1. 1 Conflicts of interest Bernard Lo, M.D. September 10, 2009

2. 2 Views of audience Student loan officer at college receives annual payment from bank. Should this relationship be disclosed to college, students and parents? 1. Yes 2. No 3. Not sure

3. 3 Views of audience Should such a relationship be banned (even if it is disclosed)? 1. Yes 2. No 3. Not sure

4. 4 Views of audience Does the amount of payment matter? Should the relationship be banned if: 1. $500 a year 2. $5000 a year 3. Percentage of loans by bank

5. 5 Views of audience Unlike competitor, bank does not defer repayment while student works for Teach for America, VISTA, etc. Should the relationship be banned: 1. Yes 2. No 3. Not sure

6. 6 What is a conflict of interest?  Special relationships of trust, dependency  Primary interest in well-being of clients, patients, integrity of research  Secondary interest in personal gain ($, professional advancement)

7. 7 What is a conflict of interest?  Unacceptable risk that primary interest unduly influenced by secondary interest  Not proven bias

8. Points to consider 1. Arrangement may be problematic even if no bias  Hard to tell if bias exists 2. Disclosure necessary but not sufficient  May not know what risks are or how to reduce them 8

9. Points to consider 3. Some arrangements should be managed or prohibited  Permit honorarium for talk to meeting of all banks 9

10. Points to consider 4. Goal of COI policies to prevent bias and loss of trust, not respond to misbehavior 5. COI policies should consider Risk of relationship Burdens and unintended adverse effects of policies 10

11. 11 Spiral CT for lung cancer screening  Advocates have pushed states to pay for screening  NY bill would pay only at Cornell

12. 12 Spiral CT for lung cancer screening  Screened >31,000 high risk persons  F/u Stage 1 cancers who had surgical resection 10 year estimated survival 92%  “Could prevent 80% of deaths from lung cancer”

13. 13 Methodologic concerns  No concurrent control group  Lead time bias  Few patients followed for 5 years  Assume at all persons found to have cancer would die without screening  Ignore false positive scans

14. 14 Spiral CT for lung cancer screening  $200 million NIH trial comparing CT screening vs. CXR  “Allowing hundreds of thousands to die is unethical”

15. 15 Financial relationships  $3.6 million from parent company of cigarette manufacturer  Grant to Foundation for Lung Cancer  PI, co-PI as officers  Dean, vice-chair of overseers as directors Didn’t know origin of money  Gift announced publicly

16. 16 Financial relationships  Not disclose 10 patents on CT screening in some articles and CME lectures  Claim not relevant  Cornell receives royalties

17. 17 Financial relationships  Not disclose funding as required  To NEJM Would not have published  On American Cancer Society grant Prohibit funding if also tobacco support

18. 18 Concerns about COIs  Are errors due to  Honest disagreement, lack of skill, lapse, slip?  Self-interest

19. 19 Concerns about COIs  Voluntary disclosure ineffective  Impetus for public disclosure of payments  Institutions have their own COI  Bright people find loopholes

20. 20 Biederman case  Research supporting diagnosis of bipolar disorder in children and treatment with antipsychotics

21. 21 Biederman case  Ties to manufacturers of psychiatric drugs  Research funding and consulting  Director of J & J Center for Pediatric Psychopathology Research “Move forward the commercial goals of J & J”

22. 22 Biederman case  Failed to report $1.4 million in income from drug companies, as required by  Universities  NIH

23. 23 The New York Times Expert or shill?

24. 24 Concerns about COIs  Disagreements and errors inevitable  Due to reasonable differences of opinion, slip, or financial profit?  Disclosure not remove risk of bias

25. 25 Interactions between physicians and industry

26. 26 Academia-industry collaboration to develop new therapies  Antiretrovirals for HIV infection  Pulmonary surfactant  Imatinib, tyrosine kinase inhibitor for CML  Rituximab, MAB against CD20 on B cells

28. 28 Concerns about industry-sponsored clinical trials  Academic investigators lack  Access to data  Independent statistical analysis  Drafting of papers by medical writers

29. 29 Concerns about industry-sponsored clinical trials  Favorable conclusions  Not report negative findings

30. 30 Association between funding and conclusions  Investigator ties to manufacturer  3.6 times more likely to find drug effective  Sponsored by manufacturer  4.0 times more likely to find drug effective JAMA 2003; 289: 454 BMJ 2003; 327: 1167

31. 31 Explanations for association  Publication bias  Investigators  Journals  Less rigorously designed  Evidence not support this

32. 32 Explanations for association  Manufacturers sponsor trials that are likely to succeed

33. 33 Not report negative findings  Celecoxib  6-month data reported, showed benefit.  12-month data known, no benefit BMJ 2002; 324: 1287 JAMA 2001; 2886: 2398

34. 34 Not report negative findings  SSRIs in children  Aprotinin  Ezetimibe plus statin

35. 35 Mission of drug companies  “Drug companies have to continue to be successful businesses… But their primary mission is products that save lives and improve lives.”  “This is an area that’s different from ice cream, bubble gum, and automobiles.”

36. 36

37. Responses to conflicts of interest 1. Disclosure  To university Annually With grant submission (NIH requirement)  To IRB  To research subjects 37

38. Responses to conflicts of interest 1. Disclosure  To public Required for some companies by legal settlements Voluntary by some companies Some state laws Proposals in Congress 38

39. IOM recommendation  Public website  All payments from drug, device, biotech companies  To MD, researcher, medical institution  Can aggregate all payments 39

40. 40 Arguments for disclosure  “Sunshine the best of disinfectants”  May deter questionable behavior  May also deter desirable behaviors

41. 41 Concerns about disclosure  Not specific or standardized  Categories like “consultant” ambiguous  May be misinterpreted  Discrepancies due to different requirements  Not prevent undue influence or bias  Necessary but limited first step

42. 42 Disclosure of conflicts of interest  Necessary but limited first step

43. Responses to conflicts of interest 1. Disclosure 2. Management of relationship 3. Prohibition 43

44. Clinical trial investigators with significant conflicts of interest  Default or presumption is that may not participate  Patent, royalties  Stock options  Management position in sponsor 44

45. Clinical trial investigators with significant conflicts of interest  Exceptions permitted  For safety of participants Inventor of medical device  For validity of study Only lab that can conduct assay 45

46. Clinical trial investigators with significant conflicts of interest  Limit role of conflicted investigator  Not tasks that others can carry out Recruitment of subjects Data analysis Drafting of manuscript  May not be PI  Alternatively, may end conflicting role 46

47. 47

48. Responses to conflicts of interest 1. Disclosure 2. Management of relationship 3. Prohibition 4. Reduce undue influence and bias 48

49. Reporting on clinicaltrials.gov  Required  For FDA consideration  By leading medical journals  Before trial begins  Protocol 49

50. Reporting on clinicaltrials.gov  After completion  Basic results  Serious adverse events  Important exceptions 50

51. 51