USF Health Conflict of Interest Committee New Member Orientation

USF Health USF Health Conflict of InterestConflict of Interest

CommitteeCommittee

New Member New Member OrientationOrientation

VOTING MEMBERSVOTING MEMBERS

At least:At least:

1 faculty member representing each of the USF Health 1 faculty member representing each of the USF Health Core facilities. Core facilities.

COM: Anthony Morrison, Robert Hauser, Bill COM: Anthony Morrison, Robert Hauser, Bill Marshall, Richard Heller, Barry BercuMarshall, Richard Heller, Barry Bercu

CON: Mary Evans, Maureen Groer (alternate)CON: Mary Evans, Maureen Groer (alternate) COPH: John LargeCOPH: John Large

Who’s on the USF Health COI Who’s on the USF Health COI Committee?Committee?

Who’s on the USF Health COI Who’s on the USF Health COI Committee? (con’t)Committee? (con’t)

VOTING MEMBERSVOTING MEMBERS (con’t) (con’t)

1 faculty member from the College of Arts and Sciences.1 faculty member from the College of Arts and Sciences.

CAS: Stefan FrischCAS: Stefan Frisch

2 faculty member clinicians who conduct human subjects 2 faculty member clinicians who conduct human subjects research.research.

Anthony Morrison, Robert Hauser, Barry BercuAnthony Morrison, Robert Hauser, Barry Bercu

1 faculty member who conducts basic sciences research.1 faculty member who conducts basic sciences research.

Richard Heller, Bill MarshallRichard Heller, Bill Marshall


VOTING MEMBERSVOTING MEMBERS (con’t) (con’t)

1 representative affiliated with the USF IRB (recused from 1 representative affiliated with the USF IRB (recused from voting on institutional conflicts of interest in research voting on institutional conflicts of interest in research involving human subjects).involving human subjects).

Barry Bercu, Paul Stiles (alternate)Barry Bercu, Paul Stiles (alternate)

1 community representative.1 community representative.

Richard OliverRichard Oliver

Others? An ethicist?Others? An ethicist?


EX OFFICIO MEMBERS (NON-VOTING)EX OFFICIO MEMBERS (NON-VOTING)

A representative from the USF Health Office of Research.A representative from the USF Health Office of Research.

Phil MartyPhil Marty

The USF Health Conflict of Interest in Research Program The USF Health Conflict of Interest in Research Program Administrator.Administrator.

Camille McWhirterCamille McWhirter


EX OFFICIO (NON-VOTING)EX OFFICIO (NON-VOTING)

The Director of the USF Health Office of Faculty Affairs.The Director of the USF Health Office of Faculty Affairs.

Olga JoanowOlga Joanow

The Office of Research Conflict of Interest in Research The Office of Research Conflict of Interest in Research Program Administrator.Program Administrator.

Vinita WitanachchiVinita Witanachchi


EX OFFICIO (NON-VOTING)EX OFFICIO (NON-VOTING)

A representative from the Office of Research, Division of A representative from the Office of Research, Division of Sponsored Research.Sponsored Research.

Liz O’ConnellLiz O’Connell

A representative from the Office of the General Counsel.A representative from the Office of the General Counsel.

Megan Pritts, R.B. Friedlander (alternate)Megan Pritts, R.B. Friedlander (alternate)

Ad Hoc: A representative from any affiliate for whom the Ad Hoc: A representative from any affiliate for whom the Committee reviews a COI disclosure. Committee reviews a COI disclosure.

Point of ClarificationPoint of Clarification

There are There are twotwo COI committees (and two COI committees (and two COI policies) at USF:COI policies) at USF:

USF Health Conflict of Interest CommitteeUSF Health Conflict of Interest Committee USF Conflict of Interest in Research USF Conflict of Interest in Research

CommitteeCommittee

USF Health Conflict of Interest USF Health Conflict of Interest CommitteeCommittee

Reviews disclosures for all human subjects Reviews disclosures for all human subjects research (regardless of the origin) research (regardless of the origin)

Reviews disclosures for research Reviews disclosures for research conducted by employees of USF Healthconducted by employees of USF Health

