Transcript Slide 1

The Responsible
Conduct of Research
Diana D. Cardenas, MD, MHA
Professor and Chair
Dept of Rehabilitation Medicine
University of Miami Miller School
Medicine, Miami, FL
of
What is RCR about?
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Scientific Misconduct
Data Management
Conflict of Interest
Collaborative Science
Responsible Authorship
Mentoring
Peer Review
Human Subjects Protection
• Lab animal welfare
Integrity in Human Subjects
Research is The Key to Success
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Reduces risks to subjects.
Conserves resources.
Promotes acceptance of the research.
Minimizes the time for implementation of
new effective therapies.
Preserves the public trust.
The Public Trust
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Research with human subjects is a
privilege and not an entitlement.
Society trusts investigators to conduct
research ethically. Public trust must be
protected.
• Public trust maintained through accountability.
• Accountability is accomplished through
documentation of ethical conduct.
• Federal Regulations specifically require
documentation of ethical behavior.
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Regulatory requirements to document
are designed to preserve the public trust
in research.
Human Subjects Protection
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It goes without saying that to do
clinical research you need to get IRB
approval which is intended to protect
human subjects.
The Old IRB
Frans Hals, Regents of the St Elizabeth Hospital of Haarlem - 1641
The Modern IRB
Violation of the Public Trust is Nothing
New
Antoine Lavoisier 1778
• Failed to credit Scheele
and Priestly for prior
discovery of O2.
By J.L. David
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Piltdown Man
• Fraud by Charles
Dawson went
undiscovered for 40
years.
• >500 doctoral theses
written on the subject.
Violation of the Public Trust is Nothing New
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Isaac Newton (1642) & Gregor Mendel (1822-1884)
• Data too good, may have altered original data to fit the model
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Louis Pasteur 1822 -1895
• May have plagiarized the work of others
• May have been less than candid about how his anthrax vaccine was
prepared.
Tuskegee Syphilis Study
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Persons enrolled did not give
informed consent and were not told
of their diagnosis; instead they were
told they had “bad blood” and could
receive free treatment, a free ride to
the clinic, one hot meal per day, and,
in the event of death, $1,000 for the
funeral.
There were 399 mostly illiterate AfrAmer sharecroppers with syphilis &
200 controls
Tuskegee Syphilis Study
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Study ran from 1932-1972
Also known as the Pelkola Syphilis
Study, the Public Health Service
Syphilis Study or the Tuskegee
Experiment
By 1947, penicillin had become the
std treatment for syphilis. Rather
than close the study, and treat the
syphilis subjects, the scientists
continued the study.
Tuskegee Syphilis Study
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Participants were prevented from
accessing syphilis treatment programs
available in the area. Subjects were
studied for 6-8 months and then treated
with Salvarsan, mercurial ointments and
bismuth which were somewhat effective
but toxic.
The original investigator disagreed with
the practices of other investigators and
retired the year after the study began.
Tuskegee Syphilis Study
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In 1932 “consent” obtained for spinal
taps to look for neurosyphilis by
calling the taps “special free
treatment.”
During the Depression patients would
get free exams, hot meals, and free
treatment of minor ailments.
During WW II the PHS officials
prevented 250 of the subjects who
entered the military from being
treated.
Tuskegee Syphilis Study
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In 1966, Peter Buxtum, a PHS
venereal disease investigator sent a
letter expressing concerns about the
morality of the study. The CDC
reaffirmed the need to continue the
study until all subjects had died and
had been autopsied.
The news reported the story in the
Washington Star (1972),then NY
Times.
Tuskegee Syphilis Study
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When the study was ended in 1972,
only 74 subjects were still alive. 28
had died of syphilis, 100 died of
related complications, 40 of their
wives had been infected, and 19 of
their children were born with
congenital syphilis.
Tuskegee Syphilis Study
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Public outcry resulted in an ad hoc
panel that ordered termination of the
study.
Class action lawsuit filed by NAACP
resulted in a 9M settlement.
In 1997 with 5 of the 8 remaining
survivors of the study at the White
House, President Clinton formally
apologized to the Tuskegee
participants.
Implications
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In the 30’s there were not effective
treatments for syphilis but this study
exploited a vulnerable subpopulation and some argue was a
product of racism. Once penicillin
was found to be effective, continuing
the study was indefensible and has
been compared with experimentation
of the Nazi physician Josef Mengele.
Afterwards
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This study is said to have directly led
to the establishment of the National
Commission for the Protection of
Human Subjects of Biomedical and
Behavioral Research and the National
Research Act which requires IRBs at
institutions receiving federal grants.
Recent Violations of the Public Trust
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2005 Woo Suk Hwang, fabricated and falsified Stem Cell lines.
• 8-2006, Advanced Cell Technology “Ethical Stem Cells” report
misleading and false.
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2005 Eric Poehlman fabricated and falsified data from clinical
aging studies.
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June 28, 2006, Eric Poehlman was sentence to 366 days in jail.
8-2006 40 Ohio U Engineering grad students accused of
plagiarism.
• Revocation of degrees
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8-2006 Ward Churchill, Professor of Ethnic Studies.
• Fired for Research Misconduct.
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9-1-06 Elizabeth Goodwin. Resigned - falsification and
fabrication of data.
• Graduate students found false data in NIH grant proposal .
Scientific Misconduct
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Poelman published more than 200 articles
including research on the genetics of
obesity and the impact of exercise.
His stellar career unraveled when a former
lab technician exposed scientific
misconduct.
Poelman pleased guilty to falsifying 17
grant applications to the NIH & fabricating
data in 10 papers!
