Managing Conflict of Interest in Research

1. Managing Conflict of Interest in Research January 27, 2009 UHCMC Department of Surgery Research Conference Maureen Landies, M.A. Conflict of Interest AdministratorOffice of Outside Interests Case Western Reserve University Philip A. Cola, M.A. Vice President Research and Technology University Hospitals of Cleveland

2. Outside Interests Committee of Case Western Reserve University Membership: Faculty investigators (SOM, CSE, CAS, SON) Case officials: Spons Proj, TTO, IRBs, IACUC Hospital officials (also representing IRBs) Responsibilities Collect Financial Interest reports (faculty, research) Develop, monitor COI management plans Work to develop, harmonize policy, procedure Participate in national dialogue regarding COI

3. Topics of Presentation Conflict of Interest in the news Overview of changes under new Case policy COI management by the Outside Interests Committee Case study Examples of informed consent language

4. COI in the News: Public Web Sites Kohl-Grassley reintroduced "Physician Payments Sunshine Act" (drugs, devices, biologics) in early 2009 DHHS will maintain public website Companies to report payments >$100, gifts honoraria, travel awards, purpose, date, what was received in exchange Similar laws in MN, VT, DC, ME, WV Eli Lilly, Merck, Medtronic to post in 2009 CCF website posts physician interests > $5000 In 2007, Department of Justice required five orthopedic device manufacturers to post payments to physicians on public web sites

5. Congressional Investigations 20 universities investigated (Psychiatry, Orthopedic, Cardiology researchers--Harvard, Stanford, 22 cardiologists at Columbia, U. Cincinnati). NIH grant stopped (Emory); PI left the university Amounts reported by Universities compared with amounts reported by industry Concerns regarding industry influence: --Physician payments drive up cost of drugs --Prescribing brand-name vs. generic drugs --Inducements in medical device selection --Bias in research and medical education

6. PHS, FDA COI Regulations 42 CFR 50 Subpart F �Responsibility of Applicants for Promoting Objectivity in Research for which PHS Funding is Sought� (PHS 1995) 45 CFR 94 �Responsible Prospective Contractors� (PHS revised 2004) 21 CFR 54 �Financial Disclosure by Clinical Investigators" (FDA revised 2000) 42CFR50 - maintain written policy, designate university officials to implement; inform NIH by the time of award, or within 60 days of becoming aware of COI, that COI is reduced, managed or eliminated. 45 CFR 94 - by the time an application is submitted, each investigator has submitted to the designated official a list of SFIs; abide by COI policy of the source institution, or provide proof of compliance with one's own policy. Recently - provide assurance that COIs are reduced, managed or eliminated. 21CFR54 - inform FDA on marketing application, inform sponsor of COIs with any investigators. 42CFR50 - maintain written policy, designate university officials to implement; inform NIH by the time of award, or within 60 days of becoming aware of COI, that COI is reduced, managed or eliminated. 45 CFR 94 - by the time an application is submitted, each investigator has submitted to the designated official a list of SFIs; abide by COI policy of the source institution, or provide proof of compliance with one's own policy. Recently - provide assurance that COIs are reduced, managed or eliminated. 21CFR54 - inform FDA on marketing application, inform sponsor of COIs with any investigators.

7. NIH: Manage, reduce, eliminate Financial conflicts of interest must be reported by the grantee institution to the NIH. NIH must be informed whether the COI is being managed, reduced or eliminated. 1995 NIH Financial COI - Workgroup Report

8. NIH, FDA Reporting Thresholds NIH definition of "significant financial interest" Salary > $10,000 Equity > $10,000 or 5% (publicly traded company) FDA definition of "significant payments, equity" Salary > $25,000 Equity > $50,000 (publicly traded company) Most Universities previously: Used reporting threshold (variant of NIH, FDA) Not required by law to ask exact amounts New NIH regulations expected in 2009: "zero threshold" Have asked exactly what the government requires: Is your equity interest over $10,000, yes or no?Have asked exactly what the government requires: Is your equity interest over $10,000, yes or no?

