Presentation on IRB History

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IRB Workshops
Initially will be given in three parts 1. Human
subject research ethics ?History of research
ethics ?History of unethical research 2.
Regulatory ?IRB responsibilities ?Investigator
responsibilities ?Informed consent
requirements 3. Logistics ?Office
contacts ?Completion of forms and reports
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What Do These Institutions Have in Common?
-Rush Presbyterian - St. Lukes Medical
Center -West Los Angeles VA Medical Center -Duke
University -The University of Illinois at
Chicago -The City University of New York -Mt.
Sinai School of Medicine -University of South
Florida -University of Colorado
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Origins of Human Subject Research Ethics
? Hippocrates (400 B.C.) -medical practice and
medical ethics -physicians should abstain
from whatever is deleterious and
mischievous. -does not deal with research or
experimentation with human subjects -does not
mention the principle of informed consent
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Origins of Human Subject Research Ethics (Cont.)
?Thomas Percival (1803) -code of medical
ethics -and new methods of chirurgical
treatment should be devised but should be
scrupulously and conscientiously governed by
sound reason, just analogy, or
well-authenticated facts previous
consultation of the physicians or surgeons to
the nature of the case. -must have good
methods and competent investigators -no mention
of consent
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Origins of Human Subject Research Ethics (Cont.)
?William Beaumont (1833) -Oldest American
document dealing with research -Experimentation
is needed information cannot be otherwise
obtained -Investigator must be conscientious
and responsible methodological approach no
random studies -Voluntary consent is
necessary -Discontinuation of experiment when
it causes distress to the subject or the
subject objects or becomes dissatisfied
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Origins of Human Subject Research Ethics (Cont.)
?Claude Bernard (1865) -Textbook - An
Introduction to the Study of Experimental
Medicine -Permissible to save, cure, or gain
personal benefit for the subject -Cant be
harmful to the subject in the name of
science -Those experiments that can only
harm are forbidden. Those that are innocent are
permissible, and those that may do good are
obligatory.
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Origins of Human Subject Research Ethics (Cont.)
?The 1900 Prussian Directive -Response to public
debate on human subject experimentation -Prohibi
ted experiments in minors and those not fully
competent -Unequivocal consent required after
explanation of the experiment and possible
adverse consequences -Only certain people were
allowed to do the research and they must keep
written records -Did not apply to medical
treatment for diagnosis, therapy, or
immunization
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Origins of Human Subject Research Ethics (Cont.)
?Reich Health Council Regulations (1931) -14
points which demanded complete responsibility of
the medical profession for carrying out human
experimentation -General, technical, and
ethical standards -Informed consent
necessary -Documented justification of protocol
deviation -Risk - benefit analysis
required -Justification for studying vulnerable
populations -Necessity for written records
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Problems With Human Subject Experimentation
Relationship to codes of research ethics
?From Hippocrates to Percival -Uncontrolled,
unscientific human experiments Purely
empirical -Vivisection was common -Experiments
on Condemned Criminals --Newgate Prison
(1721) - offered pardons for participation in
inoculations -Jenner (1776) inoculated an 8 yr
old boy with cowpox material
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Problems With Human Subject Experimentation
Relationship to codes of research ethics
?Beaumont -Gunshot wound open fistula tract
physiology of the stomach -Consent was needed
and obtained ?Bernard -Supported using dying
patients in experiments that caused no
suffering -Endorsed giving intestinal
parasites to a condemned woman to be examined
at autopsy -Practice what he preached?
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Problems With Human Subject Experimentation
Relationship to codes of research ethics
?1900 Prussian Directive -Response to Case of
Neisser -Dr Neisser studied immunization of
healthy persons against syphilis by inoculating
them with serum from syphilitic patients -3
prostitutes inoculated all contracted
syphilis -No consent obtained ?Reich Health
Council -75 children died in experiments with
tuberculosis vaccinations
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Problems With Human Subject Experimentation Nazi
Germany
?Dr. Mengeles Experiments -Infected one twin
with a germ. When he/she died, the other twin
was killed and their organs compared at
autopsy. No one ever attempted to explain
anything to us. There was never an attempt to
minimize our riskswe were there for one
reason to be used as experimental object and
then to be killed.
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Problems With Human Subject Experimentation Nazi
Germany
?Dr. Mengeles Experiments (Cont.) -Sewed twins
together to create a Siamese twin -Studied
subjects with genetic defects and genetic traits
so as to better purify the Aryan
superrace -performed cross transfusions to
make boys into girls and girls into boys
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Nazi Military Experiments
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Problems With Human Subject Experimentation Nazi
Germany
?Experiments with Military Relevance -High
altitude simulation -Malaria pathogenesis and
treatment -Bone, muscle and nerve
regeneration and bone transplantation -Render
ing sea water drinkable -Endemic
jaundice -Chemical sterilization -Typhus
pathogenesis and treatment
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Nuremberg Doctors Trial
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Post War Response
The Case Against the Nazi Physicians ?Nuremberg
Doctors Trial - 1946-47 -23 defendants 3
non-physicians -15 found guilty -7 were hanged
(4 physicians) -5 sentenced to life in
prison -4 sentenced to 10-20 yrs in prison -7
were acquitted and freed ?Separate Trial -31
underlings were also found guilty 22 of them
were hanged
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Post War Response
?Nuremberg Code of Medical Ethics - first
authoritative , most stringent pronouncement on
the rights of research subjects (Annas,
1992) -adopted by the World Medical
Association in 1948 -True informed consent
freely given prior to experimental
procedures -Truly necessary, well thought out
experiments in which the expected benefits
justify the risks and there is no unnecessary
physical or mental suffering or injury
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Post War Response Nuremberg Code
-The person performing the task is
qualified -No experiment shall be undertaken
where death or disabling injury will likely
occur (except that experimental physicians can
serve as subjects) -Proper preparation and
adequate facilities to protect subjects must be
present to prevent further injury -Subjects
should be allowed to discontinue participation
at any time -Upon observing the likely risk of
injury, disability or death, the researcher
should terminate the experiment
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Acceptance of the Nuremberg Code International
?World Medical Association (WMA) -Helsinki
Declaration (1964) --praised the
Code --rejected it for widespread
use --modified the code -Further
modifications --Tokyo (1975) --Hong Kong
(1989)
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Acceptance of the Nuremberg Code U.S.
