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Shared Responsibility, Individual Integrity Shared Responsibility, Individual Integrity Financial Conflicts of Interest in ResearchFinancial Conflicts of Interest in Research

Laura M. Brockway, Ph.D.Laura M. Brockway, Ph.D.Senior Science Policy AnalystSenior Science Policy Analyst

FASEB Office of Public AffairsFASEB Office of Public Affairs

Society for Scholarly PublishingSociety for Scholarly PublishingNovember 13, 2006 – Washington, DCNovember 13, 2006 – Washington, DC

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OverviewOverview

• Academia-industry relationships Academia-industry relationships in research (focus on biomedical in research (focus on biomedical and life sciences)and life sciences)

• Define Define financialfinancial conflict of interest in conflict of interest in sciencescience

• Why this issue is importantWhy this issue is important• The role of investigators and authorsThe role of investigators and authors• FASEB effortFASEB effort• Journal policies and proceduresJournal policies and procedures

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Academia-industry relationshipsAcademia-industry relationships• Arrangements in which academic scientists carry out Arrangements in which academic scientists carry out

research, and provide the benefits of their knowledge or research, and provide the benefits of their knowledge or intellectual property to industry. In return, they receive intellectual property to industry. In return, they receive considerations such research support, honoraria, considerations such research support, honoraria, consulting fees, royalties, equity, and/or other payments consulting fees, royalties, equity, and/or other payments and gifts.and gifts.11

• A fundamental part of the modern life science enterpriseA fundamental part of the modern life science enterprise – Funding: One-quarter of life science academic faculty have Funding: One-quarter of life science academic faculty have

industry fundingindustry funding22 (totaling $2 billion in 2004 (totaling $2 billion in 200433))– Licensing: 4,516 new licenses by 195 research institutions in Licensing: 4,516 new licenses by 195 research institutions in

2003200344 – Consulting: 80% of life science firms retain faculty as Consulting: 80% of life science firms retain faculty as

consultantsconsultants22

– Training: 38% of life science firms support training grantsTraining: 38% of life science firms support training grants22

1EG Campbell; 2Blumenthal et al, 1996; 3NSF; 4AUTM, 2004

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Relationships have benefits and risksRelationships have benefits and risks

• There are many benefitsThere are many benefits– New products and medicines: 2,230 products were New products and medicines: 2,230 products were

produced through institutional licensing in FY 1998 – produced through institutional licensing in FY 1998 – 2003200344

– Increased resources for academic projectsIncreased resources for academic projects– Bi-directional flow of knowledge and materialsBi-directional flow of knowledge and materials– Academic faculty participate in application of researchAcademic faculty participate in application of research

• Financial interests have potential risks Financial interests have potential risks – Introduce bias into the conduct or reporting of research Introduce bias into the conduct or reporting of research

(which can affect clinical care)(which can affect clinical care)– Decrease “openness” and sharing of data and materialsDecrease “openness” and sharing of data and materials– Delay traineesDelay trainees– Decrease public trust in medical researchDecrease public trust in medical research

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Financial conflict of interest in scienceFinancial conflict of interest in science

• One definition: One definition: Situations in which financial Situations in which financial considerations may compromise, or have considerations may compromise, or have the appearance of compromising, an the appearance of compromising, an investigator’s professional judgement in investigator’s professional judgement in conducting or reporting research.conducting or reporting research.5 5

• A A situationsituation, not a , not a behavior/outcomebehavior/outcome

5AAU and AAMC

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Federal Regulation – PHS/NSFFederal Regulation – PHS/NSF

• Investigators must disclose any “significant financial Investigators must disclose any “significant financial interests” to the institution that would reasonably interests” to the institution that would reasonably appear to be affected by the proposed researchappear to be affected by the proposed research– Anything of monetary value including, but not limited to, Anything of monetary value including, but not limited to,

salary or payment for services (e.g., consulting fees or salary or payment for services (e.g., consulting fees or honoraria), equity interests, and intellectual-property rights honoraria), equity interests, and intellectual-property rights that exceed $10,000 in value and represent more than 5% that exceed $10,000 in value and represent more than 5% ownership interest in any single company.ownership interest in any single company.

