1. Research Ethics: Conflicts of Interest Michael Kalichman San Diego Research Ethics Consortium La Jolla Institute for Allergy and Immunology August 24, 2011

2. What is a conflict of interest? Increased risk of bias or poor judgment because of an obligation or commitment to two or more competing interests Financial Conflicts of Interest…

3. Dennis Selkoe Harvard Scientist, Massachusetts General Hospital 1998: NIH report endorsing blood test for Alzheimer’s Selkoe signed the report, but failed to note: Test manufactured by Athena Selkoe helped found Athena When Athena went public in 1993, Selkoe had 225,000 shares worth $3 million Another Harvard scientist (and a developer of competing test): “I have conflicts too, but I don’t sit on a committee telling people to use the test.”

4. What might be biased? Choice of research focus Framing of research questions Choice of research methods and design Selection of research participants Collection and selection of research data Analysis and interpretation of research data Deciding how and if to publish …in all cases, bias might be either intentional or unintentional

5. Positive Findings Stelfox, Chua, O’Rourke, and Detsky, New England Journal of Medicine, 1998 Reviewed reports on safety of calcium channel antagonists Endorsements more likely to come from those receiving company support

6. Percent reports with Direct or Any commercial support

7. Disclosure? Krimsky et al., 1998 Reviewed 789 scientific papers 34% of articles authors owned stock served as consultants had a financial stake 62,000 papers only 0.5% included disclosure statements

8. If a newly published study demonstrates that a new drug is effective, before making use of that study in your own research, do you need to know what financial stake, if any, the authors have in the success of that drug? Questions for Discussion: 1 of 2

9. What about other conflicts of interest? Publishable results Academic advancement Fame Life outside of work? Pet theories

10. Questions for Discussion: 2 of 2 If a newly published study reports a genetic basis for depression, before making use of that study in your own research, do you need to know whether any of the authors have a clinical diagnosis of depression?

11. Regulatory Path 2007Environmental Science and Technology journalist (Thacker) joins Senator Grassley 2008Based on Thacker’s investigation: “Researchers Fail to Reveal Full Drug Pay” (NY Times, June 2008) Grassley expressed concerns about COIs in NIH-supported institutions to NIH Director Zerhouni 2009Grassley and Senator Kohl urge  transparency at NIH IG Report: 9 cases of failure to report >$1 million 2010New proposed rules for COIs

12. Final Rule on Financial Conflict of Interest Regulations August 23, 2011 42 CFR Part 50 | 45 CFR Part 94 RIN 0925-AA53 [Docket Number NIH-2010-0001] Responsibility of Applicants for Promoting Objectivity in Research for which Public Health Service Funding is Sought and Responsible Prospective Contractors AGENCY: Department of Health and Human Services. ACTION: Final Rule. http://grants.nih.gov/grants/FCOI_Final_Rule_inspection_Desk.pdf

13. § 50.601 Purpose. This subpart promotes objectivity in research by establishing standards that provide a reasonable expectation that the design, conduct, and reporting of research funded under Public Health Service (PHS) grants or cooperative agreements will be free from bias resulting from Investigator financial conflicts of interest. Final Rule on Financial Conflict of Interest Regulations August 23, 2011

14. Significant financial interest means: “...investigators are required to disclose to an official(s) designated by the institution a listing of Significant Financial Interests... that would reasonably appear to be affected by the research proposed for funding by the PHS.” “...anything of monetary value, including, but not limited to, salary or other payments for services …; equity interests …; and intellectual property rights.” “…exceed $10,000” Existing Public Health Service Policy

15. Significant financial interest means: (1) A financial interest consisting of one or more of the following interests of the Investigator (and those of the Investigator’s spouse and dependent children) that reasonably appears to be related to the Investigator’s institutional responsibilities: (i) With regard to any publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity in the twelve months preceding the disclosure and the value of any equity interest in the entity as of the date of disclosure, when aggregated, exceeds $5,000…; New Public Health Service Policy

