financial conflicts of interest in connection with research national human research protections...

FINANCIALFINANCIALCONFLICTS OF INTERESTCONFLICTS OF INTEREST

IN CONNECTION WITH IN CONNECTION WITH RESEARCHRESEARCH

National Human Research Protections Advisory CommitteeNational Human Research Protections Advisory CommitteeWorking Group on Conflicts of InterestWorking Group on Conflicts of Interest

April 9, 2001April 9, 2001

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© 2001 PROSKAUER ROSE LLP

Overview Of RequirementsOverview Of Requirements

Multiple federal and state regulations and policies Multiple federal and state regulations and policies dictate procedures affecting human researchdictate procedures affecting human research

Public policy interests in avoiding improper Public policy interests in avoiding improper incentives to conduct research on humans, or incentives to conduct research on humans, or improperly to report the results of such research improperly to report the results of such research

Included among the various regulations and policies Included among the various regulations and policies are requirements for management and disclosure of are requirements for management and disclosure of certain financial conflicts of interest affecting certain financial conflicts of interest affecting researchersresearchers

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Overview Of Requirements Overview Of Requirements (cont.)(cont.)

Under the regulations, certain financial conflicts of Under the regulations, certain financial conflicts of interest must be disclosed to the institution where the interest must be disclosed to the institution where the researchers conduct their studies, or to the sponsor researchers conduct their studies, or to the sponsor who conducts the researchwho conducts the research

A subset of those conflicts must, in turn, be disclosed to A subset of those conflicts must, in turn, be disclosed to governmental agencies funding or reviewing the research governmental agencies funding or reviewing the research conducted by the relevant researchersconducted by the relevant researchers

State Law Requirements for Professional Conduct by State Law Requirements for Professional Conduct by PhysiciansPhysicians

State and federal requirements prohibit research State and federal requirements prohibit research reviews by IRB members with conflicts reviews by IRB members with conflicts

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Risks of Conflicting Financial InterestsRisks of Conflicting Financial Interests

New York Post articles in 1999 criticized physicians New York Post articles in 1999 criticized physicians who accepted honoraria and other consulting fees from who accepted honoraria and other consulting fees from pharmaceutical companies when those physicians were pharmaceutical companies when those physicians were responsible for enrolling subjects in research protocols responsible for enrolling subjects in research protocols sponsored by the same pharmaceutical companiessponsored by the same pharmaceutical companies

January 2000 JAMA article: considered 29 studies January 2000 JAMA article: considered 29 studies published in peer review journals, concluding that:published in peer review journals, concluding that: the extent of physician-industry interactions appears to affect the extent of physician-industry interactions appears to affect

prescribing and professional behavior and should be further prescribing and professional behavior and should be further addressed through policy and educationaddressed through policy and education

interactions with pharmaceutical representatives included gifts, interactions with pharmaceutical representatives included gifts, samples, free meals, funding for travel to attend educational samples, free meals, funding for travel to attend educational symposia, exposure to pharmaceutical representative speakers, CME symposia, exposure to pharmaceutical representative speakers, CME sponsorship, honoraria, research funding, and employmentsponsorship, honoraria, research funding, and employment

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Risks of Conflicting Financial InterestsRisks of Conflicting Financial Interests

Gelsinger case – death of 18 year old enrolled in Gelsinger case – death of 18 year old enrolled in gene therapy research gene therapy research

Significant financial ties of co-PI to sponsor have been Significant financial ties of co-PI to sponsor have been questionedquestioned

Led to May 2000 policy adopted by American Society of Led to May 2000 policy adopted by American Society of Gene Therapy (organization representing 2500 Gene Therapy (organization representing 2500 professionals) prohibiting gene therapy researchers professionals) prohibiting gene therapy researchers from owning equity, stock options or other ownership from owning equity, stock options or other ownership interest in the companies whose products they are interest in the companies whose products they are testing in clinical trials testing in clinical trials

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Risks of Conflicting Financial Interests Risks of Conflicting Financial Interests (cont’d)(cont’d)

Multiple articles in late 2000 in JAMA and NEJM Multiple articles in late 2000 in JAMA and NEJM analyzing institutional policies on conflicts of interest analyzing institutional policies on conflicts of interest and disclosuresand disclosures Institutional policies ranged from disclosures to FDA Institutional policies ranged from disclosures to FDA

and/or PHS only as required by regulation, to voluntary and/or PHS only as required by regulation, to voluntary disclosures and review by IRBs and even patientsdisclosures and review by IRBs and even patients