50/50 expedited/full committee reviews50/50 expedited/full committee reviews COI Administrator: Camille McWhirterCOI Administrator: Camille McWhirter

USF Committee for Conflicts of USF Committee for Conflicts of Interest in ResearchInterest in Research

Resides within the USF Office of Research, Resides within the USF Office of Research, Division of Research Integrity and Division of Research Integrity and Compliance Compliance

Reviews disclosures (for non-human Reviews disclosures (for non-human subjects research) for the rest of the subjects research) for the rest of the University system University system

Primarily expedited reviewsPrimarily expedited reviews COI Administrator: Vinita WitanachchiCOI Administrator: Vinita Witanachchi

What Does the USF Health COI What Does the USF Health COI Committee Do?Committee Do?

Primary Mission:Primary Mission:

To To reviewreview disclosures/management plans disclosures/management plans of USF Health employee investigators and of USF Health employee investigators and those conducting human subjects those conducting human subjects research; research; andand

To To ensureensure (by imposing appropriate (by imposing appropriate management controls) that the disclosing management controls) that the disclosing investigator’s financial interests will not investigator’s financial interests will not bias the design, conduct or reporting of bias the design, conduct or reporting of the research project. the research project.

Also, the Committee…Also, the Committee…

Implements, oversees and enforces the Implements, oversees and enforces the USF Health Conflict of Interest and USF Health Conflict of Interest and Commitment policyCommitment policy

In cooperation with the USF IRB, considers In cooperation with the USF IRB, considers conflicts of interest that might affect the conflicts of interest that might affect the relationship with human subjects relationship with human subjects participants in research or the outcome of participants in research or the outcome of the research, and manages such conflicts.the research, and manages such conflicts.

And the Committee And the Committee WillWill Be… Be…

Monitoring the management of Monitoring the management of identified conflicts of interest in identified conflicts of interest in research during the conduct of the research during the conduct of the research.research.

Assisting the Vice President for USF Assisting the Vice President for USF Health as needed in tasks related to Health as needed in tasks related to conflicts of interest in research.conflicts of interest in research.

And May Eventually Be…And May Eventually Be…

Participating in discussion and the Participating in discussion and the development of policy on conflicts of development of policy on conflicts of interest in general…not related to interest in general…not related to research.research.

Acting as a resource upon request in Acting as a resource upon request in the review of situations involving the review of situations involving conflicts of interest with University conflicts of interest with University employment and conflicts of employment and conflicts of commitmentcommitment

A COI Committee Member Should A COI Committee Member Should Be Able To:Be Able To:

Define a conflict of interestDefine a conflict of interest Identify potential conflicts of interest Identify potential conflicts of interest

in research situationsin research situations Be familiar with the process for COI Be familiar with the process for COI

review at USFreview at USF Differentiate between an institutional Differentiate between an institutional

and an individual COIand an individual COI

Identify the three government agencies Identify the three government agencies who have rules regulating COI in who have rules regulating COI in researchresearch

Understand when each agency’s rules Understand when each agency’s rules applyapply

Define a “significant financial interest” Define a “significant financial interest” for each agency that regulates COIfor each agency that regulates COI

Understand some general principles and Understand some general principles and concepts in dealing with COIconcepts in dealing with COI

Understand the procedure for review of Understand the procedure for review of a disclosure under USF Health policya disclosure under USF Health policy

Identify some special considerations in Identify some special considerations in dealing with human subjects researchdealing with human subjects research

Identify some management controls for Identify some management controls for dealing with COIdealing with COI

Bonus: Explain the significance of the Bonus: Explain the significance of the Bayh-Dole ActBayh-Dole Act

Definition and Types of Self-Definition and Types of Self-InterestInterest

Conflict of InterestConflict of Interest - - A conflict of interest A conflict of interest exists when professional or ethical obligations exists when professional or ethical obligations may be compromised by self-interest. Self-may be compromised by self-interest. Self-interest could manifest in the form of interest could manifest in the form of

A financial benefitA financial benefit Enhanced reputationEnhanced reputation Personal relationshipsPersonal relationships Professional relationshipsProfessional relationships Other interests (political, religious, Other interests (political, religious,

intellectual)intellectual)

Conflict of Interest in ResearchConflict of Interest in Research refers to refers to situations in which financial or other situations in which financial or other personal considerations may compromise, personal considerations may compromise, or have the appearance of compromising, or have the appearance of compromising, an Investigator's professional judgment in an Investigator's professional judgment in the conduct, evaluation or reporting of the conduct, evaluation or reporting of research. research.

