
Social Vulnerability
• Does
Does the individual belong to a socially the individual belong to a socially
undervalued group?
Kipnis’ Conclusions
Kipnis
Conclusions
• Some
Some individuals/populations will exhibit individuals/populations will exhibit
multiple vulnerabilities
• More attention to medical vulnerability
More attention to medical vulnerability
• Need to consider “fair entitlements of research subjects who are disadvantaged in h bj
h
di d
di
economic and others ways”
• Need for more resources to help guide decision‐making re: appropriate protections
Criticisms of Kipnis (Levine et al)
Criticisms of Kipnis
(Levine et al)
• Leads to problematic inferences
– Everyone who fits into any of these categories is vulnerable
– Anyone who is capable of free consent is NOT
• More focus needed on
–
–
–
–
Features of the research
Institutional environment
Institutional environment
Social/economic context
Timing of research
• Women in labor, right after a natural disaster
Women in labor, right after a natural disaster
– Emotional factors
• Disease that killed a loved one
– Prior personal experience
p
p
Are we all vulnerable?
Are we all vulnerable?
• Benefits
Benefits of research can never be guaranteed of research can never be guaranteed
in advance • Much clinical research is combined with care Much clinical research is combined with care
(i.e. participants are sick)
• If it applies to everyone, If it applies to everyone, “every
every research research
protocol requires some type of special attention and IRBs have no guidance on where to concentrate their limited attention and resources” (Levine et al)
“Special
Special Scrutiny
Scrutiny” (Levine et al)
(Levine et al)
• Translates
Translates new scientific advances to humans new scientific advances to humans
for the 1st time (especially when intervention is novel and/or irreversible)
is novel and/or irreversible)
• Known/credible risk of significant harm AND NO potential of direct medical benefit
NO potential of direct medical benefit
• Raises ethical questions about research design or implementation for which there is no i l
i f
hi h h
i
consensus
Challenges to Traditional Conceptions of Vulnerability
f l
bl
• NIH
NIH policy on inclusion of women and policy on inclusion of women and
minorities (1994, updated 2001)
• NIH policy on inclusion of children (1998)
NIH policy on inclusion of children (1998)
• Increased funding for health disparities research, research on minority health
h
h
i i h lh
Question for Discussion
Question for Discussion
• If the research is minimal risk, should t e esea c s
a s , s ou d
extra/special protections, safeguards be required? Why or why not? Does your answer d ff d
differ depending on the population?
d
h
l
?
• “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in it d f h
di
f t ti i t d i
the research are not greater in and of themselves than those ordinarily encountered in daily life or
than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
DISCUSSION/BRAINSTORM
WHAT ARE APPROPRIATE WHAT
ARE APPROPRIATE
PROTECTIONS?
• You’ve
You ve been funded to conduct a survey with been funded to conduct a survey with
LGBT teens on drug and alcohol use. You assumed you’d
assumed you
d request a waiver of parental request a waiver of parental
consent, but you’ve heard from others that your IRB doesn’tt like to waive parental your IRB doesn
like to waive parental
consent.
• You’re planning research at a health clinic that ou e p a
g esea c at a ea t c c t at
involves a survey, an intervention, a post‐test, and an in‐depth interview. You’re told that the clinic has a policy that research involving their l
h
l
h
h
l
h
patients can only pay $10 per research interaction You expect the interviews to last an
interaction. You expect the interviews to last an hour and have paid $30 for other similar research. When you ask for an exception, the y
p
administration tells you that the subjects are vulnerable and that more than $10 is coercive. • A
A tornado touches down in the middle of tornado touches down in the middle of
Logan Square. Perfect timing for your dissertation! You want to study the effects of
dissertation! You want to study the effects of social networks on coping with natural disasters Time is of the essence and you
disasters. Time is of the essence, and you really want your protocol to be approved the first time around
first time around. Category 2 Exemption
Category 2 Exemption
Research involving the use of educational tests g
(cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior unless: (i)
observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or th
through identifiers linked to the subjects; and (ii) h id tifi li k d t th
bj t
d (ii)
any disclosure of the human subjects' responses outside the research could reasonably place the yp
subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability or reputation
employability, or reputation.
• For
For patients with Alzheimer
patients with Alzheimer’ss disease, it
disease it’ss highly likely that their LAR is going to be a child – possibly someone with an increased child possibly someone with an increased
risk (real or perceived) of developing the disease themselves Does anyone else think
disease themselves. Does anyone else think these individuals should be prohibited from giving consent for parental participation in
giving consent for parental participation in research that is greater than minimal risk?