Conflict of Interest – opportunities abound

1. Conflict of Interest – opportunities abound John Slattery, Ph.D. Vice Dean for Research and Graduate Education School of Medicine

2. More than theoretical… Risk Was Known as FDA OKd Fatal Drug Study New documents show Warner-Lambert trivialized liver toxicity of diabetes pill Rezulin while seeking federal approval. Inside help from senior regulators is trumpeted in company memos. Los Angeles Times March 11, 2001 Standing up to industry: As corporations increasingly hold their purse strings, many researchers feel pressed to deliver favorable results -- Baltimore Sun June 26, 2001 Drug testing under ethics microscope USA Today August 7, 2000 • The Scientist, May 28, 2001 • When Corporations Pay for Research: • UCSF researcher disputes trial results from drug company Standing up to industry: As corporations increasingly hold their purse strings, many researchers feel pressed to deliver favorable results -- Baltimore Sun June 26, 2001

3. Overview: Four Key Points Conflicts of interest are omnipresent. Conflicts of interest are not unethical per se. Managing conflicts of financial interest is part of research design process. Disclosure of interests promotes the public character of science and is the first step towards management of COI.

4. The Source of Conflict • Professional responsibility • To act in the interest of the client without regard to self interest • Personal gain • Is a result of the work we are doing • Comes in many ways • University salary • Forms of professional recognition • Companies or other interest • Equity, consulting income, etc.

5. “Traditional” Obvious COI’s • Self-dealing • Acting in dual roles that conflict • Ghostwriting, an academic accepting authorship of an article written by a company or company’s agent • Accepting gifts and personal benefits • Influence peddling • Personal use of another’s property • Personal use of another’s confidential information • Conflicting outside employment • “Revolving doors”

6. Defining “Conflicts of Financial Interest” Conflicts of financial interest occur “whenever financial considerations may have the potential to compromise or have the appearance of compromising an investigator’s professional judgment and independence in the design, conduct, or publication of research.” Public Health Service

7. Concerns • Our actions are not always deliberate • Avoid or manage conflicts • Sometimes they are • Avoid or manage conflicts • When they are, actual scientific misconduct is likely to have taken place • Falsification, fabrication (distortion) of the research record

8. Issues • Perceptions and appearances of COI play a major role • Public trust, confidence and support • Political factors • Press attention • Avoid risks of • Governmental audits and investigations • Civil liabilities • Damaging publicity • Higher standards of conduct in order to protect • Research integrity • Human subjects

9. The Appearance of a Conflict • Why it is important - • When something goes wrong and there is a COI, it will be named as the cause • Can destroy the value of the research • Erodes public support – financial or participation • Avoidance of legal liability

10. Investigators, including students, postdocs and others Staff in key roles Immediate family members of these individuals (e.g., spouse, children, siblings, parent, grandparents) Institution (including IRB members, officials) Whose Financial Interests are of Concern?

11. Salary, honoraria, consulting fees or other payments from sponsors. Stock, stock options, or other ownership interests. Intellectual property rights. Royalties from the University for work in the field of inquiry. What Financial Interests of Individuals are Relevant ?

12. Conflict of Interest Reviews • GENERAL OBJECTIVES – • Compliance with all applicable COI requirements • Prevent bias in research • Protect human subjects • Protect students/ trainees • Comply with Washington State ethics act, including not engaging in appropriate use of UW and state resources

13. UW COI Reviews • Disclosure Thresholds • 100 disclosures/year (70 in SOM) – recent declines • Management plan (self or active) • Disclosure – IRB, publication, researchers • Protection of human subjects • Research integrity (data and design) • Open publication • Startup and intellectual property situations • Oversight • Coordination with IRB • Coordination with outside employment reviews

14. Disclosure thresholds Clinical trials: Any financial interest Other human subjects Financial interest exceeding $5,000 Any equity interest Any intellectual property interest All other Financial interest (compensation or equity and IP interest) exceeding $10,000 Any equity interest exceeding 5% ownership of a single entity UW COI Reviews

15. UW COI Process • GIM 10 (http://www.washington.edu/research/gcs/gim/gim10.html) • SFI Disclosure Form – submitted with GC-1 • Upon informal notice of funding – • Initial review and recommendation by SOM’s RGE/IRO • Final decision/closing letter – Vice Provost for Research • Development of management plan • Use of committees in complex or policy issue cases • Copy of closing letter to IRB • 2 to 4 weeks, more if complex or involving policy issues • Related questions on IRB application

16. Management Tools • Modification of financial interest • Compliance with other processes • Restrictions on role in data generation • Safeguarding data • Changes to research plan • Other restrictions in research role • Limitations on recruitment/consenting • Changes in research agreement • Independent advisory board • Independent Co-PI’s • Pre-publication review of manuscripts • Divestiture

17. Management Plans • Disclosure – the primary requirement • Self-Management • Relies on voluntary investigator compliance • Appropriate for lesser interests, low-risk situations • Active Management • Continuing oversight and reporting • Specific measures tailored to the needs of the case • Attention to data generation, analysis and safeguarding • Human subjects protections • Intellectual property and startup relationships • Outside employment • Compliance with other institutional processes

18. Principles and Practices at the UW • Disclosure of Financial Interests • Journal editors and conference organizers • Other researchers • Staff and students • Sponsors • IRB’s • Human subjects

19. Principles and Practices at the UW • Protecting Human Subjects and Students • Restrictions on recruitment and consenting • IRB’s advised of financial interests and review results • IRB’s have independent authority • Protection of student academic activities from commercial exploitation

20. Principles and Practices at the UW • Research Integrity/Open Publication • Safeguarding data generation and analysis • Research data and results available for usual and customary public review • Only minor restrictions allowed on publication of results of industry-sponsored research

21. Principles and Practices at the UW • Startup Companies • Startup situations reviewed most intensively • Cannot be researcher on clinical trial sponsored by researcher’s startup company • Cannot be researcher on clinical trial sponsored by company in which researcher is a director or officer

22. Principles and Practices at the UW • Intellectual Property • IP situations reviewed more intensively • Researcher involvement in industry-sponsored research is re-reviewed if that research leads to licensing negotiations • Special oversight committees are regularly appointed in cases involving intellectual property, student researchers, and the potential for inappropriate use of state property

23. Principles and Practices at the UW • General Ethics • No participation in contract or license negotiations • Outside employment reporting (Form 1460) • No overlap with outside employment • Oversight for complex or higher risk situations

24. Licensing Activities Spur Additional Review… • Researchers with financial interests are not allowed to participate in negotiating the terms and conditions of contracts or licenses involving the University. • Researcher involvement in industry-sponsored research is re-reviewed if that research leads to licensing negotiations. • Special oversight committees are appointed in cases involving intellectual property, student researchers, and the potential for inappropriate use of state property. • University does not do clinical trials on its own technologies.

25. Summary… Handling conflicts of interest is not about who’s good or bad. It is about making design and staff decisions that protect and enhance the credibility of research. Recognize and avoid temptations that lead to inappropriate practice or actual misconduct. Disclosure and management are the key. IRBs and Conflict of Interest Reviewers play, separate but related, sequential roles.