Shared Responsibility, Individual Integrity Financial Conflicts of Interest in Research

1. Society for Scholarly Publishing November 13, 2006 – Washington, DC Shared Responsibility, Individual Integrity Financial Conflicts of Interest in Research Laura M. Brockway, Ph.D. Senior Science Policy Analyst FASEB Office of Public Affairs

2. Overview • Academia-industry relationships in research (focus on biomedical and life sciences) • Define financial conflict of interest in science • Why this issue is important • The role of investigators and authors • FASEB effort • Journal policies and procedures

3. Academia-industry relationships • Arrangements in which academic scientists carry out research, and provide the benefits of their knowledge or intellectual property to industry. In return, they receive considerations such research support, honoraria, consulting fees, royalties, equity, and/or other payments and gifts. • A fundamental part of the modern life science enterprise • Funding: One-quarter of life science academic faculty have industry funding1 (totaling $2 billion in 2004) • Consulting: 80% of life science firms retain faculty as consultants1 • Training: 38% of life science firms support training grants1 • Licensing: 4,516 new licenses by 195 research institutions in 20032 1Data from Campbell, Blumenthal et al, 1996; 2AUTM data, 2004

4. Relationships have benefits and risks • There are many benefits • New products and medicines: 2,230 products were produced through institutional licensing in FY 1998 – 2003 (AUTM) • Increased resources for academic projects • Bi-directional flow of knowledge and materials • Academic faculty participate in application of research • Financial interests have potential risks • Introduce bias into the conduct or reporting of research • Decrease “openness” and sharing of data and materials • Delay trainees • Harm human research participants and patients • Decrease public trust in medical research

5. Financial conflict of interest in science • One definition: Situations in which financial considerations may compromise, or have the appearance of compromising, an investigator’s professional judgement in conducting or reporting research.3 • A situation, not a behavior/outcome 3 AAU and AAMC

6. Federal Regulation – PHS/NSF • Investigators must disclose any “significant financial interests” to the institution that would reasonably appear to be affected by the proposed research • Anything of monetary value including, but not limited to, salary or payment for services (e.g., consulting fees or honoraria), equity interests, and intellectual-property rights that exceed $10,000 in value and represent more than 5% ownership interest in any single company. • Institutions determine whether or not investigators’ financial interests could directly and significantly affect the design, conduct, or reporting of the research (present conflicts of interest) and how to proceed (eliminate, reduce, manage).

7. Why this issue is important: The public trust is at stake • “The tentacles of those ethics problems with NIH researchers…does a lot to undermine the faith the public has in NIH.” Rep. Blackburn, September 13, 2006. • “Leading medical journals seem to be having a difficult time disentangling themselves from the pharmaceutical and medical device industries.” NYT editorial, July 23, 2006

8. JAMA scandal • “Financial Ties to Industry Cloud Major Depression Study” (Wall St. Journal) • February ’06 article concluded that stopping the use of antidepressants during pregnancy greatly increases the risk of relapse. • In total, the authors failed to disclose 60 different financial relationships (mainly consulting, lecturing, and prior grants) with drug companies related to the research reported in the article. • Resulted in more changes to JAMA COI policy

9. Neuropsychopharmacology scandal • “Journal Editor Quits Over Conflict Scandal” (The Scientist) • Editor steps down in after he published a paper (July ‘06) in the journal reporting positively about a depression therapy (device) without disclosing that 8 of 9 authors were consultants to the company that makes the device. • The authors say that disclosures were submitted to the journal but due to an “oversight” were not included in the published version. • The journal is currently revising its procedures.

10. What does all this attention tell us? • The press is interested • They think the public is interested • Conflicts of interest are on the radar screen • “Misbehavior” by scientists is on the radar screen, and having conflicts of interest equates with “misbehavior” in the press/public’s mind • Voluntary standards are made to appear not to be working, and may in fact not be working • The scientific community has been paying attention, but it may be time for a stronger stand

11. Role of investigators/authors • The vast majority of biomedical researchers are guided by the highest ethical and professional motives. • Scientists want to do the right thing, if they know what the right thing is. • Investigators, as a group, determine the effectiveness of policies and practices. • The perspective of investigators had not been well-articulated in the policy debate.

