ethical issues in clinical research bernard lo, m.d. august 24, 2011 1
TRANSCRIPT
STD transmission research 1946-8
Intentionally infected subjects with syphilis, GC, chancroid
Female sex workers Males directly innoculated
Prisoners, patients in mental hospitals
In Guatemala
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STD studies 1946-8
Intentionally infected subjects with
syphilis, GC, chandroid Female sex workers inoculated on cervix Males directly inoculated into skin or
urethra
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STD studies 1946-8
Study carried out in Guatemala
Subjects were prisoners, residents of
mental asylums
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STD studies 1946-8
Most but not all treated with penicillin One subject died of status epilepticus
US government involved: NIH, PHS,
Surgeon General
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Senior PHS official
“I am a bit, in fact more than a bit, leery
of the experiment with the insane
people. They can not give consent, do
not know what is going on, and if some
goody organization got wind of the
work, they would raise a lot of smoke”
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Fundamental ethical tension in research
Primary goal is generalizable
knowledge, benefit to society
Participants experience risks but
benefit to others
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Ethical violations
1. Serious harm to participants Deliberately cause harm
2. No informed consent
3. Unfair selection of participants Take advantage of vulnerable population
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Regulations respond to scandal
1. Beneficence Risks must be acceptable in light of benefits Risks must be minimized Independent IRB must approve study
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Regulations respond to scandal
2. Respect for persons Informed and voluntary consent Not capable of consent (children, adults
who lack decision-making capacity)
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Regulations respond to Tuskegee
3. Justice Equitable selection of subjects Protections for vulnerable subjects
Federal regulations
1. Risks acceptable in light of benefits
2. Informed and voluntary consent
3. IRB review and approval
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Only need IRB review if
Participants identifiable OR
Interact with participants OR
Questionnaire covers sensitive topics
Ask IRB staff
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Bone growth factors
Recombinant human bone
morphogenetic protein-2
13 early trials claimed no
complications compared to controls
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Bone growth factors
Serious adverse events actually 10%-
50% Male sterility, infection, bone loss and
unwanted bone growth
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Bone growth factors
Original studies were sponsored by
manufacturer
Authors received up to $12-$16 million
in payments from company
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Federal definition of research misconduct
Fabrication
Falsification
Plagiarism
Must be intentional
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Research misconduct excludes
Unintentional “honest” error
Sloppiness, incompetence, laziness
Differences of opinion or interpretation
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Research misconduct excludes
Lack of IRB approval
Lack of informed consent
Financial mismanagement
Discrimination
Poor mentoring
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Federal definition of misconduct
Legal requirements set a minimum
standard
Ethical and professional standards
may be higher
How do people respond to plagiarism?
Using computer programs, identify 212
pairs of similar articles
Survey to authors, journal editors of
these articles
Science 2009; 323; 1293.
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Individual response to misconduct
“It is my understanding that copying
someone else’s description virtually
word-for-word is considered a
compliment to the person whose words
were copied.”
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Individual response to misconduct
“I have no idea why the pieces are
similar, except that I am sure I do not
have a good enough memory to have
allowed me to ‘copy’ his piece.”
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Consequences of research misconduct
Suspension of federal grant
Debarment from future grants
Institutional penalties Termination of employment
Civil and criminal liability