2. MANAGING CONFLICTS OF INTEREST IN UM/JHS HUMAN SUBJECT RESEARCH 1.GENERAL PRINCIPALS AND PROCEDURES 2. REGULATIONS, POLICIES AND UM PROCESS Human Subjects Research Office 1500 NW 12th Avenue, Ste. 1000, Miami, FL 33136 Tel. 305-243-3195

4. www.hsro.miami.edu www.hsro.miami.edu STILL THE DULLEST WEBSITE AT UM! Investigator Resources Ancillary Committee Information Ancillary Committee Information eProst New User Instructions on left side of home pageeProst New User Instructions TranslationsTranslations -- click to link WIRB Submission Coversheet News & EventsNews & Events About the HSROAbout the HSRO Institutional Review Boards eProst Ethics Federal Regulations & Guidance HSRO Forms & Documents Policies & Procedures HIPAA Other Resources

5. www.hsro.miami.edu Human Subjects Research Office The Human Subjects Research Office (HSRO) provides administrative support for the University of Miami Institutional Review Boards…. Recent Updates REMINDER: The HSRO is continually reviewing and revising its written Policies and Procedures… During the month of April, 2007, the following Policies were updated: –General Principles of Informed Consent –Lapse in IRB Approval –CIRB

6. TABLE OF CONTENTS Preface Background Topics A. History Approved 11/30/05History Approved 11/30/05 B. Ethical Principles Approved 11/30/05 Ethical Principles C. Federal Regulations Approved 11/30/05 Federal Regulations D. Federal Wide Assurance (FWA) Approved 11/30/05Federal Wide Assurance (FWA) E. Does a Project Constitute Human Subjects Research Approved 7/24/06 Does a Project Constitute Human Subjects Research F. Medical Case Reports Approved 2/22/07Medical Case Reports Approved 2/22/07 G. Retrospective Chart Reviews Approved 2/22/07Retrospective Chart Reviews Approved 2/22/07 H. Off-Label Use of Marketed Drugs, Biologics or Medical Devices Approved 2/22/07Off-Label Use of Marketed Drugs, Biologics or Medical Devices Definitions Approved 2/8/05Definitions Approved 2/8/05 Authorities and Responsibilities A. IRB Authority Approved 7/24/06 IRB Authority Approved 7/24/06 B. HSRO Responsibility Approved 2/13/06HSRO Responsibility Approved 2/13/06 C. IRB Policy and Procedures Committee Approved 10/11/05IRB Policy and Procedures Committee Approved 10/11/05 D. Responsibility of Principal Investigators Approved 2/13/06Responsibility of Principal Investigators Approved 2/13/06 E. Responsibilities of UM Deans/Department Chairs Approved 2/13/06Responsibilities of UM Deans/Department Chairs Approved 2/13/06 F. Responsibilities of Students and Faculty Advisors Approved 2/13/06 Responsibilities of Students and Faculty Advisors Approved 2/13/06

7. Institutional Review Boards A. IRB Membership and Structure Approved 2/23/06IRB Membership and Structure Approved 2/23/06 B. IRB Chairs and Vice-Chairs Approved 2/23/06IRB Chairs and Vice-Chairs Approved 2/23/06 C. IRB Members Approved 2/23/06. IRB Members Approved 2/23/06 Conflict of Interest A. General Principles Approved 10/27/06 A. General Principles B. IRB Members, Alternate Members, Ad Hoc Members and Guests Approved 10/27/06 B. IRB Members, Alternate Members, Ad Hoc Members and Guests Approved 10/27/06 C. Principal Investigators and Key Personnel Approved 10/27/06C. Principal Investigators and Key Personnel Approved 10/27/06 D. Human Subject Conflict of Interest Committee Approved 10/27/06D. Human Subject Conflict of Interest Committee Approved 10/27/06 E. IRB Review and Approval of Conflict Management Approved 10/27/06E. IRB Review and Approval of Conflict Management Approved 10/27/06 IRB Meetings A. Agenda Approved 3/14/06 A. Agenda B. Minutes Approved 3/14/06 B. Minutes Approved 3/14/06 C. Reviewer Assignments Approved 3/14/06 C. Reviewer Assignments Approved 3/14/06 D. Consultants and Ad Hoc Reviewers Approved 3/14/06 D. Consultants and Ad Hoc Reviewers Approved 3/14/06 E. Confidentiality of IRB Meetings and Guest Policy Approved 3/14/06 E. Confidentiality of IRB Meetings and Guest Policy Approved 3/14/06 F. Meetings and Quorum Approved 3/14/06 F. Meetings and Quorum Approved 3/14/06 G. Voting Approved 3/14/06 G. Voting Approved 3/14/06

