Presented by: Arthur O. Anderson MD Director Office of Human Use and Ethics, US Army Medical Research Institute of Infectious Diseases The opinions presented here are the personal views of the author and are not to be construed as official or as representing the Department of Defense.

       1962-1966 I had 16 credit hr in philosophy before med school and pathology training 1962-1974 HQS Human Research Committee 1974- Questionable Tularemia study 1975-Appointed chair (OGE-450) 1993-Research Integrity added to duties 1999-2005 FCPS ethics panel, faculty COI 2008-Consultant to a major university to review faculty and institutional COI

     We all have personal interests Some are financial and some are not (e.g., prestige, desires, career advancement) An interest is not necessarily a conflict An interest becomes a conflict when it has the potential (or the appearance of the potential) to affect our judgment Conflicts may be potential or actual, perceived or real, harmful or insignificant.

Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

 “Conflicts of Interest in Health Care” has emerged as a “hot-button” issue for Congress and the media.

 Financial conflicts of interest raise concerns about the objectivity and trustworthiness of research conduct and publications, the prudent management of scientific investigations and other activities in the public interest , and the commitment of health care professionals best interests of patients .

to the  Failures of individuals and institutions to disclose and appropriately manage financial ties with industry (including pharmaceutical, medical device, medical supply, and insurance companies) contribute to questions about whether industry has undue influence in research and other activities.

 As medical research, professional education, health care, and institutional management have become vastly more complex, the task of managing conflicts of interest has become more challenging.  Industry - leading funder of medical research, and research conducted in nonacademic settings.  ◦ Industry also funds the “development of evidence reviews” and “practice guidelines” that are intended to help translate research findings into practice.

Such guidelines may shape clinical choices and may even be used to evaluate professional or institutional performance.

  Federal Government employees are prohibited by criminal statute (18 U.S.C. §§ 201-209) participating personally and substantially in a particular matter as part of official duties which will have a direct and predictable effect on their financial interest or the financial interest of their spouse, minor child, outside employer from , or certain others. Code of Federal Regulations Title 5, Volume 3, Chapter XVI Office of Government Ethics Executive Branch, Subpart D Part 2635 Standards of Ethical Conduct for Employees of the _Conflicting Financial Interests, interests Sec.2635.402

Disqualifying financial 6

     ◦ 32 CFR 219, Protection of Human Subjects Paragraph 219.107(e) No IRB Member COI.

AR 70-25, Use of Volunteers as Subjects of Research, Appendix C-7 Conflict of Interest HRPP Conflict of Interest - Policy/Procedure 21 CFR 54, Financial Disclosure by Clinical Investigators (1 April 2008) 42 CFR 50, Subpart F, & 45 CFR 94, (11 July 1995) Responsibility of Applicants for Promoting Objectivity in Research for which PHS Funding is Sought * * (Revisions & Proposed Rule , comment period ended 21 August 2010)



This biblical quote

“

And why beholdest thou the mote that is in thy brother's eye, but considerest not the beam that is in thine own eye?”

Matthew 7:3-5 

May show how long we have known about our problem with self-perception

Lester M. Crawford, Commissioner of the U.S. Food and Drug Administration (FDA), was charged October 16, 2006, in federal court "for conflict of interest and making false statements related to his investments." "Crawford, 68, falsely stated in a 2004 government filing that shares of Sysco Corp. and Kimberly-Clark Corp. had been sold when he and his wife continued to hold them, U.S. Attorney Jeffrey Taylor said in the charging documents. Crawford also failed to disclose income from exercising stock options in Embrex Inc., the documents said."