Example: where an investigator has a Example: where an investigator has a financial or business interest related to the financial or business interest related to the research that would be affected by the research that would be affected by the outcome of the research. outcome of the research.

More DefinitionsMore Definitions

InvestigatorInvestigator - Any person responsible - Any person responsible for the design, conduct or reporting of for the design, conduct or reporting of research (includes extended family).research (includes extended family).Interested InvestigatorInterested Investigator - An - An Investigator who has a financial or Investigator who has a financial or other business interest that could other business interest that could reasonably be affected by a research reasonably be affected by a research study in which the Investigator is study in which the Investigator is participating. participating.

Some Noteworthy Points About Some Noteworthy Points About Our Policy at USF HealthOur Policy at USF Health

USF Health Policy (and most other university USF Health Policy (and most other university COI policies) focus on potential COI policies) focus on potential financial financial benefitsbenefits and the and the professional relationshipsprofessional relationships (but not other personal considerations, like (but not other personal considerations, like reputation) of investigators that create a reputation) of investigators that create a conflict of interest in research.conflict of interest in research.

(Why?)(Why?)

Noteworthy…Noteworthy…

USF Health Conflict of Interest and USF Health Conflict of Interest and Commitment Policy has a “zero Commitment Policy has a “zero threshold” requirement for the disclosure threshold” requirement for the disclosure of financial interests in a research study. of financial interests in a research study.

(This means that investigators must (This means that investigators must disclose their financial interests even if disclose their financial interests even if they do not rise to the level of a they do not rise to the level of a Significant Financial Interest.) Significant Financial Interest.)

Noteworthy…Noteworthy…

USF Health Conflict of Interest and USF Health Conflict of Interest and Commitment Policy states as a Commitment Policy states as a rebuttable presumption that rebuttable presumption that interested investigators may not interested investigators may not conduct human subjects research.conduct human subjects research.

The presumption must be overcome The presumption must be overcome by “compelling circumstances”.by “compelling circumstances”.

Yet Another Definition…Yet Another Definition…

Compelling CircumstancesCompelling Circumstances (paraphrased):(paraphrased):

Any circumstances that convince the Any circumstances that convince the COI Committee that the interested COI Committee that the interested investigator investigator shouldshould be able to be able to conduct the research.conduct the research.

(More on that later….)(More on that later….)

COI Review ProcessCOI Review Process1.1. Investigator becomes associated with a Investigator becomes associated with a

research proposal in which the research proposal in which the investigator has a financial or business investigator has a financial or business interest related to the research.interest related to the research.

2.2. Investigator recognizes that his or her Investigator recognizes that his or her financial interest in the research may financial interest in the research may create an actual or potential conflict of create an actual or potential conflict of interest.interest.

3.3. Investigator completes the Investigator completes the Financial Financial Interests Disclosure Form.Interests Disclosure Form.

4.4. Investigator submits completed form to Investigator submits completed form to supervisor for review and signature.supervisor for review and signature.

6.6. Supervisor routes form to the Supervisor routes form to the appropriate office based on certain appropriate office based on certain criteria (e.g., sponsored or non-criteria (e.g., sponsored or non-sponsored, COM or not COM).sponsored, COM or not COM).

7.7. The appropriate office routes the The appropriate office routes the form to the USF Health COI form to the USF Health COI Administrator.Administrator.

8.8. COI Administrator reviews form for COI Administrator reviews form for adequacy, contacts investigator to adequacy, contacts investigator to acknowledge receipt, obtain any acknowledge receipt, obtain any add’tl info needed, and advise as to add’tl info needed, and advise as to timeframe for review.timeframe for review.

