1. USF Health Conflict of Interest Committee New Member Orientation

2. VOTING MEMBERS At least: 1 faculty member representing each of the USF Health Core facilities. 1 faculty member representing each of the USF Health Core facilities. COM: Anthony Morrison, Robert Hauser, Bill Marshall, Richard Heller, Barry Bercu COM: Anthony Morrison, Robert Hauser, Bill Marshall, Richard Heller, Barry Bercu CON: Mary Evans, Maureen Groer (alternate) CON: Mary Evans, Maureen Groer (alternate) COPH: John Large COPH: John Large Who’s on the USF Health COI Committee?

3. Who’s on the USF Health COI Committee? (con’t) VOTING MEMBERS (con’t) 1 faculty member from the College of Arts and Sciences. 1 faculty member from the College of Arts and Sciences. CAS: Stefan Frisch CAS: Stefan Frisch 2 faculty member clinicians who conduct human subjects research. 2 faculty member clinicians who conduct human subjects research. Anthony Morrison, Robert Hauser, Barry Bercu Anthony Morrison, Robert Hauser, Barry Bercu 1 faculty member who conducts basic sciences research. 1 faculty member who conducts basic sciences research. Richard Heller, Bill Marshall Richard Heller, Bill Marshall

4. Who’s on the USF Health COI Committee? (con’t) VOTING MEMBERS (con’t)  1 representative affiliated with the USF IRB (recused from voting on institutional conflicts of interest in research involving human subjects). Barry Bercu, Paul Stiles (alternate) Barry Bercu, Paul Stiles (alternate) 1 community representative. 1 community representative. Richard Oliver Richard Oliver Others? An ethicist? Others? An ethicist?

5. Who’s on the USF Health COI Committee? (con’t) EX OFFICIO MEMBERS (NON-VOTING) A representative from the USF Health Office of Research. A representative from the USF Health Office of Research. Phil Marty Phil Marty The USF Health Conflict of Interest in Research Program Administrator. The USF Health Conflict of Interest in Research Program Administrator. Camille McWhirter Camille McWhirter

6. Who’s on the USF Health COI Committee? (con’t) EX OFFICIO (NON-VOTING) The Director of the USF Health Office of Faculty Affairs. The Director of the USF Health Office of Faculty Affairs. Olga Joanow Olga Joanow The Office of Research Conflict of Interest in Research Program Administrator. The Office of Research Conflict of Interest in Research Program Administrator. Vinita Witanachchi Vinita Witanachchi

7. Who’s on the USF Health COI Committee? (con’t) EX OFFICIO (NON-VOTING) A representative from the Office of Research, Division of Sponsored Research. A representative from the Office of Research, Division of Sponsored Research. Liz O’Connell Liz O’Connell A representative from the Office of the General Counsel. A representative from the Office of the General Counsel. Megan Pritts, R.B. Friedlander (alternate) Megan Pritts, R.B. Friedlander (alternate) Ad Hoc: A representative from any affiliate for whom the Committee reviews a COI disclosure. Ad Hoc: A representative from any affiliate for whom the Committee reviews a COI disclosure.

8. Point of Clarification There are two COI committees (and two COI policies) at USF:  USF Health Conflict of Interest Committee  USF Conflict of Interest in Research Committee

9. USF Health Conflict of Interest Committee  Reviews disclosures for all human subjects research (regardless of the origin)  Reviews disclosures for research conducted by employees of USF Health  50/50 expedited/full committee reviews  COI Administrator: Camille McWhirter

10. USF Committee for Conflicts of Interest in Research  Resides within the USF Office of Research, Division of Research Integrity and Compliance  Reviews disclosures (for non-human subjects research) for the rest of the University system  Primarily expedited reviews  COI Administrator: Vinita Witanachchi

11. What Does the USF Health COI Committee Do? Primary Mission: To review disclosures/management plans of USF Health employee investigators and those conducting human subjects research; and To ensure (by imposing appropriate management controls) that the disclosing investigator’s financial interests will not bias the design, conduct or reporting of the research project.

12. Also, the Committee… Implements, oversees and enforces the USF Health Conflict of Interest and Commitment policy Implements, oversees and enforces the USF Health Conflict of Interest and Commitment policy In cooperation with the USF IRB, considers conflicts of interest that might affect the relationship with human subjects participants in research or the outcome of the research, and manages such conflicts. In cooperation with the USF IRB, considers conflicts of interest that might affect the relationship with human subjects participants in research or the outcome of the research, and manages such conflicts.