• Institutions determine whether or not investigators’ Institutions determine whether or not investigators’ financial interests could directly and significantly financial interests could directly and significantly affect the design, conduct, or reporting of the affect the design, conduct, or reporting of the research (present conflicts of interest) and how to research (present conflicts of interest) and how to proceed (eliminate, reduce, manage).proceed (eliminate, reduce, manage).

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Why this issue is important: The Why this issue is important: The public trust is at stakepublic trust is at stake

• ““The tentacles of those ethics problems The tentacles of those ethics problems with NIH researchers…does a lot to with NIH researchers…does a lot to undermine the faith the public has in NIH.” undermine the faith the public has in NIH.” Rep. Blackburn, September 13, 2006.Rep. Blackburn, September 13, 2006.

• ““Leading medical journals seem to be Leading medical journals seem to be having a difficult time disentangling having a difficult time disentangling themselves from the pharmaceutical and themselves from the pharmaceutical and medical device industries.” medical device industries.” NYT NYT editorial, editorial, July 23, 2006July 23, 2006

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JAMA case

• ““Financial Ties to Industry Cloud Major Financial Ties to Industry Cloud Major Depression Study” (Depression Study” (Wall St. JournalWall St. Journal))

• February ’06 article concluded that stopping the February ’06 article concluded that stopping the use of antidepressants during pregnancy greatly use of antidepressants during pregnancy greatly increases the risk of relapse.increases the risk of relapse.

• In total, the authors failed to disclose 60 different In total, the authors failed to disclose 60 different financial relationships (mainly consulting, financial relationships (mainly consulting, lecturing, and prior grants) with drug companies lecturing, and prior grants) with drug companies related to the research reported in the article. related to the research reported in the article.

• Resulted in more changes to Resulted in more changes to JAMAJAMA COI policy COI policy

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NeuropsychopharmacologyNeuropsychopharmacology case case

• ““Journal Editor Quits Over Conflict Scandal” Journal Editor Quits Over Conflict Scandal” ((The ScientistThe Scientist))

• Editor steps down in after he published a paper Editor steps down in after he published a paper (July ‘06) in the journal reporting positively about (July ‘06) in the journal reporting positively about a depression therapy (device) without disclosing a depression therapy (device) without disclosing that 8 of 9 authors were consultants to the that 8 of 9 authors were consultants to the company that makes the device.company that makes the device.

• The authors say that disclosures were submitted The authors say that disclosures were submitted to the journal but due to an “oversight” were not to the journal but due to an “oversight” were not included in the published version.included in the published version.

• The journal is currently revising its procedures.The journal is currently revising its procedures.

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What does all this attention tell us?What does all this attention tell us?

• The press is interestedThe press is interested• They think the public is interestedThey think the public is interested• Conflicts of interest are on the radar screenConflicts of interest are on the radar screen• ““Misbehavior” by scientists is on the radar Misbehavior” by scientists is on the radar

screen, and having conflicts of interest equates screen, and having conflicts of interest equates with “misbehavior” in the press/public’s mindwith “misbehavior” in the press/public’s mind

• Voluntary standards are made to appear not to Voluntary standards are made to appear not to be working, and may in fact not be workingbe working, and may in fact not be working

• The scientific community has been paying The scientific community has been paying attention, but it may be time for a stronger standattention, but it may be time for a stronger stand

Modified from S. Ehringhaus, June 5, 2005

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Role of investigators/authorsRole of investigators/authors

• The vast majority of biomedical The vast majority of biomedical researchers are guided by the highest researchers are guided by the highest ethical and professional motives.ethical and professional motives.

• Scientists want to do the right thing, if they Scientists want to do the right thing, if they know what the right thing is.know what the right thing is.

• Investigators, as a group, determine the Investigators, as a group, determine the effectiveness of policies and practices.effectiveness of policies and practices.

• The perspective of investigators had not The perspective of investigators had not been well-articulated in the policy debate. been well-articulated in the policy debate.

