Identifying and Managing Conflict of Interest and Conflict of Commitment

1. Identifying and Managing Conflict of Interest and Conflict of Commitment Tom Hazinski, MDProfessor and Associate DeanCo-Chair, Medical Center Conflict of Interest Committee

2. Conflict of Interest and Commitment • Background and Principles • Key Issues at Vanderbilt • “Significant Financial Interest” of faculty and institution • Human Subjects Research • Conflicts of Commitment • COI processes • Case Studies

3. Conflict of Commitment • Can arise when faculty engage in “activities that are in addition to a member’s primary University appointment….and that may have adverse effects on the performance of University obligations.” • Activities that are usually permitted: Service on scientific boards, study section, expert panels, external consultations, CME, foundation and organizational leadership, editorial boards, etc. Full-time faculty appointment implies a full-time professional obligation to University. • External and non-job related internal commitments cannot exceed 50 days per year without approval. http://www.vanderbilt.edu/compliance/html/conflict_of_interest_policy.pdf

4. COI - The Quick Version • Real Estate: “Location, location, location” • COI: “Disclosure, disclosure, disclosure” • COI/COC test: • Would public discovery of the activity or situation adversely affect (or appear to affect) patient safety, my medical judgment, the scientific integrity of my research, embarrass the University, or violate a standard of conduct?

5. Conflicts of Interest in Academic Medicine -Non-Financial • Desire for faculty advancement • Compete for sponsored research • Receive accolades from peers • Receive prestigious prizes • Alleviate pain and suffering -Financial gain by physician or investigator Society and regulators have focused on financial conflicts of interest.

6. COI - Definition • “A situation in which an individual’s financial, professional or personal considerations may directly or indirectly affect, or have the appearance of affecting, an individual’s professional judgment in exercising any University duty or responsibility, including research.” • Faculty should “evaluate and arrange their activities to avoid compromising their ability to carry out their primary obligations to the University.” http://www.vanderbilt.edu/compliance/html/conflict_of_interest_policy.pdf

7. “Conflicts of interest are ubiquitous and inevitable in academic life, indeed, in all professional life. The challenge for academic medicine is not to eradicate them, which is fanciful and would be inimical to public policy goals, but to recognize and manage them sensibly and effectively.” David Korn JAMA 284, 2234-2236, 2000

8. Belmont Report – 1979http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm • Set boundaries between practice and research. • Emphasized basic ethical principles • Respect for persons • Beneficence • Justice • Set human subject protection policies • Informed consent; IRB’s established. • Assessment of risks and benefits • Selection of subjects

9. Bayh-Dole Act of 1980 • Designed to promote use, development and promotion of technology invented with federal funding. • Recipients of federal funding have the right to retain ownership to inventions developed with federal funding. • Recipient must share royalties, or other income, derived from the invention with the inventor(s). • Result: Investigators and institutions sought commercial opportunities.

10. Patents to Universities1986-1999 Source: Association of University Technology Managers

11. U.S. University & Hospital Royalties(millions of dollars)

12. Existence of Potential Conflict of Interest • Describes a situation • Not a judgement on appropriateness of behavior or personal integrity. • Faculty members must disclose potential COI’s.

13. Situations That Should be DisclosedSome Examples • A significant financial interest in a company that does business with Vanderbilt. • Income from a drug or device company that exceeds reporting thresholds. • Acceptance of a gift >$300 from a single entity. • Financial relationship with a sponsor of your research. • Use of trainees in industry-sponsored research. • University investment in your research. • Supervision of a family member employed at Vanderbilt. • External commitments that exceed 50 days per year.

14. A.A.M.C. Policy & GuidelinesDecember, 2001 • Protection of students and trainees • Legal obligations • Sanctions • IRB will not approve research until COI situation is clarified. • Office of Research will not release grant funds until COI is assessed. • Office of Tech Transfer cannot execute a final contract until COI situation is clarified. • Department Chair or COI Committee may prohibit or modify the disclosed activity.

