1. 1 FINANCIAL CONFLICTS OF INTEREST IN RESEARCH Avoiding Adverse Consequences by Disclosing, and then Reducing, Eliminating or Managing Conflicts Susan H. Frey, J.D. Assistant Provost for Research Compliance and Health Information Privacy 88 E. Newton Street M-840 Boston University Ph: 1-617-414-4736 Fx: 1-617-414-4738 September 2009 http://www.bu.edu/research/compliance/financial-conflict/index.shtml

2. 2 Learning objectives What is a conflict of interest affecting research? What is a conflict of interest affecting research? How can conflicts of interest adversely affect the integrity and credibility of your research-related decision? How can conflicts of interest adversely affect the integrity and credibility of your research-related decision? How to comply with BUMC policies by filing Investigators’ Project-Specific Disclosures (PSD) How to comply with BUMC policies by filing Investigators’ Project-Specific Disclosures (PSD) How to work with the Advisory Committee on Investigators’ Conflicts of Interest if you file a positive disclosure How to work with the Advisory Committee on Investigators’ Conflicts of Interest if you file a positive disclosure

3. 3 UNIVERSITY RESEARCH PROGRAM COMPANY or INTELLECTUAL PROPERTY INVESTIGATOR FINANCIAL INTEREST Should I decide for University about its research-related activities in which I have a personal, external financial interest? Professor X RESEARCH COULD AFFECT FINANCIAL INTERESTS

4. 4 Examples of Investigators’ Decisions Conflicted Decisions as an investigator on research projects could affect: Conflicted Decisions as an investigator on research projects could affect: Your research (design, conduct, reporting) Your research (design, conduct, reporting) Your selection of research aims Your selection of research aims Your protection of human subjects and patient populations Your protection of human subjects and patient populations Your involvement of trainees Your involvement of trainees

5. Public scrutiny of conflicts of interest that appear to affect decisions in research involving drugs, devices and diagnostics in development or on the market. 5

6. 6 News Flash Senator Grassley of Iowa – Investigating Senator Grassley of Iowa – Investigating payments to physicians for consulting to drug companies (whose drugs being studied) payments to physicians for consulting to drug companies (whose drugs being studied) Question: Are Institutions and NIH adequately managing COI? Question: Are Institutions and NIH adequately managing COI? New NIH rules are now under consideration. New NIH rules are now under consideration.

7. BUMC Policies on Investigators’ COI Filing PSDs 7

8. 8 Policies on Investigators’ Conflicts of Interest (BU & BMC) Requires Project Specific Disclosures (PSD) on potential conflicts affecting institutional research projects http://www.bu.edu/handbook/policies/ethics/c onflict.html http://internal.bmc.org/policies/display_policy. asp?policy_id=692

9. 9 Project Specific Disclosures (PSD) Who must file? All BU and BMC “Investigators” must file Project Specific Disclosures. All BU and BMC “Investigators” must file Project Specific Disclosures.

10. Investigators= Individuals responsible for “designing, conducting or reporting” BUMC research Examples of individuals who would normally be considered Investigators include: All faculty BU/BMC researchers on the project All faculty BU/BMC researchers on the project All non-faculty BU/BMC researchers on the project who will All non-faculty BU/BMC researchers on the project who will Make a significant intellectual contribution to the research Make a significant intellectual contribution to the research Have independent responsibilities that could significantly affect the integrity of design, conduct or reporting of the research Have independent responsibilities that could significantly affect the integrity of design, conduct or reporting of the research Be included as authors on any presentation or publication of the research Be included as authors on any presentation or publication of the research Be listed on an IRB protocol for the research project and have independent responsibilities that could significantly affect the integrity of Be listed on an IRB protocol for the research project and have independent responsibilities that could significantly affect the integrity of data management and analysis, subject recruitment or enrollment, data collection, or any other aspect of subject safety and welfare or scientific integrity. data management and analysis, subject recruitment or enrollment, data collection, or any other aspect of subject safety and welfare or scientific integrity. PI is responsible for appending PSDs from all Investigators

11. 11 Project Specific Disclosure (PSD) When & where must PSD be filed? A PSD must be filed at the time of: Funding applications submitted to Research Administration (BUMC or BMC) – submit PSDs to OSP-MED or to BMC Grants Administration Funding applications submitted to Research Administration (BUMC or BMC) – submit PSDs to OSP-MED or to BMC Grants Administration BUMC IRB applications – submit PSDs, only if unfunded, to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738 BUMC IRB applications – submit PSDs, only if unfunded, to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738 Any unfunded research project affected by significant financial interest – submit PSDs to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738 Any unfunded research project affected by significant financial interest – submit PSDs to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738 Material change not previously disclosed (more below) – submit supplemental information to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738 Material change not previously disclosed (more below) – submit supplemental information to Compliance Office, Attn. M. Johnson, Fax: 617-414-4738

12. 12 You should answer “Yes” on the PSD if your answer is yes to both parts of the question “Do you, your spouse, or dependent children “Do you, your spouse, or dependent children 1. have a “significant financial interest (SFI)”? 1. have a “significant financial interest (SFI)”?AND 2. that could reasonably appear to be affected by the research? 2. that could reasonably appear to be affected by the research?

