Transcript Ethics and Human Subject Issues in Research: Informed Consent

Human Subject
Issues in Research:
Informed Consent
Jill M. Baren, MD
What is Ethics?
The study of standards and conducts
and moral judgment
 The system or code of morals of a
particular person, religion, group, or
profession

Identifying Ethical Issues
Write down 2 ethical issues, problems
or questions that you have encountered
since becoming an academic associate
 How were they resolved?
 Did you feel the resolution was
satisfactory?

INFORMED CONSENT
What is it?
 Why do we need it?
 From whom do we get it?
 How do we get it?
 How can we be sure we’re doing it
right?

Informed Consent

What it’s not
 A legal document
 A risk
management tool
for an
investigator or an
institution
 A formality

What it is
 A Process
 Acknowledging
respect for
persons
(Autonomy)
Goal

“The goal of the informed consent
process is to provide people with
sufficient information so they can
make informed choices about whether
to begin or continue participation in
clinical research.”
The process

“…involves a dynamic and continuing
exchange of information between the
research team and participant
throughout the research experience…”
The document
“…a starting point for the necessary
exchange of information between
investigator and potential participant.”
 “…the foundation not the entirety…”

Why do we need it?
Respect for persons
 Respect for autonomy of decision
making
 True limit on investigative authority
 Sense of formality

Historical Perspective
Research ethics policies
 From singular events and the
reactions to them
 Rarely proactive

Sentinel events

Nazi war crimes

Human radiation
experiments, etc.

Tuskegee Syphilis
study
Nuremberg trial
(1948)
Declaration of
Helsinki (1963)
National Commission
Belmont Report
(1977)
Nuremberg, Germany
December 9, 1946 to August 20, 1947
Required voluntary
consent prior to
participation
 Investigator
responsibility to
obtain consent
 Information gained
by using human
subjects would be
unprocurable any
other way

Declaration of Helsinki
(World Medical Association)
Articulated ethical principles for use
by physicians conducting human
research
 Affirmed the autonomy of the
individual
 Universally adopted to ensure the
rights and welfare of human subjects
of research

Tuskegee Syphilis Study
Post- Tuskegee Events
National Research Act 1974
 National Commission for the
Protection of Human Subjects of
Biomedical and Behavioral Research
 Belmont Report
 Ethical foundation for US federal
regulations on human subjects
research

Belmont Report

3 basic principles that should govern
all research involving human subjects
 Respect for persons
 Beneficence (maximize benefits,
minimize risks, avoid harm)
 Justice (benefits and burdens equally
distributed)
Federal regulations (DHHS)

1991 Federal Policy for Protection of
Human Subjects (The Common Rule)
 Adopted by all agencies which
conduct, supervise, regulate, fund or
sponsor human research
 Two major requirements:
Informed Consent
IRB approval
What does someone need to know?
Disclosure (what’s going to happen)
 Risks
 Benefits
 Alternatives
 Confidentiality
 Compensation

“It’s a very simple procedure. We slice off the
top of your head, scoop out your innards with a
spoon, and carve out your eyes and mouth.”
Standards for Disclosure
Subjective
 “The reasonable volunteer”
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Are we doing it right?

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Voluntariness:
 Freely coming to a decision
 Free from coercion or undue influence
 Assumes capacity
Capacity
 Understand nature and ramifications
Who is not able to do this?
Vulnerable populations
Children ?
 Prisoners?
 Mentally retarded individuals
 Dementia/Coma/Vegetative state
 Mental illness
 Pregnant women
 Emergency patients? (pain, fear, etc.)

Vulnerable Populations: Children
If child can understand (> age 6-8)
 We are obligated to obtain assent
 Can parents overrule?
 In studies with more than minimal
risk and not without prospect of
direct benefit

Other vulnerable populations
Research on individuals who lack
capacity also requires prospect of
benefit
 Not promulgated in federal regulations
 Family member can consent
 If consistent with state law

How do we get informed consent?
Will vary according to study design
and nature of participation
 Verbal vs. Written
 Investigator vs. proxy

Are we doing it right?

Behaviors during informed consent
(>1000 ED patients taking a survey)
 41%
did not read
 57% who read spent < 60 seconds
 22% asked questions
 44% did not accept the form
Informed consent behaviors
 No
relationship with gender,
education, marital status, or
self-reported health status
 We need to do better to correct
these behaviors
Baren et al: AEM May 2000
Informed consent gone wrong?
Jesse Gelsinger (gene transplant)
 James Quinn (artificial heart)
 Johns Hopkins (hexamethonium death)
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Gene therapy business:
“The tragic case of Jesse Gelsinger”

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18 year old with
partial ornithine
transcarbamylase
deficiency
Usually fatal in
infancy
The first person to
die from gene
therapy
Reactions

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FDA suspended all gene therapy trials and
other experiments
Hearings on quality of oversight and safety
President Clinton demanded improvements
in consent and access to information about
gene therapy research
James “Butch" Quinn:
Artificial Heart Recipient
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52 year old who
received the
Abiomed heart
Lived for 10 months
with the device
Sustained fatal
stroke
Reactions
Lawsuit over consent process
 Recipient's widow says she and her
husband were misinformed and misled
on risks, benefits and the potential for
pain and suffering
 “There was no quality of life. It was too
painful. He said he wished he'd never
done it."
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Was it wrong?

13-pages detailing "significant risks"
 stroke,
brain and organ damage,
discomfort and pain.
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“New and experimental operation”
Complications could occur (previously
unknown or unforeseen)
Potential benefits “uncertain and not
proven”
Volunteer in Asthma Study
Dies After Inhaling Drug
24 hours after inhaling
hexamethonium reported dry cough,
shortness of breath, muscular aches
and fever
 2 days later admitted with concern for
possible reaction
 Died one month later
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Reactions
Research suspended
 Federal government temporarily shut
down most research involving human
subjects at JHU
 Hexamethonium not approved by the
FDA and IRB did not provide adequate
oversight

Healthy volunteers
Volunteers may not stand to benefit
directly, but could ultimately
contribute to development of a new
therapy that the participant might then
use.
 Require particularly close monitoring,
because they can pose a risk to a
volunteer's health or life.

Why do people participate in
biomedical research?
Altruism
 Free medical care and medications
 Trust
 Self-interest
 Attention
 Do we want to constrain people if they
are doing things for the wrong
reasons?

“A motion has been made and seconded that
we stick our heads in the sand.”
Role of the IRB
Protect the institution
 Can introduce complexity
 Responsibility of PI to terminate if they
sense the patient is not really involved
in the process
 No one knows how risk is really
determined

How can we make it better?
Start with the document
Finish with the process
Discussion
Current studies
 Ethical issues
 Your opinions?
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