First academic in US to be jailed for false
data
Menopause Doc Fudged Data
BURLINGTON, Vt., June 21, 2005 Dr. Eric Poehlman (CBS)
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QUOTE from CBS NEWS
"I was outraged. I felt exploited. And I was really amazed
that anyone would be doing something like that."
Susan Real
menopause study participant
(CBS) Millions of women have taken hormone therapy, only to
learn in recent years that its health benefits were never proved
and there were risks involved instead.
Now it turns out a key researcher who touted the benefits of
hormone replacement is facing a five year jail term, reports CBS
News Correspondent Sharyl Attkisson.
Dr. Eric Poehlman was renowned for his groundbreaking research
on women and menopause. He theorized that menopause makes
women lose muscle and gain fat, and causes health problems
hormones could help fix.
Motivation to commit scientific
misconduct
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Why does scientific misconduct
occur?
• Career Pressure – imperative to “publish
or perish”
• Believing that one “knows the right
answer”
• $$$ & fame
• The ability to get away with it
• Inadequate mentoring
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Ignorance of the rules.
Poor ethical decision skills.
Ill prepared to “do the right thing”
Guidelines
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World Medical Association
Declaration of Helsinki: ethical
principles for medical research
involving human subjects.
http://www.wma.net/e/policy/pdf/17
c.pdf..
Declaration of Helsinki
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A.8. “…Some research populations
are vulnerable and need special
protection. The particular needs of
the economically and medically
disadvantaged must be recognized.
Special attention is also required for
those cannot give or refuse consent,
…for those whom the research is
combined with care.”
The Grey Zone
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The usual problems that arise are often
more difficult to delineate and are often
subtle:
• Authorship –who belongs as an author?
What order?
• When should you enter someone with a
“borderline” diagnosis?
• When is it okay to throw out a case? Is
it ever ok? (Data Management)
etc. etc.
Responsible Authorship
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Is it better to be first or last? Who
should be first author?
Example: a large multicenter study
was conducted in SCI on an
experimental drug. 10 centers were
involved. You are a site PI. You
examined all subjects enrolled at
your site. You approved the final
version of the draft but did not draft
or revise it. Should you be listed as
an author?
International Committee of Medical Journal
Editors Uniform requirements for
manuscripts submitted to biomedical
journals.
 Authorship credit should be based on
1) substantial contributions to
conception and design, or acquisition
of data, or analysis and
interpretation of data; 2) drafting the
article or revising it critically for
important intellectual content; and
3) final approval of the version to be
published. Authors should meet
conditions 1, 2, and 3.
International Committee of Medical Journal Editors
Uniform requirements for manuscripts submitted to
biomedical journals. http://www.icmje.org.
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“When a large, multi-center group has
conducted the work, the group should
identify the individuals who accept direct
responsibility for the manuscript. These
individuals should fully meet the criteria
for authorship ... When submitting a group
author manuscript, the corresponding
author should clearly indicate the
preferred citation and should clearly
identify all individual authors as well as
the group name.”
JAMA guidelines
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Group Authorship. All members of
the group must meet the full criteria
and requirements for authorship (13). If not, a group must designate 1
or more individual authors or
members of a writing group who
meet full authorship criteria. Other
group members who are not authors
may be listed in an Acknowledgment.
Authorship Example
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Cardenas DD, Ditunno J, Graziani V,
Jacksom AB, Lammertse D, Potter P,
Sipski M, Cohen R, Blight AR. Phase
2 Trial of Sustained-Release
Fampridine in Chronic Spinal Cord
Injury. Spinal Cord, 2006 Jun 13.
Data Management
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Subject doesn’t return for follow-up
– what do you do? Throw out the
data?
Example: Follow-up survey data
collected in a large study at 1 year
post SCI and then every 5 years up
to 25 years. The number of subjects
was very small at 25 years. Is it okay
to throw out the 25 year data?
Q: How many is too few?
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There were >11,000 interviews with data
for rehospitalizations at 1, 5, 10, 15, 20,
and 25 years post injury but so few at 25
yrs that those data were not included.
• Year 1, N=3978
• Year 5, N=2451
• Year 10, N=1714
Cardenas et al, Arch Phys
204;85:1757-63.
Year 15, N=1653
Year 20, N=1251
Year 25, N= ?
Med Rehabil
Conflict of Interest
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Journals request that you note when
you have received financial support
from an entity that could be
perceived as a conflict of interest.
The concern is that a conflict of
interest could potentially bias your
opinions and your interpretation of
the results of the study.
Conflict of Interest
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JAMA says that conflict of interest
“may exist when an author (the
author’s institution or employer) has
financial or personal relationships or
affiliations that could influence (or
bias) the author’s decisions, work, or
manuscript.”
Disclosures must be listed in the
Acknowledgment section.
No Conflict of Interest statement
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“No commercial party having a direct
financial interest in the results of the
research supporting this article has
or will confer a benefit upon the
author(s) or upon any organization
with which the author(s) is/are
associated.”
Also says at bottom: “Supported by
the (funding agency and grant no.)”
Plagiarism
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“Is the unauthorized use or close
imitation of the language and
thoughts of another author and the
representation of them as one’s own
original work.” –from Wikipedia
Copyright infringement involves the
rights of the copyright holder – use
without consent. But it is legally ok
to copy a small portion of a text in
quotes and cite original source for a
review or criticism.
Mentoring
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A good mentor will point out and
teach you as you go along in your
research that certain things are okay
and other aren’t.
The key is that the mentor must
have the highest of standards.
Remember the movie “A Few Good
Men” –if you are told to do
something that ain’t right, don’t do
it!
The End