9.9. If disclosure qualifies for expedited If disclosure qualifies for expedited review, COI Administrator will review review, COI Administrator will review and approve or develop an and approve or develop an appropriate management plan in appropriate management plan in cooperation with the investigator cooperation with the investigator based on similar disclosures with based on similar disclosures with existing approved management existing approved management plans.plans.

10.10. If the disclosure does not qualify for If the disclosure does not qualify for expedited review (e.g., involves expedited review (e.g., involves human subjects), the COI human subjects), the COI Administrator will forward the Administrator will forward the disclosure for review by the COI disclosure for review by the COI Committee. Committee.

11.11. The COI Committee will review the The COI Committee will review the disclosure and determine whether the disclosure and determine whether the conflict is subject to management and if conflict is subject to management and if so, develop and approve a management so, develop and approve a management plan.plan.

12.12. If the research involves HSR, the COI If the research involves HSR, the COI Administrator will notify the investigator Administrator will notify the investigator and any other appropriate parties of the and any other appropriate parties of the COI Committee’s decision and will forward COI Committee’s decision and will forward the disclosure, management plan and the disclosure, management plan and related documents to the IRB for review related documents to the IRB for review at its next meeting. at its next meeting.

13.13. If the research does not involve HSR, the If the research does not involve HSR, the COI Administrator will notify the COI Administrator will notify the investigator and any other appropriate investigator and any other appropriate parties of the COI Committee’s decision. parties of the COI Committee’s decision.

Individual vs. Institutional COIIndividual vs. Institutional COI

What is an What is an individualindividual conflict of conflict of interest?interest?

A conflict that may influence the A conflict that may influence the individual’sindividual’s ability to act impartially, such ability to act impartially, such as having a financial interest in an entity as having a financial interest in an entity related to the research.related to the research.

Individual vs. Institutional COIIndividual vs. Institutional COI

What is an What is an institutionalinstitutional conflict of conflict of interest?interest?

A conflict that may influence the A conflict that may influence the institution’sinstitution’s ability to act impartially. These types of ability to act impartially. These types of conflicts occur when an institution’s financial conflicts occur when an institution’s financial or other interests may affect how it reviews or other interests may affect how it reviews or conducts research. Must also consider or conducts research. Must also consider the financial interests of institutional officials the financial interests of institutional officials as an institutional conflict.as an institutional conflict.

Bayh-Dole Act (Patent & Bayh-Dole Act (Patent & Trademark Act Amendments of Trademark Act Amendments of

19801980 ) )Pre Bayh-Dole:Pre Bayh-Dole:

Federal government owns and licenses Federal government owns and licenses technology coming out of federal support. technology coming out of federal support. (But studies showed that only 2% of federally (But studies showed that only 2% of federally sponsored technology made it to the market!)sponsored technology made it to the market!)

Bayh-Dole represented a fundamental change Bayh-Dole represented a fundamental change in federal government outlook on IP. It gave in federal government outlook on IP. It gave universities and inventors incentive to transfer universities and inventors incentive to transfer the benefits of scientific research to the benefits of scientific research to commercial applications for public benefit.commercial applications for public benefit.

Bayh Dole Act (1980, 1982)Bayh Dole Act (1980, 1982)

Post Bayh-Dole:Post Bayh-Dole:

Funding agencies can assign IP rights Funding agencies can assign IP rights resulting from resulting from agency sponsored research to agency sponsored research to the academic the academic institution. institution.

Academic institutions are encouraged to Academic institutions are encouraged to license IP license IP to for-profit entities for development to for-profit entities for development and and commercialization.commercialization.

Federal government retains the non-Federal government retains the non-exclusive, exclusive, royalty free right to use the results for royalty free right to use the results for government government purposes.purposes.

BUT…BUT…

Bayh-Dole has complicated Bayh-Dole has complicated relationships between researchers, relationships between researchers, research institutions and commercial research institutions and commercial businesses.businesses.

Regulatory FrameworkRegulatory Framework There is widespread debate but no real There is widespread debate but no real

consensus on the best way to handle consensus on the best way to handle conflicts of interest. Consequently, there conflicts of interest. Consequently, there are no universal or government-wide are no universal or government-wide regulations covering them.regulations covering them.