9. Academic Medical Center Initiatives The Cornell University Institute on Medicine as a Profession (IMAP) reported after conducting a 2007 survey that, "many schools are in the process of revising and adding to their policies, a result that is not surprising with consideration to the increased attention to transparency."

10. Case Policies on Individual Conflicts of Interest and Institutional Conflicts of Interest will be finalized in 2009 (revision of 2001 COI policy) An individual conflict of interest exists when an individual covered by this policy has an outside interest that might adversely affect or appear to a reasonable person to adversely affect the individual�s judgment in carrying out University responsibilities, or that might adversely affect or appear to a reasonable person to adversely affect the University�s responsibility to the public, the safety of research subjects, or the integrity of research--draft Case Policies on Individual Conflicts of Interest and Institutional Conflicts of Interest, 2009. An institutional conflict of interest arises when the financial interests of the University, or of a University official acting within his or her authority on behalf of the University, may influence or appear to a reasonable person to influence the research, education, clinical care, business transactions, or other activities of the University. In the case of research, the concern is that the financial interests of the University, or of a University official acting within his or her authority on behalf of the University, might affect�or appear to a reasonable person to affect�University processes for the conduct, review, or oversight of the research--draft Case Policies. draft Case Policies on Individual Conflicts of Interest and Institutional Conflicts of Interest, 2009. All University officers and senior officials, all University faculty (whether or not engaged in research), all faculty (except volunteer faculty in the School of Medicine or special faculty members not paid by the University, unless engaged in sponsored research); emeritus faculty (who have an ongoing relationship with the University or who are engaged in sponsored research); and senior (investigators)/key personnel and other individuals who contribute to the scientific development or execution of a research project in a substantive way, and any other employees at the request of their supervisor. An individual conflict of interest exists when an individual covered by this policy has an outside interest that might adversely affect or appear to a reasonable person to adversely affect the individual�s judgment in carrying out University responsibilities, or that might adversely affect or appear to a reasonable person to adversely affect the University�s responsibility to the public, the safety of research subjects, or the integrity of research--draft Case Policies on Individual Conflicts of Interest and Institutional Conflicts of Interest, 2009. An institutional conflict of interest arises when the financial interests of the University, or of a University official acting within his or her authority on behalf of the University, may influence or appear to a reasonable person to influence the research, education, clinical care, business transactions, or other activities of the University. In the case of research, the concern is that the financial interests of the University, or of a University official acting within his or her authority on behalf of the University, might affect�or appear to a reasonable person to affect�University processes for the conduct, review, or oversight of the research--draft Case Policies. draft Case Policies on Individual Conflicts of Interest and Institutional Conflicts of Interest, 2009. All University officers and senior officials, all University faculty (whether or not engaged in research), all faculty (except volunteer faculty in the School of Medicine or special faculty members not paid by the University, unless engaged in sponsored research); emeritus faculty (who have an ongoing relationship with the University or who are engaged in sponsored research); and senior (investigators)/key personnel and other individuals who contribute to the scientific development or execution of a research project in a substantive way, and any other employees at the request of their supervisor.

11. What's new in 2009? 2009 draft COI policy makes explicit the following: Report any "financial interest" "Special" (not full-time) faculty if paid by Case are required to report Covered individual reports financial interest of self, spouse, dependent children, domestic partner, or any other person living in the same household as the individual." Deans receive COI management plans of their faculty Clarification in the policy of "institutional conflict of interest," e.g., a financial interest held by an institutional official can create an institutional conflict of interest. 2008 COI procedures addressed items not specified in policy: For COIs related to research: reported >$10,000 annual compensation, and/or >$10,000 or 5% in a publicly held company. "Special" faculty were not required to report (except researchers). Individual reported financial interest of self, spouse, dependent children Deans received a list of names, and could request COI plans for their faculty. COIs were managed where institutional official had an interest related to research.

