Transcript The Belmont Report

Life is all about choices …
Human Subjects Research Ethics
Welcome to the Ethical Time
Machine
Join me as we journey back to an age
where
•The field of Medicine comes into its own,
and
•Optimism, Progress, and Science sit on the
Throne of GOD
All Aboard!
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Nazi Germany at beginning of
World War II
• Was the most scientifically and
technologically advanced country
in the world,
• Had a proposed code of research
ethics,
• Supported midwifery, nutrition
programs,
• ecology, public health, human
genetics, cancer, radiation, and
asbestos research
However …
• The Nazis also …
• exploited people’s trust in
the medical community
• by performing unethical
experiments
• on populations they
discriminated against.
Nazi Battlefield Medicine
Experiments
• 1942: High altitude or low pressure experiments
at Dachau
• 1942-1943: Freezing experiments at Dachau
• 1942-1945: Malaria experiments at Dachau
• 1943-1944: Phosphorus burn experiments at
Buchenwald
• 1944: Seawater experiment at Dachau
At Ravensbruck
• women were shot or slashed
on the legs.
• The wounds stuffed with
glass, dirt, and bacteria
cultures and sewn shut
• then treated with experimental
anti-infective agents.
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
The Nuremberg Code
• Key Ideas
– Voluntary Informed Consent
– Right of the Subject to Withdraw from the
Experiment at any Time
– A Human Subject Cannot be Sacrificed for the
Greater Good of Science
– Investigator must terminate the experiment at
any time the well-being of his/her subjects is
threatened.
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Human Radiation Experiments
• In 1994, President Clinton
appointed the Advisory
Committee on Human
Radiation Experiments
(ACHRE)
• To investigate unethical
experiments conducted
by our government during
WWII and the Cold War
Era
http://tis.eh.doe.gov/ohre/roadmap/achre/
ACHRE’S Investigation Revealed …
• testing on soldiers
• feeding radioactive cereal to
teenagers at a school for the mentally
retarded,
• irradiating the testicles of prison
inmates,
• injecting plutonium into hospital
patients,
• intentional releases of radiation into
the environment …
4000 human radiation experiments
conducted
• In a two prong effort by the US to
– Provide for National Security
– Provide medical studies to improve human health
• Too often deceptively, secretly, and/or without
informed consent
Testimony before ACHRE, 1995
• “My mother, Jan Stadt, had a number, HP-8. She
was injected with plutonium March 9, 1946. She
was 41 years old, and I was 11 years old at the time.
My mother and father were never told or asked for
any kind of consent to have this done to them.
• “My mother went in (to the hospital) for
scleroderma...and a duodenal ulcer, and somehow
she got pushed over into this lab where these
monsters were.”
Milton Stadt
Son of subject in the Rochester University experiments
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
The Thalidomide Tragedy
Thalidomide was prescribed for morning
sickness
• Approved in Europe in late 1950’s but not in US due
to diligent efforts by one USDA doctor.
• However as was common practice among
pharmaceutical companies …
• some U.S. doctors were supplied samples
• and paid to study its safety and efficacy.
It was subsequently discovered that …
• Thalidomide causes severe deformities in babies
• and its effects are even passed on to later
generations.
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
1962 Kefauver-Harris Amendments
Food, Drug and Cosmetic Act
• Looked at practices of
pharmaceutical
companies
• Required more testing
before widespread use
• Informed consent from
patients receiving
experimental drugs
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Socio-Behavioral Studies
• Milgram’s Study of Obedience to Authority
– Subjects coerced into feeling they had seriously
injured somebody
• The Stanford Prison Experiment
– What happens when you put good people in an evil
place?
– http://www.prisonexp.org/
• Radiation experiments on soldiers
– Fear
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Declaration of Helsinki 1964
• Research with humans should be based on the
results from laboratory and animal experimentation
• Research protocols should be reviewed by an
independent committee prior to initiation
• Informed consent from research participants is
necessary
• Research should be conducted by
medically/scientifically qualified individuals
• Risks should not exceed benefits
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
“Dr. Beecher began his famous article in the
NEJM by stating:
• “… medicine is sound, and most progress is
soundly attained …”
He then went on to describe …
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22 examples of research studies
with controversial ethics
conducted by reputable researchers and
published in major journals.
• "Until this article we assumed that unethical research
could only occur in a depraved regime like the
Nazis.“
Robert J. Levine, MD
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Syphilis the AIDS of an earlier time
• Untreated, it can lead to
– severe heart disease,
– brain damage,
– paralysis, and
– death.
• The problem was, until 1907, no one could
treat it.
Then Nobel Prize-winning microbiologist Paul Ehrlich
discovered Salvarsan
• an arsenic-based compound.
• It was the first chemotherapy.
The 1920’s was a progressive era in medicine
• Armed with confidence and the
Scientific Method,
• Public Health Service officials were
determined
• to control syphilis in their time.
• They set up free treatment clinics
throughout the south,
• including Macon county, Alabama,
• home to the Tuskegee Institute.
But in 1932, the funding for treatment ran out.