Most institutions today have their own Most institutions today have their own policies and procedures for managing policies and procedures for managing conflicts of interest, and those policies conflicts of interest, and those policies may differ from one institution to another.may differ from one institution to another.

In addition, a number of government In addition, a number of government agencies and professional organizations agencies and professional organizations have established their own conflict of have established their own conflict of interest guidelines.interest guidelines.

Federal RegulationsFederal Regulations

Food and Drug AdministrationFood and Drug Administration - Applies in - Applies in research involving a drug, device or biologic. research involving a drug, device or biologic. Requires disclosure of certain financial interests Requires disclosure of certain financial interests of the investigator at the time of application for of the investigator at the time of application for approval of a drug device or biologic. FDA will approval of a drug device or biologic. FDA will evaluate the impact of the researcher’s financial evaluate the impact of the researcher’s financial interests on the reliability of the study data. interests on the reliability of the study data.

Public Health Service Public Health Service & National Science Foundation& National Science Foundation - Require - Require institutions receiving grants from these agencies institutions receiving grants from these agencies to develop a COI policy that meets certain to develop a COI policy that meets certain minimum requirements while permitting flexibility minimum requirements while permitting flexibility in the administration of policy. PHS and NSF in the administration of policy. PHS and NSF regulations were developed cooperatively to regulations were developed cooperatively to make the regulations consistent.make the regulations consistent.

FDA RegulationsFDA Regulations

““Anyone who submits a marketing Anyone who submits a marketing application of any drug, biological application of any drug, biological product or device must submit certain product or device must submit certain information concerning compensation information concerning compensation to, and financial interests of, any to, and financial interests of, any clinical investigator conducting studies clinical investigator conducting studies covered by this rule.”covered by this rule.”

21 CFR Part 5421 CFR Part 54

What is Significant to the FDA?What is Significant to the FDA? Significant equity interestSignificant equity interest means means

any ownership interest, stock options, or other any ownership interest, stock options, or other financial interest whose value cannot be readily financial interest whose value cannot be readily determined via reference to public pricesdetermined via reference to public prices

any equity interest in a publicly traded any equity interest in a publicly traded corporation that exceeds corporation that exceeds $50,000$50,000 during the during the time the investigator is carrying out the study and time the investigator is carrying out the study and for 1 year following completion of the study. for 1 year following completion of the study.

Significant payments of other sortsSignificant payments of other sorts means means payments made to the investigator (or the payments made to the investigator (or the

institution to support activities of the investigator) institution to support activities of the investigator) of more than of more than $25,000$25,000 during the time the clinical during the time the clinical investigator is carrying out the study and for 1 investigator is carrying out the study and for 1 year following the completion of the study. year following the completion of the study.


Applicant must Applicant must EITHEREITHER certify that: certify that:

• No financial arrangements have been No financial arrangements have been made with an INV where study outcome made with an INV where study outcome could affect compensation.could affect compensation.

• INV has no proprietary interest in the INV has no proprietary interest in the tested product.tested product.

• INV does not have significant equity in INV does not have significant equity in sponsor and sponsor has not made sponsor and sponsor has not made significant payments of other sorts to INV significant payments of other sorts to INV or to institution on behalf of INVor to institution on behalf of INV


OROR

Disclose the specified financial arrangement Disclose the specified financial arrangement and any steps taken to minimize the and any steps taken to minimize the potential for bias.potential for bias.

Then, FDA will determine whether conflicting Then, FDA will determine whether conflicting interest could jeopardize the integrity of the interest could jeopardize the integrity of the study. Such a determination can result in study. Such a determination can result in severe delays and significant financial losses. severe delays and significant financial losses. So….institutions are doing it for themselves. So….institutions are doing it for themselves.

