Ethics, Authorship and Merit

1. Ethics, Authorship and Merit Ian R. Holzman, MD

2. Conflicts of Interest • I have no conflicts to report

3. Research Misconduct • History of federal oversight -essentially none before 1980s -high profile cases in the 80s led to Health Research Extension Act(1985) -required procedures for oversight and reporting -1989 PHS final rule and creation of both an NIH and HHS Office of Scientific Integrity -Merged to become Office of Research Integrity which reviews institutional findings and has an appeal process -Appeal Board overturned a number of findings by ruling misconduct had to include intent to deceive

4. Research Misconduct -A number of cases made it clear that the Appeal Board did not believe the researcher bore the burden of proving him/herself innocent -An intent to mislead would be required, the evidence would have to be strong and the burden of proof falls on the ORI -But, no due process required during investigations, accused scientists can’t sue Fed for negligence, invasion of privacy or defamation -Final definition defines misconduct as fabrication, falsification, plagiarism and other practices that seriously deviate from common practices in science; honest error excluded

5. Research Misconduct • Guidelines SUGGESTED safeguards -Institutions should inform scientist of investigation -Should allow scientist to confront witnesses -Allow for full access to evidence -Allow them to present their own evidence at initial inquiry and during full investigation -Right to be represented by counsel throughout the proceedings

6. Accusation of misconduct Preliminary institutional assessment of whether alleged conduct fit definition of misconduct Does not fit definition End Initial institutional inquiry Insufficient evidence Inquiry report determines if evidence warrants full investigation

7. Full institutional investigation, if warranted Report to ORI recommending a finding of guilt or innocence and appropriate sanctions No misconduct End Investigator appeal at institution, if available ORI review of institutional report ORI referral for independent investigation by DHHS Office of Inspector General, if warranted (~5%) Formal finding by Assist Sec of Health accepting or rejecting institutional recommendations No misconduct End

8. ORI imposition of sanctions or negotiation of voluntary exclusion agreement Investigator appeal to Departmental Appeals Board, if desired

9. Research Misconduct • Unfortunately, due process at the institutional level is often missing • In an ORI survey in 2000 only 53% gave the scientist the right to be interviewed • Only 32% allowed access to all the evidence • Only 21% allowed the scientist to present his/hew own witnesses

10. Research Misconduct • Research misconduct proceedings only require a “preponderance of the evidence” standard for proof • Criminal justice requires “beyond a reasonable doubt” • Some argue that research misconduct should require, at the minimum a standard such as “clear and convincing evidence”

11. Whistleblowers • While there are serious concerns about the fairness afforded researchers accused of misconduct there is also a concern about the treatment of whistleblowers • Many believe that institutional design: *ignores serious ethical problems *regards whistleblowers as enemies of the institution and punishes them *fails to provide an ethical environment

12. Whistleblowers • Pamela Berge case is a good example • In 1987, as a Cornell Univ grad student she did her dissertation research at U of Alabama on CMV transmission • In 1990, a year after she got her PhD she heard her work presented at a national meeting by a UAB prof with no attribution to her • When her efforts and those of Cornell to get UAB to do something were ineffective she went to court

13. Whistleblowers • In 1995 court found for her and required UAB to pay damages • A UAB investigation had found no fault with the faculty member’s use of her work without attribution • There are numerous other well known cases where institutions refused to pursue allegations about faculty and staff • Multiple reasons why institutions choose to play down wrongdoing

14. Changing Face of Scientific Misconduct • While scientific fraud use to be a larger problem one study suggests the major issues now are: *duplicate publications *ethical issues *editorial complaints *conflicts of interest *authors’ squabbles

15. But wait….continued research fraud is an unresolved problem The Fujii Story

16. The Fujii Story • Dr. Yoshitaka Fujii is a Japanese anesthesiologist • In March of 2012, an Expression of Concern was published in the Canadian Journal of Anesthesia regarding 39 published articles by Dr. Fujii • As early as 2000 there was a concern about Dr. Fujii’s data from the previous decade including a letter by a Dr. Kranke.