8. General Principles for IRB Reviews A. Submission of New or Continuing Studies Approved 3/14/06 A. Submission of New or Continuing Studies Approved 3/14/06 B. Recommendations for Review Category Approved 3/14/06 B. Recommendations for Review Category Approved 3/14/06 C. Criteria for IRB Approval Approved 3/14/06 C. Criteria for IRB Approval Approved 3/14/06 D. Approval Duration Approved 3/14/06D. Approval Duration Definition of IRB Review Types A. Exempt Studies Approved 3/31/06 B. Expedited Reviews Approved 3/31/06 C. Reviews Requiring The Convened IRB Approved 3/31/06A. Exempt Studies Approved 3/31/06B. Expedited Reviews Approved 3/31/06C. Reviews Requiring The Convened IRB Approved 3/31/06 IRB Review Of Initial Studies A. Initial Studies-Exempt Approved 3/31/06 B. Initial Studies-Expedited Approved 3/31/06 C. Initial Studies-Convened IRB Review Approved 7/24/06A. Initial Studies-Exempt Approved 3/31/06B. Initial Studies-Expedited Approved 3/31/06C. Initial Studies-Convened IRB Review Approved 7/24/06 IRB Review of Continuing Studies A. General Principles For Review Of Continuing Studies Approved 3/31/06 B. Continuing Studies-Expedited Approved 3/31/06 C. Continuing Studies-Convened IRB Review Approved 7/24/06A. General Principles For Review Of Continuing Studies Approved 3/31/06 B. Continuing Studies-Expedited Approved 3/31/06C. Continuing Studies-Convened IRB Review Unanticipated Problems and Adverse Events A. Problems and Events that Require Prompt Reporting Approved 4/27/06Problems and Events that Require Prompt Reporting Approved 4/27/06 B. Definitions Approved 4/27/06Definitions Approved 4/27/06 C. Review of Problems or Events that Require Prompt Reporting Approved 4/27/06Review of Problems or Events that Require Prompt Reporting Approved 4/27/06 D. Reportable Problems/Events at Continuing Review Approved 4/27/06Reportable Problems/Events at Continuing Review Approved 4/27/06 E. Safety Notice/Report from Sponsor or Central Site Approved 4/27/06Safety Notice/Report from Sponsor or Central Site

9. SOURCES OF CONFLICTS 1.IRB MEMBERS 2.IRB STAFF (WHOSE RECOMMENDATIONS MAY INFLUENCE MEMBERS) 3.PRINCIPAL INVESTIGATORS 4.KEY PERSONNEL 5.DSMB MEMBERS 6.INSTITUTIONAL

10. EACH COI SOURCE HAS THE POTENTIAL TO: 1. Introduce bias into research design, conduct or reporting 2. Place human subjects at greater risk or decrease research benefits to them 3.Compromise investigators’ or students’ academic pursuit 4.Misuse University resources

11. IRB MEMBERS AND STAFF 1. apply regulations and UM policies 2. apply UM ethical standards 3. question: might a COI challenge the integrity of a reasonable individual 4. question: might a situation appear to a reasonable member of the public to be a ` conflict that could challenge the integrity of the conflicted party

12. INVESTIGATORS 1. most investigators deny that funding or other putative COIs would compromise their findings 2. media have raised issues of ‘funding effects’ biasing results toward sponsors 3. perceptions vs realities

13. INSTITUTIONAL CONFLICTS complicating factors 1. institutions seek financial gains from faculty discoveries 2. COI must be defined independently from investigator COIs 3. all investigators, IRB members and staff are involved 4. COI is potential rather than real. COI cannot be defined quantitatively

14. UM-JHS PROCESS 1. Investigator indicates COI 2. UM Contracts and Compliance ` Committee 3. [JHS Clinical Research Review Committee] 4. IRB Conflict of Interest Committee 5. IRB

15. CONFLICT OF INTEREST COMMITTEE UNDERSTANDS CONFLICTS ARE INEVITABLE REQUIRES DISCLOSURE AND TRANSPARENCY RECOMMENDS TO IRB A) SHOULD THE CONFLICT BE PERMITTED B) IS THE CONFLICT MANAGEABLE C) HOW SHOULD THE CONFLICT BE MANAGED

16. SUMMARY 1. managing COIs is complex 2. COI management requires disclosure and transparency 3. thoughtful policies and strict compliance are required 4. science is not broken

17. BUT…

18. Importance of Public Trust Kelly Insignares, Ph.D., MBA, CIP

19. Regulations Public Health Service Act - DHHS –42 CFR 50.604(b), 45 CFR 94.4 (b) –42 CFR 50.603, 45 CFR 94.3 –42 CFR 50.605(a), 54 CFR 94.5 (a) –45 CFR 46.107 (e) FDA –21 CFR 54, 21 CFR 56.107 (e)

20. When in doubt, disclose! Mechanisms for disclosure –Outside consulting form – annual Faculty Affairs –HSRO / IRB application and notifications – disclosure is required on a per study basis –Contracts and Compliance Committee / CRIS Updates if a new conflict arises or an existing conflict changes within 10 days after onset –Submit notification to the HSRO with COI disclosure form

21. Current Thresholds SFI $10,000 or more in any preceding or anticipated 12 month period 5% or greater ownership equity interest Serving in a management position such as director, officer or partner Intellectual property rights – patents, licensing agreements, copyright or royalties

22. Institutional Conflicts Disclosure of institutional conflict –Research involves a drug, device or other invention created at UM by the PI, or by anyone employed at UM who may derive financial benefit –UM may gain financially by the research Compelling circumstances (research could not be conducted as safely or effectively anywhere else)

23. HSRO Procedures for COI COI submitted by PI and key personnel PI recommendation on managing the COI Reviewed by the HSCOIC –Includes community representative HSCOIC recommendation sent to the IRB Final conflict management plan –Determined by the IRB Communication to the PI and Department Chair

24. Conflict Management Plans Disclosure of the financial interest –COI ICF template language Independent external monitoring Modification of the study Divestiture of the financial interest Severance of conflicting relationship

25. Conclusion Conflicts of Interest in research are not illegal but they can influence decisions and actions Let’s be proactive and address these situations in a collaborative manner as they arise Protect the rights and well being of our research subjects – disclose!