Transcript Slide Master

Protection of Vulnerable
Subjects in Research
Melody Lin, Ph.D.
December 2012
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Objectives
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What ? Why ?
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Background for additional protections
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US requirements for protection of
vulnerable subjects in research
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“Vulnerable” Subject
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Ethical principles
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Respect for persons
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Respect for persons
Beneficence
Justice
Autonomous
Decreased Autonomy
Vulnerable subjects are those with
diminished autonomy
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Autonomy
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Capacity
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Voluntariness
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Ability to understand and process information
Freedom from the control or influence of
others
Full autonomy
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Capacity to understand and process
information
Freedom to volunteer without coercion or
undue influence
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What subjects are vulnerable?
A limitation of capacity or voluntariness
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Capacity
children
 subjects who are mentally disabled
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Voluntariness
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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Vulnerable Populations
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Children, minors
Pregnant women
Prisoners
Fetuses
Cognitively impaired
persons
Economically
disadvantaged persons
Educationally
disadvantaged persons
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Military
Students
Elderly
Workers
Veterans
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What are subjects
vulnerable to?
 Physical
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control
Nazi hypothermia experiments
 Coercion:
threat of harm or force to
control another
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Nursing home resident forced to choose research
study or leaving nursing home
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What are subjects
vulnerable to?
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Undue Influence: misuse of power or position
to lead someone to make a decision that would
not otherwise be made
─
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Entering research study, in spite of knowing that this
is not in patient’s best interest
Manipulation: intentional management of
conditions or information that leads another to
make decision not otherwise made
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Lying, withholding information, exaggeration
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Why Study Vulnerable Subjects?
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Improve diagnosis and treatment of the
disease & condition
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Special Protections
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Why?
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Past abuses of the rights of subjects,
especially vulnerable subjects
Ethical principles of justice and respect of
persons
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Additional Protections
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What?
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Federal regulations
State statutes
Special review by IRB
Risk/benefit of the study
Researcher sensitivity to the particular
category of vulnerability
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Research Involving
Vulnerable Subject
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Important to conduct ethical research into
conditions affecting vulnerable individuals
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Be certain information provided is
understandable
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Protection of human rights
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Above all – do no harm
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Vulnerability
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If vulnerable once – Is subject vulnerable
forever?
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When is a child not a child?
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Are emotionally disabled persons always
vulnerable?
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Where does vulnerability start and end?
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Definition
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Vulnerability – susceptible to harm
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“those who are relatively (or absolutely
incapable of protecting their own interests.”
(Levine, 1986 p.72)
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Harm – social, economic, legal,
psychological, and physical (Belmont Report)
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Specific Vulnerability
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Cognitive or communicative –diminished
capacity to understand
Institutional – subject to formal authority of
others
Deferred – subordinate to others
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cultural or societal norms
physician and patient
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Specific Vulnerability
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Medical – serious illness; research may be
believed to be offering ‘hope’
Economic – benefits offered by research
Social – participant groups may subject
participants to risk/benefit unacceptable to
other groups
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US Regulations
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45 CFR 46 & 21 CFR 56 – Subparts B-D
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Subpart B: women, fetuses and neonates
Subpart C: prisoners
Subpart D: children
State Regulations
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Requirements for
Research Involving
Pregnant Women and
Fetuses
45 CFR 46 Subpart B
FR 66, No. 219, 11/13/01
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Requirements
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Appropriate pre-clinical studies have been
completed on pregnant animals and non-pregnant
women.
The risk to the fetus is caused solely by
interventions that offer direct benefit for the
woman or fetus
or
If there is no prospect of benefit
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The risk to the fetus is not greater than minimal.
The purpose of the study is to develop important
biomedical knowledge
The knowledge cannot be obtained by any other means
45 CFR 46.204
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Requirements cont’d
Any risk to the pregnant woman or the
fetus is the least possible to achieve the
research objective.
 Consent of the pregnant woman and
father (if available) is required if the
research may only benefit the fetus.
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Requirements cont’d
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Consent of the pregnant woman only is
required for research which
May benefit the woman only
─ May benefit the woman and fetus
─ Will not benefit the woman or fetus but
there is minimal risk to the fetus
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The purpose of the research is to develop
important biomedical knowledge
 The data cannot be obtained by any other means
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Requirements cont’d
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The consent form must fully disclose
reasonably foreseeable risks to the fetus
There are no inducement offered to
terminate a pregnancy
The investigator will not be involved in any
decisions to terminate a pregnancy
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Requirements for Research
Involving Prisoners
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IRB Composition
§46.304
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Majority have no association with the
prison
One member must be a prisoner or
prisoner representative
All other requirements under §46.107
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Additional duties
§46.305
(1) Approved categories
(2) No undue influence
(3) Risks are same as non-prisoners
(4) Fair subject selection
(5) Understandable language
(6) No impact on parole
(7) Follow-up care
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Subpart D
Additional DHHS Protections for
Children Involved as Subjects in
Research
March 8, 1983
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IRB Duties
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Not greater than minimal risk. (§46.404)
Greater than minimal risk, prospect of
direct benefit. (§46.405)
Greater than minimal risk, no prospect of
direct benefit but generalizable knowledge.
(§46.406)
Not otherwise approvable. Further
understanding, prevent or alleviate.
(§46.407)
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Assent of Children
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IRB determines when children are capable
of assent based on age, maturity, and
psychological state. §46.408(a)
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IRB determines whether and how assent
is to be documented §46.408(e)
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Parental Permission
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Adequate provisions are made to solicit
permission of each child’s parent or
guardian.
Under §46.404 and §46.405, one parent
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Parental Permission, cont.
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Under §46.406 and §46.407, two parents
unless one is deceased, unknown,
incompetent or not reasonably available.
Or in case of sole custody.
Waiver of parental consent (§46.116,
Subpart A) Abused or neglected children
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Summary

What ? Why ?

Background for additional protections

US requirements for protection of
vulnerable subjects in research
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Summary
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Ethical research is guided by principles of
justice, respect for persons, and
beneficence
Vulnerable subjects should be included
but also deserve special protections
Take steps to ensure their rights and
welfare are protected
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