Conflict of Interest in Human Subjects Research

1. Conflict of Interest in Human Subjects Research Guy M. Chisolm, III, Ph.D. Vice Chair, Lerner Research Institute Cleveland Clinic Presentation to the Secretary’s Advisory Committee on Human Research Protections SACHRP Arlington, Virginia July 22, 2009

2. CoI Topics and Issues • Means of uniform public disclosure • Educating the public on CoI • Determining the effectiveness of CoI Management • Giving guidance for disposition of CoI in human subjects research

3. “Reporting” versus “Disclosing”

4. Public Disclosure Websites • Feds -- US Att’y Gen’l’s settlement with 5 device mfgrs • Feds -- Grassley & Kohl’s “Sunshine Act” • States -- Minnesota, Massachusetts, Vermont… • Companies -- Eli Lilly, Merck, Pfizer, Edwards, GSK, Medtronic,…others • AMCs -- Cleveland Clinic (went live, 10/28/08) Univ of Pennsylvania, Stanford,…others (pending)

5. Go to www.clevelandclinic.org … Click on ‘FIND A DOCTOR… Guy Chisolm, Ph.D. Professional Staff Affairs Office Director, Innovation Management and Conflict of Interest Program Cell Biology Staff/Professor Lerner Research Institute Vice Chair Phone: (216) 444-5854 Location: Cleveland Clinic Main Campus Mail Code NB21 9500 Euclid Avenue Cleveland, OH 44195 * Brief Biosketch * Research & Publications * Education & Fellowships * Request an Appointment * Specialty Interests * Industry Relationships

6. Education & Fellowships Fellowship: Karolinska Institute, Stockholm, Sweden Fellowship: Massachusetts Institute of Technology, Cambridge, MA Other Education: (Doctorate)University of Virginia, Charlottesville, VA Other Education: (Masters)University of Virginia, Charlottesville, VA Other Education: (Undergraduate)University of Pennsylvania, Philadelphia, PA Specialty Interests Lipoprotein oxidation, vascular diseases, lipoprotein-cell interactions, atherosclerosis. Research & Publications [Click through to PubMed] Industry Relationships Cleveland Clinic physicians and scientists report if they have any collaborations with the pharmaceutical or medical device industries as part of the Cleveland Clinic’s procedures. The Cleveland Clinic publicly discloses payments for speaking and consulting of $5,000 or more per year, and any equity, royalties, and fiduciary relationships in companies with which they collaborate. In publicly disclosing this information, the Cleveland Clinic tries to provide information as accurately as possible about its doctors’ connections with industry and those of their immediate family members. As of 6/26/2008, Dr. Chisolm has reported no financial relationship with industry that is applicable to this listing. Patients should feel free to contact their doctor about relationships with industry and how the relationships are overseen by the Cleveland Clinic. To learn more about the Cleveland Clinic’s policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.

7. Consulting. Dr. Chisolm receives fees of $5,000 per year or more as a paid consultant or speaker for the following companies: None listed Royalty Payments. Dr. Chisolm has the right to receive royalty payments for inventions or discoveries related to the companies shown below: None listed Equity. Dr. Chisolm owns stock or stock options from the following companies for activities as a founder, inventor, or consultant: None listed Fiduciary Role. Dr. Chisolm serves in a fiduciary capacity, such as an officer or director, for the following companies: None listed Inventor Share. Dr. Chisolm may receive future financial benefits from the Clinic for inventions or discoveries related to the companies shown below: None listed

8. Host: Moderator: State Government: Device Industry: Pharma Industry: Public AMCs: Private AMCs: Guy M. Chisolm, Ph.D. Cleveland Clinic Susan Ehringhaus, J.D. AAMC James Daniel, MPH State of Massachusetts Christopher White, Esq. AdvaMed Bruce P. Garren Edwards Lifesciences Corp Kathy E. DiGiorno Medtronic Jack Harris, M.D. Eli Lilly Geralyn S. Ritter Merck & Co., Inc. Cathryn M. Clary, M.D., MBA Pfizer, Inc. Jeffrey Paden GSK Raymond Hutchinson, M.D. University of Michigan Medical School Deborah Biggs, J.D. UNC Chapel Hill School of Medicine Neal Cohen, M.D., MPH, MS UCSF School of Medicine Barry D. Burgdorf, J.D. The University of Texas System Lynn Zentner University of Minnesota Ross McKinney, M.D. Duke University School of Medicine Claudia Adkison, JD, PhD Emory University School of Medicine Julie Gottlieb, M.A. Johns Hopkins University School of Medicine Marianne Hockema Mayo Clinic Christopher Clark, J.D. Partners Health Care (B&W, MGH, Harvard) Glen Gaulton, Ph.D. University of Pennsylvania School of Medicine Harry Greenberg, M.D. Stanford University School of Medicine CoI Disclosure Website Working Group Cleveland Clinic, March 27, 2009

9. What we learned from convening entities planning web-based disclosure It is very clear that over the next two years there will be multiple websites for disclosure set up by the federal government, state governments, companies and academic medical centers that disclose industry relationships of physicians in various and non-uniform fashion. Discrepancies are inevitable!