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FASEB Phase I effort (’05-’06)FASEB Phase I effort (’05-’06)

• June 2005 conference – Elias Zerhouni, Bill June 2005 conference – Elias Zerhouni, Bill Brody, Gail Cassell and others Brody, Gail Cassell and others

• Steering Committee – FASEB Board members, Steering Committee – FASEB Board members, Bob Gussin (J&J), Lou Sherwood (Merck/APPI), Bob Gussin (J&J), Lou Sherwood (Merck/APPI), Eric Campbell (Harvard), Ann Hammersla and Eric Campbell (Harvard), Ann Hammersla and Jim Severson (AUTM), Carol Blum (COGR), Jim Severson (AUTM), Carol Blum (COGR), Josephine Johnston (Hastings Center)Josephine Johnston (Hastings Center)

• White paper, “Shared responsibility, individual White paper, “Shared responsibility, individual integrity: Scientists addressing conflicts of interest integrity: Scientists addressing conflicts of interest in biomedical research”in biomedical research”66

6http://opa.faseb.org/pages/Advocacy/coi.htm and FASEB J, In press

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FASEB Principles for InvestigatorsFASEB Principles for Investigators

• ObjectivityObjectivity

• TransparencyTransparency

• AccountabilityAccountability

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FASEB Phase II effort (’06-’07)FASEB Phase II effort (’06-’07)

• Funding: ORI-AAMC RCR Program for Funding: ORI-AAMC RCR Program for Academic SocietiesAcademic Societies

• ObjectivesObjectives– Increase awareness and understanding of Increase awareness and understanding of

conflict of interest issues on the part of conflict of interest issues on the part of investigatorsinvestigators

– Develop more standard practices for conflict Develop more standard practices for conflict of interest disclosure and management in of interest disclosure and management in biomedical researchbiomedical research

• Generate buy-in at the national level Generate buy-in at the national level (target completion – Summer 2007)(target completion – Summer 2007)

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Phase II CoalitionPhase II Coalition• FASEB: Leo Furcht (Chair), Laura Brockway, FASEB: Leo Furcht (Chair), Laura Brockway,

Howard GarrisonHoward Garrison• AAMC: Susan EhringhausAAMC: Susan Ehringhaus• AAU: Patrick WhiteAAU: Patrick White• AAAS: Mark FrankelAAAS: Mark Frankel• ARVO: Todd MargolisARVO: Todd Margolis• ASCB: Joan GoldbergASCB: Joan Goldberg• ORI: Lawrence Rhoades, Nick SteneckORI: Lawrence Rhoades, Nick Steneck• NIH: Norka Ruiz Bravo, Ezekiel EmanuelNIH: Norka Ruiz Bravo, Ezekiel Emanuel• U of Washington: James SeversonU of Washington: James Severson• Harvard/Mass General Hospital: Eric CampbellHarvard/Mass General Hospital: Eric Campbell• ASM and Eli Lilly Corp: Gail CassellASM and Eli Lilly Corp: Gail Cassell

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Purpose of financial disclosure in Purpose of financial disclosure in publicationspublications

• Essential for transparencyEssential for transparency

• To the editor: To the editor: – So that the manuscript is evaluated with So that the manuscript is evaluated with

knowledge of its circumstancesknowledge of its circumstances– Responsibility of the authorResponsibility of the author

• To the reader: To the reader: – Assures the reader will have this Assures the reader will have this

information to interpret the workinformation to interpret the work– Responsibility of the journal and Responsibility of the journal and

authorauthor

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Why might some authors not Why might some authors not disclose?disclose?

• Indifference/insensitivity about the issuesIndifference/insensitivity about the issues

• Confusion about policies (In the JAMA case, the authors Confusion about policies (In the JAMA case, the authors explained that the research was financed by a federal explained that the research was financed by a federal agency, and, in their view, no conflict existed. “It didn’t agency, and, in their view, no conflict existed. “It didn’t seem relevant.”)seem relevant.”)

• Authors think that it’s somehow embarrassingAuthors think that it’s somehow embarrassing

• Authors are confident that Authors are confident that they are not affected by they are not affected by conflicts of interestconflicts of interest

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What do journal policies look like?What do journal policies look like?