August 2000, NIH hosted national conference on “Human August 2000, NIH hosted national conference on “Human Subject Protection and Financial Conflicts of Interest”; Subject Protection and Financial Conflicts of Interest”; solicited public comments on subjectsolicited public comments on subject

Late 2000: Late 2000: Draft Interim Guidance: Financial Draft Interim Guidance: Financial Relationships in Clinical ResearchRelationships in Clinical Research; comments due ; comments due March 2001March 2001

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Federal Agencies With RequirementsFederal Agencies With RequirementsOn Financial Disclosures By ResearchersOn Financial Disclosures By Researchers

Public Health Service of the U.S. Department of Public Health Service of the U.S. Department of Health and Human Services (HHS) (includes NIH)Health and Human Services (HHS) (includes NIH)

National Science Foundation (NSF)National Science Foundation (NSF)

Food and Drug Administration (FDA)Food and Drug Administration (FDA)

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PHS Financial Disclosure RequirementsPHS Financial Disclosure Requirements

Does not apply to privately funded researchDoes not apply to privately funded research Applies only to human research funded by a PHS Applies only to human research funded by a PHS

agency, or proposed for PHS fundingagency, or proposed for PHS funding Basic requirement:Basic requirement:

Each “Investigator” who will participate in PHS-funded research must Each “Investigator” who will participate in PHS-funded research must submit for review to an official at the research institution, a listing of submit for review to an official at the research institution, a listing of Investigator’s “Significant Financial Interests”:Investigator’s “Significant Financial Interests”:

(i)(i) That would reasonably appear to be affected by the research for which That would reasonably appear to be affected by the research for which PHS funding is sought; andPHS funding is sought; and

(ii)(ii) In entities whose financial interests would reasonably appear to be In entities whose financial interests would reasonably appear to be affected by the research.affected by the research.

42 C.F.R. § 50.604(c)(1)42 C.F.R. § 50.604(c)(1) Financial disclosures to the institution by the Investigators must be Financial disclosures to the institution by the Investigators must be

made by the time a grant application is submitted to PHS, and then made by the time a grant application is submitted to PHS, and then updated either annually or as new reportable Significant Financial updated either annually or as new reportable Significant Financial Interests are obtainedInterests are obtained

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Definitions For PHS RequirementsDefinitions For PHS Requirements

What is “reasonably appears to affect the research”?What is “reasonably appears to affect the research”? Regulations don’t provide guidance on this issue. Institution can set Regulations don’t provide guidance on this issue. Institution can set

guidelines or definitionsguidelines or definitions

What is a “Significant Financial Interest”?What is a “Significant Financial Interest”? Anything of monetary value, including cash, consulting fees or honoraria, Anything of monetary value, including cash, consulting fees or honoraria,

stocks or other ownership interests, and patents, copyrights or other stocks or other ownership interests, and patents, copyrights or other intellectual property rights, and royalties from intellectual property rights, intellectual property rights, and royalties from intellectual property rights, if all the payments in one year to the Investigator (including payments to if all the payments in one year to the Investigator (including payments to his or her spouse and dependent children) are expected to be more than his or her spouse and dependent children) are expected to be more than $10,000, or if the relevant ownership interest of the Investigator and $10,000, or if the relevant ownership interest of the Investigator and spouse and children is worth more than $10,000 and/or constitutes more spouse and children is worth more than $10,000 and/or constitutes more than a five (5%) percent ownership interest in a single organizationthan a five (5%) percent ownership interest in a single organization

DOES NOT INCLUDE salary and other compensation from the research DOES NOT INCLUDE salary and other compensation from the research institution, income from seminars, teaching or lectures sponsored by, as institution, income from seminars, teaching or lectures sponsored by, as well as income from serving on advisory committees or review panels for, well as income from serving on advisory committees or review panels for, public or not-for-profit entities; does not apply to holdings in mutual public or not-for-profit entities; does not apply to holdings in mutual fundsfunds

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Reporting Of Interests Reporting Of Interests By The Research InstitutionBy The Research Institution

