Responsible publishing to translate
science into clinical practice: the
why and the how
Margaret Rees
AfRE Chair Elect
Twitter EMAS @AfREnews
Editor in Chief Maturitas
Reader Emeritus in Reproductive Medicine, University of Oxford
Visiting Professor, University of Glasgow, Karolinska Institute and
University of Turku
Adjunct Associate Professor Robert Wood Johnson Medical
School, at Rutgers University.
Why
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Can adversely affect human health, flawed guidelines and
systematic reviews eg Wakefield and MMR.
Research agendas and funding can be inappropriate
Can lead to retraction of papers
Adverse effects on the reputation of researchers and their
institution
May lead to dismissal/ imprisonment eg Reuben in US.
Retraction: COPE 2009
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Journal editors should consider retracting a publication if:
they have clear evidence that the findings are unreliable, either as a result of
misconduct (e.g. data fabrication) or honest error (e.g. miscalculation or
experimental error)
the findings have previously been published elsewhere without proper crossreferencing,
permission or justification (i.e. cases of redundant publication)
it constitutes plagiarism
it reports unethical research
Effects of fabricated data: MMR vaccine
and Wakefield
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The Lancet paper was a case series of 12 child patients; it reported a
proposed “new syndrome” of enterocolitis and regressive autism and
associated this with MMR as an “apparent precipitating event.” But in fact:
Three of nine children reported with regressive autism did not have autism
diagnosed at all. Only one child clearly had regressive autism
Despite the paper claiming that all 12 children were “previously normal,” five
had documented pre-existing developmental concerns..........................
Cite this as: BMJ 2011; 342:c5347
MMR scare and consequences
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Wakefield AJ, Murch SH, Anthony A, Linnell,
Casson DM, Malik M, et al. Ileal lymphoid
nodular hyperplasia, non-specific colitis, and
pervasive developmental disorder in children.
Lancet 1998;351:637-41 [retracted].2010
Reduced use of vaccines in children
In addition to measles outbreaks UK and US,
other infections are resurgent, California 2010
seeing 10 babies dead from whooping cough, in
the worst outbreak since 1958.
Fujii and Boldt
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Anaesthesiologist Yoshitaka Fujii, formerly of Toho University in Tokyo 200
retractions: bogus studies, 126 involved randomized controlled trials
Joachim Boldt 89 retractions: leading advocate of colloids
http://blogs.bmj.com/bmj/2012/07/24/steve-yentis-infamous-names-inanaesthesia-part-one/
Boldt : retractionx2
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Anesthesia & Analgesia:
November 2014 - Volume 119 - Issue 5 - p 1225
doi: 10.1213/ANE.0000000000000417
Retraction:
lack of ethical approval
Evidence of data fabrication
Guidelines
These guidelines were first published in 2008.
They were then revised in 2011, when the authors
learnt that Professor Joachim Boldt is under
investigation following allegations of research
fraud. Whilst remaining open minded as to whether
these allegations would prove to be true or false,
they felt that since the guidelines used six of his
references there was a need to review them to see
if any changes were needed after removing these
six references.
The text and recommendations remained exactly
as before and one review reference was added to
replace the Boldt references removed.
Jon Sudbo
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In January 2006 it was revealed that his October 2005 fast track submission to The Lancet was based
upon fraudulent patient data. The article had suggested that non-COX2-NSAIDs like ibuprofen diminish
the risk of oral cancer in smokers. However, it turned out that the whole patient material was fictional.
The Norwegian newspaper Dagbladet reported that of the 908 subjects in the Lancet study 250 had the
same birthday.
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Sudbø has later acknowledged that he has used fictional data in at least two more papers, published in
the New England Journal of Medicine and the Journal of Clinical Oncology.
Jon Sudbo
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An independent Commission of Inquiry was set up by Rikshospitalet and the University of Oslo to
discern the details of the fraud. The commission deemed much of Sudbø's work invalid because of
manipulation and fabrication of raw data: of the 38 articles he had published since 1993, 15 were
condemned as fraudulent, including his doctoral dissertation. Because of this, the dissertation and the
other fraudulent articles will be rescinded. The commission also criticised the co-authors of Sudbø's
papers However, the commission found no evidence that any of his co-authors had taken part in the
fraud or otherwise been party to the deceit (although Sudbø's supervisor accepted criticism for lack of
vigilance and follow-up).