   ◦ ◦ ◦ Institutional Private sponsor is spin-off from institution Institution holds stock in sponsor Institution holds patent on test article IRB Member ◦ ◦ ◦ ◦ ◦ ◦ Member is a co-investigator on study Member’s spouse is a member of study team Member owns or buys stock in sponsor Investigator Principal investigator (PI) has personal interest the article under study, product inventor or PI’s prestige is linked to its success PI financially invested in sponsor company or on payroll Sponsor rewards PI for meeting study goals Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

 Identify individuals whose interests may result in prohibited conflicts, and what are the reporting thresholds and categories  Have written procedures and criteria for interpreting information about interests  Have a management plan to enable decisions, disclosure requirements, and monitor activities if conflicts of interest are found Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

 ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Institute officials must Foster research productivity Balance numerous institutional interests Support IACUC/HUC/QARCO/IBC etc. – protect and reinforce their authority, freedom and autonomy Recruit and retain outstanding researchers Enforce high standards for research integrity Rake in and distribute the royalties, MIPRs etc Facilitate product development Keep institution off front page of newspaper Pressure to accomplish mission objectives Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

    Not an easy answer within DOD Presently any institutional or individual COI Management is referred to the JAG office and an attorney issues a legal opinion Often these opinions fail to deal with ethical issues related to factors other than money Universities include information about COI in faculty/student handbooks and define conflict of interest pretty clearly. They also define conflict of commitment

COI in Educational Institutions

    ◦ Recommend member notify the IRB Chair or the IRB office of a COI in advance (use form) Elicit COI information from members at beginning of IRB meeting (This is a good opportunity to update COI Information if an annual COI form was used) IRB members with a COI must leave the meeting during deliberation and actions on activities for which the COI exists Members with COI may answer questions but must be absent during deliberation and voting.

IRB minutes must record the name of the IRB member with the COI, state they were recused and what time they left & returned to the meeting Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

      Disclosure to subjects, funders, journals, audiences Oversight/monitoring (Who does this?) (Use OGE 450, Separate review of financial disclosures by IRB Subcommittee for relevant holdings, interests, exceeding $10,000 or outside employment (*) Independent consent process (i.e., someone other than the PI does the consenting) Recusal from studies (i.e. ,the PI abstains from any involvement with studies linked to his COI) Divestiture of interests Are there “compelling exceptions” – ◦ think of PI COI vs national emergency laws that repeal COI considerations – after the emergency has passed has harm been done to subjects or confidence in integrity of agency Adapted from a 2009 PRIM&R Conflict of Interest Presentation by Suzanne M. Rivera, PhD.

Income from Pharma kept issues quiet = Affected Advice to Pharma vs Pharma’s Advice to PI, = ? Research Results, = ?Treatment Advice, = Self vs Patient’s Interest? e.g. FDA Estimates Vioxx Caused 27,785 Deaths.

And, Phase I studies on SSRI drugs did not report Suicides among normal volunteers in Phase I trials because no Federal Dollars were used.

    42CFR50, 45CFR94 mandate that IRB/IO have: Adequate disclosure mechanisms/transparency ◦ ◦ IRB review of COI management plans Procedures to reduce, eliminate, or manage COI COI disclosure included in Informed consent A poll of subjects gave counterintuitive results. COI by PI was seen by subjects as a plus without raising concern about lapsed clinical judgment or conflicted interest Duty to crosscheck investigator reports against websites that disclose payments

    Before Belmont, personal integrity and other values held by medical researchers directly determined whether or not patients were treated with care and respect or merely exploited for personal gain As you can see from this presentation, there are many places where personal integrity and character may have influences on the quality of COI information or whether disclosure of any COI is forthcoming Do we need to become integrity police?

“Conflict of interest represents the potential for biased judgment. But , it is not an indicator of the likelihood or certainty that such judgment or compromises will occur.”

Jeff Cohen. 2001 Acad. Med. 76.2 209-214

   ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ As long as we are human beings Have friends and business associates Are employed or are an employer Are passionate about our discoveries Invent industry Seek profits There will be opportunities that COI occur Therefore, it is important to: become COI self-aware, have systems in place to prevent COI from affecting judgment or allowing harm to subjects, and for management of COI if found

Arthur O. Anderson MD,

email: (COL MC Ret.) Director, Office of Human Use and Ethics, and Research Integrity Officer US Army Medical Research Institute of Infectious Diseases Fort Detrick, Frederick MD 21702-5011 [email protected]

Office Phone: 301 619 4723