15. Annual Faculty Disclosure Form Faculty Member I.R.B. Office of Research Tech Transfer/ Legal Source of Disclosure Triage by MCCOIC and Associate Dean (Hazinski/Gotterer) • C.O.I. Subcommittees • Human Investigation • Basic Research/Technology • Consulting/Business Seek more information Approval Faculty Conflict of Interest Disclosures Are Reviewed by the Medical Center Conflict of Interest Office (MCCOIC)

16. Medical Center Conflict of Interest Committee - 2005 Tom Hazinski (Gerald Gotterer), Chair Sherrie Leach, Staff Clinical Investigation Italo Biaggioni Tom Graham John Murray Alastair Wood Basic Research/Technology Richard Caprioli Peng Liang Donald Rubin Consultations/Business Lonnie Burnett Rolanda Johnson At-Large Richard Chappell Stuart Finder Fred Goad, Jr. Ex Officio Diana Marver (Research & Training) Leona Marx (General Counsel) Chris McKinney (Tech Transfer)

17. Annual Faculty Disclosure Form Faculty Member I.R.B. Office of Research Tech Transfer/ Legal Source of Disclosure Triage by MCCOIC and Associate Dean (Hazinski/Gotterer) • C.O.I. Subcommittees • Human Investigation • Basic Research/Technology • Consulting/Business Seek more information Approval Faculty Conflict of Interest Disclosures

18. Annual COI Faculty Disclosure Form • Web-based form for 2003-2004 academic year for SOM faculty. • 99.3 % compliance rate • New Vanderbilt University policies in place for 2005. • Online form sent to faculty April, ’05 • ALL FACULTY MUST COMPLETE THIS ANNUAL REQUIREMENT.

20. Annual Faculty Disclosure Form Faculty Member I.R.B. Office of Research Tech Transfer/ Legal Source of Disclosure Triage by MCCOIC and Associate Dean (Hazinski/Gotterer) • C.O.I. Subcommittees • Human Investigation • Basic Research/Technology • Consulting/Business Seek more information Approval Faculty Conflict of Interest Disclosures

21. Annual Faculty Disclosure Form Faculty Member I.R.B. Office of Research Tech Transfer/ Legal Source of Disclosure Triage by MCCOIC and Associate Dean (Hazinski/Gotterer) • C.O.I. Subcommittees • Human Investigation • Basic Research/Technology • Consulting/Business Seek more information Approval Faculty Conflict of Interest Disclosures

22. Vanderbilt University IRBApplication for Human Research

23. Annual Faculty Disclosure Form Faculty Member I.R.B. Office of Research Tech Transfer/ Legal Source of Disclosure Triage by MCCOIC and Associate Dean (Hazinski/Gotterer) • C.O.I. Subcommittees • Human Investigation • Basic Research/Technology • Consulting/Business Seek more information Approval Faculty Conflict of Interest Disclosures

24. Office of Research • COI disclosure form required for all federal grants and contracts. • Separate disclosure form for information about P.I. and all participants. • Significant financial interest: • >$10,000 annual income from one entity. • the equity interest exceeds 5% ownership. • Equity interest is > $10,000 at fair market value. • Royalty payments exceed $10,000 annually.

25. Office of Research(continued) • Situation reviewed when notice of funding received. • Any conflicts of interest issues must be resolved before funding is released. • Further information available from Office of Research website: http://medschool.mc.vanderbilt.edu/oor/gm/

26. FORM USED AT VANDERBILT TO GATHER COI DETAILS

27. Growth of Industry-sponsored clinical research and University investments prompts increased federal scrutiny

28. Points for Consideration (1) • Financial Details • Does the research involve financial relationships that could create conflicts of interest? • How is the research supported or financed? • Is individual or institutional compensation influenced positively by study outcome? • Do individuals or institutions involved in the research: • Have proprietary interests in the product? • Have equity interest in the research sponsor and is it a publicly or non-publicly held company? • Receive payments of other sorts? • How should the financial relationships that create a conflict of interest be managed?

29. Points for Consideration (2) • Study Design Details • Where and by whom was the study designed? • What is the nature of the study? • E.g., Mechanistic in vitro study vs a clinical study that will increase the value of the financial interest. • Will investigators with financial interests obtain consent from patients?

30. Points for Consideration (3) • Data Analysis Details • Where and by whom will the resulting data be analyzed? • Will investigators with financial interests or their subordinates be involved in primary data analysis? • Is there an independent DSMB and patient safety monitoring plan?