A reportable conflict of interest exists when the designated official A reportable conflict of interest exists when the designated official at the institution “determines that a Significant Financial Interest at the institution “determines that a Significant Financial Interest could directly and significantly affect the design, conduct or could directly and significantly affect the design, conduct or reporting of PHS-funded research.” 42 C.F.R. § 50.605(a) reporting of PHS-funded research.” 42 C.F.R. § 50.605(a)

The institution is not required to report the nature of the interest The institution is not required to report the nature of the interest or other details of the conflict, but must assure PHS that it will or other details of the conflict, but must assure PHS that it will manage, reduce or eliminate the conflict in accordance with the manage, reduce or eliminate the conflict in accordance with the regulationsregulations

The reports must be made before spending any grant money, and The reports must be made before spending any grant money, and the institution has 60 days to report any conflicting interests that the institution has 60 days to report any conflicting interests that it identifies after submitting the initial reportit identifies after submitting the initial report

Note: the category of financial interests reportable to PHS is Note: the category of financial interests reportable to PHS is narrower than the category of Significant Financial Interests that narrower than the category of Significant Financial Interests that researchers must report to their institutionsresearchers must report to their institutions

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Management of ConflictsManagement of ConflictsThrough Internal PoliciesThrough Internal Policies

Under PHS regulations, an institution must establish Under PHS regulations, an institution must establish guidelines for its designated official to take action to guidelines for its designated official to take action to ensure that the conflicting interests are managed, ensure that the conflicting interests are managed, reduced or eliminated. The institution must maintain reduced or eliminated. The institution must maintain a system to enforce these policies and to sanction a system to enforce these policies and to sanction violators as appropriate violators as appropriate

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Management of ConflictsManagement of ConflictsThrough Internal Policies Through Internal Policies (cont.)(cont.)

Some of the potential methods and conditions that an Some of the potential methods and conditions that an institution may utilize to manage the conflicts of institution may utilize to manage the conflicts of interests, include:interests, include: Publicly disclosing the financial interestPublicly disclosing the financial interest Having independent reviewers monitor the researchHaving independent reviewers monitor the research Modifying the research planModifying the research plan Disqualifying certain Investigators from participation in the Disqualifying certain Investigators from participation in the

researchresearch Requiring the Investigator to divest the “Significant Requiring the Investigator to divest the “Significant

Financial Relationship” Financial Relationship” Severing relationships that create actual or potential Severing relationships that create actual or potential

conflictsconflicts Reasonable alternative solutions for managing the Reasonable alternative solutions for managing the

conflicting interests may be developed by the conflicting interests may be developed by the institutioninstitution

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National Science Foundation:National Science Foundation:Distinctions From PHS RequirementsDistinctions From PHS Requirements

Conflict disclosure requirements very similar to PHS Conflict disclosure requirements very similar to PHS requirementsrequirements

Applies to institutions receiving NSF funds if they Applies to institutions receiving NSF funds if they have more than 50 employeeshave more than 50 employees

Definitions of “investigators” and their “significant Definitions of “investigators” and their “significant financial interests” that must be disclosed to the financial interests” that must be disclosed to the institution are the same as set forth in PHS institution are the same as set forth in PHS regulationsregulations

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FDA Financial Disclosure RequirementsFDA Financial Disclosure Requirements

Apply to a pharmaceutical company, device Apply to a pharmaceutical company, device manufacturer or other party that has submitted a manufacturer or other party that has submitted a marketing application (and is therefore an “applicant”) to marketing application (and is therefore an “applicant”) to the FDA for approval of a human drug, device or biologic the FDA for approval of a human drug, device or biologic product and that submits to the FDA the results of product and that submits to the FDA the results of “covered clinical studies,” as a proposed basis for FDA “covered clinical studies,” as a proposed basis for FDA approval — thus, approval — thus, retrospectiveretrospective in application (as in application (as opposed to opposed to prospectiveprospective PHS requirements) PHS requirements)

Clinical investigators and their research institutions do Clinical investigators and their research institutions do not have a direct reporting obligation to the FDA, BUT not have a direct reporting obligation to the FDA, BUT are obligated by the regulations to provide the research are obligated by the regulations to provide the research sponsor with sufficient financial information to enable sponsor with sufficient financial information to enable the study sponsor to meet its disclosure obligations to the study sponsor to meet its disclosure obligations to the FDAthe FDA

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Basic FDA Disclosure ObligationBasic FDA Disclosure Obligation

