Ethical Challenges Related to Financial Conflicts of Interest

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Ethical Challenges Related to Financial Conflicts of Interest in Research Jeremy Sugarman, MD, MPH,

Ethical Challenges Related to Financial Conflicts of Interest in Research Jeremy Sugarman, MD, MPH, MA Berman Bioethics Institute Johns Hopkins University Baltimore, Maryland USA

At the Newsstand o “Safeguards Get Trampled in Rush for Research Cash” o o

At the Newsstand o “Safeguards Get Trampled in Rush for Research Cash” o o “Senators Ask Drug Giant to Explain Grants to Doctors” o o Chicago Tribune, 9/5/99 New York Times, 7/06/05 “How Tightly Do Ties Between Doctor and Drug Company Bind” o New York Times, 7/27/05

At the Bookstore o Science in the Private Interest : Has the Lure of

At the Bookstore o Science in the Private Interest : Has the Lure of Profits Corrupted Biomedical Research? o o The Truth About the Drug Companies: How They Deceive Us and What to Do About It o o Krimsky, 2003 Angell, 2004 On The Take: How Medicine's Complicity with Big Business Can Endanger Your Health o Kassirer, 2004

At the Medical Library o “Handling conflicts of interest between industry and academia” o

At the Medical Library o “Handling conflicts of interest between industry and academia” o o "Regulating academic-industrial research relationships--solving problems or stifling progress? " o o JAMA 2003; 3240 -1 NEJM 2005; 1060 -5 "Reporting Conflicts of Interest, Financial Aspects of Research, and Role of Sponsors in Funded Studies" o JAMA 2005; 110 -111

In the Beltway o Institutional Review Boards: A Time for Reform o o OIG,

In the Beltway o Institutional Review Boards: A Time for Reform o o OIG, June 1998 Recruiting Human Subjects: Pressures in Industry-Sponsored Clinical Research o OIG, June 2000

Conflict of Interest Timeline 1999 o 2000 o 2001 o 2002 o 2004 o

Conflict of Interest Timeline 1999 o 2000 o 2001 o 2002 o 2004 o Jesse Gelsinger dies in University of Pennsylvania trial HHS begins policy review o Human Subject Protection and Financial Conflicts of Interest Conference o HHS issues draft interim guidelines 11 major medical journals require authors to disclose financial role of sponsor o AAU issues report on financial conflicts o AAMC issues guidelines for individual conflicts of interest NIH releases Review of Financial Conflict of Interest Policies of Grantee Institutions o AAMC guidelines for institutional conflicts of interest HHS Final Guidance Document released

Ethical Foundations o o o Scandals, codes, regulations and principles Fiduciary obligations Reservoir of

Ethical Foundations o o o Scandals, codes, regulations and principles Fiduciary obligations Reservoir of trust

Fiduciary o o “a person holding the character of trustee, in respect of the

Fiduciary o o “a person holding the character of trustee, in respect of the trust and confidence involved in it and scrupulous good faith and candor which it requires. ” a “person having duty, created by his undertaking, to act primarily for another’s benefit in matters connected with such understanding. ” Black’s Law Dictionary

Fiduciary Obligations o o o Put aside self-interest Focus primarily on the interests of

Fiduciary Obligations o o o Put aside self-interest Focus primarily on the interests of the person for whom he or she serves as fiduciary Act to promote that individual’s interest and so earn the trust of that individual Mc. Cullough, et al 1998

Reservoir of Trust o o o Individual physicians and investigators Specific institutions The research

Reservoir of Trust o o o Individual physicians and investigators Specific institutions The research enterprise as a whole

Trust and Trustworthiness “Not all things that thrive when there is trust between people…are

Trust and Trustworthiness “Not all things that thrive when there is trust between people…are things that should be encouraged to thrive…There are immoral as well as moral trust relationships. ” Baier A, 1986

Spectrum of Conflicts o o Initial considerations Research design Prospective review In process n