13. And the Committee Will Be… Monitoring the management of identified conflicts of interest in research during the conduct of the research. Monitoring the management of identified conflicts of interest in research during the conduct of the research. Assisting the Vice President for USF Health as needed in tasks related to conflicts of interest in research. Assisting the Vice President for USF Health as needed in tasks related to conflicts of interest in research.

14. And May Eventually Be… Participating in discussion and the development of policy on conflicts of interest in general…not related to research. Participating in discussion and the development of policy on conflicts of interest in general…not related to research. Acting as a resource upon request in the review of situations involving conflicts of interest with University employment and conflicts of commitment Acting as a resource upon request in the review of situations involving conflicts of interest with University employment and conflicts of commitment

15. A COI Committee Member Should Be Able To: Define a conflict of interest Define a conflict of interest Identify potential conflicts of interest in research situations Identify potential conflicts of interest in research situations Be familiar with the process for COI review at USF Be familiar with the process for COI review at USF Differentiate between an institutional and an individual COI Differentiate between an institutional and an individual COI

16. Identify the three government agencies who have rules regulating COI in research Identify the three government agencies who have rules regulating COI in research Understand when each agency’s rules apply Understand when each agency’s rules apply Define a “significant financial interest” for each agency that regulates COI Define a “significant financial interest” for each agency that regulates COI Understand some general principles and concepts in dealing with COI Understand some general principles and concepts in dealing with COI

17. Understand the procedure for review of a disclosure under USF Health policy Understand the procedure for review of a disclosure under USF Health policy Identify some special considerations in dealing with human subjects research Identify some special considerations in dealing with human subjects research Identify some management controls for dealing with COI Identify some management controls for dealing with COI Bonus: Explain the significance of the Bayh-Dole Act Bonus: Explain the significance of the Bayh-Dole Act

18. Definition and Types of Self- Interest Conflict of Interest - A conflict of interest exists when professional or ethical obligations may be compromised by self-interest. Self-interest could manifest in the form of A financial benefit A financial benefit Enhanced reputation Enhanced reputation Personal relationships Personal relationships Professional relationships Professional relationships Other interests (political, religious, intellectual) Other interests (political, religious, intellectual)

19. Conflict of Interest in Research refers to situations in which financial or other personal considerations may compromise, or have the appearance of compromising, an Investigator's professional judgment in the conduct, evaluation or reporting of research. Example: where an investigator has a financial or business interest related to the research that would be affected by the outcome of the research.

20. More Definitions Investigator - Any person responsible for the design, conduct or reporting of research (includes extended family). Interested Investigator - An Investigator who has a financial or other business interest that could reasonably be affected by a research study in which the Investigator is participating.

21. Some Noteworthy Points About Our Policy at USF Health USF Health Policy (and most other university COI policies) focus on potential financial benefits and the professional relationships (but not other personal considerations, like reputation) of investigators that create a conflict of interest in research. (Why?)

22. Noteworthy… USF Health Conflict of Interest and Commitment Policy has a “zero threshold” requirement for the disclosure of financial interests in a research study. (This means that investigators must disclose their financial interests even if they do not rise to the level of a Significant Financial Interest.)

23. Noteworthy… USF Health Conflict of Interest and Commitment Policy states as a rebuttable presumption that interested investigators may not conduct human subjects research. The presumption must be overcome by “compelling circumstances”.

24. Yet Another Definition… Compelling Circumstances (paraphrased): Any circumstances that convince the COI Committee that the interested investigator should be able to conduct the research. (More on that later….)

25. COI Review Process 1. Investigator becomes associated with a research proposal in which the investigator has a financial or business interest related to the research. 2. Investigator recognizes that his or her financial interest in the research may create an actual or potential conflict of interest. 3. Investigator completes the Financial Interests Disclosure Form. 4. Investigator submits completed form to supervisor for review and signature.

26. 6. Supervisor routes form to the appropriate office based on certain criteria (e.g., sponsored or non- sponsored, COM or not COM). 7. The appropriate office routes the form to the USF Health COI Administrator. 8. COI Administrator reviews form for adequacy, contacts investigator to acknowledge receipt, obtain any add’tl info needed, and advise as to timeframe for review.

27. 9. If disclosure qualifies for expedited review, COI Administrator will review and approve or develop an appropriate management plan in cooperation with the investigator based on similar disclosures with existing approved management plans. 10. If the disclosure does not qualify for expedited review (e.g., involves human subjects), the COI Administrator will forward the disclosure for review by the COI Committee.

