Ethical issues in selection of research subjects Bernard Lo, M.D. July 28, 2001.
1 Ethical issues in clinical research Bernard Lo, M.D. January 25, 2007.
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Transcript of 1 Ethical issues in clinical research Bernard Lo, M.D. January 25, 2007.
1
Ethical issues in clinical research
Bernard Lo, M.D.
January 25, 2007
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Timeline of Hwang case
2/04 SCNT yielded 30 blastocysts and
one stem cell line
5/05 11 SCNT cell lines from 185
oocytes, 31 blastocysts
8/05 Cloning of dog, Snuppy
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S. Korean investigation
Could not verify genetic identity of
donors and lines
9 lines identical with embryonic stem
cell line
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S. Korean investigation
2261 oocytes from 119 donors Papers reported only 427 oocytes 66 compensated, contrary to publication Technicians, grad student donated, contrary
to previous statements Failed to fully explain risks 15/79 treated for ovarian hyperstimulation
syndrome
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Protections for human subjects
IRB review Assess risks and benefits of research Independent of researchers
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Protections for human subjects
Informed and voluntary consent Respect people’s right to decline to
participate in research Hard to say no if dependent Exceptions for research with existing
records and materials
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Federal definition of research misconduct
Fabrication
Falsification
Plagiarism
Must be intentional
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Why is research misconduct problematic?
Question validity of data
Question conclusions of study
Unmerited rewards
Undermines public trust and support
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Research misconduct excludes
Unintentional “honest” error
Sloppiness, incompetence, laziness
Differences of opinion or interpretation
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U Pitt investigation of Schatten
Senior author of 2005 paper Revised paper, negotiated with journal
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U Pitt investigation of Schatten
“Concerted and deliberate effort to
distance self from Dr. Hwang and joint
publication” “In sharp contrast to full participation…in
media spotlight following publication”
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Appropriate authorship
Co-authors took credit for work
Did not meet criteria for authorship
Not willing to take responsibility for
work
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Why have authorship?
Recognition Job, grants, promotions
Accountability Prevent fabrication, fraud, plagiarism
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Criteria for authorship
Conception and design or data
analysis and interpretation, and
Drafting or substantially revising
article, and
Approving final manuscript
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VIGOR
Published in NEJM 11/200
Fewer GI side effects on rofecoxib than
naproxen (2.1 vs. 4.5)
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VIGOR
More Mis on refecoxib (0.4 vs 0.1) Attributed to protective effect of naproxen
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Rofecoxib
Sales over $2.5 billion annually
80,000 patients
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VIGOR
3 additional MIs on refecoxib reported
to FDA before publication but not to
academic authors or to NEJM Known to 2 employee / authors
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APPROVe study (2/05)
Thrombotic events 1.50 on rofecoxib
vs. 0.78 on placebo Led to voluntary withdrawal of drug Increased risk after 18 months
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Public events
Vioxx withdrawn from market 9/04 Attributable MI, CVA 160,000
Lawsuits by patients
Defense strategy At high risk for MI Weren’t taking drug long enough
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APPROVe problems
Count only events while on Rx or up to
14 days after stopping Academic authors claimed they were just
following the protocol
Presented all events to FDA 5/06 Curves diverge at 4 months, not 18
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APPROVe problems in peer review
“Going out on limb by emphasizing 18
month issue”
“Hand of sponsor is too evident ..
Written consistently in manner
designed to support the company’s
public positions.”
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APPROVe problems in peer review
“Aggressively promotes safety of up to
18 months of use … beyond the data of
the study”
Journal originally asked authors to
drop references to 18 months
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Ethical issues raised
Must publish all results, both negative
and positive
Investigators must control study Sponsor has self-interest, bias
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Ethical issues raised
People harmed by unethical research Evidence base for clinical practice depends
on valid research
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Take home messages
Informed consent
IRB review
Authorship
Publish unfavorable results
Integrity of researcher
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