Spectrum of Conflicts o o Initial considerations Research design Prospective review In process n n n o Recruitment Informed consent Integrity of the data Reporting

Selected Types of Financial Interests o o Per capita payments Money received outside the

Selected Types of Financial Interests o o Per capita payments Money received outside the study Investigator holds equity Institution holds equity

Potential Solutions o o o Divest Minimize Disclose

Potential Solutions o o o Divest Minimize Disclose

Important Empirical Questions Regarding Disclosures of COI o o Who, What, When, Where, and

Important Empirical Questions Regarding Disclosures of COI o o Who, What, When, Where, and How? How will these data be used? What are the effects on trust? What are the effects on the research enterprise?

COINS Conflict of Interest Notification Study o Johns Hopkins n o Duke n n

COINS Conflict of Interest Notification Study o Johns Hopkins n o Duke n n n o Jeremy Sugarman Kevin Weinfurt Rob Califf Kevin Schulman Joelle Friedman Jennifer Allsbrook Michaela Dinan Wake Forest n Mark Hall NHLBI Grant: 1 R 01 HL 075538 -01

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of Disclosure

Policy Review o o o Online and written policies of US academic medical centers

Policy Review o o o Online and written policies of US academic medical centers (AMCs) February-August, 2004 Identified materials for 98% of 123 AMCs Weinfurt et al, Academic Medicine 2006; 81: 113 -118.

Policy Review o o Online and written policies of US academic medical centers (AMCs)

Policy Review o o Online and written policies of US academic medical centers (AMCs) February-August, 2004 Identified materials for 98% of 123 AMCs 48% mentioned disclosure to subjects as an option n o 58% of those contained required or suggested verbatim language Few suggested more than disclosure of sponsor Weinfurt et al, Academic Medicine 2006; 81: 113 -118.

Interviews With Officials and Investigators o Types of Institutions Sampled n n o Academic

Interviews With Officials and Investigators o Types of Institutions Sampled n n o Academic Medical Centers Independent Hospitals Independent IRBs Non- Affiliated Research Entities Participation n 23 IRB Chairs 14 COIC Chairs or similar official 7 investigators Weinfurt et al, J Law Med Ethics 2006; 581 -591.

Disclose the Amount of the Financial Interest? o “No!” according to investigators n n

Disclose the Amount of the Financial Interest? o “No!” according to investigators n n o Complexity of the disclosure Amount “might detract from what really needs to be decided” No consensus among officials n PRPs overestimate value and the power to influence o n Do not disclose amount Investigators underestimate the power to influence, lay people do not o Do disclose

We have not ever asked anyone to express the amount of money involved, really

We have not ever asked anyone to express the amount of money involved, really thinking that $1000 may be as bad as $20, 000. --IRB Chair

Describe Possible Implications of Financial Interest? o o o No, let them draw their

Describe Possible Implications of Financial Interest? o o o No, let them draw their own conclusions. Yes, warn them like we do on cigarette ads. Difficult balance

I think that is sort of leading the subject to where they might think

I think that is sort of leading the subject to where they might think that this is what is going to happen. I think that if the relationship between the risk and the study was not clear, you might need to spell that out. But, to some degree I think you are just informing the subject. You are not trying to tell them what they should think about it. --COIC Chair

PRP Focus Groups o 16 groups (6 -8 people each) n n n o

PRP Focus Groups o 16 groups (6 -8 people each) n n n o o Healthy adults (6 Groups) Mildly/Chronically ill adults (6 Groups) Severely ill adults (2 Groups) Parents with healthy children (1 Group) Parents of children with illnesses (1 Group) Stratified by race/ethnicity Conducted in New York, Chicago, and Durham, NC Weinfurt et al, J Gen Intern Med 2006; 21: 901 -6.