12. How to Report a COI Annual "Outside Financial Interest Report for Faculty and Investigators" - annually and update, as needed Report to grants/contracts officer: Case University Review Form; UHCMC Proposal Information Form (checkbox) Report to IACUC Report to IRBs (on New Protocol application, at Continuing Review or once a COI exists)

13. Report what? Investigator's individual financial interest, e.g. Paid consulting Equity Officer or Board member Intellectual Property (IP) rights (listed as inventor on licensed IP) Non-research COIs: Purchases, vendor relationships (to Case or to hospital) Institutional financial interest (Case or affiliate) Institution owns equity Institution has IP rights (licensor of IP) Institutional official has an individual COI

14. Research COI Management: Considerations Human subjects research? Animal research? NIH sponsorship? Supervision of staff or academic advisees? Will publications be generated? Who will analyze the data? Is there independent data review? Is there an institutional conflict of interest? Precedent decisions, AAMC, AAU guide OIC

15. COI Management template: Basic, animal, human subjects research Disclose to sponsor if NIH Data Integrity (individual, institutional COIs) --Disclosure on publications / presentations --Disclosure to research staff / advisees --Disclosure to IACUC for animal research Conflicts of mentoring --Designate non-conflicted advisee supervisor --Protect student thesis work, inventions

16. COI Management Template: Human Subjects Research Determination of "compelling circumstances" for participation of conflicted investigator (AAMC) Delimit investigator role (surgery, lab etc). Recuse from subject selection, informed consent Recuse from primary data analysis/interpretation Designate non-conflicted PI / RI Designate monitor or DSMB For institutional COI, designate monitor(s) from outside Case and affiliates

17. OIC-IRB Collaboration in COI Management IRB, OIC conduct concurrent review IRB asks that IRB Protocol and consent document address the conflict of interest. IRB can be more stringent than the OIC, not less so. The IRB may require: Disclosure of annual income <$10,000 in protocol & consent form (not required by OIC) Disclosure of unlicensed patent interest in protocol & consent form (not required by OIC)

18. Case Study #1 Dr. Denton consults for two device companies and is compensated $3,000 by one and $13,000 by another. She has been trained on the implantation of devices manufactured by both companies, and each company would like Dr. Denton to test these devices in a clinical trial at UHCMC. The study coordinator has been asked to prepare the IRB protocols. How should the study coordinator proceed? Are there COI issues? If so, to whom should they be reported? What COI management should be applied?

19. Case Study #2 Dr. Blair is listed as an inventor on a device to treat kidney stones that has been licensed by Case and UHCMC to a company in which he has founder's equity. The company has been conducting animal research at Case funded by an NIH grant, and a clinical trial agreement to test the device in humans is planned with UHCMC. Dr. Blair is also a co-investigator on another clinical trial testing a device invented by him and patented by Case, but not licensed. Are there COI issues? If so, to whom should they be reported? What COI management should be applied?

20. Sample Informed Consent Language One of the investigators on this study, Dr. X, is an inventor of the device being studied, and could earn royalty payments if the device is commercially successful. Dr. X is a co-owner and consults for a company that is developing the device for commercial use. Case and UHCMC could also gain royalty payments, and they co-own the company commercializing Dr. X�s invention. A co-investigator, Dr. Y, is a co-inventor and an officer in the company sponsoring this research, and he is an official with both Case and UHCMC.

21. More Sample Consent Language One of the co-investigators of the study, Dr. Q, receives honoraria for lectures, as well as consulting income from study sponsor. This study is being done and supported by XYZ Pharmaceuticals Corporation. The institution where this study doctor works is being paid by XYZ Pharmaceuticals to run this study. Your study doctor sometimes provides assistance to XYZ Pharmaceuticals and other companies and he may receive payment outside of this study for that work.

22. Acknowledgment Thank you to Phil Cola and Erin Zaletel for their contribution to the PowerPoint presentation.

23. Contact Information: Maureen Landies, M.A. COI Administrator for Case Office of Outside InterestsSears Library Sixth Floor (Engineering Quad) Phone: 368-0838 Email: maureen.landies@case.edu http://ora.ra.cwru.edu/research/orc/coi/index.cfm Philip A. Cola, M.A. Vice President Research and Technology University Hospitals Case Medical Center Lakeside 1400 Phone: 844-5936 Email: Philip.cola@UHhospitals.org