Publication ethics: an embarrassing amount of room for improvement

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Publication ethics an embarrassing amount of
room for improvement

• Richard Smith
• Editor, BMJ
• www.bmj.com/talks

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What I want to talk about

• Why research misconduct matters
• Britains most dramatic case of misconduct
• Other 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)
• An editors intray

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Why research misconduct matters

• Its like child abuse we didnt 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

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Britains most dramatic case of fraud
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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

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August 1996 a major breakthrough

• Achieved by Malcolm Pearce, a senior lecturer in
  at St Georges 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.
• 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 Georges.
• The same issue contained a randomised controlled
  trial also by Malcolm Pearce others

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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 hadnt 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
  hadnt done much.

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What had happened?

• A young doctor at St Georges 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.

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The case of Peter Nixon, cardiologist

• A television programme accused him of fraud. He
  sued for libel. His case collapsed.
• Rigged the results of a breathing test
• Had not written or even read papers published in
  the Journal of the Royal Society of Medicine over
  his name

10
The case of Peter Nixon, cardiologist

• Admitted errors could not be due to honest error
• In case control studies applied different tests
  to cases and controls
• Found effort syndrome in virtually all patients
  who consulted him with chronic fatigue
  syndrome--but failed to report that 55 of
  controls were also positive

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John Anderton, former registrar of the Royal
College of Physicians of Edinburgh

• In a drug trial forged consent of 17 patients who
  were never given the drug
• Invented echocardiographs and magnetic resonance
  images for patients

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Britains slowest case?
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Britains 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

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Britains 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

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Britains 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

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Does medicine have a culture that turns a blind
eye to research misconduct?
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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

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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.

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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."

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A preliminary taxonomy of research misconduct
(ranked by seriousness) I

• 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

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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

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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

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A preliminary taxonomy of research misconduct
(ranked by seriousness) IV

• Not attempting to publish completed research
• Failure to do an adequate search of existing
  research before beginning new research

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What is fraud?

• We need a full taxonomy
• Better we need codes of good research
  practice--and we now have several

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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?

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What is the relation of minor to serious research
misconduct?
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What is the relation of minor to serious research
misconduct?
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How common is fraud?

• How many of you know of a case?
• In how many of those cases was there a proper
  investigation, punishment if necessary, and a
  correction of the scientific record?

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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

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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 100 cases

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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 libtle or nothing
• Most authors of studies in medical journals have
  conflicts of interest, yet they are declared in
  less than 5 of cases

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Conflict of interest a case study in poor
performance within biomedicine
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How common are competing interests?

• 75 articles
• 89 authors
• 69 (80) responded
• 45 (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

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Why dont authors declare conflicts of interest?

• Some journals dont require disclosure
• The culture is one of not disclosing
• Authors think that its somehow naughty
• Authors are confident that they are not affected
  by conflicts of interest

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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.

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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

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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

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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)
• The sponsored study with a relative risk of 1.5
  has been reanalysed several times, yielding lower
  relative risks after this failed to convince, a
  new reanalysis was sponsored by another company.

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Why does scientific fraud happen?

• Why wouldnt 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.

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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

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Does your country have these characteristics
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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

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COPEs 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)

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COPEs 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)

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Three cases from an editors intray
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Case 1

• A major RCT showing that an nutritional
  intervention can improve cognitive function in
  the elderly
• An editor, a statistician, and a reviewer all
  raise doubts about the data and the tests used
• Approach the university
• It investigates no problem
• BMJ queries investigation
• Researcher flees university seems to see this as
  an admission of guilt
• Should we notify the editors of a journal that
  published another paper from the same trial?

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Case 2

• Two people write to me to suggest (with evidence)
  that many papers by an author, including several
  that we have published and two we are considering
  are fraudulent
• Statistician agrees
• We ask for raw data
• Raw data arrives in a box, written out by hand
  after six months
• Statistician takes years to analyse--says I
  would go to court to say that these data are
  fraudulent
• Researcher owns his own hospital

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Case 3

• Ive been on this case for 12 years
• Should we publish something in the BMJ?
• We are about to publish a paper on chronic
  fatigue syndrome
• An anonymous letter says the work is fraudulent
• What should we do?

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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