Research and publication ethics: why and how

1. Research and publication ethics: why and how Margaret Rees Reader Emeritus in Reproductive Medicine, University of Oxford Visiting Professor, University of Glasgow, Karolinska Institute and University of Turku Adjunct Associate ProfessorRobert Wood Johnson Medical School, at Rutgers University. Editor in Chief Maturitas Editor in Chief Case Reports in Women’s Health Conflict of interest: none declared

2. Background: who am I Ethics and Research • Member Open University Human Research Ethics Committee 2013-present • Advisor UKRIO 2010-present • Chair UK Association for Research Ethics (AfRE) 2014-2016 • Member Northumbria University Research Ethics Committee 2015-2017 • Chair Health Research Authority Ethics Committee (HRA)2006-2013 • Council member University of Oxford Research Ethics Committee (CUREC)2009-2014 • Researcher and supervisor: basic science, clinical trials and PI Publication • Editor in Chief Maturitas, Elsevier 2008- present • Editor in Chief Case Reports in Women’s Health Elsevier 2017- present • Editor in Chief J Br Menopause Soc/ Menopause International 1998-2008 • News editor COPE 2015-2016 • Secretary and Council member of the Committee on Publication Ethics (COPE) 2005-2015 • Member Elsevier ethics committee

3. The basics • Journals want to publish honest reproducible data without data fabrication/ falsification/ duplication/ salami slice or plagiarism • Studies in human beings need to comply to international norms for ethical approval and informed consent • Studies need to comply to international reporting guidelines ( CONSORT, STROBE, CARE, PROCESS etc)

4. MaturitasSize of ball indicating number of corresponding authors over last 5 years

5. Ethics principles • Guidance • Organisations • Consequences of misconduct

6. Ethics principles • Ensuring the dignity, safety and privacy of participants • National ethical, legal and regulatory norms and standards for research involving human subjects as well as applicable international norms and standards must be adhered to. • Ethical review should occur before the study begins and participants enrolled. • Assurance of ethical review/ consent is required for publication

7. Research integrity • includes: • the use of honest and verifiable methods in proposing, performing, and evaluating research. • reporting research results with particular attention to adherence to rules, regulations, guidelines, and. • following commonly accepted professional codes or norms. • https://grants.nih.gov/grants/research_integrity/whatis.htm

8. Integrity, organisations, statements • UKRIO http://ukrio.org/ • UUK Concordat to support research integrity http://www.universitiesuk.ac.uk/policy-and-analysis/reports/Pages/research-concordat.aspx • The Singapore Statement on Research Integrity 2010 http://www.singaporestatement.org/ • The Montreal Statement on Research Integrity in Cross-Boundary Research Collaborations 2013 http://www.equator network.org/2013/11/14/montreal-statement-on research-integrity-in-cross-boundary-research collaborations/ • COPE http://publicationethics.org/

9. UKRIO • The UK Research Integrity Office (UKRIO) is an independent charity, offering support to the public, researchers and organisations to further good practice in academic, scientific and medical research. We promote integrity and high ethical standards in research, as well as robust and fair methods to address poor practice and misconduct. We pursue these aims through our publications on research practice, in-depth support and services for research employers, our education and training activities, and by providing expert guidance in response to requests for assistance from individuals and organisations. • Established in 2006, our aims are to: • Promote the good governance, management and conduct of academic, scientific and medical research. • Share good practice on how to address poor practice, misconduct and unethical behaviour. • Give confidential, independent and expert advice on specific research projects, cases, problems and issues.

10. UUK Concordat

11. Singapore statement 2010 • Honesty in all aspects of research • Accountability in the conduct of research • Professional courtesy and fairness in working with others • Good stewardship of research on behalf of others

14. Code of practice/ professional bodies • Office of Research Integrity in US • GMC • British Psychological Society • Royal Society

15. COPE • Promoting integrity in research publication • COPE is a forum for editors and publishers of peer reviewed journals to discuss all aspects of publication ethics. It also advises editors on how to handle cases of research and publication misconduct. • Flow charts

16. Retraction watch and PubPeer • Retraction Watch is a blog that reports on retractions of scientific papers and on related topics. The blog was launched in August 2010 and is produced by science writers Ivan Oransky and Adam Marcus. Retraction database launched 2018 • https://retractionwatch.com/ • The PubPeer Foundation is a California-registered public-benefit corporation with 501(c)(3) nonprofit status in the United States. The current focus is maintaining and developing the PubPeer online platform for post-publication peer review. • https://pubpeer.com/static/about

18. https://ori.hhs.gov/content/case-summary-elqutub-maria-cristina-mironhttps://ori.hhs.gov/content/case-summary-elqutub-maria-cristina-miron

19. Consequences of misconduct • Human health (MMR) • Sanctions by institutions and professional bodies/ dismissal • Imprisonment • Adverse effects on reputation of institutions and their staff and co authors • Waste of research money • Expression of concern, retraction or removal of publications (RW database: nearly 17,000 retractions)

20. Data fabrication/ falsification • Completely fabricated data set • Alteration of the data set • Image manipulation https://www.nature.com/authors/policies/image.html