31. Points for Consideration (4) • Given these details: • Is Vanderbilt an appropriate site for the research? • Can the faculty member perform the research at Vanderbilt? • “Rebuttable presumption of non-participation”: special expertise and patient safety issues can override financial considerations.

32. COI Management Options • Disclosure of financial interests to prospective subjects and in publications/presentations. • Reduction of financial interest to below threshold. • Data analysis and safety monitoring by individuals unaffiliated with investigator or company. • Additional oversight or monitoring of the research by external overseer. • Modification of role of particular staff/trainees. • Elimination of the financial interest. • Perform research at non-Vanderbilt sites.

33. Consequences of Failure to Disclose COI • Human subjects in research studies could question the motives of the faculty member and investigator equipoise. • Loss of public support and confidence in academic health centers and in research. • Institutional and Federal audit of Vanderbilt research programs. • Public embarrassment of faculty member, Medical Center and School. • Violation of faculty code of conduct could lead to disciplinary action.

34. Case Study #1 • Faculty member of a clinical department owns 1,000 shares of a publicly traded pharmaceutical companies A. The value is in excess of $10,000. • Company A sponsors a large multi-centered, double-blind study involving over 10,000 patients and 100 sites studying the effects of a new pharmaceutical. The faculty member is responsible for the Vanderbilt site, which has ~40 patients enrolled. An independent DSMB monitors the trial. • Data analysis is performed by a data coordinating center independent of the company.

35. Case Study #1(continued) • Both the IRB application and the patient consent forms indicate the existence of a potential conflict of interest. • Faculty member discloses a financial interest in company A. • There are no trainees involved with the study. • There is no VU investment. • The faculty member discloses his stock ownership in all relevant publications and presentations.

36. Case Study #1(continued) • Does the faculty member have a potential conflict of interest? • If so, what management or oversight is necessary?

37. Case Study #2 • A faculty member discovers a potentially useful new application of an existing drug. Under Vanderbilt’s policies, Vanderbilt licenses the rights to the database concerning this new application to a private pharmaceutical company. • The faculty member has a significant financial interest in this activity as the medical director of and with an ownership position in the private pharmaceutical company. He also is actively involved with the Vanderbilt I.R.B.

38. Case Study #2(continued) • It should be noted that successful development and marketing of this new application will financially benefit the faculty member, the company, and Vanderbilt University. • The faculty member proposes that studies in human subjects relating to the efficacy of this new application be undertaken at Vanderbilt. Though he himself will not carry out the study, faculty members reporting to him will do so. The proposed Data Safety Monitoring Board contains a faculty member at another medical school, a Vanderbilt statistician, and physician in private practice – a former fellow of the faculty member.

39. Case Study #2(continued) • Final Recommendation: • Special expertise of Vanderbilt faculty warranted study being carried out at Vanderbilt. • Study reviewed by IRB of another medical school. • Principal Investigator on the study is faculty member who does not report to the inventor and who has no financial interest in the outcome. • Data Safety Monitoring Board should have no members with any relationship to inventor.

40. Case Study #2(continued) • The only person with access to blinding code is statistician who prepared randomization sequence. • Statistical analysis of the data will be carried out by an independent company, with access to randomization codes only after the database is locked. • If needed for patient safety, unblinded statistician will provide code only to the Data Safety Monitoring Board. • Medical Director of pharmaceutical company (the inventor) is blinded to randomization code until final analysis is performed by independent CRO contractor.

41. Conflicts of Interest At Vanderbilt • Additional information: • Your Chair or academic supervisor • MCCOIC Office (320 Light Hall) • University Conflicts Policies: http://www.vanderbilt.edu/compliance/html/conflict_of_interest_policy.pdf http://www.vanderbilt.edu/compliance/html/conf_comm.pdf • Office of Research website • Faculty Manual • Office of Compliance

42. COI in ResearchKey Points to Remember • Conflicts of interest are part of academic life. • They can usually be avoided and minimized by personal judgment, discretion and disclosure. • Consult with your academic supervisor if you have questions. • Some situations must be reconciled by peer review, management and additional oversight. • Level of management and oversight is highly situation-dependent and respectful of faculty member’s academic freedom. • Faculty members must disclose potential COI’s to MCCOIC annually and when new situations occur. • Research situations that require review involve industry sponsorship, clinical research, use of trainees, University financial investment, and when PI has an SFI.