Conflict of Interest & Informed Consent

for Department of Pediatrics Fellows Presented by University of Pittsburgh’s COI Office David T. Wehrle, CPA, CIA, CFE/Director Khrys X. Myrddin/Associate Director

July 3, 2008

What is a Conflict of Interest?

 A potential Conflict of Interest (COI) may exist if an individual’s outside interests (especially financial) may affect, or perceive to affect, his/her research, teaching, or administrative activities at the University.

Example of Potential Conflict of Interest

 Dr. Karola Kinderschuh developed an orthopedic device for pediatric patients;  The technology is owned by Strait & Narrow, Inc., in which Dr. Kinderschuh has an ownership interest;  Dr. Kinderschuh is conducting federally sponsored research to further evaluate the device.

Why should you care about COI?

 Your COIs can affect:  Your role in studies;  Your potential research subjects’ willingness to participate in the research;  How your research is viewed by the academic community and the public.

Importance of COI Management

If COI is not managed…  protection of human subjects may be compromised;   integrity of research may be at risk; the public may lose trust in the University and its research findings;  the investigator/faculty member may lose the respect of the academic community;

Importance of COI Management

cont’d   violation of scientific norms may result; University may lose public support and funding for academic science;  may violate terms of research grants and contracts (including failure to disclose COI) and federal regulations.

 research results may be excessively delayed or not published;

Importance of COI Management

cont’d     there may be a negative impact on students; University resources may be improperly used; increased government regulations may result; scandals or negative media attention may occur.

COIC’s Standard COI Management Plan for Human Subject Research

 University of Pittsburgh’s primary management tool is the Conflict of Interest Committee’s Standard COI Management Plan for Human Subject Research (SMP).

COIC’s Standard COI Management Plan for Human Subject Research

Details     I will not serve as Principal Investigator (PI) on this protocol, although I may serve as a co-investigator.

I will not be involved in the recruitment of volunteer subjects, nor will I administer the informed consent.

I will not engage in the recording of research data.

I will not be involved in clinical assessments of study eligibility criteria and intervention outcomes.

COIC’s Standard COI Management Plan for Human Subject Research

Details cont’d    I will not participate in data and safety monitoring activities.

I will not solely be involved in the interpretation of study results, although I may be involved as part of a committee that evaluates study results. Final decisions about the appropriate interpretation and presentation of research results shall be the responsibility of the PI. The existence of my Significant Financial Interest will be disclosed in the informed consent form.

COIC’s Standard COI Management Plan for Human Subject Research

Details cont’d  If other individuals (such as students, staff, or other faculty members) will be involved in research under this protocol, I will notify them of the existence of my Significant Financial Interest through the use of a standard notification form. Students will be engaged in the protocol only with the approval of their department chair or dean.

COIC’s Standard COI Management Plan for Human Subject Research

Details cont’d   I will disclose the existence of my Significant Financial Interest in any abstracts, presentations, press releases, or publications and in any proposals or applications for research funding related to the nature of that interest.

I will notify the chair of the Conflict of Interest Committee (Dr. Jerome Rosenberg; [email protected]

) of the titles and numbers of any present or future federal research grants supporting this protocol.

Aspects of Informed Consent Requirements

   “Clinical” aspects of Informed Consent: it is a matter of both ethics and federal regulation that research subjects  enter a study voluntarily;  be informed about risks and benefits;  understand the difference between experiment and treatment  understand the information provided.* COI aspects of Informed Consent: consistent with recommendations of professional organizations and federal guidance, University policy requires disclosure of financial COIs as part of the Standard Management Plan.

*Cf. Bramstedt, KA: A guide to informed consent for clinician-investigators; Cleveland Clinic Journal of Medicine 2004;71:11. http://www.ccjm.org/PDFFILES/Bramstedt11_04.pdf

Text of Informed Consent in SMP (Example)

 One or more of the investigators conducting this research has a financial interest in or a patent for the development of this pediatric heart valve. This means that it is possible that the results of this study could lead to personal profit for the individual investigator(s) and/or the University of Pittsburgh. This project has been carefully reviewed to ensure that your well-being holds more importance than any study results. Any questions you might have about this will be answered fully by Dr. Getrude Kleinherz, 412-123-4567, or by the Human Subject Protection Advocate of the University of Pittsburgh (866-212-2668).

Discussion

 Putting yourself in the place of a potential research subject, what are your thoughts on the financial disclosure in the Informed Consent document in terms of  Necessity to disclose;  Your ability to understand it;  The amount of information provided;  Your willingness to be a participant …?

The COINS* Study

 Purpose of study: analyze aspects of financial disclosure to potential research participants & provide data and recommendations for the development of best practices surrounding such disclosures.

 3-year study  $5 million of funding  NIH-sponsored  Parents of pediatric patients are included in this study *Conflict of Interest Notification Survey

COINS Study: Views of investigators, et.al.

