Why does responsible conduct of research matter?

1. Why does responsible conduct of research matter? Bernard Lo, M.D. August 18 and 26, 2010

2. Kuklo case • Orthopedic surgeon in Army • Research on bone-growth product • Recombinant human bone morphogenic protein-2 • Claimed benefit in soldiers with severe leg injuries

3. Kuklo allegations • Data fabricated • Reported more cases than in Army records • Co-authors had not seen manuscript prior to publication • Forged signatures of co-authors

4. Kuklo allegations • Paid by manufacturer as consultant • Almost $800,000 for two years • Spoke on company’s behalf • Taught other physicians • Manufacturer did not sponsor study • Denied knowledge of misconduct

5. Kuklo case • Paid by manufacturer as consultant • Did not get permission from Army • Did not disclose payments to Army or Washington University

6. Reuben case • Peri-op analgesia with COX-2, NSAIDs • Reduce opioid use, improve function • Pre-emptive pre-op administration reduces post-op and chronic pain • Use for regional anesthesia or for intra-articular injection • Celecoxib + pregabalin superior to opioids

7. Reuben case • Fabricated data in 21 / 72 articles • Pleaded guilty to fraud charges • Co-authors exonerated

8. Reuben case • Served on speakers’ bureau for manufacturer of celecoxib • Also research funding

9. Editorial on impact of misconduct • Retraction does not correct problems with meta-analyses, reviews, CME • Confirmatory studies unlikely to be published • “We might be heading in wrong direction or toward blind ends”

10. Darsee case • 109 papers as a fellow • Fabricated data in view of colleagues • Patients and collaborators did not exist

11. Slutsky case • Faculty member in radiology • Fellow in cardiology • Resident in nuclear medicine

12. Slutsky case • 137 papers while a resident and fellow • One paper every ten days • Two studies had same mean and SD for different populations

13. Why is research misconduct problematic? • Data and conclusions not valid • Harm to science, other researchers • Harm to patients • Wasted resources • Unmerited rewards • Undermines public trust and support

14. Congressman Dingle • “Every time a researcher takes taxpayer money and publishes fabricated, falsified, or plagiarized findings, the taxpayer has in effect been swindled. Furthermore, given our budget deficit, there is never enough money to go around.”

15. Consequences • When self-regulation fails, government will step in • NIH requires ethics training • Conflict of interest disclosures when submit grant

16. Social science research

17. How you will encounter misconduct? • Review manuscript or grant • As PI of large project • Serve on selection committee • Challenges to your work by others • Serve on investigation panel

18. What would you do? • You review paper on prevention trial for cancer. • Accrual extremely rapid. • Point estimate not vary across sites. • Confidence interval very narrow.

19. What would you do? • You decided to call the editor about concerns but did put them in writing. • One month later you are sent a revised manuscript for re-review • Your concerns not raised with authors • None of your concerns addressed.

20. What would you do? • Decline to review the article • Recommend biostatistical review of the article • Describe your concerns in a written review • Other?

21. Why not? • Not your job • Don’t look for trouble • Don’t be a snitch or tattletale • Don’t ruin a career if you’re not sure

22. Encounter misconduct as PI? • Progress too good to be true • Enrollment at site >> other sites • Phenomenal productivity • Data are too good to be true • Discrepancy from other sites • Variation too small

23. Encounter misconduct on selection committee? • Plagiarism of personal essay • 5.2% of resident essays match Internet pages, previous essays, printed resources • Falsification of publication record • 4.9% of residency and fellowship applicants

24. Falsification of publication record • Article not in journal • Not an author • Change order of authors • List abstract as article • Change journal

25. Federal definition of research misconduct • Fabrication • Falsification • Plagiarism • Must be intentional

26. Research misconduct excludes • Unintentional “honest” error • Sloppiness, incompetence, laziness • Differences of opinion or interpretation

27. Research misconduct excludes other ethical problems • Lack of IRB approval • Lack of informed consent • Financial mismanagement • Discrimination • Poor mentoring

28. Federal definition of misconduct • Legal requirements set a minimum standard • Ethical and professional standards may be higher

29. How do people respond to plagiarism? • Using computer programs, identify 212 pairs of similar articles • Survey to authors, journal editors of these articles Science 2009; 323; 1293.

30. Individual response to misconduct • “There is no way under the stars we could have picked that up ourselves.”

31. Individual response to misconduct • “It is my understanding that copying someone else’s description virtually word-for-word is considered a compliment to the person whose words were copied.”

32. Individual response to misconduct • “I have no idea why the pieces are similar, except that I am sure I do not have a good enough memory to have allowed me to ‘copy’ his piece.”

33. Responses to allegations • I didn’t know it was wrong • Course precludes this defense • It’s just a personal vendetta • This is just creative science

34. Institutional response to alleged misconduct • Inquiry • Is a full investigation warranted? • Investigation • Is there misconduct?

35. Criticisms of institutional inquiry • Self-interest • Can be unconscious • Underestimate problems • Assumption of trust

36. Institutional responses to allegations of misconduct • Both whistleblower and accused have rights • No retaliation • Written charges • Accused may respond to charges • Right to have lawyer • Timely decision

37. Federal response to allegations of misconduct • May conduct own inquiry or investigation

38. Consequences of research misconduct • Suspension of federal grant • Debarment from future grants • Institutional penalties • Termination of employment • Civil and criminal liability

39. Questions about misconduct • Are you responsible for work of colleagues in collaborative project? • How much do you have to learn about their specialty?

40. Dilemmas for co-investigators • Value in multidisciplinary projects • Encouraged by NIH • Do not have expertise in other specialties • Accountable for misconduct of others • Trust colleagues • What review is reasonable to expect?

41. How to prevent misconduct • Close involvement during all phases of research • Look at primary data • Challenges with direct computer entry of data • Data audits • Realistic expectations of progress and productivity

42. How to prevent misconduct • Know enough about other fields to ask tough questions • Specify your exact role in project • Reconsider loose collaborations

43. Take home points • Misconduct a serious offense, with grave consequences • Address allegations of misconduct