University/Industry Relationships and Conflict of Interest

1. University/Industry Relationships and Conflict of Interest John Jay Gargus, M.D., PH.D. Professor, Physiology & Biophysics/Pediatrics Chair, Conflict of Interest Oversight Committee April 24, 2013

2. Agenda • University/Industry Relationships • Conflict of Interest • Disclosure Requirements • Conflict of Interest Oversight Committee • Conflict of Interest and Graduate Education • Resources

3. The Bayh-Dole Actor University and Small Business Patent Procedures Act is United States legislation dealing with intellectual property arising from federal government-funded research. Adopted in 1980, it gave US universities, small businesses and non-profits intellectual property control of their inventions and other intellectual property that resulted from such funding. Birch Evans Bayh II Dem Senator Indiana ‘61-’81 Robert Joseph Dole Rep Senator Kansas ‘69-’96

4. University/Industry Relationships University vs. Industry • University and Industry have fundamental differences in their motives that can never be fully reconciled

5. University/Industry Relationships University and Industry Overlap • With new knowledge comes new technology which leads to new products resulting in the Industry’s need to consult Academic Scientists for their expertise • Potential Conflict of Interest since University researchers have an obligation to put research integrity and the education of their trainees and peers first when faced with a choice between making money or doing their duty

6. University/Industry Relationships “Drugs and Disclosure”Reported October 11, 2008 • “Dr. Charles Nemeroff of Emory University—the principal investigator on a government-financed study of antidepressant drugs made by GlaxoSmithKline—repeatedly promised to keep his consulting fees from Glaxo below $10,000 a year in compliance with federal and university conflict-of-interest rules…Dr. Nemeroff failed to report some half-a-million dollars in fees and expenses from Glaxo while he led the study.” • Dr. Nemeroff had to step down from university research projects funded by NIH and NIH “froze funds for a $9.3 million project on depression led by Nemeroff” • NIH also “instituted tighter rules on approving grants for Emory” Editorial by The New York Times White, Gayle and Schneider, Craig. “Depression Expert at Emory Pulls out of Research Projects.” The Atlanta Journal Constitution, October 14, 2008.

7. University/Industry Relationships “University Sues Researcher”Reported January 3, 2012 • “Craig Thompson, current president of Memorial Sloan-Kettering Cancer Center, is being sued by his former employer, the Leonard and Madlyn Abramson Family Cancer Research Institute at the University of Pennsylvania, which he headed for 12 years, for not disclosing industry activities” for $1 billion dollars • Failed to disclose that he “founded biotech company called Agios pharmaceuticals” • University claims “it has rights to intellectual property that the company was founded on” http://the-scientist.com/2012/01/03/university-sues-researcher/

8. University/Industry Relationships Summary • Articles highlight some consequences of failing to disclose financial interests • Failure to disclose affects the perception of the researcher’s integrity and work and the university’s reputation once the undisclosed financial interests are uncovered

9. University/Industry Relationships Research FundingA non-trivial high stakes activity • NSF spent $5.7 billion in research and related activities in FY 2012 • NIH awarded $30.9 billion in research grants in 2012 • America’s biopharmaceutical research companies invested a record $49.5 billion in 2011 in research and development of new medicines and vaccines http://www.nsf.gov/pubs/2013/nsf13002/pdf/06_chapter1_mannagement_discussion_and_analysis.pdf http://www.nih.gov/about/budget.htm http://www.phrma.org/sites/default/files/159/phrma_industry_profile.pdf

10. University/Industry Relationships UCI Statistics(Year ending June 30, 2011) • 178 invention disclosures • 869 active inventions • 315 active UC patents • 3 startup companies formed • $7,354,000 total licensing income UC Technology Transfer Annual Report 2011 http://www.ucop.edu/ott/genresources/documents/IASRptFY11.pdf