• N = 21 journals (1 of each FASEB society)N = 21 journals (1 of each FASEB society)

• Clinical and basic biomedical journalsClinical and basic biomedical journals

• Analysis of on-line editorial policies, Analysis of on-line editorial policies, instructions to authors, and submission instructions to authors, and submission forms when available forms when available

• Accessed November 7-9, 2006Accessed November 7-9, 2006

• Of 21 journals, 14 had COI policies on-lineOf 21 journals, 14 had COI policies on-line

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0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Of the 14 journals – Author disclosureOf the 14 journals – Author disclosure

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2

9

13

23

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55

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Of the 14 journalsOf the 14 journals

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

7

56 6

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General observationsGeneral observations• Clinical and basic research journals differ in COI Clinical and basic research journals differ in COI

policiespolicies• There are cases in which language used in There are cases in which language used in

editorial policies is not the same as in editorial policies is not the same as in instructions to authors or authorship formsinstructions to authors or authorship forms

• Examples of disclosure statements, if required in Examples of disclosure statements, if required in the text, are usefulthe text, are useful

• Some policies do not explain if disclosure to the Some policies do not explain if disclosure to the editor is or is not kept confidential in the revieweditor is or is not kept confidential in the review

• Many policies do not make clear what the COI Many policies do not make clear what the COI policy is trying to achievepolicy is trying to achieve

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FASEB recommendationsFASEB recommendations• Investigators should be aware of and adhere to Investigators should be aware of and adhere to

journal policies.journal policies.66

• If researchers are unclear about these policies, If researchers are unclear about these policies, contact with the editor is encouraged.contact with the editor is encouraged.66

• When in doubt, investigators should err on the When in doubt, investigators should err on the side of transparency. Failure of authors to side of transparency. Failure of authors to disclose does not automatically translate to the disclose does not automatically translate to the article being flawed. Nevertheless, it does create article being flawed. Nevertheless, it does create the perception that the authors had something to the perception that the authors had something to hide and decreases public trust in medical hide and decreases public trust in medical research.research.77

6FASEB white paper, July 2006 and 7Brockway and Furcht, JAMA letter to editor, in press

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Recommendations (cont.)Recommendations (cont.)• It would be beneficial to focus on “relationships” and It would be beneficial to focus on “relationships” and

not “conflicts of interest”not “conflicts of interest”• Journal disclosure policies should avoid requiring Journal disclosure policies should avoid requiring

investigators to judge whether there may or may not investigators to judge whether there may or may not be a relationship that could create bias and to be a relationship that could create bias and to simply require disclosure of relevant industry simply require disclosure of relevant industry relationships.relationships.66

• There is a clear need for some consistency in There is a clear need for some consistency in disclosure requirements. Variable policies may disclosure requirements. Variable policies may result in confusion and non-compliance by result in confusion and non-compliance by investigators.investigators.66

• Editors and readers should have access to this Editors and readers should have access to this background information.background information.77

Also see Council of Science Editors Guidance

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ConclusionsConclusions• Academia-industry relationships are a beneficial Academia-industry relationships are a beneficial

and fundamental part of the modern life science and fundamental part of the modern life science enterprise. The challenge is disclose and enterprise. The challenge is disclose and oversee these relationships to maximize the oversee these relationships to maximize the benefits and minimize risks. benefits and minimize risks.

• This is achieved through individual and shared This is achieved through individual and shared responsibility (investigators, institutions, responsibility (investigators, institutions, industry, government, journals, societies).industry, government, journals, societies).

• Journals play an important role because they Journals play an important role because they communicate research results to the public.communicate research results to the public.

• It is essential to preserve the public trust through It is essential to preserve the public trust through maintaining objectivity, transparency, and maintaining objectivity, transparency, and accountability. accountability.

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AcknowledgementsAcknowledgements

• Dr. Brockway is a recipient of a grant from Dr. Brockway is a recipient of a grant from the AAMC-ORI Responsible Conduct of the AAMC-ORI Responsible Conduct of Research Program for Academic Research Program for Academic Societies.Societies.

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Questions?Questions?Comments?Comments?

Laura BrockwayLaura BrockwayFASEB Office of Public AffairsFASEB Office of Public Affairs

lbrockway@faseb.org301-634-7650301-634-7650