Transcript Research misconduct and biomedical journals Richard Smith

Research
misconduct and
biomedical journals
Richard Smith
Editor, BMJ
www.bmj.com/talks
What I want to talk about
• Why research misconduct matters
• Some of medicine’s ’s most dramatic
cases
• What is research misconduct?
• How common is it?
• Conflict of interest as a case study
• Why does misconduct happen?
• What does a country need to do to
respond?
• A comment on COPE (Committee on
Publication Ethics)
Why research misconduct
matters
• It’s like child abuse: we didn’t
recognise it, now we see a lot
• It undermines public trust in
medical research and health
workers
• It corrupts the scientific record
and leads to false conclusions
• Most countries do not have good
systems of either treatment or
prevention
William Summerlin from the
Sloan-Kettering, New York, 1974
• Claimed to have transplanted
human corneas into rabbits
• Faked transplantation experiments
in white mice by blackening
patches of their skin with a pen
• His misconduct was long ignored
• Eventually attributed to a mental
health problem
• A form of scientific denial
Vijay Soman, Yale,
exposed 1980
• A diabetologist and the author of 12
papers where data were either missing or
fraudulent--all eventually retracted
• A paper co-authored with Philip Felig, a
senior researcher, was stolen from
another author when Felig was sent a
paper to review and passed it on to Soman
• Felig had to resign
• Senior figures putting their names on
papers which eventually turn to be
fraudulent is a recurrent problem
John Darsee, department of
cardiology, Harvard, 1981
• Observed falsifying data
• His boss, Eugene Braunwald decided that
this misconduct was an isolated incident
and so did not fire him
• A few months later it became clear that
results he had obtained in a multicentre
study were very different from those of the
others
• An investigation going showed that many
of his more than a 100 studies were
fraudulent
• Again many of the studies included
distinguished authors
Robert Slutsky, cardiological
radiologist, University of
California
• Published 137 papers between 1978 and
1985--sometimes one every 10 days
• A reviewer raised anxieties about some
of Slutsky’s work, illustrating how peer
review sometimes can pick up on fraud
• An investigation decided that 12 of
Slutsky’s studies were definitely
fraudulent and 49 questionable
• Many were retracted, although journals
declined to retract the studies
Congressional hearings into
scientific misconduct
• “Problems of scientifc misconduct are
rare— and the product of psychopathic
behaviour’ originating in temporarily
deranged minds” President of the National
Academy of Sciences
• “One reason for the persistence of this
type of problem is the reluctance of
people high in the science field to take
these matters very seriously.” Al Gore,
chairman of the hearing
Britain’s most dramatic
case of fraud
August 1996: a major
breakthrough
• Worldwide media coverage of
doctors in London reimplanting
an ectopic pregnancy and a
baby being born
• Doctors had been trying to do
this for a century. It was a huge
achievement
August 1996: a major
breakthrough
• Achieved by Malcolm Pearce, a
senior lecturer in at St George’s
Hospital Medical School in London
• A world famous expert on
ultrasonography in obstetrics
• A story from a paper in the British
Journal of Obstetrics and
Gyneacology. Pearce was an
assistant editor.
August 1996: a major
breakthrough
• A second author on the case
report was Geoffrey Chamberlain,
editor of the journal, president of
the Royal College of Obstetricians
and Gynaecologists, and professor
and head of department at St
George’s.
• The same issue contained a
randomised controlled trial also
by Malcolm Pearce -- and others.
Autumn 1996: both
papers are fraudulent
• A front page story in the Daily Mail
exposed the two papers as fraudulent.
• It had a full length picture of Geoffrey
Chamberlain saying that he hadn’t
known that the work was fraudulent
despite his name being on the paper.
• Chamberlain said it was common
within medicine for people to have their
name on papers when they hadn’t done
much.
What had happened?
• A young doctor at St George’s
Hospital Medical School had raised
questions about the two papers
• An investigation was promptly
started and showed:
• The patient did not exist
• The patients supposedly in the
randomised trial could not be found
• Among studies investigated back to
1989 - three others fraudulent, two
of them in the BMJ.
What had happened?
• All the papers were retracted.
Questions about ones before that.