(i)(i) any financial arrangement between the sponsor and the clinical any financial arrangement between the sponsor and the clinical investigator, where the value of the compensation to the investigator investigator, where the value of the compensation to the investigator for conducting the study could be influenced by the outcome of the for conducting the study could be influenced by the outcome of the clinical studies, such as payments which are higher for a favorable clinical studies, such as payments which are higher for a favorable study outcome, including royalty payments for sales of the product study outcome, including royalty payments for sales of the product or an ownership interest in the sponsor of the study; or an ownership interest in the sponsor of the study;

(ii)(ii) any other compensation from the sponsor of the study to the any other compensation from the sponsor of the study to the investigator or the institution to support activities of the investigator investigator or the institution to support activities of the investigator that is worth more than $25,000 (not including the costs of that is worth more than $25,000 (not including the costs of conducting the study), which is given while the clinical investigator is conducting the study), which is given while the clinical investigator is conducting the study, or within one year after completing the study. conducting the study, or within one year after completing the study. Examples of this type of compensation include grants for ongoing Examples of this type of compensation include grants for ongoing research, equipment and honoraria;research, equipment and honoraria;

For every “clinical investigator” who participates in a “covered clinical study,” the applicant must disclose to the FDA, using Form FDA 3455, the nature of the following financial interests of the clinical investigators:

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Basic FDA Disclosure Obligation Basic FDA Disclosure Obligation (cont.)(cont.)

For any clinical investigator who has no such financial For any clinical investigator who has no such financial interests, the applicant must submit a Form FDA 3454, interests, the applicant must submit a Form FDA 3454, certifying the absence of these financial interests.certifying the absence of these financial interests.

21 21 C.F.R. § 54.4(a).C.F.R. § 54.4(a).

(iii)(iii) any property or financial interest in the tested product held by the any property or financial interest in the tested product held by the clinical investigator, including patents, copyrights or licensing clinical investigator, including patents, copyrights or licensing agreements;agreements;

(iv)(iv) any ownership or other financial interest (including stock and stock any ownership or other financial interest (including stock and stock options) in the sponsor held by the clinical investigator, the value options) in the sponsor held by the clinical investigator, the value of which cannot be easily determined by reference to public prices, of which cannot be easily determined by reference to public prices, or any ownership interest in a publicly traded company that or any ownership interest in a publicly traded company that exceeds $50,000 during the time that the investigator is conducting exceeds $50,000 during the time that the investigator is conducting the study or within one year after completion of such study; andthe study or within one year after completion of such study; and

(v)(v) any steps taken to reduce the bias created by these disclosed any steps taken to reduce the bias created by these disclosed financial relationships.financial relationships.

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Differences From PHS RequirementsDifferences From PHS Requirements

Note that dollar thresholds are higherNote that dollar thresholds are higher

PHS requirements focus upon conflicts that PHS requirements focus upon conflicts that “reasonably appear to affect the research”“reasonably appear to affect the research”

FDA requirements focus upon conflicts relating to FDA requirements focus upon conflicts relating to the relationship between the investigator and the the relationship between the investigator and the research sponsorresearch sponsor

Disclosure/reporting to FDA is retrospective, at time Disclosure/reporting to FDA is retrospective, at time of application; PHS requirements are prospectiveof application; PHS requirements are prospective

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Laws and Regulations Governing IRB MembersLaws and Regulations Governing IRB Members

Multiple sources of law for IRBs:Multiple sources of law for IRBs:

State laws can be applicable to all human research State laws can be applicable to all human research conducted in a state, regardless of source of fundingconducted in a state, regardless of source of funding

FDA regulations - applicable to (subject to certain FDA regulations - applicable to (subject to certain exceptions) clinical investigations regulated by the FDA exceptions) clinical investigations regulated by the FDA and certain clinical investigations that support applications and certain clinical investigations that support applications for research or marketing permits for products regulated by for research or marketing permits for products regulated by the FDAthe FDA

Common Rule for 17 federal agencies and departments, Common Rule for 17 federal agencies and departments, extending to institutions/entities that accept funding from extending to institutions/entities that accept funding from these agencies and departmentsthese agencies and departments

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The Prohibition on IRB Member Conflicts The Prohibition on IRB Member Conflicts

HHS and FDA regulations and some state laws have provisions that:

Prohibit the participation of an IRB member in the IRB’s “review of any project in which the member has a conflicting interest,” unless that member is providing information requested by the IRB

No definitions of “conflicting interest” generally available in these regulations and laws

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The Prohibition on IRB Member Conflicts The Prohibition on IRB Member Conflicts (cont.)(cont.)

