Research Ethics
Michael Caligiuri, Ph.D.
Professor-in-Residence
Dept of Psychiatry
Director, HRPP
Part I:
Ethical Considerations in
Human Subjects Research
Human Research Abuses
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1940’s
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1950’s
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Thalidomide Tragedy
1960’s
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Nazi war crimes and Nuremburg code (1948)
Human Radiation Experiments
New York City’s Jewish Chronic Disease Hospital
Willowbrook Studies
Milgram Study
1970’s
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Tuskegee Syphilis
Stanford Prison Experiment
IRBs: Historical Background
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Declaration of Helsinki (1964-2007)
Response to Research Abuse
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Beecher, 1966
 Call for Journal editors to require ethical review
 Call for national policy on IRB review
The National Research Act (1974)
 Set-up formal IRBs
Belmont Report (1979)
The Belmont
Report
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Established Responsibilities
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IRB must ensure that the researcher and the
participant distinguish clinical practice from
research.
IRB must minimize the potential for
therapeutic misconception.
Ethical Principles
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Respect, Beneficence, Justice
Guiding Principles: Belmont
Report
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Respect for Persons
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Individuals should be treated as
autonomous agents
Persons with diminished autonomy are
entitled to protection (‘special populations’)
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Children
Mental disabilities
Prisoners
The Common Rule
“An investigator shall seek such consent
only under circumstances that provide the
prospective subject or the representative
sufficient opportunity to consider whether
or not to participate and that minimize the
possibility of coercion or undue influence.”
45 CFR 46.116
Guiding Principles: Belmont
Report
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Beneficence
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Do no harm
Maximize possible benefits and minimize
risks
Applied at both an individual level for
research participants and a societal level
for the effect of the knowledge gained
from the research
Guiding Principles: Belmont
Report
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Justice
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fair distribution of the burdens and benefits
of research
selection of research participants should
involve those groups who will benefit from
research, not ‘convenience’ populations
that are more likely to be disadvantaged
Part II:
Threats to the Ethical Conduct of
Human Subjects Research
Threats to the Principle of Respect
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Coercion
Undue Inducements
Exploitation
Coercion
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Coercion occurs when an overt threat
of harm is intentionally presented by
one person to obtain compliance from
another.
Coercion does not mean:
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involuntary or under strong influence
doing something because there are no
good options.
Coercion
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Exactly what is Coercion?
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Perceived coercion in research can occur with
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To be coercive, a subject who refuses must be
made worse off than if he/she were never asked
Requires the presence of a threat
Prisoners
Students and staff
Payment for research is not coercive:
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Payment is an offer not a threat
Inducement
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Definition:
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Inducements are offers that get people to
do things they would not otherwise do:
Acceptable Inducements:
Higher salary for greater
responsibility
 Free car wash with fill-up
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Inducement
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Inducements in Research:
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Anything that encourages participation
Usually monetary
Medical/diagnostic services
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Results from MRI scan
Knowledge of genetic testing
Neuropsychological work-up for child enrolled
as a “control”
Inducement
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Undue Inducements
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Excessively attractive offers that lead
people to do something to which they
normally would object based on risk or
other fundamental value (Dickert, 2004)
Undue Inducement
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Monetary inducement that alters
individual’s decision-making process such
that they underestimate risks;
Payments that undermine a person’s
capacity to exercise a free choice
invalidates the consent process*
*Council for International Organizations of Medical Sciences,
2002; guideline 7
Undue Inducement
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Undue inducements may prompt subjects
to lie or conceal information that, if
known, would disqualify them from
participation.
Under 45 CFR 46.111 failure of the
participant to appropriately judge risks is
considered improper informed consent.
Undue Inducement
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Ambiguities
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What is excessive?
Reasonability of risks varies among study
participants
Impact of risk can change throughout the
study, should the inducement also change?
In the absence of a standard metric, IRBs vary
in their assessment of risk and
appropriateness of payments.
Undue Inducement
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Little empirical support that the amount of
payment affects subject’s perception of
risks
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No relationship between amount of money offered
and risk (Bentley and Thacker, 2004)
Public thinks other people are more likely to have
impaired judgment as a result of payment than
they are themselves (Casarett et al., 2002)
Undue Inducement
Risk is likely more
important than
money when
considering
enrollment
Halpern, S. D. et al. Arch Intern Med. 2004
payment
-5%
-9%
Exploitation
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An exploitative transaction is one in
which person A takes unfair advantage of
person B (Wertheimer, 1999).
IRB’s are always concerned when
vulnerable individuals are paid to enroll
in medical research
Exploitation
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There is always an ethical concern when
recruiting from vulnerable populations:
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Poor; homeless
Mentally Ill
Terminally Ill
Prisoners
Students
Staff
For each group, there is a different solution
Exploitation
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Solutions to avoid exploitation:
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Pay vulnerable patients more?
Engage patient advocates?
Exclude vulnerable populations?
IRBs need to define what is “fair”
Appropriate IRB member expertise
Scientific Impact
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Undue inducements or exploitative subject payment
can impact science
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Unqualified subjects enrolling in FDA monitored studies
Conceal information important to outcome
Less likely to report adverse events
Skewing population
Not disclosing participation in multiple clinical trials
can confound results.