Dr. Henry Beecher - NEJM (1966) -Criticized
the lack of sincerity in implementing the basic
concepts of informed consent -Cited 50
episodes of potential Code violations which
were published in peer-reviewed scientific
journals in the U.S. -Suggested that journal
editors reject articles based on violations of
patient rights
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Reaction to Beechers Comments
Feb. 1966 -NIH required establishment of
IRBs for institutions receiving for medical
research -Medical, nursing and lay-public
members -Review approve research
protocols prior to conducting
experiments July 1966 -UTMB policy
accepted by PHS May 1967 -UTMB extended
the policy to all research
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Reactions (cont.)
1969, 1971, 1973 -PHS policy modified
May 1974 -National Research Act IRB review
and approval of all research involving human
subjects Apr 1979 - Belmont Report
Jan 1981 -HHS amended the policy to provide a
framework within which IRBs would function
1985- Act amended -Codification (45 CFR Part
46)
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Belmont Report
? Principles -Respect for persons autonomy
(informed consent) -Beneficence - protect
research subjects from harm (assessment of
risks/benefits) -Justice - who bears the
burden? Who receives the benefits (selection of
subjects equitable and unbiased) Basis of
all U.S. human research regulation
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Research Regulations
?DHHS - 45 CFR Part 46 ? FDA - 21 CFR (First
developed and promulgated 1962-1966) Part
50 (Informed Consent) Part 56 (IRBs) Part 312
(Drugs) Part 812 (Devices) ? Department of
Education 34 CFR Part 97 (All are reasonably
harmonized)
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DHHS (45 CFR 46) Special Protections
? Fetuses, Pregnant Women, and Human In Vitro
Fertilization - Minimal risks to fetus/mother -
Must meet health needs of fetus/mother ?
Prisoners - Minimal risk/minor inconvenience -
More than Minimal Risk with potential for
benefit ? Children - Anticipated benefit -
Solicit assent of the child -Consent of the
parents
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Major Problems With Research Ethics in the U.S.
?
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Major Problems With Research Ethics in the U.S.
1932-1972 -PHS study of the effects of
untreated syphilis on black men in Macon
County Alabama (Tuskegee Study) -399 men who
already were in the late stages of
syphilis -201Negative Controls -Treatment was
available but not used
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Major Problems With Research Ethics in the U.S.
Tuskegee Study
-No formal protocol located procedures
evolved -Not a treatment study -Studied the
effects of spontaneous evolution of syphilis on
black males -Few of the physicians and none of
the subjects really knew what the study
involved -The men were told they had bad blood
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Tuskegee Round-up
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Major Problems With Research Ethics in the U.S.
Tuskegee Study
Why participate? -Poor and illiterate most had
never seen a doctor before -Free physical
exams -Free rides to the clinic -Hot meals on
exam days -Free treatment for minor
ailments -Burial stipends -Nurse Eunice Rivers
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Nurse Rivers and the Tuskegee Study
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Major Problems With Research Ethics in the U.S.
Tuskegee Study
Nurse Rivers -Black Nurse, employed by the PHS
who tracked participants -Spoke with the men and
their families -Advised doctors not to treat
them under study -Subjects told that, if
treated, they would be dropped from the
study PHS Response - mildly uncomfortable Press
later labeled it racial medicine
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Major Problems With Research Ethics in the U.S.
Radiation Experiments
Report from the Advisory Committee on Human
Radiation Experiments (ACHRE) -81 examples of
pediatric research projects --non-therapeutic
nutritional studies at a school for retarded
children --consent was sought without
telling parents that radiation would be used
--children induced to participate even if they
refused
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Major Problems With Research Ethics in the U.S.
Radiation Experiments
Others -plutonium injections to study the
effects of radiation -radioactive iodine given
to mentally retarded children -total body
irradiation on cancer patients (as
research) -atomic bomb exposure
(military) -several thousand government
sponsored human radiation experiments and
hundreds of intentional releases of radioactive
material
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Major Problems With Research Ethics in the U.S.
Others
-Studies of hepatitis on mentally retarded
children (Willowbrook) --inadequate
consent --deliberately infected -Studies on
prisoners --coercive inducements --cash --early
release -Not limited to the above and still
occur today even with IRB oversight -Important
to know what is acceptable and what is
permissible in research