• Pearce was fired and subsequently
struck off by the General Medical
Council
• Chamberlain retired or resigned from
all his positions, a terrible end to a
distinguished career.
• His crime was gift authorship, which
was normal at the beginning of his
career, scandalous by the end.
Britain’s slowest case?
Britain’s slowest case?
• Anjan Banerjee and Tim Peters: paper
in Gut 1990 on drug induced
enteropathy in the and inflammatory
bowel disease (Gut 1990--contained
falsified data
• The same issue contained an abstract
due to be presented at the British
Society of Gastroenterology.
Withdrawn but still published in Gut
• Both papers retracted in March 2001
Britain’s slowest case?
• Banerjee was awarded a Master of
Surgery degree by the University of
London for work that included the
fraudulent work--still not retracted
• December 2000. Banerjee found guilty
of serious professional misconduct for
falsifying data and suspended
• September 2002. Banerjee found guilty
of serious professional misconduct for
financial fraud and struck off
Britain’s slowest case?
• March 2001. Tim Peters, the professor
who supervised Banerjee, was found
guilty of serious professional
misconduct for failing to take action
over the falsified research
• The GMC hearings were hampered by
notebooks being “selectively
shredded” by Kings,the medical school
• Authorities at Kings conducted an
inquiry in 1991 but did not inform the
GMC or Gut
Does medicine
have a culture
that turns a
blind eye to
research
misconduct?
What is research
misconduct?
• The Americans have argued for
years over a definition
• The Europeans have tended to
take a broad view and not
attempt a specific, operational
definition
US Commission on
Research Integrity (1996)
• Research misconduct is significant
misbehaviour that improperly appropriates
the intellectual property or contributions
of others, that intentionally impedes the
progress of research, or that risks
corrupting the scientific record or
compromising the integrity of scientific
practices. Such behaviours are unethical
and unacceptable in proposing,
conducting, or reporting research, or in
reviewing the proposals or research
reports of others.
Definition of research
misconduct proposed by a
British consensus panel
(1999)
• "Behaviour by a researcher,
intentional or not, that falls
short of good ethical and
scientific standards."
preliminary taxonomy of
research misconduct (ranked
by seriousness) I
A
• Fabrication: invention of data or
cases
• Falsification: wilful distortion of
data
• Plagiarism: copying of ideas, data
or words without attribution
• Failing to get consent from an
ethics committee for research
A preliminary taxonomy of
research misconduct (ranked
by seriousness) II
• Not admitting that some data are
missing
• Ignoring outliers without declaring it
• Not including data on side effects in a
clinical trial
• Conducting research in humans
without informed consent or without
justifying why consent was not
obtained from an ethics committee
A preliminary taxonomy of
research misconduct (ranked
by seriousness) III
• Publication of post hoc
analyses without declaration
that they were post hoc
• Gift authorship
• Not attributing other authors
• Redundant publication
• Not disclosing a conflict of
interest
preliminary taxonomy of
research misconduct (ranked
by seriousness) IV
A
• Not attempting to publish
completed research
• Failure to do an adequate
search of existing research
before beginning new research
What is fraud?
• We need a full taxonomy
• Better we need codes of good
research practice--and we now
have several
How common is fraud?
• Obviously depends on how fraud
is defined?
• How does serious fraud relate
to minor fraud?
– Are they quite separate?
– Does minor progress to serious?
What is the relation of minor to
serious research misconduct?
What is the relation of minor to
serious research misconduct?
Study by Stephen Lock
• Asked 80 researchers who were
friends, mostly British and mostly
professors of medicine. Not a random
sample.
• 100% response rate.
• Over half knew of cases:
• Over half the dubious results had
been published - only 6 “retractions” all vague and not using that term
How common is fraud?
• US congressional inquiry heard
of over 700 cases
• The British General Medical
Council has dealt with over 30
cases
• Committee on Publication
Ethics has discussed over a 150
cases
How common is
research misconduct?
• Redundant publication occurs in
around a fifth of published papers
• About a fifth of authors of studies
in medical journals have done
little or nothing
• Most authors of studies in medical
journals have conflicts of interest,
yet they are declared in less than
5% of cases
Conflict of interest: a
case study in poor
performance within
biomedicine
How common are
competing interests?