Since there is no formal definition of these “conflicts,” Since there is no formal definition of these “conflicts,” institutions may develop their own definitions, but should institutions may develop their own definitions, but should document and enforce the policies that set forth the document and enforce the policies that set forth the definition of what could constitute a “conflicting interest” definition of what could constitute a “conflicting interest” for an IRB member, including threshold dollar amounts or for an IRB member, including threshold dollar amounts or ownership interests that would trigger application of the ownership interests that would trigger application of the institution’s policiesinstitution’s policies

An institutional official — and preferably one who is not an An institutional official — and preferably one who is not an IRB member — should be given the responsibility for IRB member — should be given the responsibility for monitoring enforcement of the compliance of IRB members monitoring enforcement of the compliance of IRB members with the IRB conflict of interest policywith the IRB conflict of interest policy

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If an IRB member is a PI, such dual role can also If an IRB member is a PI, such dual role can also cause a non-financial conflict, also apparently cause a non-financial conflict, also apparently prohibited by IRB requirementsprohibited by IRB requirements

The potential for conflicts of interest should be The potential for conflicts of interest should be considered when selecting IRB members considered when selecting IRB members When IRB members frequently have conflicts (i.e., often When IRB members frequently have conflicts (i.e., often

serve as PIs) and must abstain from deliberation and serve as PIs) and must abstain from deliberation and voting, their contributions to group review process may be voting, their contributions to group review process may be diminished and could hinder review procedure diminished and could hinder review procedure

Problem is even more severe if the conflicted member is Problem is even more severe if the conflicted member is the IRB chairthe IRB chair

(Source: FDA Information Sheets Guidance for IRBs and Clinical (Source: FDA Information Sheets Guidance for IRBs and Clinical Investigators)Investigators)

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OHRP “strongly recommends” that when IRB OHRP “strongly recommends” that when IRB members have a conflicting interest:members have a conflicting interest:

They leave the room when the IRB votes on that research They leave the room when the IRB votes on that research project, andproject, and

Departure from the room is noted in IRB meeting minutesDeparture from the room is noted in IRB meeting minutes

Note that if a member’s departure from the room causes Note that if a member’s departure from the room causes the quorum to be lost, the IRB cannot continue voting until the quorum to be lost, the IRB cannot continue voting until the quorum is restoredthe quorum is restored

(Source: OHRP Compliance Activities: Common Findings (Source: OHRP Compliance Activities: Common Findings and Guidance - 9/1/2000)and Guidance - 9/1/2000)

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HHS Draft Interim GuidanceHHS Draft Interim Guidance

As a result of August 2000 NIH meeting, OHRP, citing recent As a result of August 2000 NIH meeting, OHRP, citing recent articles in NEJM and JAMA, recently released articles in NEJM and JAMA, recently released Draft Interim Draft Interim Guidance: Financial Relationships in Clinical ResearchGuidance: Financial Relationships in Clinical Research , and is , and is soliciting public comments. soliciting public comments.

Noting that many institutions have established a Conflict of Interest Noting that many institutions have established a Conflict of Interest Committee, guidance indicates that such committee is useful in keeping Committee, guidance indicates that such committee is useful in keeping IRB from bearing burden of becoming main group to consider these IRB from bearing burden of becoming main group to consider these issues, but results of committee’s reviews, and how the institution has issues, but results of committee’s reviews, and how the institution has managed the conflicts, should be shared with IRB managed the conflicts, should be shared with IRB

Guidance also contemplates “institutional” conflicts of interests when Guidance also contemplates “institutional” conflicts of interests when institutions have stake in researchinstitutions have stake in research

Recommends institution’s annual collection and review of IRB staff, chair Recommends institution’s annual collection and review of IRB staff, chair and IRB members’ financial interests in commercial sponsorsand IRB members’ financial interests in commercial sponsors

Suggests institutions educate and train investigators and IRB members on Suggests institutions educate and train investigators and IRB members on conflict of interests issuesconflict of interests issues

Draft introduces concept of IRB consideration of disclosure of financial Draft introduces concept of IRB consideration of disclosure of financial relationships/conflicts in informed consent formsrelationships/conflicts in informed consent forms