16. Significant financial interest means: (1) A financial interest consisting of one or more of the following interests of the Investigator (and those of the Investigator’s spouse and dependent children) that reasonably appears to be related to the Investigator’s institutional responsibilities: (ii) With regard to any non-publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity in the twelve months preceding the disclosure, when aggregated, exceeds $5,000, or when the Investigator (or the Investigator’s spouse or dependent children) holds any equity interest (e.g., stock, stock option, or other ownership interest); or New Public Health Service Policy

17. Significant financial interest means: (1) A financial interest consisting of one or more of the following interests of the Investigator (and those of the Investigator’s spouse and dependent children) that reasonably appears to be related to the Investigator’s institutional responsibilities: (iii) Intellectual property rights and interests (e.g., patents, copyrights), upon receipt of income related to such rights and interests. New Public Health Service Policy

18. Major Changes Effective August 25, 2011 1.Threshold decreased from $10,000 to $5,000 2.Disclosure requirements include review of not just PHS- funded research, but any investigator institutional responsibilities 3.Public disclosure now required of institution of financial conflicts of interest New Public Health Service Policy

19. Guidelines for Conflicts of Interest Individual Recognize Avoid or Minimize Disclose Who needs to know? How much detail? Manage Journals, Professional, Institutional, Organizational

20. Conflicts of Interest? Dr. Mitchell Conrad has received a grant from an industrial source to do basic research that has long-term implications for commercialization. A new graduate student, Michelle Lawless has just joined his lab following the completion of one semester of graduate coursework. Dr. Conrad outlines several projects that can be pursued by Michelle under this industrially-sponsored research program. Dr. Conrad indicates that there is a proviso listed in the industrial grant agreement which says that all material to be submitted for publication first be reviewed by the company. This review must always be completed within 120 days. Dr. Conrad points out that this presents only a minimal disruption to the normal publication process as compared to the unrestricted publication of material gathered under federal research grants. He also mentions that the positive aspects of working on this proposal include the fact that there is money in the grant for Michelle to travel to at least two meetings per year. Also the grant application provides money for a personal computer that will be placed at Michelle's lab station while she is working on the project. Dr. Conrad emphasizes that working on the project will likely give Michelle an "inside track" with the company should she want to pursue job possibilities there following graduation. Michelle agrees to work on the project. © ASM Press, 2000, Scientific Integrity by F.L. Macrina, used with permission.

21. Insider Trading? Mr. Asset, a graduate student of Dr. Bond, has been conducting physicochemical studies on the properties of a new polymer. The research is sponsored by Chemical Industries, Inc. and it is understood by Mr. Asset and Dr. Bond that the results are proprietary, confidential, and cannot be used in Mr. Asset's thesis. Mr. Cash, the technical liaison from Chemical Industries, Inc., meets with Mr. Asset and Dr. Bond and expresses his pleasure with the outcome of the recent studies and observes that the new results are the last data required to market a new generation of fire-resistant electrical insulating material. Mr. Cash further comments that this is the product that Chemical Industries, Inc. needed to regain its market share, and the stock of Chemical Industries, Inc. would soar once investors knew of the new product. That evening at dinner with his wife and brother-in-law, an investment banker, Mr. Asset tells them about Mr. Cash's enthusiasm about their recent research results and Mr. Cash's expectations that Chemical Industries' stock would greatly increase in value as soon as the new product was announced. The next day Mr. Asset's brother-in-law advises several of his clients to purchase Chemical Industries' stock. © ASM Press, 2000, Scientific Integrity by F.L. Macrina, used with permission.

22. Research Ethics Resources NIH Conflicts of Interest Page http://grants.nih.gov/grants/policy/coi UC San Diego Research Ethics Program http://ethics.ucsd.edu/research.html Responsible Conduct of Research Education Committee http://rcrec.org Resources for Research Ethics Education http://research-ethics.net