28. 11. The COI Committee will review the disclosure and determine whether the conflict is subject to management and if so, develop and approve a management plan. 12. If the research involves HSR, the COI Administrator will notify the investigator and any other appropriate parties of the COI Committee’s decision and will forward the disclosure, management plan and related documents to the IRB for review at its next meeting. 13. If the research does not involve HSR, the COI Administrator will notify the investigator and any other appropriate parties of the COI Committee’s decision.

29. Individual vs. Institutional COI What is an individual conflict of interest? A conflict that may influence the individual’s ability to act impartially, such as having a financial interest in an entity related to the research.

30. Individual vs. Institutional COI What is an institutional conflict of interest? A conflict that may influence the institution’s ability to act impartially. These types of conflicts occur when an institution’s financial or other interests may affect how it reviews or conducts research. Must also consider the financial interests of institutional officials as an institutional conflict.

31. Bayh-Dole Act (Patent & Trademark Act Amendments of 1980 ) Pre Bayh-Dole: Federal government owns and licenses technology coming out of federal support. (But studies showed that only 2% of federally sponsored technology made it to the market!) Bayh-Dole represented a fundamental change in federal government outlook on IP. It gave universities and inventors incentive to transfer the benefits of scientific research to commercial applications for public benefit.

32. Bayh Dole Act (1980, 1982) Post Bayh-Dole: Funding agencies can assign IP rights resulting from agency sponsored research to the academic institution. Academic institutions are encouraged to license IP to for-profit entities for development and commercialization. Federal government retains the non-exclusive, royalty free right to use the results for government purposes.

33. BUT… Bayh-Dole has complicated relationships between researchers, research institutions and commercial businesses.

34. Regulatory Framework There is widespread debate but no real consensus on the best way to handle conflicts of interest. Consequently, there are no universal or government-wide regulations covering them. There is widespread debate but no real consensus on the best way to handle conflicts of interest. Consequently, there are no universal or government-wide regulations covering them. Most institutions today have their own policies and procedures for managing conflicts of interest, and those policies may differ from one institution to another. Most institutions today have their own policies and procedures for managing conflicts of interest, and those policies may differ from one institution to another. In addition, a number of government agencies and professional organizations have established their own conflict of interest guidelines. In addition, a number of government agencies and professional organizations have established their own conflict of interest guidelines.

35. Federal Regulations Food and Drug Administration - Applies in research involving a drug, device or biologic. Requires disclosure of certain financial interests of the investigator at the time of application for approval of a drug device or biologic. FDA will evaluate the impact of the researcher’s financial interests on the reliability of the study data. Food and Drug Administration - Applies in research involving a drug, device or biologic. Requires disclosure of certain financial interests of the investigator at the time of application for approval of a drug device or biologic. FDA will evaluate the impact of the researcher’s financial interests on the reliability of the study data. Food and Drug Administration Food and Drug Administration Public Health Service & National Science Foundation - Require institutions receiving grants from these agencies to develop a COI policy that meets certain minimum requirements while permitting flexibility in the administration of policy. PHS and NSF regulations were developed cooperatively to make the regulations consistent. Public Health Service & National Science Foundation - Require institutions receiving grants from these agencies to develop a COI policy that meets certain minimum requirements while permitting flexibility in the administration of policy. PHS and NSF regulations were developed cooperatively to make the regulations consistent. Public Health Service & National Science Foundation Public Health Service & National Science Foundation

36. FDA Regulations “Anyone who submits a marketing application of any drug, biological product or device must submit certain information concerning compensation to, and financial interests of, any clinical investigator conducting studies covered by this rule.” 21 CFR Part 54

37. What is Significant to the FDA? Significant equity interest means Significant equity interest means any ownership interest, stock options, or other financial interest whose value cannot be readily determined via reference to public prices any ownership interest, stock options, or other financial interest whose value cannot be readily determined via reference to public prices any equity interest in a publicly traded corporation that exceeds $50,000 during the time the investigator is carrying out the study and for 1 year following completion of the study. any equity interest in a publicly traded corporation that exceeds $50,000 during the time the investigator is carrying out the study and for 1 year following completion of the study. Significant payments of other sorts means Significant payments of other sorts means payments made to the investigator (or the institution to support activities of the investigator) of more than $25,000 during the time the clinical investigator is carrying out the study and for 1 year following the completion of the study. payments made to the investigator (or the institution to support activities of the investigator) of more than $25,000 during the time the clinical investigator is carrying out the study and for 1 year following the completion of the study.

