Margaret ReesChair UK Association for Research Ethics (AfRE) Reader Emeritus in Reproductive Medicine, University of OxfordVisiting Professor, University of Glasgow, Karolinska Institute and University of Turku Adjunct Associate ProfessorRobert Wood Johnson Medical School, at Rutgers University. Editor in Chief MaturitasExecutive Director European Menopause and Andropause Society (EMAS)

Reporting and Publication @AfREnews

Background: who am I Researcher and supervisor: basic science Researcher: clinical trials and PI Chair National Health Service Research Ethics Committee (NRES)2006-

2013 Member Open University Human Research Ethics Committee Council member University of Oxford Research Ethics Committee

(CUREC)2009-2014 President European Menopause and Andropause Society (EMAS)2012-

2015 Chair UK Association for Research Ethics (AfRE) Secretary of the Committee on Publication Ethics (COPE) Member Elsevier ethics committee Editor in Chief J Br Menopause Soc/ Menopause International 1998-2008 Editor in Chief Maturitas, Elsevier 2008- present Executive Director EMAS 2015

Why Poorly written papers (student

research/ lack of supervision) The China Bazaar Filtered out by editors to avoid

wasting peer review time

Geographical Origin Published Articles 2012-2014

4

Asia11%

Europe55%

N.Amer.

18%

S.Amer.4%

Austral.10%

Africa1%

Mid.East1%

Maturitas is an international publication: almost 50% of published papers are from outside Europe.

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/)

 Systematic reviews and meta-analyses need to be written in accordance with the guidelines from the PRISMA statement (http://www.prisma-statement.org/statement.htm or www.equator-network.org/ )

China Bazaar

Companies prepare original papers from scratch with data provided by their clients or fabricate data, arrange to add scientists’ names to already accepted papers, and sell finished manuscripts.

Among the most popular options for finished manuscripts are meta-analyses, perhaps because they require no original data. One legitimate analysis published in PLOS ONE in June 2013 found that from 2003 to 2011, meta-analysis papers from China rose more than 16 times faster than did such papers from the United States.

Copycat papers with similar phrases.......

http://news.sciencemag.org/asiapacific/2014/10/copycat-papers-flag-continuing-headache-china

What else do editors look out for

Detail ethical approval and informed consent (name, date, reference number, approval letter....)

Authorship Competing interests Plagiarism Duplicate/ salami slice submission Fake data Fake peer reviewers Sting papers

Ethics and guide for authors Human and animal rights (Elsevier)

If the work involves the use of animal or human subjects, the author should ensure that the work described has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans

Authors should include a statement in the manuscript that informed consent was obtained for experimentation with human subjects. The privacy rights of human subjects must always be observed.

COPE discussion document with HRA (2014) Background There are a number of legitimate and valuable tools for gaining information

and evidence for scientific advance and improving health care. These include research, evaluation, audit, and others. There is a real danger that UK “researchers” using tools other than “research”, duly following guidance in UK research regulation stating a lack of need for ethical review, find that journal editors will not consider their manuscript for publication because editors dispute the definition of what needs or does not need ethical review.

Summary of COPE forum discussion The editor's position, when presented with a research paper, is to make sure that by

the best standards that are available, or best relevant standards, that the work has been proven to be ethical. It is hard to define when formal ethics approval is required for some types of research, and defining what is research is tricky.

The key is demonstrating to the editor that due process has been followed, and there should be transparency, including reference to the guidance and standards that the authors have followed, and proof, where required, that those standards or processes have been followed.

We need to empower and support those research communities that do not have an ethical review infrastructure in a sensitive manner, and in accordance with their cultures. There should be transparency around the constitution of ethics committees.

The minimum standards that could be applied should be institutional regulations as well as local legislation, and due process needs to be demonstrated and proved to the editor by the researcher so that the editor can be satisfied that the relevant standards have been applied.

COPE guidance: submitted manuscript

Contact the author and await explanation Stop processing of paper until satisfactory

explanation provided with evidence of ethical approval/ informed consent

If explanation unsatisfactory ask institution to investigate

http://publicationethics.org/files/u2/All_flowcharts.pdf

Example of a letter to authorThank you for submitting your paper for consideration for publication in Maturitas. This paper is not suitable for consideration for publication in Maturitas at the present time as:

We have noticed that this manuscript does not provide sufficient information for us to judge whether the study you describe in this manuscript was conducted according to accepted ethical guidelines for the treatment of humans.

There is lack of evidence of informed consent and ethical approval as specified in our guide for authors.

I would be grateful if you could clarify how this research was carried out, specifically did you have ethical approval and was consent obtained.

If you have received ethical approval could you please send me copy of the letter.

While we are aware that legislation varies throughout the world and not all research requires ethical approval, we would like you to provide supporting evidence such as a letter from the chair of your IRB stating that ethical approval was not required for this study.

  Until we have heard from you we cannot proceed further with the review/publication of your paper.