21. Data fabrication and falsification • Data fabrication: This concerns the making up of research findings. • Data falsification: Manipulating research data with the intention of giving a false impression. This includes manipulating images (e.g. micrographs, gels, radiological images), removing outliers or “inconvenient” results, changing, adding or omitting data points, etc. • With regard to image manipulation it is allowed to technically improve images for readability. Proper technical manipulation refers to adjusting the contrast and/or brightness or color balance if it is applied to the complete digital image (and not parts of the image). Any technical manipulation by the author should be notified in the cover letter to the Journal Editor upon submission. Improper technical manipulation refers to obscuring, enhancing, deleting and/or introducing new elements into an image. Generally, if an author’s figures are questionable, it is suggested to request the original data from the authors. • https://www.springer.com/gp/authors-editors/editors/data-fabrication-data-falsification/4170https://www.springer.com/gp/authors-editors/editors/data-fabrication-data-falsification/4170

22. Duplicate salami slice submission (Elsevier) • Unlike duplicate publication , which involves reporting the exact same data in two or more publications, salami slicing it involves breaking up or segmenting a large study into two or more publications. These segments are referred to as "slices“ of a study • As a general rule, as long as the "slices" of a broken up study share the same hypotheses, population, and methods, this is not acceptable practice. The same "slice" should never be published more than once. • The reason: according to the U.S. Office of Research Integrity, salami slicing can result in a distortion of the literature by leading unsuspecting readers to believe that data presented in each salami slice (i.e., journal article) is derived from a different subject sample. This not only skews the "scientific database" but it creates repetition that wastes readers' time as well as the time of editors and reviewers, who must handle each paper separately. Further, it unfairly inflates the author's citation record. • There are instances where data from large clinical trials and epidemiological studies cannot be published simultaneously, or are such that they address different and distinct questions with multiple and unrelated endpoints. In these cases, it is legitimate to describe important outcomes of the studies separately. However each paper should clearly define its hypothesis and be presented as one section of a much larger study. • Most journals request that authors who either know or suspect a manuscript submitted for publication represents fragmented data should disclose this information, as well as enclose any other papers (published or unpublished) that might be part of the paper under consideration.

23. 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

24. 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 • General reduced use of vaccines • In addition to measles outbreaks UK and US, other infections are resurgent eg whooping cough, mumps, rubella and other diseases eg dengue not being prevented • Consequences: death, disability, infertility

25. Measles 2018 (WHO) • Measles cases in Europe tripled between 2017 and 2018 to 82,596 - the highest number recorded this decade • Over 90% of cases were in 10 countries • In 1967, the year before measles vaccine was introduced in England and Wales, there were almost half a million reported cases and 99 deaths. By 1998, this had fallen to an all-time low of 56 cases and no deaths. • In 2018 in the UK, there were 953 measles cases

27. Researcher banned from federal Canadian funding after misconduct loses medical license • The files she submitted to the University of Toronto Inquiry were files she personally manipulated and not the original files of her Research Associate as she claimed. • She illegally accessed patient records to alter data and destroy and change computer files. • She disposed of an old computer so the forensic computer experts could not examine it. • She went into the Canadian Blood Services facility and changed freezer temperatures to damage blood and urine samples in a strenuous attempt to cover up her deceptions during the IC’s investigation. This prolonged deception and dishonesty is considered by the Committee to constitute serious professional misconduct. • Dr. Jamal attempted to put all the blame on other people. Retraction Watch 29 Jan 2019

28. Jon Sudbø: a Norwegian dentist, physician, and former medical researcher, who was exposed as a scientific fraudster in 2006. • Exposed when he published in the Lancet in 2005 a paper that claimed that long-term use of anti-inflammatories could reduce the risk of oral cancer in smokers. • A major phase III US-funded preventative trial for oral cancer to be led by Sudbo was planned to start in 2006 was suspended just days before it was to start. •  Permitted to work as a dentist but not allowed to do research until 2036  https://ori.hhs.gov/content/case-summary-sudbo-jon

29. Sato and Iwamoto: osteoporosis data fabrication • Sato: Data fabrication for many clinical trials, leading to retractions • Fake trials lead to real trials which find no effect/ meta-analyses and guidelines compromised • Iwamoto: Gift authorship for more than a decade • Sato died end 2016(circumstances uncertain) /Iwamoto dismissed and works in another hospital • http://science.sciencemag.org/content/361/6403/636 Osteoporosis affects 1 in 3 women and 1 in 5 men. Hip fracture has a high mortality

31. 1925 image manipulation: element 43, technetium For Science King & Country: The Life and Legacy of Henry Moseley 2018 ISBN-10: 1910500712

32. 1925: image manipulation

33. Investigating misconduct • The lead author is no longer alive • The other authors do not have functional emails • The paper was accepted when submissions were by paper or email. All the records from this time no longer exist, including the original manuscript and the peer reviewers' comments. • There is no named person or response from the institution who have been requested to investigate

34. Conclusion • Ethics and integrity are integral to good research and publication and not an option or regulatory burden