38. FDA Regulations Applicant must EITHER certify that: No financial arrangements have been made with an INV where study outcome could affect compensation. No financial arrangements have been made with an INV where study outcome could affect compensation. INV has no proprietary interest in the tested product. INV has no proprietary interest in the tested product. INV does not have significant equity in sponsor and sponsor has not made significant payments of other sorts to INV or to institution on behalf of INV INV does not have significant equity in sponsor and sponsor has not made significant payments of other sorts to INV or to institution on behalf of INV

39. FDA Regulations OR Disclose the specified financial arrangement and any steps taken to minimize the potential for bias. Then, FDA will determine whether conflicting interest could jeopardize the integrity of the study. Such a determination can result in severe delays and significant financial losses. So….institutions are doing it for themselves.

40. Potential FDA Actions If the FDA is concerned about the conflict, the FDA can: Audit the data derived from the INV in question Audit the data derived from the INV in question Request further data analysis to evaluate the effect of the INV data on overall results Request further data analysis to evaluate the effect of the INV data on overall results Request additional independent studies Request additional independent studies Refuse to use the data to support an FDA action Refuse to use the data to support an FDA action

41. PHS/NSF COI Regulations Investigator Responsibilities: Must disclose any  “significant financial interests” (including those of spouse and dependent children)  that would reasonably appear to be affected by the research  to a designated institutional official  by the time the application is submitted to PHS/NSF.

42. What is Significant to NSF/NIH? Significant Financial Interest means anything of monetary value, including salary, consulting fees or honoraria, equity interests (stock, ownership interests) and intellectual property rights.

43. EXCEPTIONS: Salary from your own institution Salary from your own institution Income from speaking engagements sponsored by government or non-profit Income from speaking engagements sponsored by government or non-profit Income from advisory boards of G or NP Income from advisory boards of G or NP Equity interest < $10,000 or 5% Equity interest < $10,000 or 5% Annual payments < $10,000 Annual payments < $10,000

44. Footnote: The PHS/NSF regulations are broader: 1. PHS/NSF covers all interests that would reasonably be affected by the research (not just income from or equity in the sponsor of the research) and 2. The threshold is lower--$10,000 (PHS/NIH) vs. $25,000 (FDA)

45. PHS/NSF COI Regulations Institutional Responsibilities: Written enforced policies on COI Designated institutional official to review COI Require that each investigator submits a disclosure form for PHS and NSF research annually Provide guidelines to review and manage COI Maintain records for 3 years Establish enforcement mechanisms and sanctions Report failures to comply to awarding agency

46. Guidance Documents COI can be subtle and complex, often involving ethical issues beyond the scope of regulation. Also, the regulations that do exist are purposefully flexible in order to allow the institutions to apply them in the way that best suits the institution. So the regulations can often seem vague and open to interpretation.

47. Industry Guidance Documents Consequently, a number of government agencies and national professional associations have published guidance documents to help individuals and institutions cope with conflict of interest issues. Consequently, a number of government agencies and national professional associations have published guidance documents to help individuals and institutions cope with conflict of interest issues. Among these organizations are the American Medical Association (AMA), the Association of American Universities (AAU), and the Association of American Medical Colleges (AAMC). Among these organizations are the American Medical Association (AMA), the Association of American Universities (AAU), and the Association of American Medical Colleges (AAMC).

48. Summary of Industry Guidance This presentation (and omitted slides that summarize the industry recommendations for COI review) will be accessible on the USF COI Committee Website.

49. General Principles in Dealing with COI COI is virtually unavoidable. COI is virtually unavoidable. COI does not preclude participation of an investigator in a project, but investigator must show “compelling circumstances” to conduct HSR COI does not preclude participation of an investigator in a project, but investigator must show “compelling circumstances” to conduct HSR Must have a culture of honest and full disclosure so that steps can be taken to manage conflicts effectively. Must have a culture of honest and full disclosure so that steps can be taken to manage conflicts effectively. Not all COI can be managed (and the more restrictive measures are appropriate). Not all COI can be managed (and the more restrictive measures are appropriate).

50. Useful Concepts in Committee Review MOTIVATION (Amount & Nature of Interest) How much incentive does the INV have to bias the design, conduct or reporting of the research? OPPORTUNITY (Contacts with Research) Is the INV in a position to bias the design, conduct or reporting of the research?

51. Useful Concepts in Committee Review DIRECT EFFECT: Outcome of research will be directly relevant to the development, manufacturing or improvement of products or services of the business entity (secondary interest). SIGNIFICANT IMPACT: Value of business entity, earnings or sales revenue will be materially affected by the outcome of the research.

