IRB Discussion
Consent and Assent Issues in
Vulnerable Populations
December 2008
irb@umn.edu
perke001@umn.edu 612-626-5922
History of Research Using
Vulnerable Populations
Nazi Experiments with Jewish and
mentally ill inmates
 Willowbrook trials with institutionalized
children with mental retardation
 Tuskegee syphilis study of poor and poorly
educated African American men
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The Nuremberg Code (1947)
As part of the verdict, the Court enumerated some rules for
"Permissible Medical Experiments", now known as the
“Nuremberg Code”. These ten rules include:
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Voluntary consent
Yield fruitful results otherwise unobtainable
Based on animal experiments
Avoid physical and mental suffering
Not done if injury expected
Risk less than importance of problem
Protect subject from injury
Conducted by qualified people
Termination by subject
Termination by investigator
Principle 1
The voluntary consent of the human subject is
absolutely essential. This means that the person
involved should have legal capacity to give consent;
should be so situated as to be able to exercise free
power of choice without the intervention of any
element of force, fraud, deceit, duress, overreaching or other ulterior form of constraint or
coercion; and should have sufficient knowledge and
comprehension of the elements of the subject
matter involved as to enable him to make an
understanding and enlightened decision.
The Belmont Report
Ethical Principles and Guidelines for the
Protection of Human Subjects of Research
The National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research
April 18, 1979
The Belmont Report
Basic Ethical Principles:
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Respect for Persons
– Individual autonomy
– Protection of individuals with reduced autonomy
Beneficence
– Maximize benefits and minimize harms
– Do good, not just avoid harm
Justice
– Equitable distribution of research costs and
benefits
45 CFR 46 – DHHS Policy for Protection of
Human Research Subjects- Subpart A
Originally adopted January 13, 1981
Revised June 18, 1991
“The Common Rule” –Federal Policy for Protection of
Human Subjects, June 18, 1991 –adopted by 17 federal
agencies
Federal Regulations and Policy
Additional Protections Included in 45 CFR 46:
Subpart B- Additional DHHS Protections Pertaining
to Research, development, and Related Activities
Involving Pregnant Women, Fetuses, and Neonates
(non-viable and those of uncertain viability)
Subpart C- Additional DHHS Protections Pertaining
to Biomedical and Behavioral Research Involving
Prisoners as Subjects
Subpart D-Additional DHHS Protections for Children
Involved as Subjects in Research
Authority:
– Federal Food, Drug, and Cosmetic Act (1962)
Regulations:
– IRB: 21 CFR 56
– Informed Consent: 21 CFR 50
 Adopted Sub Part D --- April 2001
– Investigational Drugs: 21 CFR 312
– Investigational Devices: 21 CFR 812
Inclusion of children:
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45 CFR 46 Subpart D
21 CFR 50 Subpart D
Guidelines expand inclusion
requirements
Exclusion must be justified
Guidelines do not relax requirement of
benefit
Issues of parental permission and child
assent present challenges
Federal Regulations: Children
Category
Requirements
45 CFR 46.404
21 CFR 50.51
•
Minimal risk
• Parental Permission
• Child’s assent
Federal Regulations: Children
Category
•
Requirements
45 CFR 46. 405
21 CFR 50. 52
Greater than minimal
risk; direct benefit
•
Risk justified by benefit
•
Risk/benefit is as
favorable as the
alternative
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Parental permission
Child’s assent/as
required by IRB
Federal Regulations: Children
Category
Requirements
45 CFR 46.406
21 CFR 50.53
•Minor increase over minimal risk
•Greater than
minimal risk/ no
direct benefit/ will
yield
generalizable
knowledge
•Experiences commensurate
with inherent, actual, or expected
situations
•Yield knowledge of vital
importance
•Both parents give permission
•Child assent
Federal Regulations: Children
Category
Requirements
45 CFR 46.407
21 CFR 50.54
•Otherwise not
approvable
•opportunity to
understand, prevent or
alleviate serious problem
affecting children
•HHS/FDA
consultation panel of
experts
•Public comment
Assent
• Affirmative agreement: failure to object
is not assent
• Required except when
• child not capable; age, maturity,
psychological state
• research presents direct benefit,
important to child’s well being and
available only in context of research
Age not specified in regulations
IRB determines whether and how to
document
IRBs give special consideration to
populations not protected with specific
regulatory sub parts:
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Vulnerable Subjects (regs take group approach):
– decisionally impaired including persons with
physical handicaps and mental disabilities
– economically disadvantaged persons
– educationally disadvantaged persons
Other considerations when
defining “Vulnerable”:
Language
 Culture
 Current Events or Incidents
 Age (elderly)
 Age (adolescents)
 Transient Cognitive Impairment
 Chemical Use
 Health Status
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IRB also understands
Definition of vulnerable is not black and
white
 People can go in and out of vulnerability
 Regulations are vague on this issue.
 Bottom Line: The IRB must ensure that
there are additional safeguards to protect
the rights and welfare of these
participants
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Targeting/Including Vulnerable
Populations; Appendix I
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Though not specifically referenced in the
federal regulations, the targeting or
inclusion of potentially vulnerable
populations (other than children, pregnant
women/fetuses and prisoners) in research
requires special considerations
Appendix I of IRB Application
Mentally/Emotionally/Developmentally
Disabled/Impaired Decision Making
Capacity
Targeted
Included
 Provide justification
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Explain how competency to provide consent
will be determined and plan for obtaining
surrogate consent
How to consent
Combination of “permission” from a
legally authorized representative and the
“assent” of potential participants
 Witnesses to consent process
 Periodic “re-consent”
 Formal checks of comprehension
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Legally Authorized Representative
..an individual, or judicial or other body,
under applicable law to consent on behalf
of the prospective subject to the subject’s
participation in the procedures involved in
the research.
45 CFR 46 .102 (c) and 21 CFR 50.3 (25) (l)
For Further information:
Email UMN RSPP Office: irb@umn.edu
UMN IRB Web Site:
http://www.research.umn.edu/subjects
Questions ?