“Primum,
non nocere.”
– Hippocrates
(“First, do no harm.”)
Data Ethics
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“One of the most serious ethical problems in
clinical research is that of placing subjects at
risk or injury, discomfort, or inconvenience in
experiments where there are too few subjects
for valid results, too many subjects for the
point to be established, or an improperly
designed random or double-blind procedure.”
– Journal of Medical Ethics
Nuremberg code
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1947 Doctor’s Trial at Nuremberg
Atrocities in the name of research
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Sterilization experiments
Dachau hypothermia/high altitude experiments
Led to the Nuremberg Code
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10 standards for research with
human subjects
Risk must be weighed against the
expected benefit, and that unnecessary
pain and suffering must be avoided.
Doctors should avoid actions that
injure human patients.
Voluntary consent of patient is essential
Declaration of Helsinki
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1964 Declaration of Helsinki of the World Medical
Association issued a series of “recommendations” to
guide research on human subjects
Revised at regular intervals over many years
“The interests of the subject must always prevail over
the interests of science and society.”
“In any medical study, every patient--including those
of a control group, if any--should be assured of the
best proven diagnostic and therapeutic method."
Ethics in the U.S.
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Nuremberg and Helsinki had enormous moral force
but not the force of law in the U.S.
Provisions were largely ignored for many years
In June 1966, Henry K. Beecher, an anesthesiologist
at Harvard Medical School, published a highly
influential article entitled "Ethics and Clinical
Research" in the New England Journal of Medicine.
He detailed 22 clinical trials that appeared to be
highly unethical, in which researchers risked their
patients' lives without fully informing them of the
dangers and without obtaining their permission.
Willowbrook and
Brooklyn Jewish hospital
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1963-1966 hepatitis studies carried out at Willowbrook, a New
York State institution for "mentally defective persons."
Subjects, all children, were deliberately infected with the
hepatitis virus
During the studies, Willowbrook closed its doors to new
inmates, claiming overcrowded conditions. But the hepatitis
program was able to continue to admit new patients. In some
cases, parents were unable to admit their child to Willowbrook
unless they agreed to participate in the studies.
1963 Brooklyn Jewish Chronic Disease hospital
Investigators injected live cancer cells into senile patients to
observe their immunological responses. Subjects were never
informed of the dangers.
In neither case did the research have any potential therapeutic
value to the patients under study.
Tuskegee syphilis experiment
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Study began in 1932 by the U.S. Public Health Service to
determine the history of untreated syphilis
Subjects were some 400 Black sharecroppers in Alabama
diagnosed with syphilis
Men were recruited without informed consent. Misinformed
and told that some procedures (e.g., spinal taps) were actually
"special free treatment."
By 1936, it was apparent that many more infected men than
controls had developed complications. Death rate among those
with syphilis was about twice as high as it was among the
controls.
In the 1940's, when penicillin, known to be effective in the
treatment of syphilis, became available, the men were neither
informed, nor treated with the antibiotic.
Many died from untreated syphilis
Tuskegee syphilis experiment
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Study continued until it was exposed in the national press in
1972!
1996 review: “It has come to symbolize racism in medicine,
ethical misconduct in human research, paternalism by
physicians, and government abuse . . . “
President Clinton apologized to survivors in 1997
U.S. government continues to pay millions of dollars yearly to
surviving subjects and the families of deceased subjects.
Read the book Bad Blood:
The Tuskegee Syphilis Study by James H. Jones
and see the video The Deadly Deception (Nova).
Belmont Report
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Outrage over Tuskegee and Beecher article led to some
reforms in the 1970s
Congress created the National Commission for the Protection
of Human Subjects of Biomedical and Behavioral Research
which issued the influential Belmont Report in 1979
Lays out 3 guiding ethical principles
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Respect for persons
Beneficence
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Obligation to (1) Do no harm, and (2) Maximize benefits and minimize
harms
Justice
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Benefits of research should be distributed fairly
Ethics of clinical trials
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“There is a delicate balance between when to do or
not do a randomized trial. On the one hand, there
must be sufficient belief in the agent’s potential to
justify exposing half the subjects to it. On the other
hand, there must be sufficient doubt about its efficacy
to justify withholding it from the other half of
subjects who might be assigned to placebos.”
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Dr. Charles Hennekens, Harvard Medical School (who
directed the physician’s aspirin study)
Basic standards of data ethics for
studies involving human subjects
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Informed consent
 All individuals who are subjects in a study must give their informed
consent before data are collected
 Subjects must be informed in advanced about the nature of a study and
any risk of harm it may bring
Confidentiality
 All individual data must be kept confidential
 Only statistical summaries for groups of subjects may be made public
 Not the same as anonymity where subjects’ names are not known, even
to director of study (rarely the case)
Institutional Review Boards
 Organization that carries out the study must have an institutional review
board that reviews all planned studies in advance in order to protect
subjects from possible harm
 Carleton’s IRB
Case Study #1
Dr. W is a family practitioner with interest in the
treatment of HIV infection and AIDS.
He receives a letter from the coordinator of a
study to evaluate a promising new treatment
for the prevention of HIV-related dementia.
The letter invites Dr. W to submit the names of
potentially eligible patients.
He will be paid $100 for each name provided.
Is this ethically objectionable?
Case Study #2
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A highly respected medical institution keeps a vast
amount of confidential medical data
The institution has a rule that no employee can access
this data for any personal or non-professional purpose
A statistician employee, who has access to this data,
recently had a physical check-up at the institution.
Curious, he goes on-line to look up his own
confidential medical records.
When the institution found out about this, the
statistician was immediately discharged.
Is the institution justified in this action?
Case Study #3
Dr. T, a psychiatrist, is asked to assist with a clinical
trial to test a new drug in the treatment of psychosis.
The study will enroll acutely psychotic patients with no
history of psychosis or of treatment with
antipsychotic drugs.
Patients enrolled in the study will be randomly assigned
to receive the new drug or a placebo and will remain
in the hospital for 8 weeks. During this time they will
not receive medications other than the study drug.
Informed consent will be obtained from each
participant or a proxy.
Patients may be withdrawn from the study if their
medical condition worsens substantially.
Is it ethical for Dr. T to enroll his
patients in this study?
No! Consent alone is insufficient. The study must
present “a favorable balance of benefits and harms.”
(Canadian Med J, “Bioethics for clinicians”)
The treatments being studied must be in a state of
“clinical equipoise,” that is, there is “genuine
uncertainty” within “the expert clinical community
about the comparative merits of the alternatives being
tested.”
When effective standard treatment exists for a disease
(as it does for schizophrenia) it is unethical to expose
patients to the risk of “treatment” with placebo alone,
since placebo is an inferior “treatment.”