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In November 2006 his authorization as a physician and a dentist was revoked by the Norwegian Board
of Health Supervision.
Research Misconduct, Retraction, and Cleansing the Medical Literature: Lessons from the
Poehlman Case
right arrow Harold C. Sox, Editor, and Drummond Rennie.
Annals of Internal Medicine 2006; 144:609-613
Eric T. Poehlman, Ph.D., was an
internationally recognized, tenured professor
at the University of Vermont (UVM) in
Burlington when, in October 2000, a
junior member of Poehlman's laboratory
became convinced that he had altered data
from a study on aging volunteers from the Burlington area.
 In the end, Dr. Poehlman admitted to 54 findings of scientific
misconduct made by the UVM and ORI, agreed to retract or
correct ten of his publications and to exclude himself from federal
procurement and nonprocurement transactions for life.
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But Poehlman papers are still being cited and not all
papers have been retracted.
How
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Writing in accordance with recognised guidelines ( eg
CONSORT, STROBE) http://www.equator-network.org/
Trial registration (HRA 2013)
Ethical approval and informed consent
Contributor, competing interest and funding
Publishing negative results
Publishing all results
Reporting guidelines
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Submission of randomized controlled trials requires inclusion of a checklist
and flowchart in accordance with the CONSORT guidelines
(http://www.consort-statement.org/consort-statement/ or www.equatornetwork.org/ ) and the registration number of the trial and the name of the
trial registry.
Observational studies (cohort, case-control, or cross-sectional designs) must
be reported according to the STROBE statement (www.strobe-statement.org
or www.equator-network.org/)
Trial registration
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Now a requirement
Needed for publication
Clinical trials of medicines or devices need to be submitted for
approval to regulatory bodies for approval
Lack of ethical approval
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Was the study undertaken?: Boldt ‘None of the studies examined had received an ethical opinion from the
Rhineland-Palatinate Medical Association (Landesärztekammer Rheinland-Pfalz). In the majority of these cases, the
principal investigator had failed to register planned research projects with the Rhineland-Palatinate Medical
Association, and the relevant office at Ludwigshafen Hospital. Many cases revealed no record of formal consent by
study participants or indeed evidence that study participants had been provided with sufficient information prior to
enrolment.’
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Were the participants aware they were taking part in a research study?
Risks to participants
Collaborative research between countries eg tropical medicine, approval needs to be sought
in all countries.
Journals have ethical committees
Contributor, competing interest and
funding statements
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Who did what
Credibility
Funding affecting conclusions
Contributor/author
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An “author” is generally considered to be someone who has made substantive intellectual contributions to a
published study, and biomedical authorship continues to have important academic, social, and financial implications.
An author must take responsibility for at least one component of the work, should be able to identify who is
responsible for each other component, and should ideally be confident in their co-authors’ ability and integrity
Authorship credit should be based on
1) substantial contributions to conception and design, 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.
Acquisition of funding, collection of data, or general supervision of the research group alone does not constitute
authorship.
http://www.icmje.org/ethical_1author.html
Contributor/ Authorship
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Gift eg head of department automatically put on even though
no contribution
Ghost eg medical writer
Dropped
Added
Dead
Competing interest
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Cite by company name or other description, all commercial and/or financial relationships within the past
3 years that may be relevant to the topic of the manuscript and might be perceived as a real or
potential conflict of interest.
"Relevant" means that the relationship involves the same or similar subject matter; the same, similar or
competing drug or device, product or service, intellectual property or asset, or has the potential to result
in financial, professional or other personal gain or loss for you or an immediate family member (spouse
or child).
Employment (other than primary affiliation; e.g., consulting)
Commercial Research Grant
Other Commercial Research Support
Honoraria from Speakers Bureau
Ownership Interest (including patents)
Consultant/Advisory Board
Other (e.g., expert testimony)
Publishing negative results
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Negative results are as important as positive to avoid
repetition of studies with risks to participants
Need to be presented well so significance is understood
Conclusion
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Maintaining the integrity of the
scientific record
Protecting the public
Ensuring participants are
protected
Sanctions can be severe