12. FASEB Phase I effort (’05-’06) • June 2005 conference – Elias Zerhouni, Bill Brody, Gail Cassell and others • Steering Committee – FASEB Board members, Bob Gussin (J&J), Lou Sherwood (Merck/APPI), Eric Campbell (Harvard), Ann Hammersla and Jim Severson (AUTM), Carol Blum (COGR), Josephine Johnston (Hastings Center) • White paper, “Shared responsibility, individual integrity: Scientists addressing conflicts of interest in biomedical research”4 4 http://opa.faseb.org/pages/Advocacy/coi.htm and FASEB J, In press

13. FASEB Principles for Investigators • Objectivity • Transparency • Accountability

14. FASEB Phase II effort (’06-’07) • Funding: ORI-AAMC RCR Program for Academic Societies • Objectives • Increase awareness and understanding of conflict of interest issues on the part of investigators • Develop more standard practices for conflict of interest disclosure and management in biomedical research • Generate buy-in at the national level (target completion – Summer 2007)

15. Phase II Coalition • FASEB: Leo Furcht, Laura Brockway, Howard Garrison • AAMC: Susan Ehringhaus • AAU: Patrick White • AAAS: Mark Frankel • ARVO: Todd Margolis • ASCB: Joan Goldberg • ORI: Lawrence Rhoades, Nick Steneck • NIH: Norka Ruiz Bravo, Ezekiel Emanuel • U of Washington: James Severson • Mass General Hospital: Eric Campbell • ASM and Eli Lilly Corp: Gail Cassell

16. Purpose of financial disclosure in publications • Essential for transparency • To the editor: • So that the manuscript is evaluated with full knowledge of its circumstances • Responsibility of the author • To the reader: • Assures the reader will have this information to interpret the work • Responsibility of the journal and author

17. Indifference/insensitivity about the issues Confusion about policies (In the JAMA case, the authors explained that the research was financed by a federal agency, and, in their view, no conflict existed. “It didn’t seem relevant.”) Authors think that it’s somehow “naughty” Authors are confident that they are not affected by conflicts of interest Why might some authors not disclose?

18. What do journal policies look like? • N = 21 journals (1 of each FASEB society) • Clinical and basic biomedical journals • Analysis of on-line editorial policies and corresponding submission forms when available • Accessed November 7-9, 2006 • Of 21 journals, 14 had COI policies on-line

19. Of the 14 journals – Author disclosure 13 9 6 5 5 4 3 2 2 2

20. Of the 14 journals 11 7 6 6 5 1

21. General observations • Clinical and basic research journals differ in COI policies • There are cases in which language used in editorial policies is not the same as in instructions to authors or authorship forms • Examples of disclosure statements, if required in the text, are useful • Some policies do not explain if disclosure to the editor is or is not kept confidential in the review • Many policies do not make clear what the COI policy is trying to achieve

22. FASEB recommendations • Investigators should be aware of and adhere to journal policies.5 • If researchers are unclear about these policies, contact with the editor is encouraged.5 • When in doubt, investigators should err on the side of transparency. Failure of authors to disclose does not automatically translate to the article being flawed. Nevertheless, it does create the perception that the authors had something to hide and decreases public trust in medical research.6 5FASEB white paper, July 2006 and 6Brockway and Furcht, JAMA letter to editor, in press

23. Recommendations (cont.) • It would be beneficial to focus on “relationships” and not “conflicts of interest” • Journal disclosure policies should avoid requiring investigators to judge whether there may or may not be a relationship that could create bias and to simply require disclosure of relevant industry relationships.5 • There is a clear need for some consistency in disclosure requirements. Variable policies may result in confusion and non-compliance by investigators.5 • Editors and readers should have access to this background information.6 Also see Council of Science Editors Guidance

24. Conclusions • Academia-industry relationships are a beneficial and fundamental part of the modern life science enterprise. The challenge is disclose and oversee these relationships to maximize the benefits and minimize risks. • This is achieved through individual and shared responsibility (investigators, institutions, industry, government, journals, societies). • Journals play an important role because they communicate research results to the public. • It is essential to preserve the public trust through maintaining objectivity, transparency, and accountability.

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

26. Questions?Comments? Laura Brockway FASEB Office of Public Affairs lbrockway@faseb.org 301-634-7650