Vulnerable Subject Populations: Special Issues for Consideration

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Vulnerable Subject Populations Special
Issues for Consideration
Emily Stern, MD and David Silbersweig, MD Weill
Cornell Medical College Research Coordinators
Network July 18, 2007
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Outline

• What is a vulnerable subject?
• What are subjects vulnerable to?
• What populations are vulnerable?
• Why is it important to study vulnerable subjects?
• How is decision-making capacity determined?
• Capacity in psychiatric patients
• Ex Schizophrenia
• Psychiatric symptomatology and research
• Ex Anxiety disorders
• Other Scenarios

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DHSS and FDA Regulations
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• DHHS regulation 45 CFR 46.111(b) and FDA
  regulation 21 CFR 56.111(b) require that
• "when some or all of the subjects are likely to
  be vulnerable to coercion or undue influence,
  additional safeguards have been included in the
  study to protect the rights and welfare of these
  subjects."
• Do not give definition of vulnerable
• Examples
• children
• prisoners
• pregnant women
• Handicapped persons
• mentally disabled persons
• economically or educationally disadvantaged
  persons

4
What is a vulnerable subject?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Belmont Report 3 basic ethical principles
• Respect for persons
• Benificence
• Justice
• Respect for persons at least 2 ethical
  principles
• Individuals should be treated as autonomous
  agents
• Persons with decreased autonomy are entitled to
  protection
• Vulnerable subjects are those with diminished
  autonomy

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What is autonomy?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• 2 components
• Mental capacity
• The ability to understand and process information
• Voluntariness
• Freedom from the control or influence of others
• Subjects have full autonomy when they have
• Capacity to understand and process information
• Freedom to volunteer without coercion or undue
  influence from others

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What subjects are vulnerable?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Any subject with a limitation of capacity or
  voluntariness
• Examples
• Capacity children subjects who are mentally
  disabled
• Voluntariness subjects
• in emergency situations
• in hierarchical social structures
• who are economically or educationally
  disadvantaged
• who are marginalized in society
• with fatal or incurable disease

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Do all subjects in a subject group have the same
degree of vulnerability?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• No
• Level of vulnerability of individual may change
  due to changes in capacity and/or voluntariness
• Examples
• subject on pain medication
• Patient with schizophrenia during acute psychosis
• Patient with schizophrenia during acute psychosis
  with specific delusional content

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What are subjects vulnerable to?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Physical control
• Ex Nazi hypothermia experiments
• Coercion credible threat of harm or force to
  control another
• Ex nursing home resident forced to choose
  research study or leaving nursing home
• Undue Influence misuse of power or position of
  confidnect to lead someone to make a decision
  that would not otherwise be made
• Ex MD responds affirmatively to patient inquiry
  re entering research study, in spite of knowing
  that this is not in patients best interest
• Manipulation intentional management of
  conditions or information that leads another to
  make decision not otherwise made
• Ex lying, withholding information, exaggeration

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What classes of subjects are vulnerable?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Children
• range of capacity possibility of control,
  coercion, undue influence, manipulation
• Embryos and Fetuses
• no capacity, direct control of mother
• Mentally disabled
• problems with capacity (continuous or
  fluctuating), voluntariness (if institutionalized
  or hospitalized), economically and educationally
  disadvantaged, suffer chronic disease potential
  control, coercion, undue influence or
  manipulation
• Emergency situations
• Capacity and voluntariness compromised potential
  for control, coercion, undue influence,
  manipulation
• Hierarchical Social Structures
• Voluntariness can be compromised potential for
  control, coercion, undue influence or
  manipulation

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What classes of subjects are vulnerable?(continue
d)
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Educationally Disadvantaged Subjects
• may have limitations on understanding study may
  be illiterate possibility for undue influence
  and/or manipulation.
• Economically Disadvantaged Subjects
• may have limitation on voluntariness may enroll
  only to receive monetary compensation may enroll
  to obtain medical care they cannot otherwise
  afford potential for undue influence or
  manipulation.
• Marginalized Social Groups
• may lack influence in society as a result of
  race, age, disease, or caste systems often do
  not have full access to social institutions such
  as legal system potential for control, coercion,
  undue influence, or manipulation.
• Individuals with Incurable or Fatal Diseases
• often have limitations on voluntariness may have
  problems with capacity caused by disease or
  medications may accept very high risks in
  desperation for a cure, even when little or no
  prospect of direct benefit.