Potential FDA ActionsPotential FDA Actions

If the FDA is concerned about the If the FDA is concerned about the conflict, the FDA can:conflict, the FDA can:

• Audit the data derived from the INV in Audit the data derived from the INV in questionquestion

• Request further data analysis to Request further data analysis to evaluate the effect of the INV data on evaluate the effect of the INV data on overall resultsoverall results

• Request additional independent Request additional independent studiesstudies

• Refuse to use the data to support an Refuse to use the data to support an FDA actionFDA action

PHS/NSF COI RegulationsPHS/NSF COI Regulations

Investigator ResponsibilitiesInvestigator Responsibilities::

Must disclose any Must disclose any ““significant financial significant financial interests” interests”

(including those of spouse and dependent (including those of spouse and dependent children) children)

that would reasonably appear to be affected that would reasonably appear to be affected by the research by the research

to a designated institutional official to a designated institutional official by the time the application is submitted to by the time the application is submitted to

PHS/NSF.PHS/NSF.

What is Significant to NSF/NIH?What is Significant to NSF/NIH?

Significant Financial InterestSignificant Financial Interest means anything of monetary means anything of monetary value, including salary, value, including salary, consulting fees or honoraria, consulting fees or honoraria, equity interests (stock, equity interests (stock, ownership interests) and ownership interests) and intellectual property rights.intellectual property rights.

EXCEPTIONS:EXCEPTIONS:

• Salary from your own institutionSalary from your own institution• Income from speaking engagements Income from speaking engagements

sponsored by government or non-sponsored by government or non-profitprofit

• Income from advisory boards of G or Income from advisory boards of G or NPNP

• Equity interest < Equity interest < $10,000$10,000 or or 5% 5% • Annual payments < Annual payments < $10,000$10,000

Footnote:Footnote:

The PHS/NSF regulations are broader:The PHS/NSF regulations are broader:

1.1. PHS/NSF covers PHS/NSF covers allall interests that interests that would reasonably be affected by would reasonably be affected by the research (not just income the research (not just income from or equity in the sponsor of from or equity in the sponsor of the research) the research) andand

2.2. The threshold is lower--$10,000 The threshold is lower--$10,000 (PHS/NIH) vs. $25,000 (FDA)(PHS/NIH) vs. $25,000 (FDA)

PHS/NSF COI RegulationsPHS/NSF COI Regulations

Institutional ResponsibilitiesInstitutional Responsibilities::

Written enforced policies on COIWritten enforced policies on COIDesignated institutional official to review COIDesignated institutional official to review COIRequire that each investigator submits a Require that each investigator submits a

disclosure form for PHS and NSF research disclosure form for PHS and NSF research annuallyannually

Provide guidelines to review and manage COIProvide guidelines to review and manage COIMaintain records for 3 yearsMaintain records for 3 yearsEstablish enforcement mechanisms and sanctionsEstablish enforcement mechanisms and sanctionsReport failures to comply to awarding agencyReport failures to comply to awarding agency

Guidance DocumentsGuidance Documents

COI can be subtle and complex, often COI can be subtle and complex, often involving ethical issues beyond the involving ethical issues beyond the scope of regulation. Also, the scope of regulation. Also, the regulations that do exist are regulations that do exist are purposefully flexible in order to allow purposefully flexible in order to allow the institutions to apply them in the the institutions to apply them in the way that best suits the institution. So way that best suits the institution. So the regulations can often seem vague the regulations can often seem vague and open to interpretation.and open to interpretation.

Industry Guidance DocumentsIndustry Guidance Documents Consequently, a number of government Consequently, a number of government

agencies and national professional agencies and national professional associations have published guidance associations have published guidance documents to help individuals and documents to help individuals and institutions cope with conflict of interest institutions cope with conflict of interest issues. issues.

Among these organizations are the Among these organizations are the

American Medical Association (AMA), the American Medical Association (AMA), the Association of American Universities Association of American Universities (AAU), and the Association of American (AAU), and the Association of American Medical Colleges (AAMC).Medical Colleges (AAMC).

Summary of Industry GuidanceSummary of Industry Guidance

This presentation (and omitted This presentation (and omitted slides that summarize the industry slides that summarize the industry

recommendations for COI review) will recommendations for COI review) will be accessible on the USF COI be accessible on the USF COI

Committee Website.Committee Website.

