Ethical Challenges Related to Financial Conflicts of Interest in Research

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Ethical Challenges Related to Financial Conflicts
of Interest in Research

• Jeremy Sugarman, MD, MPH, MA
• Berman Bioethics Institute
• Johns Hopkins University
• Baltimore, Maryland USA

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At the Newsstand

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

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At the Bookstore

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

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At the Medical Library

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

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In the Beltway

• Institutional Review Boards A Time for Reform
• OIG, June 1998
• Recruiting Human Subjects Pressures in
  Industry-Sponsored Clinical Research
• OIG, June 2000

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Conflict of Interest Timeline

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

• Scandals, codes, regulations and principles
• Fiduciary obligations
• Reservoir of trust

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Fiduciary

• 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 anothers
  benefit in matters connected with such
  understanding.
• Blacks Law Dictionary

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Fiduciary Obligations

• Put aside self-interest
• Focus primarily on the interests of the person
  for whom he or she serves as fiduciary
• Act to promote that individuals interest and so
  earn the trust of that individual
• McCullough, et al 1998

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Reservoir of Trust

• Individual physicians and investigators
• Specific institutions
• The research enterprise as a whole

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Trust and Trustworthiness

• Not all things that thrive when there is trust
  between peopleare things that should be
  encouraged to thriveThere are immoral as well as
  moral trust relationships.
• Baier A, 1986

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Spectrum of Conflicts

• Initial considerations
• Research design
• Prospective review
• In process
• Recruitment
• Informed consent
• Integrity of the data
• Reporting

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Selected Types of Financial Interests

• Per capita payments
• Money received outside the study
• Investigator holds equity
• Institution holds equity

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Potential Solutions

• Divest
• Minimize
• Disclose

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Important Empirical Questions Regarding
Disclosures of COI

• 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?

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COINSConflict of Interest Notification Study

• Johns Hopkins
• Jeremy Sugarman
• Duke
• Kevin Weinfurt
• Rob Califf
• Kevin Schulman
• Joelle Friedman
• Jennifer Allsbrook
• Michaela Dinan
• Wake Forest
• Mark Hall
• NHLBI Grant 1 R01 HL075538-01

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

• 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.
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Policy Review

• 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
• 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.
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Interviews With Officials and Investigators

• Types of Institutions Sampled
• Academic Medical Centers
• Independent Hospitals
• Independent IRBs
• Non- Affiliated Research Entities
• Participation
• 23 IRB Chairs
• 14 COIC Chairs or similar official
• 7 investigators

Weinfurt et al, J Law Med Ethics 2006 581-591.
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Disclose the Amount of the Financial Interest?

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

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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
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Describe Possible Implications of Financial
Interest?

• No, let them draw their own conclusions.
• Yes, warn them like we do on cigarette ads.
• Difficult balance

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I think that 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
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PRP Focus Groups

• 16 groups (6-8 people each)
• 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.
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PRPs on Disclosure and Trust

• Might decrease trust
• Might increase trust
• Transparency
• Perception that financial interest is good
• Need to maintain image of physician

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Evolution of PRPs Thoughts

• Few had considered financial interests and their
  implications in clinical research
• Opportunity to ask questions during consent
  process
• Prior to focus group, would not have known what
  to ask

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

• Expert Panel
• Mark Barnes, JD, LLM (Ropes Gray), Becky
  Coleman, PharmD (Theravance, Inc.), Joseph
  DiCesare, 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, PhD,
  MPH (University of Minnesota), Mary Faith
  Marshall, Ph.D. (University of Minnesota), S. Van
  McCrary, Ph.D., J.D., M.P.H. (State University of
  New York at Stony Brook), Erica Rose, JD
  (GlaxoSmithKline), Michael B. Waitzkin, JD
  (FoxKiser)
• Focus Groups
• Cognitive Pre-testing

Weinfurt, et al. IRB 2007 291-5
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COINS Overview
Institutional Policies
Officials/ Investigators
Effects of Disclosure
Models for Disclosure
Potential Research Participants
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Assessing Effects of Disclosure

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

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Willingness to Participate
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Change in Trust Due to Disclosure
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Self-Rated Understanding of Disclosed Financial
Benefit
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Surprise Over Disclosed Information
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Perceived Effect on Scientific Quality
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Does the Type of Interest Matter?

• 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

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

• Understanding of implications
• Some feel financial interest increases chance
  that investigators are committed, ethical, and
  confident that the experimental therapy will work
• Invitation to ask questions during consent
  process
• 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.

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The Process of Disclosure

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

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Results

• Experience
• 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
• Lack of information
• PRPs wont understand
• Investigator privacy

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Suggestions

• 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

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Next Steps

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

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