Case Scenarios
Case 1: Alexis St. Martin
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“The Intrepid Guinea Pig
of the Great Lakes”
In 1822, accidentally shot
in the gut and left with a
permanent gastric fistula.
William Beaumont paid
him room, board, and
$150 a year for use of his
stomach.
http://www.guineapigzero.com/AlexisStMartin.html
Case 2: Walter Reed’s Yellow Fever
Study
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Paid $100 in gold for
participation.
$100 bonus for
successful infection
with yellow fever.
Payable to family in
the event of death.
http://etext.lib.virginia.edu/healthsci/reed/commission.html#vol
Case 3: You
Threats to the Principle of
Beneficence
Stanford Prison Experiment
PI: Philip Zimbardo, Ph.D.; 1971
http://www.prisonexp.org/
Stanford Prison Experiment
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Purpose:
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To test the idea that the inherent
personality traits of prisoners and guards
were summarily key to understanding
abusive prison situations.
Experimental Questions:
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What happens when you put good people in
an evil place?
Does humanity win over evil, or does evil
triumph?
Stanford Prison Experiment
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Subjects answered a local newspaper ad
calling for volunteers in a study of the
psychological effects of prison life.
More than 70 applicants responded
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given diagnostic interviews and personality tests
to eliminate candidates with psychological
problems
24 college students met criteria
Earned $15/day
Stanford Prison Experiment
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Randomly assign subjects to two groups:
guards or prisoners.
The prisoners were then brought into our jail
one at a time and greeted by the warden
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Each was systematically searched, stripped naked,
deloused.
The guards were given no specific training on
how to be guards.
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Free, within limits, to do whatever they thought
was necessary to maintain law and order in the
prison.
Stanford Prison Experiment
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Less than 36 hours into the experiment, one prisoner
began suffering from acute emotional disturbance,
disorganized thinking, crying, and rage.
On the 5th night, visiting parents asked the PI to
contact a lawyer in order to get their son out of
prison.
Most prisoners were withdrawing and behaving in
pathological ways
Some of the guards were behaving sadistically
Study was then stopped after 6 days.
Stanford Prison Experiment:
Conclusions
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PI argued that the results demonstrate the
impressionability and obedience of people
when provided with a legitimizing ideology
and social and institutional support.
Results supported a situational attribution of
behavior; that is, the situation caused the
participants' behavior, rather than anything
inherent in their individual personalities.
Stanford Prison Experiment:
Scientific Challenges
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Critics challenged the generalizability of the study.
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Small sample size (n=12 in each group)
The experiment would be difficult for other researchers to
reproduce.
Screening procedures could not exclude tendencies for sadism; so
contrary to the PI’s conclusions, the “experiment” itself may not
have produced these behaviors.
It was impossible to keep traditional scientific controls.
Examiner Bias: The PI was not merely a neutral observer, but
influenced the direction of the experiment as its
"superintendent".
Stanford Prison Experiment:
Scientific Challenges
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Questionable ecological validity: blindfolding
incoming "prisoners", not allowing them to wear
underwear, not allowing them to look out of windows
or use their names
Selection Bias: Western Kentucky U. (in a similar
study later) found that students volunteering for a
prison life study possessed dispositions toward
abusive behavior.
The study was never published in a peer-reviewed
journal
Stanford Prison Experiment:
Ethical Challenges
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Questions regarding beneficence :
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What are the risks of participating in this
research?
Were they disclosed? Were they
minimized?
What were the benefits – to society?
The Milgram Study
1961
The Milgram Study
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Experiment on obedience to authority figures
The experiments began in July 1961, three
months after the start of the trial of German
Nazi war criminal Adolf Eichmann.
Milgram devised this study to answer the
question: "Was it that Eichmann and his
accomplices in the Holocaust had mutual intent,
with regard to the goals of the Holocaust or
were the accomplices merely following orders?"
The experimenter (E) orders
the teacher (T), the subject of
the experiment, to give what
the subject believes are
painful electric shocks to a
learner (L), who is actually an
actor and confederate.
The subjects (T) believed that
for each wrong answer, the
learner was receiving actual
shocks, but in reality there
were no shocks.
The confederate (L) set up a
tape recorder integrated with
the electro-shock generator,
which played pre-recorded
sounds for each shock level.
The Milgram Study
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Only the "teacher" is an actual participant,
i.e. unaware about the actual setup.
The participant and the learner were told
by the experimenter that they would be
participating in an experiment helping his
study of memory and learning in different
situations.
Deception was a necessary component.
The Milgram Study:Results
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Before conducting the experiment, respondents believed that
only a few (average 1.2%) would be prepared to inflict the
maximum voltage.
In the first set of experiments, 65 percent of the participants
administered the experiment's final massive 450-volt shock
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though many were very uncomfortable doing so;
every participant paused and questioned the experiment;
some said they would refund the money they were paid for
participating in the experiment.
Only one participant steadfastly refused to administer shocks
below the 300-volt level.
Ethical Issues
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Respect for Persons: Stanley Milgram
deceived his study's subjects (failure to
disclose important aspects of study to allow a
voluntary decision to participate)
Beneficence: Subjects (T) were placed under
more pressure than many believe was
necessary to test the study hypothesis.
Respect for Persons: Subjects were coerced
into remaining in study against their will.