General Principles General Principles in Dealing with COIin Dealing with COI

COI is virtually unavoidable.COI is virtually unavoidable. COI does not preclude participation of an COI does not preclude participation of an

investigator in a project, but investigator must investigator in a project, but investigator must show “compelling circumstances” to conduct show “compelling circumstances” to conduct HSRHSR

Must have a culture of honest and full Must have a culture of honest and full disclosure so that steps can be taken to disclosure so that steps can be taken to manage conflicts effectively. manage conflicts effectively.

Not all COI can be managed (and the more Not all COI can be managed (and the more restrictive measures are appropriate).restrictive measures are appropriate).

Useful Concepts in Committee Useful Concepts in Committee ReviewReview

MOTIVATION (Amount & Nature of MOTIVATION (Amount & Nature of Interest)Interest)

How much incentive does the INV have to bias How much incentive does the INV have to bias the design, conduct or reporting of the the design, conduct or reporting of the research?research?

OPPORTUNITY (Contacts with Research)OPPORTUNITY (Contacts with Research)

Is the INV in a position to bias the design, Is the INV in a position to bias the design, conduct or reporting of the research?conduct or reporting of the research?

Useful Concepts in Committee Useful Concepts in Committee ReviewReview

DIRECT EFFECTDIRECT EFFECT::

Outcome of research Outcome of research will be directly relevant will be directly relevant to the development, to the development, manufacturing or manufacturing or improvement of improvement of products or services of products or services of the business entity the business entity (secondary interest).(secondary interest).

SIGNIFICANT IMPACTSIGNIFICANT IMPACT: :

Value of business Value of business entity, earnings or entity, earnings or sales revenue will be sales revenue will be materially affected by materially affected by the outcome of the the outcome of the research.research.

Proposed Steps to Follow In Proposed Steps to Follow In Review of A DisclosureReview of A Disclosure

1.1. DO YOU HAVE ENOUGH INFORMATION DO YOU HAVE ENOUGH INFORMATION TO CONDUCT A MEANINGFUL REVIEW?TO CONDUCT A MEANINGFUL REVIEW?

A description of the research study.A description of the research study. A detailed description of the investigator’s A detailed description of the investigator’s

role in the research study (i.e., what aspects role in the research study (i.e., what aspects of the study are under the investigator’s of the study are under the investigator’s control)control)

The nature and amount of the investigator’s The nature and amount of the investigator’s financial interest or relationship.financial interest or relationship.

2.2. DOES THE STUDY INVOLVE HUMAN DOES THE STUDY INVOLVE HUMAN SUBJECTS?SUBJECTS?

If so, the Committee should not If so, the Committee should not allow an interested investigator to allow an interested investigator to participate unless the “compelling participate unless the “compelling circumstances” threshold is met. In circumstances” threshold is met. In other words, there is a rebuttable other words, there is a rebuttable presumption that the investigator presumption that the investigator may not conduct the research.may not conduct the research.

2.a.2.a. Is the “compelling Is the “compelling circumstances” circumstances” threshold met?threshold met?

FLASHBACKFLASHBACKCompelling CircumstancesCompelling Circumstances are are

circumstances that convince the COI circumstances that convince the COI Committee that the interested Committee that the interested investigator investigator shouldshould be able to conduct be able to conduct the research.the research.

Factors That Might Support Factors That Might Support “Compelling Circumstances”“Compelling Circumstances”

1.1. No significant connection between No significant connection between the research study and the the research study and the investigator’s financial interest,investigator’s financial interest,

THEREFORE, the investigator's THEREFORE, the investigator's financial involvement with the financial involvement with the business entity will not in any way business entity will not in any way affect or impair the conduct of the affect or impair the conduct of the research.research.

Factors That Might Support Factors That Might Support “Compelling Circumstances”“Compelling Circumstances”

2.2. There is a significant connection There is a significant connection between the research study and the between the research study and the investigator’s financial interest,investigator’s financial interest,

BUT, the interested investigator is BUT, the interested investigator is uniquely qualified by virtue of expertise uniquely qualified by virtue of expertise and experience and the research could not and experience and the research could not otherwise be conducted as safely or otherwise be conducted as safely or effectively without that individual…effectively without that individual…

AND, there are adequate AND, there are adequate mechanisms in place to prevent the mechanisms in place to prevent the introduction of bias into critical introduction of bias into critical aspects of the research study.aspects of the research study.

