Conflicts of Interest in Conflicts of Interest in ResearchResearch::

Perspective of the IRB Perspective of the IRB Human Subject ProtectionsHuman Subject Protections

Monika S. Markowitz, PhDMonika S. Markowitz, PhDDirector, Office of Research Compliance and Director, Office of Research Compliance and

EducationEducationChair, Conflict of Interests CommitteeChair, Conflict of Interests Committee

Vice President’s Office for ResearchVice President’s Office for Research

Financial Interests/Relationships Financial Interests/Relationships may lead to Conflicts of Interestmay lead to Conflicts of Interest

Holding financial interests is not inherently ‘wrong’Holding financial interests is not inherently ‘wrong’ COI:COI: A set of conditions in which an investigator’s A set of conditions in which an investigator’s

judgment concerning a primary interest (e.g. judgment concerning a primary interest (e.g. subject welfare, integrity of the research) could be subject welfare, integrity of the research) could be biased by a secondary interest (e.g. personal or biased by a secondary interest (e.g. personal or financial gain). financial gain).

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - The COIC fosters research integrity on behalf of The COIC fosters research integrity on behalf of

the universitythe university The IRB ensures that subject protections are not The IRB ensures that subject protections are not

compromised by conflicts of interestcompromised by conflicts of interest

Unmanaged financial interests may be Unmanaged financial interests may be implicated in subject harmimplicated in subject harm

Case of Jesse GelsingerCase of Jesse Gelsinger – 1999 – 199919 years old, metabolic disorder (OTC deficiency)19 years old, metabolic disorder (OTC deficiency)

Gene transfer studyGene transfer study

Died of massive organ failureDied of massive organ failure

Allegations of conflicts of interest against research Allegations of conflicts of interest against research team and universityteam and university

No causal relationship established, but a remaining No causal relationship established, but a remaining suspicion that money clouded judgmentsuspicion that money clouded judgment

Underlying Principles for COI Underlying Principles for COI Consideration by the IRBConsideration by the IRB

Respect for personsRespect for persons Beneficence Beneficence Belmont PrinciplesBelmont Principles

JusticeJustice

These should not be compromised by These should not be compromised by financial relationships that comprise financial relationships that comprise conflicts of interestconflicts of interest

What do federal regulations for What do federal regulations for IRBs say about COI?IRBs say about COI?

§46.107 IRB membership§46.107 IRB membership

(e) No IRB may have a member (e) No IRB may have a member participate in the IRB's initial or participate in the IRB's initial or continuing review of any project in continuing review of any project in which the member has a which the member has a conflicting conflicting interestinterest, except to provide information , except to provide information requested by the IRB.requested by the IRB.

However…However…

……Reasonable inferences abut COI Reasonable inferences abut COI from regulationsfrom regulations

§46.111/56.111§46.111/56.111 Criteria for IRB approval of research. 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§46.116/50.20 General requirements for informed General requirements for informed consent.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.

What does AAHRPP say about COI?What does AAHRPP say about COI?

Domain I – OrganizationDomain I – Organization

Standard I.3.GStandard I.3.G

The Organization has and follows written The Organization has and follows written policies and procedures to identify, manage, policies and procedures to identify, manage, and minimize individual conflicts of interest and minimize individual conflicts of interest of investigators. The Organization works of investigators. The Organization works with the IRB regarding conflicts of interest, with the IRB regarding conflicts of interest, when appropriate.when appropriate.

Minimizing/Managing Conflicts of Minimizing/Managing Conflicts of Interest at VCU: Interest at VCU: ProcessProcess

Completed COI Reporting Form sent to VCU Conflict of Completed COI Reporting Form sent to VCU Conflict of Interests Committee (COIC) – no monetary threshold for Interests Committee (COIC) – no monetary threshold for financial interests related to human subjects researchfinancial interests related to human subjects research

Based on investigator’s report (extent of relationship, Based on investigator’s report (extent of relationship, assessment of relatedness, involvement in other similar assessment of relatedness, involvement in other similar activities in the past), COIC makes a determination: activities in the past), COIC makes a determination: via via expedited review and/or full COIC determinationexpedited review and/or full COIC determination

Determination reported to Sponsored Programs AND/OR Determination reported to Sponsored Programs AND/OR to IRB (VCU and WIRB). Latter report includes more info to IRB (VCU and WIRB). Latter report includes more info and recommendations for further IRB action, if any. and recommendations for further IRB action, if any.