PRPs on Disclosure and Trust o o Might decrease trust Might increase trust n

PRPs on Disclosure and Trust o o Might decrease trust Might increase trust n n o Transparency Perception that financial interest is good Need to maintain image of physician

Evolution of PRPs’ Thoughts o o Few had considered financial interests and their implications

Evolution of PRPs’ Thoughts o o Few had considered financial interests and their implications in clinical research Opportunity to ask questions during consent process n Prior to focus group, would not have known what to ask

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of Disclosure

Models for Disclosure o Expert Panel n o o Mark Barnes, JD, LLM (Ropes

Models for Disclosure o Expert Panel n o o Mark Barnes, JD, LLM (Ropes & Gray), Becky Coleman, Pharm. D (Theravance, Inc. ), Joseph Di. Cesare, MPH, RPh (Novartis Pharmaceuticals Corporation), John M. Falletta, MD (Duke University Medical Center), Robert Gatter, JD, MA (Penn State University), Julie Gottlieb, MA (Johns Hopkins University), Jeffrey Kahn, Ph. D, MPH (University of Minnesota), Mary Faith Marshall, Ph. D. (University of Minnesota), S. Van Mc. Crary, Ph. D. , J. D. , M. P. H. (State University of New York at Stony Brook), Erica Rose, JD (Glaxo. Smith. Kline), Michael B. Waitzkin, JD (Fox. Kiser) Focus Groups Cognitive Pre-testing Weinfurt, et al. IRB 2007; 29: 1 -5

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of

COINS Overview Institutional Policies Officials/ Investigators Potential Research Participants Models for Disclosure Effects of Disclosure

Assessing Effects of Disclosure o Online survey of 3, 520 participants n o o

Assessing Effects of Disclosure o Online survey of 3, 520 participants n o o Diabetics and asthmatics Hypothetical clinical trial 1 of 5 financial interests disclosed n n n Per capita payments Money received outside the study Investigator holds equity Institution holds equity Generic

Willingness to Participate

Willingness to Participate

Change in Trust Due to Disclosure

Change in Trust Due to Disclosure

Self-Rated Understanding of Disclosed Financial Benefit

Self-Rated Understanding of Disclosed Financial Benefit

Surprise Over Disclosed Information

Surprise Over Disclosed Information

Perceived Effect on Scientific Quality

Perceived Effect on Scientific Quality

Does the Type of Interest Matter? o o Greater concern over investigator holding equity

Does the Type of Interest Matter? o o Greater concern over investigator holding equity compared to per capita payment Other types of financial interest did not differ substantially in their effects on participants

Before leaving it up to the PRP to assess risk. . . o Understanding

Before leaving it up to the PRP to assess risk. . . o Understanding of implications n o Invitation to ask questions during consent process n o Some feel financial interest increases chance that investigators are committed, ethical, and confident that the experimental therapy will work People might not know what to ask With greater medical risk, some people may not pay attention to financial disclosure, but it is still important to them.

The Process of Disclosure o Study of 300 clinical research coordinators to understand their

The Process of Disclosure o Study of 300 clinical research coordinators to understand their role in disclosing financial interests in research, and possible barriers to such disclosures o Survey domains n n n Awareness of financial interests in research Experience and comfort with disclosure of such interests Barriers to disclosure

Results o Experience n n o o 41% reported disclosing financial interests to PRPs

Results o Experience n n o o 41% reported disclosing financial interests to PRPs 28% reported being asked about financial interests 28% somewhat or not at all comfortable with answering questions about financial interests Barriers n n n Lack of information PRPs wont understand Investigator privacy

Suggestions o o More education and training would facilitate the disclosure of financial interests

Suggestions o o More education and training would facilitate the disclosure of financial interests in research to PRPs during the informed consent process Failure to provide such training could result in discomfort that might discourage the effective communication of financial disclosures in research to PRPs

Next Steps o o Vignette study with patients with coronary artery disease n Provided

Next Steps o o Vignette study with patients with coronary artery disease n Provided with a copy of an informed consent document for a hypothetical trial n Three disclosure arms (per capita, equity, none) n Telephone review to simulate the informed consent process n Survey regarding willingness to participate, trust, etc Conflict of interest management study n Determine how and when disclosure is selected as a management strategy