17. The Fujii Story • DrKranke pointed out that, in 13 articles, the frequency of headache was reported as identical in all groups and in 8 other papers the difference varied by only one patient. • Kranke said, “there must be an underlying influence causing such incredibly nice data” • 10 years later a detailed and innovative analysis of 168 randomized controlled trials written or co-authored by Fujii was published

18. The Fujii Story • This analysis, written by Dr. J.B. Carlisle came to the conclusion that the likelihood of the occurrence of such distributions was between one in 25 to one in 1033!!!! • The deans of the six universities where Dr. Fujii worked were asked to provide unequivocal evidence of IRB approval of the studies as well as data veracity

19. The Fujii Story

20. Diederik Stapel • A Dutch Social Scientist now known as the “Lying Dutchman” • Made up data in 55 of 137 papers and in the Ph.D. theses of 10 students he supervised • Also committed minor sins that weren’t outright fraud • New Dutch word for sloppy science Slodderwetenschap

21. Diederik Stapel • A number of other researchers, including one at Harvard and two at Erasmus University (one of whom is a cardiologist with 600 publications) are under review • How did Stapel do it? • He designed studies with Ph.D. students and colleagues and then insisted on doing the actual data collection himself usually at high schools or colleges where he had good personal contacts

22. Changing Face of Scientific Misconduct • The other area great concern is the relationship with pharmaceutical companies • At issue is who owns the data and the right to publish it • The International Committee of Medical Journal Editors issued guidelines in 2001

23. Changing Face of Scientific Misconduct • Authors should have *full access to the data *freedom from interference in its analysis and interpretation *liberty to publish all results • Editors retain the right to review protocol • These guidelines have not been effective since a survey showed that 1% of authors in a multicenter trial had access to all data

24. Changing Face of Scientific Misconduct • Only 10% of institutions had any influence on data collection and monitoring • Only 17% of institutions had a policy limiting the duration of data confidentiality

25. Publication Requirements • Almost everything you ever wanted to know about publication rules and regulations can be found in the massive tome know as “Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication” put out by the International Committee for Medical Journal Editors • It can be accessed from the web site www.ICMJE.org

26. Publication Requirements Who is an author? • Substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data • Drafting the article or revising it critically for important intellectual content • Final approval of the version published • AUTHORS SHOULD MEET ALL THREE

27. Publication Requirements • All those who don’t fit into the author list can be acknowledged BUT you are supposed to obtain written consent to be listed in the acknowledgement section • The order of the authors should be a joint decision of the co-authors and the authors should be prepared to explain the particular order

28. Authorship for Research Groups • Number of collaborative and multicenter studies has increased dramatically • 22% of the research articles in JAMA in 2001 were collaborative • Complex decision on how to list study name (e.g.,Framingham Study) and the relevant authors

29. Authorship for Research Groups • List of authors with statement that they are writing for the Framingham investigators. The listed authors are the only true authors • Can also use “Writing Group for the XXX” and list them separately • Can just say “Framingham Investigators” and then list who the real authors are • Not listing authors has a problem for bibliographic services and citation lists • Read JAMA, Dec 25, 2002, vol 288:3166-3168

30. Registering Clinical Trials • An important change in how we publish clinical trials • There is a worldwide concern that suppression of neutral or unfavorable clinical trial outcomes has been harmful to patient • Journals have little interest in publishing results of trials suggesting the Rx is inferior to existing treatments or trials that are inconclusive

31. Registering Clinical Trials • To deal with this problem all journals that belong to the ICMJE required that any trial starting enrollment after July 1, 2005 had to register the trial. Trials that began before that date needed to register by September 13, 2005 • Clinical trial is defined as ANY research project that prospectively assigns humans to intervention or comparison groups to study cause and effect b/w medical intervention and health out

32. Registering Clinical Trials • Any registry that is publicly accessible for free and run by a non-profit is acceptable • The registry must have a mechanism to assure validity of registration data and be electronically searchable • There are other details as well that presently are only met by US National Library of Medicine at www.clinicaltrials.gov

33. Registering Clinical Trials • Some of the journals that have signed on to this include NEJM, JAMA, the Lancet, Annals of Internal Medicine • I am sure others have as well and it is probably worth checking with journals you might plan to publish in to ascertain whether you will be able to publish the studies you are now doing or plan to start soon