Conflict of Interest in Research, Clinical Care & Education

1. Conflict of Interest in Research, Clinical Care & Education Ross McKinney, Jr, MD Duke U School of Medicine

2. Increasing Attention • COI in clinical care hits home to patients • Many MDs in speakers’ bureaus, on scientific advisory boards • Consulting payments at times appear to exceed fair compensation for effort • Ghost writing is a problem

3. Increasing Attention • COI in clinical care hits home to patients • Many MDs in speakers’ bureaus, on scientific advisory boards • Consulting payments at times appear to exceed fair compensation for effort • Ghost writingis a problem • OIG just audited NIH COI Management • OIG local audits expected this year

4. OIG Findings • NIH does not track COI closely enough • Institutions do not report COI to NIH adequately • NIH should require detailed reports of how all instances of COI are being managed locally [NIH disagreed – resolution pending]

5. Basic Question • Is the public more worried about notepads or bribes?

6. Basic Question • Is the public more worried about notepads or bribes? • A current example of the public view

7. New York TimesFront 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.”

8. 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.

9. 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.

10. 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.”

11. 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.)

12. Senator Charles Grassley – September 6, 2007 • “Payments to a doctor can be big or small.  They can be a simple dinner after work or they can add up to tens of thousands and even hundreds of thousands of dollars each year.   That’s right – hundreds of thousands of dollars for one doctor.  It’s really pretty shocking.  • Companies wouldn’t be paying this money unless it had a direct effect on the prescriptions doctors write, and the medical devices they use.  Patients, of course, are in the dark about whether their doctor is receiving this money.”

13. Kohl-Grassley Physician Payment Sunshine Act • “A federal law requiring public disclosure of payments to doctors could be very effective if it was carefully monitored and consistently applied.” • Bill currently proposed with bi-partisan sponsorship

14. Kohl-Grassley • Kohl-Grassley will require that companies report all payments, gifts, honoraria, and travel awards, given to physicians • Also the purpose, date, and what was received in exchange • Feds will publish on a publically accessible web site • Already law in MN, with similar laws in VT, DC, ME, WV

15. Universities Responses • Several institutions have banned minor gifts, travel, meals, and even samples from pharmaceutical companies (Yale, Penn, Stanford, Pitt, U Mass) • Several institutions tightly regulate what faculty can do in terms of consulting (e.g. Mayo, Emory)

16. Duke Policy • Duke School of Medicine COI policies are rooted in NIH policy (42 CFR 50, subpart F) and in the Duke University COI policy of 1992 • Annual reporting on-line (February each year) for previous calendar year and for what is anticipated in the current year

17. COI Committee • Duke COI Policy and interpretation involves the faculty through a COI Committee that meets monthly • Made up of faculty from Schools of Medicine and Nursing • Includes clinicians, clinical researchers, and basic scientists

18. Duke Policy - 2 • Currently must report any payments from a company that provides an IRS Form 1099, W-2, or K-1 (except the PDC) [Effective threshold is $600] • If <$10,000 in annual payment, institution considers this below de minimis and does not require action (other than reporting). However, disclosure in presentations & publications is a good idea, and required for CME if payments >$0

19. Duke Policy - 3 • Payments between $10,000 and $25,000 mean disclosure is required in publications & presentations. • Payments >$25,000 mean an individual may not be PI on a grant from the company, nor on projects that relate to the company’s products. • Public Equity holdings treated by same rule as payments

20. Duke Policy - 4 • Privately held equity – Treat as >$25,000 in most cases, since it can be hard to value • Options (public or privately held company) – in most cases, treated as >$25,000 since research results may effect values.

21. Intellectual Property • Licensed IP with royalties needs to be reported and evaluated

22. Gifts • The COI Committee will also evaluate gifts to Duke that are deposited into a faculty discretionary account to consider whether they may represent an attempt to sway a faculty member

23. Management of COI • Most cases of COI can be managed • Disclosure • Divestiture • New PI • Discussing a Pooled-equity approach for inventors • Voluntary donation of equity into a “mutual fund” in trade for fixed portion of final distribution when mutual fund liquidated

24. Personal vs. Institutional COI • Personal COI involves individual faculty members • Institutional COI involves the institution itself and senior officials of the institution • Duke is developing an Institutional COI policy

25. Classical I-COI Situation • A faculty member invents a technology • Duke owns the IP and licenses it to a start-up company • Because most start-ups lack capital, Duke receives equity in trade • Since Duke has a “stake” in the technology’s success, there can be a public perception it doesn’t provide oversight that’s as careful as it should

26. Gelsinger Case • The paradigmatic example of ICOI involved the case of Jesse Gelsinger, an 18 year old with OTC Deficiency who died in a gene therapy trial at Penn • Although Penn took many steps in regard to ICOI, the lead attorney (Alan Milstein) made a persuasive public case, and Penn settled • Currently sets a precedent

27. Managing ICOI • When Duke has ICOI, there is a “rebuttable presumption” human subjects research on the IP should not be done here. • In “compelling circumstances”, the work may be allowed (also true for personal COI) • COI Committee reviews the circumstances

28. Managing ICOI - 2 • If there is a good reason to do the work at Duke, we require some external oversight • DSMB-Plus • Reviews study design • Monitors study conduct (esp. for evidence of COI) • Reviews endpoints • Monitors and approves publications • External IRB • Duke’s interest should be disclosed in publications

29. Annual Reporting Form 2008 • Similar to last year’s form • Re-wrote the underlying code so that the separate fields are in a database • Will allow better “pre-population” next year and during updates • Form Online Location • coi.duke.edu/coi_form

30. Who Must Report? • All regular rank faculty (University-wide) • All faculty who participate in research • Any staff who independently contribute to the design, conduct, or reporting of research • At present, students are generally exempt, unless they clearly have an independent role

40. Contact Info • Conflict of Interest Office • Michelle Evans (michelle.evans@duke.edu) • Susan Brooks (brook003@mc.duke.edu) • 684-6739