Conflict of Interest & Informed Consent for Pediatrics Fellows & Pediatric Neurology Residents

Conflict of Interest & Informed Consentfor Pediatrics Fellows & Pediatric Neurology Residents Presented by University of Pittsburgh’s COI Office David T. Wehrle, CPA, CIA, CFE/Director Khrys X. Myrddin/Associate Director September 23, 2010

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. Carol Kleinhertz developed a pediatric heart valve; • The technology is owned by Ebb & Flow, Inc., in which Dr. Kleinhertz has an ownership interest; • Dr. Kleinhertz is conducting federally sponsored research to further evaluate the device.

Why should you care about COI? • COIs can affect… • investigators’ role in studies; • potential research subjects’ willingness to participate in the research; • how 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 Managementcont’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 Managementcont’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.

Case of Failure to Disclose Consulting Income Researchers Fail to Reveal Full Drug Pay By GARDINER HARRIS and BENEDICT CAREY PUBLISHED: JUNE 8, 2008 in The New York Times [Dr. Joseph Biederman], a Harvard child psychiatrist whose work has helped fuel an explosion in the use of antipsychotics in children earned at least $1.6 million in consulting fees from drugmakers from 2000 to 2007 but for years did not report much of the income to university officials, according to information given Congressional investigators, The New York Times reports.

Federal Regulations • PHS—42 CFR Part 50 Subpart F for Grants • PHS—45 CFR Part 94 for Contracts • FDA—21 CFR Part 54 • NSF Grants Policy Manual – Investigator Financial Disclosure Policy

University of Pittsburgh’s new COI Policy • Conflict of Interest Policy (11-01-03) for Faculty, Scholars, Researchers, Research Staff/Coordinators

COI Questions on IRB Protocols • Section 7 - Qualifications of Investigators and Sources of Research Study Funding • 7.3 Does any investigator* involved in this study: a) possess an equity interest in the publicly-traded entity that either sponsors this research or owns the technology being evaluated that exceeds 5% ownership interest or a current value of $10,000? b) possess any equity interest in the non-publicly-traded entity that either sponsors this research or owns the technology being evaluated? * 'Investigator' means any member of the study team who participates in the design, conduct, or reporting of this research, as well as his/her spouse, registered domestic partner, dependents, or other members of his/her household.

COI Questions on IRB Protocols cont’d c) receive salary, consulting fees, honoraria, royalties or other payments from the entity that either sponsors this research or owns the technology being evaluated that is expected to exceed $10,000 in any twelve-month period? d) have rights to the intellectual property (IP) being evaluated, as either the inventor of the IP for which a patent has been issued, or as the inventor of the IP that has been optioned or licensed to a company? e) have a financial relationship with a Licensed Start-up Company (which is being monitored by the COI Committee) that has an option or license to utilize the technology being evaluated? f) receive compensation of any amount when the value of the compensation would be affected by the outcome of the research, such as compensation that is explicitly greater for a favorable outcome than for an unfavorable outcome or compensation in the form of an equity interest in the entity that either sponsors this research or owns the technology being evaluated.

Standard COI Management Plan for Human Subject ResearchDetails • 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.

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.

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.

Standard COI Management Plan for Human Subject ResearchDetails 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; jrosenb@pitt.edu) 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. Hilary Heart, 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 both a potential investigator and a research subject, what are your thoughts about the financial disclosure on the Informed Consent Form (ICF) with respect to • the 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. • $5 million NIH-sponsored study • 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.: Resultscont’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 Form.

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 No. 1* : 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 of healthy adults, adults with mild chronic illness, healthy children, parents of children with leukemia or brain tumors, 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 No. 1: 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. • What participants wanted to know about financial interest: [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 no idea of. We’ve got little folks with lives on the line, and I think we deserve and ought to know.”

COINS Study No. 1: 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 No. 1: 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 others felt they would not want to know the amount.

COINS Study No. 2*: Views of Potential Research Participants: Results • When financial information was included in the ICF • Research participants were less willing to participate if investigator held equity: • 5.3% refusal vs. 1.4% if no COI • 18.9% made negative comments *Weinfurt K, Hall M, et al. Effects of disclosing financial interests on participation in medical research: A randomized vignette trial. American Heart Journal, Vol 156, Number 4 (October 2008)

COINS Study: Authors’ Conclusions & Recommendations* • Disclosure is not the remedy that many seek; but it may have positive effects on people’s satisfaction with and trust in research process; • Those who oversee potential COIs in research should be explicit about the goals to be achieved and should design disclosure statements to meet those goals; * Weinfurt, KP, Hall, MA., et.al.: Disclosure of Financial Relationships to Participants in Clinical Research. New England Journal of Medicine 2009, 361:9

COINS Study: Authors’ Conclusions & Recommendations cont’d • Disclosure during consent process should be brief, simple, and allow for participants’ questions; • Study personnel administering informed consent should receive training to effectively answer participants’ questions about investigators’ or institution’s financial relationships;

COINS Study: Authors’ Conclusions & Recommendations cont’d • Study participants should not be the sole decision makers with respect to acceptable risks of investigators’ financial relationships in clinical research; • Investigators’ equity interests should be limited, if not avoided, rather than simply disclosed.

Contacts/Assistance/Resources • Jerome L. Rosenberg, PhD/Chair, COI Committee 412-624-3007 jrosenb@pitt.edu • David T. Wehrle, CPA, CIA, CFE/Director, COI Office 412-383-1774 wehrledt@upmc.edu • Khrys X. Myrddin/Associate Director, COI Office 412-383-2828 myrddink@upmc.edu • Hannelore Rogers, MA/Coordinator, COI Office 412-383-1968 rogershn@upmc.edu • COI Web site: www.coi.pitt.edu • Superform Web site:https://coi.hs.pitt.edu

Conflict of Interest & Informed Consent for Pediatrics Fellows & Pediatric Neurology Residents