The Complex Ethics of Academic-Industry Collaborations

1. The Complex Ethics of Academic-Industry Collaborations Ross McKinney, Jr, MD Duke University School of Medicine

2. Outline • What is Conflict of Interest? (COI) • Areas of Concern • Federal rule changes • Duke processes

3. Don’t get the wrong message • In health care, almost no good idea will affect significant number of patients if it isn’t commercialized • Pharmaceutical & device companies don’t take care of patients – they need advice from people who do • Conflict of interest isn’t intrinsically bad – it’s a normal part of life • At Duke, we encourage working with industry (as distinct from for industry)

4. But… • Professionalism means putting the interests of your patients above your own self-interest • In research, professionalism means putting your science above your self-interests • Economic (promotion, salary, grants) • Social (status) • Identification with an idea • We need to educate, but we should do so without marketing (e.g. CME v. speakers bureaus)

5. Definition - COI • A conflict of interest exists when a primary interest or responsibility is (unduly) affected by a secondary interest or responsibility

6. Real World Examples • Dental work • Devils and Tar Heels

7. Example An obvious charge - ignored...

8. Key to the Example • Our perception is flavored by pre-set expectations and rationalizations of which we may not be aware • The whole crowd saw the same data, but drew very different conclusions

9. COI is part of every day life • Human beings are very aware of COIs • Every sales encounter • All fee-for-service medical encounters

10. The Human Response • We consider the paradigm, past history • We consider the secondary influences we can identify • Can we trust the provider? • If we break that trust as medical providers, what happens? • Decreased adherence / worse outcomes • Poor word-of-mouth • Malpractice cases

11. Be Aware • The public is paying increasing attention to examples of physicians appearing to act in self interest instead of the best interest of their patients • Should we collectively care?

12. A few industries • Airlines • Pharmaceuticals • Banking (71% trust in 2008 to 25% in 2011) • If people don’t respect and value physicians, will Congress use Medicare (i.e. physician payments) to balance the budget?

13. Areas of Concern • Clinical Research • Clinical Care • Education • Commercialization of ideas

14. Concerns: In Clinical Research • In science, reproducibility is the key test for validation • In clinical research, trials are often too expensive to reproduce • Don’t want to put people at risk unnecessarily • Primary means of validation is audit • Audit is not generally effective as a means to identify bias

15. Goals of COI Management in Research • Protect research subjects from biased decisions by conflicted investigators • Scientific integrity • Do not want clinical decisions based on data from biased studies • Don’t want conflicted investigators interpreting data • Role of the Academic as the fair-broker • Free of bias (at least financial)

16. JAMA – 2003 – Als-Nielsen, et al • 370 randomized trials • Considered: 1) Outcome of trial; 2) Sponsor • Non-profit Sponsor - 16% recommended experimental drug as treatment of choice • Funding not reported: 30% • Mixed funding: 35% • For-profit organization: 51% • Difference significant (p<0.001)OR: 5.3; 95% CI 2.0-14.4)

17. NEJM Study - 2008 • Studies of 12 anti-depressants, 12,564 patients • 38 studies with positive FDA results, of which 37 were published, 1 not published • 36 with negative FDA results • 3 published, 22 not published • 11 published with data selection to appear positive • In literature, 94% of publications were positive • Turner: NEJM 2008;258:252-260

18. Merck’s ADVANTAGE study - 2003 • ADVANTAGE study: Assessment of Differences between Vioxxand Naproxynto Ascertain Gastrointestinal Tolerance and Efficacy • After 3 months, 27% more people stopped taking Naproxyn than Vioxx

19. Brief Illustration • After 3 months, 27% more people stopped taking Naproxyn • Of course, that was 5.9% vs 8.1%

20. Brief Illustration • After 3 months, 27% more people stopped taking Naproxyn • Of course, that was 5.9% vs 8.1%

21. Brief Illustration • or better, 94% vs 92% tolerance

22. Seeding Study • ADVANTAGE was designed by the marketing department at Merck • Real subjects were the MDs • Did use of study increase prescription rate? • Complimented enrolling doctors • Used many primary care sites, rather than a few high enrolling centers

23. Brief Illustration • Personal experience – cost difference to me was 30x ($150 vs $5) [actually Celebrex vs ibuprofen] • Points like this have Congress’s eye as potential cost savings & unnecessary expenses • Migrate decision making from physicians to non-experts because of failure of physicians to perform the work of an expert adequately

24. The Complicated Question • Bayh-Dole Act of 1980 • Inventions • Personal and institutional conflict • Safety concerns increase in import • The “rebuttable presumption” • Where’s the right balance?

