Scientific Integriy in Medical Research Partnerships and Ethical Implications

1. Scientific Integriy in Medical ResearchPartnerships and Ethical Implications FEAM Conference � December 15th Lisbon

2. �Scientific� has become an all purpose term of epistemic praise meaning �strong, reliable, good� and yet... like all human enterprises it is thoroughly fallible, imperfect, uneven in its achievements, often fumbling, sometimes corrupt, and of course incomplete

8. Some key ideas Legally scientific fraud is a deliberate misrepresentation of truth (misconduct may be a better term)?

9. Wrong observations Wrong analysis Undeclared conflict of interest Publication bias Undeserved authorship Supressing data Plagiarism Falsification Fabricacion

10. Science does not exist until it is published.

11. Publications are fundamental units of information exchange, proof of productivity and creativity, and bases for future research and development �The Audit Society�

12. 27% of the scientific papers are never cited Papers published Papers published in Nature 1999 citations in 2001 � 10 % (80 papers) = half of citations

13. There are more >16000 medical journals

15. Committee on Publication Ethics (COPE)? Falsification Fabrication Plagiarism Failure to get ethical approval Not admitting that some data are missing Ignoring outliers without declaring it Not including data on side effects on a clinical trial Conducting research without informed consent Publication of post-hoc analysis without declaring it Gift /honorary authorship Not attributing other authors Redundant publication Not disclosing conflicts interest Not attempting to publish completed research Failure to do an adequate search of existing research before beginning new research �Shotgunning� - simultaneous submission of a manuscript to more than one journal.

16. Fraud in Publishing Major research institutions and high impact journals Biological sciences Clinical research

17. You catch them in the �NET�

18. What happens after Retraction � ignore it Expression of concern � we are looking into it Correction substitute information papers continue to be quoted after retraction

19. The Peer-review system JAMA 9% Academic Medicine 15% Nature 5%

20. The Malefices of Covert Duplicate Publication Ondasetron on post-operative emesis 9 trials published in 14 further reports duplicating data from 3325 patients Inclusion of duplicate data in meta-analysis led to a 23% overestimation of the drugs antiemetic efficacy

21. Pressure to publishUnhealthy competition? �They chose reviewers who they knew to be positive (...) They did not allow their experiments to be reproduced� Robert Laughlin (Nobel Prize physics) �Given the exciting claims made by the papers, we were certainly hoping that the outcomes would be positive� Karl Ziemeli (Chief physical sciences editor, Nature)?

22. The Editors� Pressure Manipulation of the impact factor of the journal, encouraging the citation of other papers published in the journal (*)? and yet �Impact factors tell you more about sociology of science than about science itself� S. Brenner

23. Date withholding Protect priority [�races�] Strictures of commercial funding Material and financial costs of responding to requests for biomaterials Scientists in trainning are discouraged to show data 42% genetic 38% of OLS

24. Industry support of biomedical research USA 1980 32% 2000 62% Lead authors 1 every 3 articles hold relevant financial interests.* In biomedicine, with rare exceptions, is the private sector, not academics that develops diagnostic, therapeutic and preventive products and brings them to market. 2/3 of academic institutions hold equity in �start-up� businesses that sponsor research by their faculty

25. - Industry supported faculty is as productive as those who do not receive support - more productive commercially - 2 x trade secrecy or withhold results from colleagues -encourage research with commercial applicability and may reduce fundamental research. Blumenthal et al. N Engl J Med 335:1734, 1996 Industrial support and academic productivity

26. Academic investigators � Industry � Competing goals in medical research

27. - Death of volunteer in phase I gene therapy trial: doctor and institution had financial interest in therapy Publication biases Authors whose work support safety of calcium � channel antagonists had more frequently financial ties with industries.* Results favoring new therapy over traditional one are more likely if study is funded by therapy manufacturer.** 5% of industry supported pharmoeconomic studies of cancer drugs reached unfavourable conclusions; non funded studies reached the same conclusion in 38% of the studies.***

30. �Does declaration of competing interests affect reader�s perceptions? A randomized trial�* Results of study on impact of pain in herpes were found less interesting , important, relevant, valid and believable when the authors were employees of fictitious pharmaceutical company than with ambulatory care centers. Conflict of Interest

31. Biomedical Research, what is the public interest? The research that it supports is for the search of truth, uncontaminated by any bias Discoveries with potential therapeutic benefit are rapidly translated into practice by clinical trials. Participation in development of new therapies will be safe, with full informed consent, and access to outcome and follow-up. Right to know about potential side effects that might influence decision to participate Must be assumed that decision to ask patients to participate or the assessment of risks will not be determined by pressure on the investigator.

32. A convenient omission The journal sold 929.000 offprints (Revenue $ 679.000 to $ 836,000)?

33. What does academy have to do?(little scholarship on this topic!)? - Protection of human participants safety and welfare Academic freedom Objectivity Data integrity Right to publish Financial and non financial incentives should address institutional, senior and junior investigator needs - Separate human research responsibilities from investment management and technology transfer*

34. (The Editors of Ann Int Med, JAMA, New England J Med, Canad MAJ, J Danish M A, Lancet, Medline, etc, Sep 2001)? When authors submit manuscript they are responsible for disclosing all financial and personal relationships that might bias their work Researchers should not enter in agreements that interfere Their access to the data Ability to analyze data independently Prepare manuscripts Publish them Sponsorship, authorship, and accountability (1)?

35. Should describe the role of the study sponsor Collection, analysis and interpretation of data Writing the report: �The non-author writer syndrome�, the guest author. Avoid selecting external peer reviewers with C.I. (e.g. same department)? Reviewers must disclosed C.I. (Drug therapy reviews)? Editors most have no personal, professional or financial involvement in any issues they might judge. Sponsorship, authorship, and accountability (2)?

36. How to improve Research � Funding agencies establish research grant programs to identify, measure, and assess those factors that influence integrity in research. Institutional Commitment � Institutions to develop and implement comprehensive programs Education � Effective educational programs Self-assessment � Implement self-assessment and external review process. If possible this should be part of existing processes accreditation

37. �Many people say that is the intellect which makes a great scientist. They are wrong: it is character�.