Review by the IRB may be concurrent, however, IRB Review by the IRB may be concurrent, however, IRB approval is not final until IRB reviewers consider the approval is not final until IRB reviewers consider the COIC determination and whether further actions apply.COIC determination and whether further actions apply.

Minimizing or managing conflicts – Minimizing or managing conflicts – examples from COICexamples from COIC

Disclosure of financial interest in publications, Disclosure of financial interest in publications, presentations and to involved students/traineespresentations and to involved students/trainees

PI is removed from portions or all of the PI is removed from portions or all of the investigator roleinvestigator role

Oversight of research by non-conflicted faculty Oversight of research by non-conflicted faculty member in Schoolmember in School

Data monitoring committeeData monitoring committee Remove self from financial interest during the Remove self from financial interest during the

researchresearch

Attitudes/views about COI in research – 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 Weinfurt, Friedman, et al J. of Law, Medicine and Ethics, 2006, J. of Law, Medicine and Ethics, 2006, 3434: 581-91: 581-91

Survey of 300 research coordinators. Almost ½ disclose Survey of 300 research coordinators. Almost ½ disclose financial interests to potential participants. Comfort in disclosing financial interests to potential participants. Comfort in disclosing is related to research experience. ICF is not the source of info is related to research experience. ICF is not the source of info about financial interest for most. Many responded that they about financial interest for most. Many responded that they don’t have enough info about financial interests to answer don’t have enough info about financial interests to answer participant questions. participant questions.

Friedman, Sugarman, et al Friedman, Sugarman, et al Clinical Trials, 2007, Clinical Trials, 2007, 44: 272-8: 272-8

Attitudes/views about COI in Attitudes/views about COI in research: participantsresearch: 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 Kim, Millard, et al J Medical Ethics 2009; J Medical Ethics 2009; 3030: 73-9: 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 Weinfurt, Friedman, et al J Gen Intern Med. 2006; J Gen Intern Med. 2006; 2121: 901-6: 901-6

Removing or minimizing conflicts of Removing or minimizing conflicts of interest to better protect subjectsinterest to better protect subjects

Disclosure of financial interests in Disclosure of financial interests in informed consent form – informed consent form – may not be may not be enough to decrease the risks to subjectsenough to decrease the risks to subjects

In addition to ICF disclosure,In addition to ICF disclosure,questions for IRB considerationquestions for IRB consideration

Under what circumstances, if any, should a Under what circumstances, if any, should a conflicted individual be allowed to participate in:conflicted individual be allowed to participate in:

Subject recruitment?Subject recruitment? Subject selection, including prescreening for Subject selection, including prescreening for

inclusion/exclusion criteria?inclusion/exclusion criteria? The consent process?The consent process? Clinical treatment of subjects, separate from the Clinical treatment of subjects, separate from the

research interventions or procedures?research interventions or procedures? Clinical evaluation of subjects during the research, Clinical evaluation of subjects during the research,

separate from research interventions or procedures, separate from research interventions or procedures, including adverse evaluation and reporting?including adverse evaluation and reporting?

From: AAU From: AAU Association of American Universities Association of American Universities AAMC AAMC Association of American Medical Colleges - Letter to NIHAssociation of American Medical Colleges - Letter to NIH

VCU Resources about VCU Resources about Researcher COIResearcher COI

VCU VCU Researcher Conflict of Interests PolicyResearcher Conflict of Interests Policyhttp://http://www.research.vcu.edu/p_and_g/coi_research.htmwww.research.vcu.edu/p_and_g/coi_research.htm

IRB Written Policy and Procedure (WPP) VIII-10IRB Written Policy and Procedure (WPP) VIII-10 Evaluating Investigator Potential Conflicts of InterestEvaluating Investigator Potential Conflicts of Interesthttp://www.research.vcu.edu/irb/wpp/flash/wpp_guide.htm#VIII-10.htmhttp://www.research.vcu.edu/irb/wpp/flash/wpp_guide.htm#VIII-10.htm

Coming soon:Coming soon:-Modified COI Reporting and Supplement FormsModified COI Reporting and Supplement Forms-COI websiteCOI websiteANDAND

What about institutional COI?What about institutional COI?

The ‘elephant in the room’The ‘elephant in the room’

An institutional COI may exist whenever An institutional COI may exist whenever the financial interests of the institution, or the financial interests of the institution, or of institutional officials acting on behalf of of institutional officials acting on behalf of the institution, (reasonably) affect the institution, (reasonably) affect institutional processes for the design, institutional processes for the design, conduct, reporting, review, or oversight of conduct, reporting, review, or oversight of human subjects research.human subjects research.