HHS HHS Draft Interim GuidanceDraft Interim Guidance

Comments received:Comments received: Draft guidance too directive/not APA compliantDraft guidance too directive/not APA compliant Wait until private associations have actedWait until private associations have acted Need additional consultation with stakeholdersNeed additional consultation with stakeholders Roles of IRB and COI committees confused/overburdened Roles of IRB and COI committees confused/overburdened

IRBsIRBs COI function should be vested in COI function should be vested in

dean/provost/administrator, not new committeedean/provost/administrator, not new committee ““Institutional” COI is a new concept and guidance goes too Institutional” COI is a new concept and guidance goes too

far into uncharted territoryfar into uncharted territory Research-related compensation (Research-related compensation (i.e.i.e., compensation for the , compensation for the

research) should be included in COI analysis; “enrollment research) should be included in COI analysis; “enrollment bonuses” require attentionbonuses” require attention

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HHS HHS Draft Interim GuidanceDraft Interim Guidance (cont.)(cont.)

Comments received: (cont’d)Comments received: (cont’d) Disclosure of financial interests/conflicts to subjects is Disclosure of financial interests/conflicts to subjects is

undefined; no practical experience; little dataundefined; no practical experience; little data Attention needed to COI process in independent IRBs and Attention needed to COI process in independent IRBs and

CROsCROs Draft guidance promotes bureaucracy, stifles researchDraft guidance promotes bureaucracy, stifles research No need for guidance:No need for guidance:

““a few bad apples only” a few bad apples only” ““anecdotes shouldn’t drive policy”anecdotes shouldn’t drive policy”

PHS/FDA/NSF disclosure regulations and practices should PHS/FDA/NSF disclosure regulations and practices should be standardizedbe standardized

COI is not only financial (COI is not only financial (e.g.e.g., academic advancement, , academic advancement, prestige)prestige)

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HHS HHS Draft Interim GuidanceDraft Interim Guidance (cont.)(cont.)

Comments received: (cont’d)Comments received: (cont’d)

Draft guidance has unclear goals: avoid COI, or manage Draft guidance has unclear goals: avoid COI, or manage COI? Is there “zero tolerance” for COI?COI? Is there “zero tolerance” for COI?

Goal of COI process: assure research integrity or Goal of COI process: assure research integrity or protect subjects, or both?protect subjects, or both?

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NHRPAC Proposed Comments onNHRPAC Proposed Comments onHHS HHS Draft Interim GuidanceDraft Interim Guidance

ProcessProcess

Working group chargedWorking group charged

Review of Review of Draft Interim GuidanceDraft Interim Guidance

Conference calls with roundtable discussionConference calls with roundtable discussion

Face-to-face meeting (March 21)Face-to-face meeting (March 21)

Draft commentsDraft comments

April 9 presentation to NHRPACApril 9 presentation to NHRPAC

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Goals/ObjectivesGoals/Objectives

Assure integrity of informed consent processAssure integrity of informed consent process

Promote research by assuring research integrityPromote research by assuring research integrity

Deter misinterpretation of data or misprision of research Deter misinterpretation of data or misprision of research and professional dutiesand professional duties

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HHS/OHRP should proceed with guidelines, in careful, HHS/OHRP should proceed with guidelines, in careful, step-wise mannerstep-wise manner

Need for revisiting/review/evaluationNeed for revisiting/review/evaluation

Integrate private association guidelines as developedIntegrate private association guidelines as developed

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Defining Conflicts of InterestDefining Conflicts of Interest

Financial disclosure Financial disclosure conflict of interest conflict of interest

Confidentiality needed in financial disclosure processConfidentiality needed in financial disclosure process

Threshold amounts needed; Threshold amounts needed; de minimisde minimis exceptions exceptions

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Defining Conflicts of Interest (cont’d)Defining Conflicts of Interest (cont’d)

PHS standards preferred, due to PHS/FDA/NSF PHS standards preferred, due to PHS/FDA/NSF inconsistenciesinconsistencies

Apply to all research, regardless of source of fundingApply to all research, regardless of source of funding

Analyze research compensation also for fair market value Analyze research compensation also for fair market value assurance, not just honoraria, trips and investmentsassurance, not just honoraria, trips and investments

““Compelling and necessary” exceptionsCompelling and necessary” exceptions

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Conflict of Interest ProcessConflict of Interest Process

