Research misconduct and biomedical journals

1
Research misconduct and biomedical journals

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

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What I want to talk about

• Why research misconduct matters
• Some of medicines 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)

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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

4
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

5
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

6
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

7
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
  Slutskys work, illustrating how peer review
  sometimes can pick up on fraud
• An investigation decided that 12 of Slutskys
  studies were definitely fraudulent and 49
  questionable
• Many were retracted, although journals declined
  to retract the studies

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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

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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.

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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 Georges.
• The same issue contained a randomised controlled
  trial also by Malcolm Pearce -- and 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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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.

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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?
31
What is the relation of minor to serious research
misconduct?
32
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 150 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 little 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.
• One sponsored study finding an increased risk has
  not been published.
• Vandenbroucke JP, Helmerhorst FM, Frits R
  Rosendaal FR. Competing interests and controversy
  about third generation oral contraceptives. BMJ
  2000 320 381.

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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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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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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

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The same probably goes for physics--and youre
even slower than us, wow