•
•
•
•
75
89
69
45
articles
authors
(80%) responded
(63%) had financial conflicts of interest
• Only 2 of 70 articles disclosed
the conflicts of interest
• Stelfox HT, Chua G, O'Rourke K, Detsky AS.
Conflict of interest in the debate over calcium
channel antagonists. N Engl J Med 1998; 338:
101-105
Why don’t authors declare
conflicts of interest?
• Some journals don’t require
disclosure
• The culture is one of not
disclosing
• Authors think that it’s somehow
“naughty”
• Authors are confident that they
are not affected by conflicts of
interest
Does conflict of interest
matter?
• Financial benefit makes doctors more likely
to refer patients for tests, operations, or
hospital admission, or to ask that drugs be
stocked by a hospital pharmacy.
• Original papers published in journal
supplements sponsored by pharmaceutical
companies are inferior to those published in
the parent journal.
• Reviews that acknowledge sponsorship by
the pharmaceutical or tobacco industry are
more likely to draw conclusions that are
favourable to the industry.
Does conflict of interest
matter?
• Is there a relationship between
whether authors are supportive of
the use of calcium channel
antagonists and whether they have
a financial relationship with the
manufacturers of the drugs?
• Stelfox HT, Chua G, O'Rourke K, Detsky AS.
Conflict of interest in the debate over calcium
channel antagonists. N Engl J Med 1998; 338:
101-105
Does conflict of interest matter?
• 106 reviews, with 37% concluding that
passive smoking was not harmful and the
rest that it was.
• Multiple regression analysis controlling for
article quality, peer review status, article
topic, and year of publication found that the
only factor associated with the review's
conclusion was whether the author was
affiliated with the tobacco industry.
• Only 23% of reviews disclosed the sources
of funding for research.
• Barnes DE, Bero LA. Why review articles on the health
effects of passive smoking reach different conclusions. JAMA
1998; 279: 1566-1570
Does conflict of interest matter?:
third generation contraceptive pills
• At the end of 1998 three major studies
without sponsoring from the industry
found a higher risk of venous thrombosis
for third generation contraceptives; three
sponsored studies did not.
• To date, of nine studies without
sponsoring, one study found no difference
and the other eight found relative risks
from 1.5 to 4.0 (summary relative risk
2.4); four sponsored studies found relative
risks between 0.8 and 1.5 (summary
relative risk 1.1)
Why does scientific fraud
happen?
• Why wouldn’t it happen? It happens
in all other human activities.
• Pressure to publish.
• Inadequate training. Not taught good
practice. Indeed, sometimes taught
the opposite.
• Does sloppy behaviour spill over to
fraud?
• You can get away with it. The system
works on trust.
What does a country need to
respond to research misconduct?
• A recognition of the problem by the
medical community and its leaders
• An independent body to lead with
investigations, prevention, teaching and
research
• An agreement on what fraud is
• Protection for whistleblowers
• A body to investigate allegations
• A fair system for reaching judgements
• A code of good practice
• Systems for teaching good practice
Committee on Publication
Ethics (COPE)
• Founded in 1997 as a response
to growing anxiety about the
integrity of authors submitting
studies to medical journals.
• Founded by British medical
editors--including those of the
BMJ, Gut, and Lancet
COPE’s five aims
• Advise on cases brought by editors
• Publish an annual report describing
those cases. Three published
(www.publicationethics.org.uk)
• Produce guidance on good practice
• Encourage research
• Offer teaching and training
• (Shame the British establishment into
mounting a proper response)
COPE’s first 103 cases
• In 80 cases there was evidence of misconduct.
• Several cases have been referred to
employers and to regulatory bodies
• Problems were
– undeclared redundant publication or
submission (29)
– disputes over authorship (18)
– falsification (15)
– failure to obtain informed consent (11)
– performing unethical research (11)
– failure to gain approval from an ethics
committee (10)
Conclusion
• Research misconduct is a
problem
• Most countries have not
developed a coherent response
to the problem
• They need to in order to avoid a
collapse in public trust in
medical research
The same
probably goes
for physics--and
you’re even
slower than us,
wow