 Purpose of study: to understand the attitudes, beliefs, and practices of IRB chairs, COIC chairs, and investigators regarding disclosure of financial interests to potential research participants.

 The participants included 10 academic medical centers, 10 independent hospitals, and 10 unaffiliated research entities from which respondents were recruited. *Weinfurt, KP, Friedman JY, et. al: Disclosing Conflicts of Interest in Clinical Research: Views of Institutional Review Boards, Conflict of Interest Committees, and Investigators; Journal of Law, Medicine & Ethics 2006; 34 (3) 581-591. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1850937

COINS Study: Views of investigators, et.al.

Results  Most respondents suggested that disclosure should occur under all circumstances in which a financial interest exists.

 Justifications for such disclosure included:  A participant’s right to know;  Enabling potential research participants to make better informed decisions;  Engendering participants’ trust in investigators and the research institutions;  Some respondents underscored the need for disclosure to prevent a later reaction of distrust if research participants learned about a previously undisclosed COI

COINS Study: Views of investigators, et.al.

Results cont’d  Some concerns about making disclosures  Inability of research participants to understand disclosure;  Violation of the investigator’s privacy;  Possibility that disclosure would affect potential research participants willingness to enroll;  Possible undermining of the participants’ trust in the investigator;  Increased length of the Informed Consent document.

COINS Study: Views of investigators, et.al.

Results cont’d  Much disagreement about whether the amount of the financial interest should be disclosed.

 None of the investigators thought such detailed information should be disclosed.

 Most respondents seemed to agree that the nature of the relationship was important to disclose, but that such disclosures should be kept simple.

COINS Study: Views of Potential Research Participants*

 Purpose of study: determine what participants wanted to know about financial interests, their capacity to understand the disclosure, and their reaction to proposed disclosure statement.

 Participants: 16 focus groups: healthy adults, adults with mild chronic illness, healthy children, parents of children with leukemia or brain tumor, adults with heart failure, adults with cancer.

*Weinfurt KP, Friedman JY et al: Views of Potential Research Participants on Conflicts of Interest; Journal of General Internal Medicine 2006; 901-906.

COINS Study: Views of Potential Research Participants

Results  Many participants reported that they did not know about or hadn’t thought about investigators’ financial interests in research before participating in the study.

 Participants wanted to know about financial interest, whether or not those interests would affect their participation.

 [Parent of sick child:] “It seems to me, with this kind of thing, there ought to be disclosure. I’ve never even thought of these kinds of scenarios until you brought them up here…and it’s opened my eyes to the possibilities of things that can be going on that we have not idea of. We’ve got little folks with lives on the line, and I think we deserve and ought to know.”

COINS Study: Views of Potential Research Participants

Results cont’d    Some participants indicated that the COI disclosure would affect their decision about participating in research.

Participants felt that disclosure was more important for riskier studies than for less risky ones; when participants’ health was at stake, they suggested that they might be less able to evaluate the risk posed by a financial disclosure, even though they generally believe that such risks are important to consider.

There was variation in subjects’ ability to understand the nature & implications of financial interests.

COINS Study: Views of Potential Research Participants

Results cont’d  Participants expressed the view that disclosure of financial interests was important in preserving trust in doctors/researchers.

 Some participants felt the amount of money received by investigators would be important to know, whereas other felt they would not want to know the amount.

FDA Halts Gene Experiments at University of Pennsylvania

By Rick Weiss and Deborah Nelson

Washington Post Staff Writers Saturday, January 22, 2000; Page A1 The federal government yesterday halted all human gene therapy experiments involving a prominent researcher at the University of Pennsylvania, saying an investigation into the September death of a teenager there found the school's prestigious program in serious disarray.

Case of Inadequate COI Disclosure

 Jesse Gelsinger was not informed that several monkeys injected with the vector had died.

 The informed consent document approved by the FDA was allegedly altered to exclude this information.

 Jesse was also not informed that other humans who had previously participated in the trial suffered serious adverse effects.

Case of Inadequate COI Disclosure

cont’d   The extent of the PI’s and the University of Pennsylvania’s financial COI was not adequately disclosed to Jesse.

Jesse’s entry into the trial was deemed reckless, because his blood ammonia level on the day before he received the gene transfer exceeded the limit set forth in the FDA protocol.

Contact



Jerome L. Rosenberg, PhD/Chair, COI Committee 412-624-3007 [email protected]

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David T. Wehrle, CPA, CIA, CFE/Director, COI Office 412-383-1774 [email protected]



Khrys X. Myrddin/Associate Director, COI Office 412-383-2828 [email protected]



Hannelore Rogers, MA/Coordinator, COI Office 412-383-1968 [email protected]

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COI Web site: www.coi.pitt.edu