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National Bioethics Advisory Commission (NBAC)
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• 2001 Report entitled Ethical and Policy Issues
  in Research Involving Human Participants
• New framework for understanding human research
  subject vulnerablity
• 6 categories of vulnerability
• Cognitive or Communicative Vulnerability
• Institutional Vulnerability
• Deferential Vulnerability
• Medical Vulnerability
• Economic Vulnerability
• Social Vulnerability

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Cognitive or Communicative Vulnerability
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Subjects not able to understand, deliberate, make
  decisions about participation in research study
• 3 categories
• Capacity-related cognitive vulnerability young
  children or adults with cognitive impairments
  that affect decision making lack capacity to make
  informed choice
• Situational cognitive vulnerability have
  capacity but cant use it effectively (e.g.
  stressful emergencies)
• Communicative vulnerability e.g. speak or read
  different languages

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Institutional Vulnerability
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Subjects have cognitive capacity to consent but
  are subject to the formal authority of others who
  may have independent interests in whether the
  subject agrees to enroll in the research study.
• E.g. prisoners, military personnel, college
  students
• Risk not truly voluntary personhood not fully
  respected subordinated status of these
  individuals exploited

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Medical Vulnerability
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Serious health conditions for which there are no
  satisfactory standard treatments (e.g.,
  metastatic cancer or rare disorders)
• Can be difficult to weigh risks and benefits
• Risk of misunderstanding potential benefits or
  motivation based on desire to find a treatment
• Risk of exploitation
• have unreasonable expectations about the
  potential benefits
• investigators mislead regarding risks and
  potential benefits
• risks are not reasonable in relation to potential
  benefits.  

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Economic Vulnerability
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Disadvantaged in the distribution of social goods
  and services income, housing, health care.
• Risk that potential benefits from research study
  might constitute undue inducements to enroll,
  threatening voluntary nature of the choice and
  raising danger that the potential participants
  distributional disadvantage could be exploited.
• Example
• large sums of money as payment for participation
• access to free health care services (for
  conditions not related to the research)
• could influence enrollment in research study even
  when against subjects better judgment and when
  otherwise they would not do so

16
Social Vulnerability
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Undervalued social groups, not simply
  attributable to economic vulnerability
• Function of the social perception of certain
  groups, which includes stereotyping and can lead
  to discrimination
• Perceptions devalue members of such groups, their
  interests, their welfare, or their contributions
  to society

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What makes a psychiatric patient vulnerable?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Mentally disabled
• problems with capacity (continuous or
  fluctuating), voluntariness (if institutionalized
  or hospitalized), economically and educationally
  disadvantaged, suffer chronic disease potential
  control, coercion, undue influence or
  manipulation
• NBAC Cognitive or Communicative Vulnerability
• Capacity-related cognitive vulnerability young
  children or adults with cognitive impairments
  that affect decision making lack capacity to make
  informed choice

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Why is it in important to study vulnerable
subjects?
CITI Course in The Protection of Human Research
Subjects, www.citiprogram.org David Forster JD,
MA

• Only way to work toward improved diagnosis and
  treatment is to study the disease
• For psychiatric patients one cause of
  vulnerability is often the underlying disease
• NYS Office of Mental Health lawsuit

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Decision-Making Capacity (Eyler LT and Jeste
DVmBehav Sci. Law 24552, 2006 Larkin L et al
Acad Emerg Med 8(3) 282, 2001)

• Decision-making capacity patients ability to
  make informed choice
• Includes ability to
• Receive information
• Process and understand information /
  appreciate understand the relevance to his/her
  own situation
• Deliberate / reason manipulate presented
  information especially weigh risks and benefits
  against alternative courses of action
• Make, articulate and defend choices
• Changes with subject and environmental factors
  over time
• May be competent for one decision and not another

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Functional Neuroimaging Research 3T MRI Scanner
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Capacity In Psychiatric PatientsSchizophrenia
as an example

• What is psychosis?
• Does a psychotic patient always have impaired
  decision-making capacity?
• Role of Consent Consultant
• Role of Consent Monitor

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Psychiatric Symptomatology and Research Anxiety
Disorders as an Example

• What are anxiety disorders?
• What are some symptoms of anxiety disorders?
• How does this symptomatology impact on functional
  neuroimaging research?

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Functional Neuroimaging Research 3T MRI Scanner
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Other scenarios

• Detecting psychiatric disorders in healthy
  controls
• Psychiatric symptoms in non-psychiatric research
  studies