• While writing the final report,
• Dr. Taliaferro Clark, head of the PHS
Venereal Disease Division
• conceived an idea to salvage the
study …
• Macon county “offered an
unparalleled opportunity
• for the study of the effect of untreated
syphilis”
• in the Negro male.
The Study of Untreated Syphilis in the Negro
male (1932 – 1972)
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was only supposed to last a year …
but then Dr. Raymond Vondelehr
advocated continuing the study
to get autopsies.
Autopsies would confirm clinical
observation
• and therefore greatly contribute
• to the scientific reliability
• of the study’s findings.
“Bringing them to Autopsy”
•By the time Jean Heller broke the story
•in the Washington Star in 1972
•The experiment had gone on for 40 years.
•During all this time, it was no secret
•to the wider medical community.
•Results of the study had been published
•in well known medical journals.
•Yet no one ever questioned the study.
399 Participants
•None were ever told they had syphilis.
•None were ever offered a cure
•even when penicillin became available in 1943.
•Researchers had even interfered
•to keep subjects from getting penicillin
•so the study could continue.
“Nothing Learned will Prevent, Find, or Cure
a Single Case”
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28 men died of syphilis
100 men died from related complications
at least 40 wives were infected
19 children had contracted the disease at birth
a whole people’s trust was shattered
“Bad Blood”
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Macon county residents were very poor.
They lived and died without medical care
because they could not afford it.
They didn’t distinguish between syphilis
and a host of other maladies
which they called “bad blood.”
They trusted the government doctors and
they traveled great lengths
to get a little free medical care.
They were told they were being treated for
“bad blood.”
“I, like most everybody else,
• “was horrified at the things that
were practiced upon these Jewish
people, such as doing experiments
while the patients were not only
alive but doing such things as would
cause their deaths.
• “All these sorts of things were
horrendous to me and I, like most
everyone else, deplored them.”
Dr. John R. Heller, Researcher, Tuskegee Syphilis Study
Final Report of Tuskegee Syphillis
Study
• "Society can no longer afford
• to leave the balancing of
individual rights
• against scientific progress
• to the scientific community."
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
In 1974 at Belmont, the National Commission for
the Protection of Human Subjects began
deliberations …
Kenneth John Ryan, M.D.,
Joseph V. Brady, Ph.D.,
Robert E. Cooke, M.D.,
Dorothy I. Height, President, NCNW,
Albert R. Jonsen, Ph.D.,
Patricia King, J.D.,
Karen Lebacqz, Ph.D.,
David W. Louisell, J.D.,
Donald W. Seldin, M.D.,
Eliot Stellar, Ph.D.,
Robert H. Turtle, LL.B., Attorney.
Which led in 1978 to the opening
words of the Belmont Report
• “Scientific Research has produced
substantial social benefits.
• “It has also posed some troubling
ethical questions.”
The 3 Basic Ethical Principles
of the Belmont Report
Respect
for
Persons
Benefice
Justice
Respect for Persons
Definition:
• Individuals should be treated as
autonomous agents
• Persons with diminished autonomy are
entitled to protection
Application:
• Voluntary Informed Consent
Belmont Report
Benefice
Definition:
• Do not harm
• Maximize possible benefits
• Minimize possible harms
Application:
• Assessment of risks and benefits
Belmont Report
Justice
Definition:
• Who ought to receive the benefits of
research?
• Who ought to bear its burdens?
Application:
• Equitable Selection of Subjects
Belmont Report
‘Back to the Future’
20th Century Research Ethics
Milestones
Common Rule 1991
Consolidated HHS/FDA Regulations
Belmont Report
1981
1979
1972 Syphilis Study Exposed
Declaration of Helsinki 1964
1966 The Beecher Article (NEJM)
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Nuremberg Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
‘Home free’ in the 21st Century?
• Research is still Risky
– Gene Therapy Trials
• Death of 18 year old Jesse Gelsinger in 1999
• Conflict of interest
– Cloning
– Nanotechnology
– Internet Research
– Artificial Intelligence
– Chemical and Biological terrorism
– Space travel …
Institutions where Studies have
been temporarily suspended July
1998 – July 2001
• Rush Presbyterian – St. Luke’s
Medical Center
• Friends Research Institute
• Veteran Affairs Greater LA
• Virginia Commonwealth University
• John Hopkins
Questions to Consider
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Why should we be concerned about Human Subject Research?
Do you think another Tuskegee could happen in the future?
Do you think a Tuskegee could ever happen to you?
Can you envision yourself ever being faced with an ethical dilemma in
Human Subjects research? What are some guidelines or resources you
could turn to?
And finally,
The Tuskegee Study started in the United States in 1932 and continued for
40 years, well past the Nuremberg trials. It was also no well kept secret.
Research articles were published in major medical journals during this time.
Why do you think nobody saw a connection between Nuremberg and the
Tuskegee Syphilis Study?
The 1997 Presidential Apology
to Tuskegee Participants
Life is all about
choices …
choices have consequences
Now it’s your turn how will YOU choose?