Expression of concern: The Journal of Bone and Joint Surgery

The Journal of Bone and Joint Surgery received a letter from the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, stating that the trial on which this study was based was performed without authorization from the MHRA and without a favorable ethical opinion from a recognized research ethics committee, both of which are required by the Medicines for Human Use (Clinical Trials) Regulations (2004).

Additionally, the MHRA stated that permission was not obtained from the organization where the research was undertaken, as required by the Department of Health Policy. It has been reported to me that the research patients were treated at a private practice facility. There are differing reports as to whether or not the lead author, Dr. David Connell, retained records of his research findings.

It has been reported to me that there is an ongoing investigation in the United Kingdom by the General Medical Council (GMC) into possible unethical behavior. We will inform our readers of the outcome of this investigation when it is complete.

An unethical ethics committee (COPE case) A paper was submitted, detailing a double blind placebo controlled food challenge to

a group of children. The reviewer considered the study unethical because he was concerned consent could not have been properly informed. He believed there was a very small risk of anaphylaxis—even death—and had this been explained to the parents, they would not have consented.

After investigation it transpired that the chairman of the ethics committee tagreed the proposal was part of normal clinical practice rather than a clinical trial so did not require ethics committee approval overruling the committee. The study went ahead.

There was concern that the chairman had overruled his/her own committee. The editor contacted the chief executives of the hospital trusts, detailing the

allegations and requested an investigation.

No ethics approval or informed consent (COPE case) A thesis published by a student was submitted for publication. One of the journal

editors found the research unethical and asked for confirmation of ethics committee approval.

It was found that not only was the approval obtained post research but also that the subjects were not aware that they had been randomised into two groups for surgery. The only consent forms available were those for surgery and consent that their data could be used for research. There are long term implications of the research. The author wanted to prove that omission of an expensive drug in a third world scenario could lead to no change in results. There were over a dozen articles indicating the contrary. The author seemed to base his hypothesis on one article in the literature. Following the investigation, the article was withdrawn by the author.

COPE agreed that the editorial team had a moral responsibility to take further action as there was a possibility that patients may be put at risk ie write to the ethics committee/ medical board requesting investigation.

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

Joke authors

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) NOT TO STATE MEANS THAT AUTHORS COULD BE DECEIVED

Submissions are checked for overlap with iThenticate but this will not pick up simultaneous submissions and here editors rely on

peer reviewers.

Duplicate salami slice submission 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.

Fake data

Following an investigation into research misconduct, the Journal of Clinical Investigation has retracted a cancer genetics paper from a laboratory at the National Institutes of Health due to “data falsification and fabrication” of four figures and a table in the paper.

The paper, “FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer,” describes an overexpressed gene in mouse prostate cancers that appears to suppress immune system cells.

The journal retracted the paper following an investigation into author Stephanie K. Watkins, then a postdoctoral fellow at the National Cancer Institute

Fake dataEditorial retractionScience, with the concurrence of author Donald P. Green, is retracting the 12 December 2014 Report “When contact changes minds: An experiment on transmission of support for gay equality” by LaCour and Green.The reasons for retracting the paper are as follows: (i) Survey incentives were misrepresented. To encourage participation in the survey, respondents were claimed to have been given cash payments to enroll, to refer family and friends, and to complete multiple surveys. In correspondence received from Michael J. LaCour’s attorney, he confirmed that no such payments were made. (ii) The statement on sponsorship was false. In the Report, LaCour acknowledged funding from the Williams Institute, the Ford Foundation, and the Evelyn and Walter Haas Jr. Fund. Per correspondence from LaCour’s attorney, this statement was not true. In addition to these known problems, independent researchers have noted certain statistical irregularities in the responses. LaCour has not produced the original survey data from which someone else could independently confirm the validity of the reported findings. Michael J. LaCour does not agree to this Retraction.Published online 28 May 201510.1126/science.aac6638

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 eg whooping cough

Fake peer reviewers BioMed Central uncovered about fifty manuscripts in their editorial system that involved fake

peer reviewers. Most of the cases were not published because they were discovered by a manuscript editor on a

final pre-publication check. The five or so that have been published will go through some sort of re-review, which may result in expressions of concern or retraction.

The narrative seems similar to that in the growing number of cases of peer review manipulation we’ve seen recently. What tipped off the editor was minor spelling mistakes in the reviewers’ names, and odd non-institutional email addresses that were often changed once reviews had been submitted, in an apparent attempt to cover the fakers’ tracks. Those “reviewers” had turned in reports across several journals, spanning several subjects.

It would seem that a third party, perhaps marketing services helping authors have papers accepted, was involved.

http://retractionwatch.com/2014/11/25/publisher-discovers-50-papers-accepted-based-on-fake-peer-reviews/

http://publicationethics.org/news/cope-statement-inappropriate-manipulation-peer-review-processes

Sting paper

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 Ethical approval and informed

consent must be obtained in accordance with local legislation.

Journals scrutinise papers Journals will examine whether

ethical approval and informed consent were obtained

Journals may ask ethics committees and institutions to investigate their decisions

Journals are concerned about the long term effects of poorly conducted/ unethical studies