IRBs already overburdenedIRBs already overburdened

Create adjunct COI process, with COI committee, Create adjunct COI process, with COI committee, reporting to IRB, to receive and analyze financial reporting to IRB, to receive and analyze financial disclosuredisclosure

COI analysis precedes IRB reviewCOI analysis precedes IRB review

Integrate, as appropriate, with existing COI Integrate, as appropriate, with existing COI mechanisms/ financial disclosure processesmechanisms/ financial disclosure processes

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Conflict of Conflict of Interest Interest ProcessProcess

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““Institutional” Conflicts of InterestInstitutional” Conflicts of Interest IRB members — recusal for any related financial interestIRB members — recusal for any related financial interest

Increased incidence of institutional investments/interests Increased incidence of institutional investments/interests in patentsin patents

Attenuated influence on IRB members who are affiliatedAttenuated influence on IRB members who are affiliated

NBAC recommendations: 50/50 affiliated/unaffiliated IRB NBAC recommendations: 50/50 affiliated/unaffiliated IRB membershipmembership

NHRPAC has doubts, but understands goalsNHRPAC has doubts, but understands goals

Support for attempts to define “institutional” conflicts and Support for attempts to define “institutional” conflicts and manage themmanage them

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Disclosing Conflicts of Interest to Research SubjectsDisclosing Conflicts of Interest to Research Subjects Little data on “best practices”Little data on “best practices”

““Real” information needed, not undigested information or Real” information needed, not undigested information or arcane factsarcane facts

Basic principle: if a “real” conflict exists, information Basic principle: if a “real” conflict exists, information should be reasonably available to subjects/potential should be reasonably available to subjects/potential subjectssubjects

Goal: give subjects information that is understandableGoal: give subjects information that is understandable

““Generic” disclosure of COI process and of identification/ Generic” disclosure of COI process and of identification/ management of a conflictmanagement of a conflict

Subject then may seek more informationSubject then may seek more information

Duty of institution and researchers to answer truthfullyDuty of institution and researchers to answer truthfully

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One example of “generic” disclosure of conflicts to One example of “generic” disclosure of conflicts to subjects:subjects:

Mercy Hospital maintains a financial disclosure process, by Mercy Hospital maintains a financial disclosure process, by which people who conduct research and Mercy itself must which people who conduct research and Mercy itself must disclose any significant financial investments (for example, disclose any significant financial investments (for example, stock shares or patent holdings) that are related to the stock shares or patent holdings) that are related to the products being tested in research. This sort of information products being tested in research. This sort of information about the study that you are considering joining was about the study that you are considering joining was disclosed to an internal Mercy committee, which directed disclosed to an internal Mercy committee, which directed that steps be taken in this research study to make sure that that steps be taken in this research study to make sure that these investments of either Mercy or the researchers do these investments of either Mercy or the researchers do not influence the way in which you will be treated or the not influence the way in which you will be treated or the way this research study will be conducted. If you would way this research study will be conducted. If you would like more information about the process at Mercy for like more information about the process at Mercy for disclosure of these interests and their management, or disclosure of these interests and their management, or about the actual financial interests that are present in this about the actual financial interests that are present in this study, please ask the researchers or the research study, please ask the researchers or the research coordinator, and they will assist you.coordinator, and they will assist you.

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Education and ComplianceEducation and Compliance

Once policies are adopted, compliance must be Once policies are adopted, compliance must be assuredassured

Compliance cannot occur without education of Compliance cannot occur without education of key staffkey staff

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ConclusionsConclusions

Generally supports concept of an interim Generally supports concept of an interim guidance document, carefully crafted and subject guidance document, carefully crafted and subject to review, evaluation and revisionto review, evaluation and revision

Pressing need to bolster integrity of the research Pressing need to bolster integrity of the research enterprise and assure informed choice/consent of enterprise and assure informed choice/consent of subjectssubjects

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FINANCIALFINANCIALCONFLICTS OF INTERESTCONFLICTS OF INTEREST

IN CONNECTION WITH IN CONNECTION WITH RESEARCHRESEARCH

National Human Research Protections Advisory CommitteeNational Human Research Protections Advisory CommitteeWorking Group on Conflicts of InterestWorking Group on Conflicts of Interest

April 9, 2001April 9, 2001

financial conflicts of interest in connection with research national human research protections...

Documents

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