10. Patient Survey--Preliminary Results Objective • To gauge patient perceptions of conflicts of interest due to physician relationships with industry Methods • Online survey of the Cleveland Clinic Patient Panel • Cleveland Clinic Patient Panel -- current patients of Cleveland Clinic who volunteer to assist the organization by participating in surveys that address topics related to healthcare. Study Study Description Survey Timeline June 19, 2009 – June 24, 2009 Panel Members Invited 2,319 Completed Surveys 1,153 to date Completion Rate 49.7% to date Median Survey Time 9 minutes Participation Incentive Raffle of (25) $50 USD Checks

11. Preliminary Results: Familiarity with CoI • How familiar are you with the meaning of the term Conflict of Interest as it relates to health care institutions and physicians?

12. Preliminary Results: Seeking Industry Relationship Information • If it was available online, how likely would you be to seek information about the industry relationships of your past, current or potential physicians?

13. Information of Interest • What information do you want to know about your Cleveland Clinic physician’s relationships with business?

14. Preliminary Results: Further Disclosure Wanted • What information about your physician’s business relationships do you feel is missing that you’d like to know? (Most common answers paraphrased) • Amounts of money • Other perks (vacations, gifts, meals,…) • Impact on patient treatment • Whether physician’s friends or family members are linked to the businesses • How long these relationships have been in existence • How much of the physician’s time is spent devoted to outside business activities

15. Limitations of Patient Panel Method • Results represent Cleveland Clinic Health System (Main Campus, Family Health Center and/or Regional Hospital) patients only,… • NOT the general population. • The pre-existing patient-clinic relationship has likely affected the opinions in this report.

16. What we learned from asking our patients about physician-industry ties that is likely pertinent to research subjects It is clear that patients and their families (arguably a similar population to those typically asked if they would volunteer to be research subjects) want much more information than they have.

17. Issue--Uniform Public Disclosure • Means of uniform public disclosure While disclosure is endorsed by all, and the public is hungry to know more, the non-uniformities in the making will confuse research subjects and their families rather than help them • Recommendation--Encourage broad public disclosure, but determine template for uniformity and in best interests of research subjects, patients, public

18. CoI Topics and Issues • Means of uniform public disclosure • Educating the public on CoI • Determining the effectiveness of CoI Management • Giving guidance for disposition of CoI in human subjects research

19. Issue--Educating the Public on CoI • Educating the public on CoI The public does not clearly recognize benefits of industry-academic partnerships in research, how these must be balanced against risks of bias from CoI, and how these are being evaluated and processed. • Recommendation--Determine means to educate the public of the benefits of academic-industry partnerships in research, the CoI risks and “best practices” for effective CoI management

20. CoI Topics and Issues • Means of uniform public disclosure • Educating the public on CoI • Determining the effectiveness of CoI Management • Giving guidance for disposition of CoI in human subjects research

21. Cleveland Clinic Conflict of Interest Policies • Conflicts of Commitment • CoIs in Business Affairs • Non-Human Subjects Research • Human Subjects Research • Institutional CoIs in Research • Consulting • [Clinical Practice] • [Education] © The Cleveland Clinic Foundation 2009

22. Institutional CoI in Research • Financial interests of Cleveland Clinic • Financial interests of CC’s leaders • (Department Chairs or higher; Trustees)

23. What are we looking for in CoI evaluation? (SIGNIFICANT FINANCIAL INTEREST) Are you receiving from an outside entity… • equity, stocks (options), “inventor share” • royalties • consulting or speaker fees > $10,000/yr (ACTIVITY) …while you are … • performing research related to that entity • making business decisions related to that entity • (practicing medicine related to that entity) • (educating trainees)

24. To get “approval” to perform human subjects research related to a company and have a financial interest in the company, you need… • Compelling circumstances (AAMC guidelines) • These vary among institutions (!) • Inventor--understanding the value of development • Low risk to human subjects • Unique capability/expertise • Patient population without options • A CoI Management Plan • Separate the influence of the money from the patient care and the research data (disclosure!!!; data analysis; patient selection; patient consent; multi-center; alternate principal investigator; external data & safety monitoring; no phase III, etc…) © The Cleveland Clinic Foundation 2009

25. Issue--Effectiveness of CoI Management • Determining the effectiveness of CoI Management AMCs are quickly developing the infrastructure and processes to identify and evaluate CoI, then eliminate, reduce or manage them. This is being done with only inferential reliance on the effectiveness of these endeavors. • Recommendation-- Promote research that addresses the effectiveness of current “best practices” in overseeing/managing CoI

26. CoI Topics and Issues • Means of uniform public disclosure • Educating the public on CoI • Determining the effectiveness of CoI Management • Giving guidance for disposition of CoI in human subjects research

27. Issue--Common rules for CoI in human research • Giving guidance for disposition of CoI in human subjects research AMCs are non-uniform in the application of multiple CoI guidelines to human subjects research. (Discussed by Dr. McKinney) • Recommendation-- (quoting Dr. McKinney…) Develop a “common rule” for CoI in clinical research [NIH, FDA, OHRP, DOD, etc.]

28. Recommendations • Encourage broad public disclosure, but determine template for uniformity and in best interests of research subjects, patients, public • Determine means to educate the public of the benefits of academic-industry partnerships in research, the CoI risks and effective CoI management • Promote research that addresses the effectiveness of current “best practices” in overseeing/managing CoI • (McKinney…) Develop a “common rule” for CoI in clinical research [NIH, FDA, OHRP, DOD, etc.]