1. Conflicts of Interest in Research : Perspective of the IRB Human Subject Protections Monika S. Markowitz, PhD Director, Office of Research Compliance and Education Chair, Conflict of Interests Committee Vice President’s Office for Research

2. Financial Interests/Relationships may lead to Conflicts of Interest  Holding financial interests is not inherently ‘wrong’  COI: A set of conditions in which an investigator’s judgment concerning a primary interest (e.g. subject welfare, integrity of the research) could be biased by a secondary interest (e.g. personal or financial gain). - - - - - - - - - - - - - - -  The COIC fosters research integrity on behalf of the university  The IRB ensures that subject protections are not compromised by conflicts of interest

3. Unmanaged financial interests may be implicated in subject harm  Case of Jesse Gelsinger – 1999 19 years old, metabolic disorder (OTC deficiency) Gene transfer study Died of massive organ failure Allegations of conflicts of interest against research team and university No causal relationship established, but a remaining suspicion that money clouded judgment

4. Underlying Principles for COI Consideration by the IRB  Respect for persons  Beneficence Belmont Principles  Justice These should not be compromised by financial relationships that comprise conflicts of interest

5. What do federal regulations for IRBs say about COI? §46.107 IRB membership (e) No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB. However…

6. …Reasonable inferences abut COI from regulations §46.111/56.111 Criteria for IRB approval of research. (a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied: (1) Risks to subjects are minimized (2) Risks to subjects are reasonable in relation to anticipated benefits §46.116/50.20 General requirements for informed consent. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.

7. What does AAHRPP say about COI? Domain I – Organization Standard I.3.G  The Organization has and follows written policies and procedures to identify, manage, and minimize individual conflicts of interest of investigators. The Organization works with the IRB regarding conflicts of interest, when appropriate.

8. Minimizing/Managing Conflicts of Interest at VCU: Process  Completed COI Reporting Form sent to VCU Conflict of Interests Committee (COIC) – no monetary threshold for financial interests related to human subjects research  Based on investigator’s report (extent of relationship, assessment of relatedness, involvement in other similar activities in the past), COIC makes a determination: via expedited review and/or full COIC determination  Determination reported to Sponsored Programs AND/OR to IRB (VCU and WIRB). Latter report includes more info and recommendations for further IRB action, if any.  Review by the IRB may be concurrent, however, IRB approval is not final until IRB reviewers consider the COIC determination and whether further actions apply.

9. Minimizing or managing conflicts – examples from COIC  Disclosure of financial interest in publications, presentations and to involved students/trainees  PI is removed from portions or all of the investigator role  Oversight of research by non-conflicted faculty member in School  Data monitoring committee  Remove self from financial interest during the research

10. Attitudes/views about COI in research –   Focus group of IRB/COIC Chairs, Investigators: Most frequent rationale for disclosing financial interests in ICF is enabling informed decision making about enrollment. Agreement about disclosing early in IC process and about naming sponsor. Disagreement about disclosing amount. Weinfurt, Friedman, et al J. of Law, Medicine and Ethics, 2006, 34: 581-91 Weinfurt, Friedman, et al J. of Law, Medicine and Ethics, 2006, 34: 581-91  Survey of 300 research coordinators. Almost ½ disclose financial interests to potential participants. Comfort in disclosing is related to research experience. ICF is not the source of info about financial interest for most. Many responded that they don’t have enough info about financial interests to answer participant questions. Friedman, Sugarman, et al Clinical Trials, 2007, 4: 272-8 Friedman, Sugarman, et al Clinical Trials, 2007, 4: 272-8

11. Attitudes/views about COI in research: participants   Most potential participants want to be informed (and believe this should be required) about financial interests even while still wanting to participate in the research. Kim, Millard, et al J Medical Ethics 2009; 30: 73-9 Kim, Millard, et al J Medical Ethics 2009; 30: 73-9   Focus groups: Many participants want to know about financial interests in research, but great variability in desire, and aptitude, to understand nature and implication of financial interests. Weinfurt, Friedman, et al J Gen Intern Med. 2006; 21: 901-6 Weinfurt, Friedman, et al J Gen Intern Med. 2006; 21: 901-6

12. Removing or minimizing conflicts of interest to better protect subjects  Disclosure of financial interests in informed consent form – may not be enough to decrease the risks to subjects

13. In addition to ICF disclosure, questions for IRB consideration Under what circumstances, if any, should a conflicted individual be allowed to participate in:  Subject recruitment?  Subject selection, including prescreening for inclusion/exclusion criteria?  The consent process?  Clinical treatment of subjects, separate from the research interventions or procedures?  Clinical evaluation of subjects during the research, separate from research interventions or procedures, including adverse evaluation and reporting? From: AAU Association of American Universities AAMC Association of American Medical Colleges - Letter to NIH

14. VCU Resources about Researcher COI  VCU Researcher Conflict of Interests Policy http://www.research.vcu.edu/p_and_g/coi_research.htm http://www.research.vcu.edu/p_and_g/coi_research.htm  IRB Written Policy and Procedure (WPP) VIII-10 Evaluating Investigator Potential Conflicts of Interest http://www.research.vcu.edu/irb/wpp/flash/wpp_guide.htm#VIII-10.htm Coming soon: - Modified COI Reporting and Supplement Forms - COI website AND

15. What about institutional COI?  The ‘elephant in the room’  An institutional COI may exist whenever the financial interests of the institution, or of institutional officials acting on behalf of the institution, (reasonably) affect institutional processes for the design, conduct, reporting, review, or oversight of human subjects research.