11. University/Industry Relationships Greater Scrutiny Revised PHS Regulations (Final rule published August 25, 2011) Main changes • Lower financial disclosure thresholds • Disclosure requirements broadened to include financial interests related to institutional responsibilities not just research project • New conflict of interest training requirement • Disclosure for any reimbursed or sponsored travel (no lower limit) • Disclosed information available to public Implementation began August 24, 2012 http://grants.nih.gov/grants/policy/coi/summary_of_major_changes.doc

12. University/Industry Relationships Greater Scrutiny Physician Payment Sunshine Act (Final Rule Issued February 8, 2013) • Requires all US manufacturers of drug, device, biologics, and medical supplies covered under Medicare, Medicaid, or SCHIP to report payments to physicians and teaching hospitals annually to Department of Health and Human Services, which will post information on public website • Must also disclose physician ownership or investment interest • Law exempts payments less than $10 until the aggregate annual total per company, per covered recipient, reaches $100, then all retroactive payments must be disclosed First report due on March 31, 2014 for payments made from August 1, 2013 to December 31, 2013. http://www.prescriptionproject.org/tools/sunshine_docs/files/Sunshine-fact-sheet-6.07.10.pdf

13. Conflict of Interest What is a conflict of interest? • A situation where an investigator’s outside financial interest(s) or obligation(s) bias or have the potential to bias a research project Note: Considering the public’s perception is important when considering a conflict of interest

14. Conflict of Interest What is a financial interest? Anything of economic value from an outside entity including: • Income- salary, consulting fees, honorarium, stipend • Equity interests- stock, stock options • Positions in an outside entity such as director, officer, partner, consultant, etc. • Travel payments/reimbursements • Loans

15. Conflict of Interest Important principles about Conflicts of Interests • COIs rarely arise from a bad person doing wrong (illegal, immoral, unethical, unprofessional) things. They usually arise from a good person who has two worthy objectives that conflict with one another • COIs are inevitable for faculty and institutions engaged in technology transfer • The faculty member or student/trainee is seldom consciously aware of having a COI until educated

16. Disclosure Requirements COI Disclosure Policies • State of California • Federal Government (PHS, NSF) • Human Subjects (IRB)

17. Disclosure Requirements State • Required for non-governmental sponsored research and research gifts (i.e. private companies and nonprofit organizations) • Principal investigators are required to disclose financial interests in the non-governmental sponsor

18. Disclosure Requirements State Disclosure Thresholds • If you, the Principal Investigator, have received one or more of the following from the nongovernmental sponsor of your research: • Ownership or management interests/position; consulting/employment relationship • Income ≥ $500 • Equity ≥ $2,000 • Personal gifts ≥ $50 • Travel payment • Loan …. then you would be required to submit a COI addendum for review

19. Disclosure Requirements Federal (NSF) • Required for NSF research contract/grant including subaward where NSF is the prime sponsor and funding from organizations following these federal disclosure requirements • All personsinvolved in design, conduct, or reporting of research being funded by NSF are required to disclose their significant and related financial interests

20. Disclosure Requirements NSF Disclosure Thresholds If you are responsible for design, conduct or reporting of the NSF funded research and received one or more of the following from an outside entity with interests related to the research: • Income ≥ $10,000 • Equity ≥ $10,000 or 5% • Director, Officer, Employee, Partner, Trustee, Consultant, or Management position • Intellectual Property not owned by UC …then you would indicate “Yes” on the Federal Financial Disclosure Form and submit a COI addendum for review

21. Disclosure Requirements Federal (PHS)- Revised in 2011 • Required for PHS research contract/grant including subaward where PHS is the prime sponsor and funding from organizations following these federal disclosure requirements • All persons involved in design, conduct, or reporting of research being funded by PHS are required to disclose their significant financial interests related to their institutional responsibilities

