Vulnerable Populations

Marisue Cody, PhD

Deputy Director, PRIDE

Objectives

• Describe populations likely to be vulnerable and context of vulnerability

• Discuss capacity to consent

• Determine when a surrogate can provide consent for research

Population

Subject vulnerability

“when some or all of the subjects are likely to be vulnerable to coercion or undue influence,…additional safeguards must be included in the study to protect the rights and welfare of these subjects.”

38 CFR 16.111(b)

What are they vulnerable to?

• Physical control

• Coercion

• Undue influence

• Manipulation

Diminished autonomy

• Mental capacity—ability to understand and process information

• Voluntariness—freedom from the control or influence of others

Defining the vulnerable group

Classes of subjects that

are likely to include

individuals with impaired

decision-making

Individuals who do have

impaired/diminished/limited

decision-making

Individuals who lack the

capacity to consent to

a research study

Individual vs. Contextual Considerations

“individuals with impaired decision-making”

vs.

“potential research participants who are especially likely to be have limitations in their ability to protect their interests by making an informed, competent, and

voluntary choice regarding participation.”

The nature of decisional “vulnerability”

• Contextual vs. disorder-related impairment(e.g. emergency room, “institutions” vs. stroke)

• Global vs. specific impairment (e.g. sedative overdose vs. paranoid psychosis)

• Static vs. progressive vs. episodic vs. time limited impairment (e.g. severe mental retardation vs. Alzheimer’s disease vs. manic depressive disorder vs. TBI)

• Acute vs. persistent impairment(e.g. hypoxia secondary to asthma or acute pain vs. MR, autism)

Capacity to Consent

Trajectories of Capacity Impairment

• Neurodegenerative disorders: gradual, progressive decline and eventual permanent incapacity

• Psychiatric disorders: often diminished capacity that is generally static but subject to transient fluctuations

• Developmental disabilities: diminished capacity or incapacity which is static until later life and cognitive aging

• TBI: abrupt impairment or loss of capacity followed by at least partial recovery. Improvement in capacity distinctive aspect of TBI

TBI and Capacity

• difficulty learning and retaining new information• difficulty recalling relevant historical information• difficulty understanding simple concepts• difficulty expressing preferences and choices• loss of mental flexibility and planning• impairment of judgment• distortion of reality (delusions)• vulnerability to undue influence,

exploitation/abuse

Research in AD

• Most clinical trials and many observational studies require “study partner” to insure memory and insight

• Usually a family member (spouses or children) whose role is• Supervise medication, and follow-up• Report on side effect, and efficacy outcomes

• Study partner is typically part of the consent process

0

10

20

30

40

50

60

70

80

Mild AD

Mod-Sev TBI

Changes in Understanding Consent Ability Across Time and Patient Groups

Risks of the Research

When can research be done?

• They comprise the only appropriate study population

• The research question focuses on an issue unique to subjects in this population

Degree of risk

• Minimal risk

• “Minor over minimal”

• Acceptable risk-knowledge ratio

• “Maximal potential risk”

Case study

Acceptable risk?

• Initial trials of a new drug for AD:• 63% stops the progress of the disease

• ~50% it even produces some restoration of cognitive capacity

• 20% -- no effect.

• 15% serious and, in two cases, a fatal reaction.

•Post SG, Full-spectrum proxy consent for research participation when persons with Alzheimer Disease lose decisional capacities: Research ethics and common good. Alzheimer Disease and Associated Disorders 2003; 17: S3-S11.

Limiting risks

• Inclusion/exclusion criteria

• “Aggressive monitoring”• Routine and constant

• Respect for subjects’ physical resistance or other expressed dissent

• When to halt…..

Surrogate Consent

Research Involving Human Subjects with Surrogate Consent

• Common Rule• Section 117 – “subject’s legally authorized

representative”

• VHA Handbook 1200.5• Paragraph 11• Appendix D Paragraph 6

Capacity to consent

• Presumed competent to consent unless there is evidence of serious mental disability

• Provide a plan for determining the incapacity

Competence vs. capacity

• “Competence” -- legal and moral status of individuals that entitles them to make their own decisions

• “Capacity” – cognitive, affective, and volitional abilities that underlie competence

Formal procedures for capacity assessment

• Goes against the presumption of assumed competence in adults

• Reserve for populations with high probability of decisional-impairment

• Who decides?• Structured questionnaire

• Clinical care model: leave the decision to a disinterested 3rd party

Surrogate consent

• When prospective patient is incompetent or has impaired decision-making capacity• Practitioner, in consultation with the chief of

service, or COS, after an appropriate medical exam

• Consultation with psychiatrist or licensed psychologist if based on a diagnosis of mental illness

• Consent disclosures to the surrogate• Explanation to subject

Legally authorized representative

• Court appointed guardian, only with the court’s consent

• Health care agent appointed in a durable power of attorney

• Next of kin (1200.5 pg. 20): Spouse, Adult child, Parent, Adult sibling, Grandparent, or Adult grandchild (depending on state law)

What to tell representative…

• Description of the proposed research and the risks and benefits of participation

• Their obligation as the patient’s representative, i.e., try to determine what the patient would do if competent or, what they think is the subjects’ best interests

A conflict between best interests and substituted judgment

• A patient has a documented substituted judgment that he or she would not want to be in the RCT study but their study partner feels being in the study would maximize the patient’s well-being. What should the study partner choose?• Study partners generally chose what would maximize

the patient’s well-being (43/59, 73%)

• Fifteen (26%) chose to decide based on what the patient would want.