Responsible publishing to translate science into clinical practice: the

why and the how

Margaret ReesAfRE Chair Elect

Twitter EMAS @AfREnews Editor in Chief Maturitas

Reader Emeritus in Reproductive Medicine, University of OxfordVisiting Professor, University of Glasgow, Karolinska Institute and

University of Turku Adjunct Associate Professor Robert Wood Johnson Medical

School, at Rutgers University.

Why

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 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

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 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

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-in-

anaesthesia-part-one/

Boldt : retractionx2

Anesthesia & Analgesia: November 2014 - Volume 119 - Issue 5 - p 1225 doi: 10.1213/ANE.0000000000000417 Retraction: lack of ethical approval Evidence of data fabrication

GuidelinesThese 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

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.

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 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).

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 Caseright 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 laboratorybecame 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.

But Poehlman papers are still being cited and not all papers have been retracted.

How

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

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.equator-network.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

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 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.’

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

Who did what Credibility Funding affecting conclusions

Contributor/author 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

Gift eg head of department automatically put on even though no contribution

Ghost eg medical writer Dropped Added Dead

Competing interest 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

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

Maintaining the integrity of the scientific record

Protecting the public Ensuring participants are

protected Sanctions can be severe