22. Disclosure Requirements Federal Disclosure Thresholds If you are responsible for design, conduct or reporting of the PHS funded research and received one or more of the following from an outside entity with interests related to your institutional responsibilities: • For publicly traded entities, total compensation and equity interest >$5,000; • For non-publicly traded entities, income >$5,000, or anyequity interest; • Income received related to intellectual property (not owned by UC Regents) >$5,000 • Any reimbursed or sponsored travel related to the institutional responsibilities …then you would indicate “Yes” for each type of financial interest on the Form 800

23. Disclosure Requirements Human Subjects (IRB) • Required for any study involving human subjects • All individualslisted in the protocol application as research personnel must disclose their financial interests related to the research

24. Disclosure Requirements IRB Disclosure Thresholds If you are listed as research personnel on the protocol application and received one or more of the following from an outside entity with interests related to the research: • Income ≥ $10,000 • Equity ≥ $10,000 or 5% in a publicly traded entity • Any equity in a privately held company • Director, Officer, Employee, Partner, Trustee, Consultant, or Management position • Intellectual Property not owned by UC …then you would indicate “Yes” on the IRB application and submit a COI addendum for review

25. COIOC Conflict of Interest Oversight Committee (COIOC) • Faculty advisory committee appointed to 3 year terms by the Vice Chancellor for Research • Representatives from Office of Technology Alliances and Research Administration are non-voting • Committee meets once a month; recommendations are forwarded to Institutional Official for final determination

26. Current Composition of UCI’s COIOC Faculty (3 year terms; appointed by VC-Research) School of Biological Sciences – 0 School of Medicine – 4 College of Health Sciences – 0 School of Engineering – 1 School of Physical Sciences – 2 School of Information and Computer Sciences – 0 School of Social Sciences – 1 Merage School of Business – 0 Ex officio Bruce Morgan – Assistant Vice Chancellor of Research Kevin Kennan, J.D. – Office of Res-Tech Alliances Grace Park, J.D. – COI Administrator Nadia Wong – COI Analyst

27. Our function is to protect… • Human research subjects. • Student researchers. • Reputation of the University. • Public funds (NIH/NSF), California tax payers. • … by reviewing COI disclosures of research projects and making recommendation to the VC-Research for: • (1) approval, • (2) management • (3) disapproval

28. COIOC COIOC • Not a punitive body • Protect integrity of research related to university/industry partnerships, personal investments, or consulting NOT discourage those activities

29. COIOC COIOC Procedures • Investigator/Researcher discloses financial interests….YOUR RESPONSIBILITY • COIOC reviews disclosure • We review WHAT YOU DISCLOSE • We are not responsible for DISCOVERING your conflict • Determines whether or not conflict is manageable • Send recommendation to Institutional Official • Implement management plan

30. COIOC COI Management Strategies • Public disclosure in publications and presentations • Monitoring by independent reviewers • Disqualification from project participation • Divestiture • Severance of relationships that create COI • Notification of sponsor (NIH, NSF, others)

31. Example of a proper COI disclosure in a publication. PNAS 2009 vol. 106 4906-4911

32. COIOC COI Management Strategies • Public disclosure in publications and presentations • Monitoring by independent reviewers • Disqualification from project participation • Divestiture • Severance of relationships that create COI • Notification of sponsor (NIH, NSF, others)

33. COIOC What the COIOC considers… • Professionalism • Protection of human subjects • Protection against exploitation of students/trainees • Integrity of data • Trust • Setting standards in education • Reputations and credibility

34. COIOC Potential Risks of a COI • Compromise of scientific integrity • Improper direction of student or employee’s work • Inappropriate delay or restriction on publications • Unbalanced allocation of faculty member’s time or effort • Appearance of impropriety

36. COI and Graduate Education Graduate Education COI policy addresses conflicts that might stem from any financial interest of the graduate student’s mentor/thesis/dissertation advisor that has the potential to harm the student’s academic interests and degree progress

37. When is the best time to raise a concern about a COI? > When thesis advisor and project are chosen or anytime student has a concern. School has a form that must be signed at the end of the first year when student transfers from the Gateway Program to a lab. • Who can identify and report a conflict of interest? > The student, advisor, dept. chair or grad. advisor, assoc. dean or director of grad program, the campus COIC. • What are the responsibilities of my academic unit? > Notify students of the nature of COI and UC policy. > Provide students with name of Designated Resource Person – typically the dept. grad advisor. • > Ensure faculty are informed about COI policy and procedures (APM-028), and how these might affect their relationship with students.