25. Concerns: In Clinical Care • The fee for service model • Note articles about inappropriate use of open breast biopsies (vs. needle), stenting of chronic stable angina, of spine surgery, of in-house diagnostic and treatment devices, of infusion therapies where the primary beneficiary seems to be the infuser rather than the infused • Insertion of flawed devices by physician developers and advocates • Routine procedures with reimbursement (EKGs, etc)

26. Concerns: In Education • FDA Rules about talking off label • Speaker’s bureaus • If you know someone is being paid to give a talk, does it change your perception of the message?

27. Concerns: In Education • FDA Rules about talking off label • Speaker’s bureaus • If you know someone is being paid to give a talk, does it change your perception of the message? • What if it’s true, but you don’t know?

28. Physician Sunshine Act • Section 6002 of the Affordable Care Act • As of January 2012, pharmaceutical and device manufacturers must report all gifts and payments to physicians and teaching hospitals to a federal database • Threshold is $10 per item, or $100 per year • Results will be published in 2013 in a web based, searchable format

29. Public awareness • What will the ramifications be of public disclosure? • An example, using the fact Minnesota has had a public database for several years

30. New York Times article • Front Page – May 10, 2007 • “Psychiatrists, Children and Drug Industry’s Role” • “When Anya Bailey developed an eating disorder after her 12th birthday, her mother took her to a psychiatrist at the University of Minnesota who prescribed a powerful antipsychotic drug called Risperdal.”

31. The problem • Anya gained weight but within two years developed a crippling knot in her back. She now receives regular injections of Botox to unclench her back muscles. She often awakens crying in pain.

32. The COI • In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta.

33. The COI • In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta. • However, not clever to say – • “Academics don’t get paid very much. If I was an entertainer, I think I would certainly do a lot better.”

34. The COI • In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta. • However, not clever to say – • “Academics don’t get paid very much. If I was an entertainer, I think I would certainly do a lot better.” • (Dr. Realmuto’s university salary is $196,310.)

35. Minnesota case • Was it really the result of COI? • Amount of money was small • Adverse events happen • Perception of outsiders may differ from our own • Malpractice attorneys eagerly awaiting the federal database

36. The role of gifts • Duke rules prohibit gifts, including meals, from pharmaceutical and device reps • Unrestricted educational grants to the institution are allowed • True CME can be supported – no quid pro quo allowed • Gifts are a part of relationship building • Reps goal is to convert the relationship from a business one to a personal one • Airline example

37. NIH Rules Recently Changed • $5,000 threshold for management and reporting to the NIH • All cases of FCOI of $5K or more. • Must report all sponsored travel (other than government, universities, and medical centers) • Require review of all personal FCOIs prior to any NIH grant expenditures (even on renewal) • Web site to post all FCOIs linked to grants (perhaps)

38. Process • Annual report in March • Review (in order) • Review each grant application • Review IRB submissions • Review each grant award • Now consider purchasing, research, and (to a degree) clinical issues

39. Limits • Require annual reporting of all relationships >$600/year (likely to except universities, academic medical centers, government, and research institutes) • As of January 1, management at $5K/year if there is an overlap with research • At $25K/year, can no longer be PI on related research

40. Other limits • Treat equity as if it’s payments ($20,000 in stock is the same as $20,000 in payments) • Non-publically traded equity is treated as >$25K • Stock options are treated as >$25K • We look at royalty arrangements case-by-case

41. Summary • Conflict of Interest is present in everyday life • Providing transparency is critical • Public perception may different from the insider’s view • If we want to remain professionals, we need to maintain the interests of our patients first