In other words…there is an In other words…there is an appropriate management plan in appropriate management plan in place to eliminate or reduce bias in place to eliminate or reduce bias in the design, conduct or reporting of the design, conduct or reporting of research. research.

Special Considerations for HSRSpecial Considerations for HSR The presumption against allowing an The presumption against allowing an

interested investigator to conduct HSR is interested investigator to conduct HSR is not to suggest that every financial not to suggest that every financial interest jeopardizes the welfare of HS or interest jeopardizes the welfare of HS or the integrity of research.the integrity of research.

Each situation must be carefully Each situation must be carefully evaluated and a judgment made about evaluated and a judgment made about “compelling circumstances” based on “compelling circumstances” based on

the nature of the science, the nature of the science, the nature of the interest, the nature of the interest, how closely the interest is related to the how closely the interest is related to the

research, research, and the degree to which the interest may be and the degree to which the interest may be

affected by the research.affected by the research.

When the financial interest is directly When the financial interest is directly related to the research and may be related to the research and may be substantially affected by it, the risk is substantially affected by it, the risk is greatest and the standard for greatest and the standard for scrutiny must be high.scrutiny must be high.

Disclosure alone is NOT sufficient to Disclosure alone is NOT sufficient to manage the interest.manage the interest.

View each instance of an interested View each instance of an interested investigator conducting HSR as investigator conducting HSR as “potentially problematic and requiring “potentially problematic and requiring strict scrutiny”.strict scrutiny”.

Carefully evaluate all aspects of the Carefully evaluate all aspects of the investigator’s involvement in the study investigator’s involvement in the study including, including,

trial designtrial design evaluating and reporting adverse eventsevaluating and reporting adverse events result reporting result reporting andand conduct or administration of the research conduct or administration of the research

study.study.

More considerations in reviewing More considerations in reviewing HSRHSR

Whether an interested investigator should Whether an interested investigator should be permitted to consent, recruit or be permitted to consent, recruit or randomize subjects and under what randomize subjects and under what circumstances is a current topic of circumstances is a current topic of discussion by the COI Committee.discussion by the COI Committee.

When compelling circumstances warrant When compelling circumstances warrant that an interested investigator participate that an interested investigator participate in research: “rigorous, effective, and in research: “rigorous, effective, and disinterested monitoring” should take disinterested monitoring” should take place.place.

Back to the Proposed Steps to Back to the Proposed Steps to Follow In Review of A DisclosureFollow In Review of A Disclosure

3.3. CONSIDER THE PROPOSED MANAGEMENT CONSIDER THE PROPOSED MANAGEMENT PLANPLAN

Is it sufficient to eliminate or reduce the Is it sufficient to eliminate or reduce the investigator’s influence in the investigator’s influence in the designdesign and/or and/or conductconduct of the research study of the research study and/or the and/or the reportingreporting of the research of the research results? Take into account the closeness of results? Take into account the closeness of the connection between the financial the connection between the financial interests and the outcome of the research.interests and the outcome of the research.

4.4. DETERMINE WHETHER AND UNDER WHAT DETERMINE WHETHER AND UNDER WHAT CIRCUMSTANCES THE RESEARCH MAY CIRCUMSTANCES THE RESEARCH MAY PROCEEDPROCEED..

Approval (with or without management Approval (with or without management plan)plan)

Stipulated minor changes or Stipulated minor changes or clarifications requiredclarifications required

Deferral (more information needed)Deferral (more information needed) Disapproval (i.e., elimination of interest Disapproval (i.e., elimination of interest

or change of personnel required before or change of personnel required before research may proceed.)research may proceed.)

Examples of Possible Steps to Examples of Possible Steps to Manage COIManage COI

Elimination of the conflicting interestElimination of the conflicting interest

Substitution of personnel on the Substitution of personnel on the projectproject

Public disclosure of significant financial Public disclosure of significant financial interestsinterests

Monitoring of research by independent Monitoring of research by independent reviewersreviewers

QUESTIONS?QUESTIONS?