38. What is the responsibility of the thesis advisor? • > Disclose any pertinent COIs to student and the dept. grad. advisor in a timely manner. (more later!) • Is there COI-related documentation that I should be aware of ? • > Departmental Transfer Agreement: end of 1st year. • > Advancement to Candidacy.

39. COI and Graduate Education Graduate Education

40. COI and Graduate Education Managing COI when involves Graduate Students • Process may be initiated by student, faculty mentor, departmental representative, or COIOC • Report potential COI to Designated Resource Person (usually departmental graduate advisor) or Department Chair • If DRP determines COI issue may be harmful to student, DRP notifies Dean of Graduate Studies requesting an Oversight Member be appointed • Dean of Graduate Studies selects an Oversight Member from a list of 3 nominations agreed upon by the student, faculty research advisor, and DRP

41. COI and Graduate Education Oversight Member • Participates as a non-voting Ex Officio Member in all student research advisory and/or thesis/dissertation committee meetings. • Is aware of COI issues and relevant campus policies

42. COI and Graduate Education Oversight Member • Determine whether any harmful results from COI issues • If no harmful results from COI issues, sign brief statement to that effect after each committee meeting and sign advancement to candidacy and final exam forms • If problem arising from COI issues, does not sign advancement to candidacy or final exam forms and does inform Dean of Graduate Studies of problem • Dean of Graduate Studies responsible for determining solution

43. COI and Graduate Education COI and Graduate Education One priority of the COIOC and COI Policies regarding financial interests is to protect the academic interests and degree progress of graduate students

44. Research conflicts NOT related to financial interests • Whistleblower Policy • http://www.evc.uci.edu/whistleblower/ • If you suspect that a UC employee is engaged in improper governmental activities (such as corruption, bribery, theft or misuse of university property, fraudulent claims, fraud, coercion, willful omission to perform duty; or economic waste; or gross misconduct, gross incompetence or gross inefficiency; or any condition that may significantly threaten the health or safety of employees or the public).  (An "improper governmental activity" has to directly involve the university as either the victim of the improper activity or the perpetrator of the improper activity via the action of an employee.)  The report can be submitted anonymously by calling 800-403-4744 or submitting a report online at http://universityofcalifornia.edu/hotline.  • Research Misconduct • http://www.research.uci.edu/ora/misconduct_FAQ.html • Research Misconduct is defined by federal law and University policy as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results. • Fabrication is making up data or results and recording or reporting them. • Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research records. • Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit. • If you suspect that research misconduct has occurred, contact the Research Integrity Officer (RIO) at (949) 824-5796 to submit an oral or written complaint.  If you are unsure whether a suspected incident falls within the definition of research misconduct, you may consult with the RIO to discuss the incident informally. • Office of the Ombudsman • http://www.ombuds.uci.edu/homepage.shtml • The Office of the Ombudsman provides a safe and comfortable environment to discuss complaints, concerns or problems confidentially.  The office is confidential, informal, and neutral.  To make an in person or telephone appointment, or if you have any questions, please contact the office at (949) 824-7256 or (714) 456-5605.

45. Resources • COI in Graduate Education FAQs http://www.grad.uci.edu/forms/faculty-and-staff/faq_coi.pdf • Conflict of Interest Office • http://www.research.uci.edu/ora/coi/index.htm • Grace Park, COIOC Administrator parkgj@uci.edu • Nadia Wong, COI Analyst nadiaw@uci.edu