52. Proposed Steps to Follow In Review of A Disclosure 1. DO YOU HAVE ENOUGH INFORMATION TO CONDUCT A MEANINGFUL REVIEW? A description of the research study. A description of the research study. A detailed description of the investigator’s role in the research study (i.e., what aspects of the study are under the investigator’s control) A detailed description of the investigator’s role in the research study (i.e., what aspects of the study are under the investigator’s control) The nature and amount of the investigator’s financial interest or relationship. The nature and amount of the investigator’s financial interest or relationship.

53. 2. DOES THE STUDY INVOLVE HUMAN SUBJECTS? If so, the Committee should not allow an interested investigator to participate unless the “compelling circumstances” threshold is met. In other words, there is a rebuttable presumption that the investigator may not conduct the research.

54. 2.a.Is the “compelling circumstances” threshold met? FLASHBACK Compelling Circumstances are circumstances that convince the COI Committee that the interested investigator should be able to conduct the research.

55. Factors That Might Support “Compelling Circumstances” 1.No significant connection between the research study and the investigator’s financial interest, THEREFORE, the investigator's financial involvement with the business entity will not in any way affect or impair the conduct of the research.

56. Factors That Might Support “Compelling Circumstances” 2.There is a significant connection between the research study and the investigator’s financial interest, BUT, the interested investigator is uniquely qualified by virtue of expertise and experience and the research could not otherwise be conducted as safely or effectively without that individual…

57. AND, there are adequate mechanisms in place to prevent the introduction of bias into critical aspects of the research study.

58. In other words…there is an appropriate management plan in place to eliminate or reduce bias in the design, conduct or reporting of research. In other words…there is an appropriate management plan in place to eliminate or reduce bias in the design, conduct or reporting of research.

59. Special Considerations for HSR  The presumption against allowing an interested investigator to conduct HSR is not to suggest that every financial interest jeopardizes the welfare of HS or the integrity of research. Each situation must be carefully evaluated and a judgment made about “compelling circumstances” based on Each situation must be carefully evaluated and a judgment made about “compelling circumstances” based on the nature of the science, the nature of the science, the nature of the interest, the nature of the interest, how closely the interest is related to the research, how closely the interest is related to the research, and the degree to which the interest may be affected by the research. and the degree to which the interest may be affected by the research.

60. When the financial interest is directly related to the research and may be substantially affected by it, the risk is greatest and the standard for scrutiny must be high. When the financial interest is directly related to the research and may be substantially affected by it, the risk is greatest and the standard for scrutiny must be high. Disclosure alone is NOT sufficient to manage the interest. Disclosure alone is NOT sufficient to manage the interest.

61. View each instance of an interested investigator conducting HSR as “potentially problematic and requiring strict scrutiny”. View each instance of an interested investigator conducting HSR as “potentially problematic and requiring strict scrutiny”. Carefully evaluate all aspects of the investigator’s involvement in the study including, Carefully evaluate all aspects of the investigator’s involvement in the study including,  trial design  evaluating and reporting adverse events  result reporting and  conduct or administration of the research study.

62. More considerations in reviewing HSR Whether an interested investigator should be permitted to consent, recruit or randomize subjects and under what circumstances is a current topic of discussion by the COI Committee. Whether an interested investigator should be permitted to consent, recruit or randomize subjects and under what circumstances is a current topic of discussion by the COI Committee. When compelling circumstances warrant that an interested investigator participate in research: “rigorous, effective, and disinterested monitoring” should take place. When compelling circumstances warrant that an interested investigator participate in research: “rigorous, effective, and disinterested monitoring” should take place.

63. Back to the Proposed Steps to Follow In Review of A Disclosure 3. CONSIDER THE PROPOSED MANAGEMENT PLAN Is it sufficient to eliminate or reduce the investigator’s influence in the design and/or conduct of the research study and/or the reporting of the research results? Take into account the closeness of the connection between the financial interests and the outcome of the research.

64. 4. DETERMINE WHETHER AND UNDER WHAT CIRCUMSTANCES THE RESEARCH MAY PROCEED. Approval (with or without management plan) Approval (with or without management plan) Stipulated minor changes or clarifications required Stipulated minor changes or clarifications required Deferral (more information needed) Deferral (more information needed) Disapproval (i.e., elimination of interest or change of personnel required before research may proceed.) Disapproval (i.e., elimination of interest or change of personnel required before research may proceed.)

65. Examples of Possible Steps to Manage COI Elimination of the conflicting interest Substitution of personnel on the project Public disclosure of significant financial interests Monitoring of research by independent reviewers

66. QUESTIONS? QUESTIONS?