13. 13 First part of PSD question: Have a SFI? Yes, if the detailed definition of SFI on the PSD form applies– err on the side of disclosure Yes, if the detailed definition of SFI on the PSD form applies– err on the side of disclosure Common examples of a SFI: Common examples of a SFI: You expect to earn consulting income from a in excess of $10,000 in the past or coming twelve months You expect to earn consulting income from a company interested in the research in excess of $10,000 in the past or coming twelve months You have any equity in a You have any equity in a company interested in the research You have rights in intellectual property used or studied in the research You have rights in intellectual property used or studied in the research University base salary and financial interests in mutual funds are not SFI University base salary and financial interests in mutual funds are not SFI

14. 14 Second part of PSD question: SFI could reasonably appear to be affected by the research? Common examples : Common examples : Company sponsors the research Company sponsors the research Company will have access to pre-publication results of the research Company will have access to pre-publication results of the research Company has rights in product, invention, device, drug, program, IP, etc. studied in the research. Company has rights in product, invention, device, drug, program, IP, etc. studied in the research. You have rights in intellectual property being used or studied in the research. You have rights in intellectual property being used or studied in the research.

15. 15 Disclosure of Material Changes Investigators must disclose material changes Investigators must disclose material changes by filing an updated PSD or other notification with the research administration office and the Committee, if: by filing an updated PSD or other notification with the research administration office and the Committee, if: “No” disclosure scenario changes to “Yes” “No” disclosure scenario changes to “Yes” A COI management plan (more below) is based on facts which materially change. E.g. A COI management plan (more below) is based on facts which materially change. E.g. Human subjects or trainees were not, and now will be, involved Human subjects or trainees were not, and now will be, involved An interested company is formed An interested company is formed

16. BUMC Review of “Yes” PSDs 16

17. 17 CRC & BUMC Advisory Committees on Investigators’ Conflicts of Interest Appointed in December, 2003, by University Provost, Medical Campus Provost and BMC President Appointed in December, 2003, by University Provost, Medical Campus Provost and BMC President Composed of investigators (in diverse departments) and administrative representatives Composed of investigators (in diverse departments) and administrative representatives

18. 18 Committee Review 1. Conflict of Interest: Could SFI directly and significantly affect University research? 2. If so, impose conditions or restrictions: How can we eliminate, reduce or manage the conflict of interest?

19. 19 Conditions or Restrictions: Reduce? Reduction of COI Generally means reducing the magnitude of the financial interest Reduction of COI Generally means reducing the magnitude of the financial interest Usually is applies only if the SFI can be reduced below the $10,000 threshold for consulting income Usually is applies only if the SFI can be reduced below the $10,000 threshold for consulting income

20. 20 Conditions or Restrictions: Eliminate? Elimination generally means divestiture of the SFI Elimination generally means divestiture of the SFI BUMC policy requires the Committee to presume that a COI affecting human subjects research must be eliminated, unless: BUMC policy requires the Committee to presume that a COI affecting human subjects research must be eliminated, unless: Compelling circumstances warrant managing rather than eliminating the COI. Compelling circumstances warrant managing rather than eliminating the COI.

21. 21 Compelling circumstances Strict scrutiny must be given by the Committee to all relevant factors in the COI scenario Strict scrutiny must be given by the Committee to all relevant factors in the COI scenario Compelling circumstances likely to exist where all factors together indicate: Compelling circumstances likely to exist where all factors together indicate: Low potential for harm to human subjects and patient populations; and Low potential for harm to human subjects and patient populations; and High potential for loss of important early stage research due to unique qualification or situation of conflicted investigator. High potential for loss of important early stage research due to unique qualification or situation of conflicted investigator.

22. 22 Conditions or Restrictions: Management? Management Plans are developed by the Committee with investigator input and reviewed with Investigators before being recommended to the Provost or President Management Plans are developed by the Committee with investigator input and reviewed with Investigators before being recommended to the Provost or President

23. 23 Elements of Management Plans may include (without limitation): 1. Disclosure to chairman and dean 2. Disclosure to all co-workers on the project or in the lab ( Colleague Disclosure letter) 3. Disclosure of SFI in publications and presentations of results or in expert testimony 4. Independent Reviewer of data safety and integrity. 5. Independent monitor for co-investigators, trainees and graduate students supervised by the conflicted investigator; approval for involvement of students as being academically appropriate 6. Recusal (in whole or in part) and substitution of an unconflicted independent investigator responsible for human subject welfare and/or data integrity and analysis. 6. Recusal (in whole or in part) and substitution of an unconflicted independent investigator responsible for human subject welfare and/or data integrity and analysis.

24. On-line periodic reporting on your compliance with your Management Plan Committee requests reports, including uploading evidence of disclosure in journals, and reports from any required independent reviewers, etc. Committee requests reports, including uploading evidence of disclosure in journals, and reports from any required independent reviewers, etc. 24

25. 25 Management: Informed Consent BUMC policy at present: BUMC IRB determines whether SFI should be disclosed in informed consent BUMC policy at present: BUMC IRB determines whether SFI should be disclosed in informed consent BUMC Advisory Committee on Investigators’ Conflicts of Interest copies IRB on all decisions affecting projects of human subjects research. BUMC Advisory Committee on Investigators’ Conflicts of Interest copies IRB on all decisions affecting projects of human subjects research.

26. 26 Audit and Enforcement Failure to report a SFI or to comply with a decision of the Committee may be detected in a number of ways: Failure to report a SFI or to comply with a decision of the Committee may be detected in a number of ways: Whistleblowers, agencies reviews, internal audit, Committee requests for periodic reports Whistleblowers, agencies reviews, internal audit, Committee requests for periodic reports Depending on the seriousness of non- compliance, corrective action or sanctions are recommended to the institutional officials. Depending on the seriousness of non- compliance, corrective action or sanctions are recommended to the institutional officials.

27. 27 Disclosure Protects You!! Inevitable human errors occur in the management of science in our increasingly complex environment. Inevitable human errors occur in the management of science in our increasingly complex environment. When an error occurs, you want to be “squeaky clean” When an error occurs, you want to be “squeaky clean” “My conflict of interest was fully disclosed and has been monitored and managed in accordance with federal and University policies.” “My conflict of interest was fully disclosed and has been monitored and managed in accordance with federal and University policies.”