Conflict of Interest in Academic Research

1
Conflict of Interest in Academic Research
Presented by Julie Gottlieb, Johns Hopkins
University School of Medicine

• Presentation to the University of New Mexico
  Health Sciences Center

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Conflict of interest

• When a secondary interest competes with a primary
  objective or responsibility

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The Objective of COI Policy

• Balance the mission of transferring knowledge
  and commercializing technology with the
  imperative of protecting the safety, integrity,
  and reputation of biomedical research
• COI policy and process must be credible and
  effective

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Purpose of the COI Process

• Implementation of Universitys COI policy
• Adherence to PHS regulations
• Support ethical conduct of research
• Ensure credibility of institutions and
  investigators research

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Contents

• Overview history and regulatory environment
• Analyzing risks of COI in research
• Case studies

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Conflict of Interest PolicyA Brief History (1)

• 1980 Congress passed Bayh-Dole Act allowing
  universities to retain ownership of inventions
  made with federal funds
• Growth of university (especially medical school)
  technology licensing, startups, consulting,
  industry sponsored research
• Development of biotech industry 1994-2004
  revenues increased 410 and RD expenditures
  increased 283
• BIO Biotechnology Industry Organization
  http//www.bio.org/speeches/pubs/er/statistics.asp
  

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Significant Interactions between Industry and
Academia

• Technology licensing (fees, royalty, stock)
• FY07 5,109 licenses and options
• Research Sponsorship
• FY07 48.8 bn (total), 3.4 bn (industry)
• Consulting (cash, stock)
• Collaborations (cash, material)
• AUTM U.S. Licensing Survey FY2007

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COI Regulation, Guidance

• 1995 PHS/NSF COI regulations
• 1998 FDA COI regulations
• Gelsinger death at UPenn
• 2000 NIH Summit on COI in Human Subject
  Research (HSR)
• 2001- 2002 AAMC recommendations on COI in human
  subject research (expanded 2008)
• 2004 HHS final guidance on COI in human
  subject research

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Recent Developments

• 2004 - 61 of AMCs (voluntarily) adopted
  presumptive prohibition
• 2005-6 NIH prohibits COIs for intramural
  scientists, staff
• 2008-9 Sen. Charles Grassley investigating
  (unreported) COIs
• 2008-9 Required (orthopedic firms) and
  voluntary disclosure of industry payments to
  physicians, investigators
• 2009 NIH expected to revise, strengthen COI
  regulations

U.S. Medical School Policies on Individual
Financial Conflicts of Interest Results of an
AAMC Survey 2004
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PHS, NSF Regulations onCOI in Research

• PHS (NIH, etc.), NSF
• Grantees must identify and manage, reduce or
  eliminate COIs and report to awarding agency
  before spending award (or within 60 days of
  being notified of COI in active project)
• gt 10K/year, gt 5 stock, royalties other than
  from grantee, etc.
• Prospective review

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FDA Regulations on COIin Research

• FDA
• Applicants for marketing approval (e.g.,
  companies) for drugs, devices, biologicals, must
  disclose financial interests of investigators in
  covered studies
• Personal payments, gt 50K stock, gt 25K payments
  for research separate from costs of clinical
  study, etc.
• Retrospective

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COI and Public Trust in Biomedical Research

• Sentinel events
• Death of Jesse Gelsinger at U. Penn (1999)
• Deaths in Protocol 126 at Hutch
• Other events
• Seattle Times series on COIs in Protocol 126
• Wall St. Journal series on COIs at Cleveland
  Clinic (2005)
• COIs of NIH intramural staff exposed (2005-6)
• Dr. Charles Nemeroff resigns editorship of
  Neuropsychopharmacology after failing to disclose
  (2006)
• Cleveland Clinic revokes physicians appointment
  for failure to disclose (2006) Harvard researcher
  investigated
• NIH freezes Emory grant over Nemeroffs COIs
  (2008)

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Benefits of Relationships with Industry

• Funds and material for research (clinical trials)
• Access to information about drug and device
  development
• Ability to influence commercial strategy and move
  inventions from bench to bedside
• Ability to place graduates in industry jobs

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Potential Costs of Academic-Industry Relationships

• Risks to safety human research subjects
• Bias in research (more pro-industry results)
• Impact on students and trainees
• Impact on use of university resources
• Biased research may lead to poor decisions in
  research, product approval, and clinical care
• Associations between pro-industry research
  results and authors with COIs have been reported
  in several articles. One such article is
  Stelfox, et al., Conflict of Interest in the
  debate over calcium-channel antagonists. New
  England Journal of Medicine, 1998 338 (2)
  101-06.

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Voluntary disclosure increasing

• AMCs
• Cleveland Clinic, (forthcoming) U. Penn, Emory
• Industry
• Pfizer, Merck, Lilly
• 5 orthopedic device manufacturers as result of
  DOJ settlement
• Professional Societies
• Spine surgeons

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Analyzing risks of COI inResearch

• 3-part process
• Reporting
• Review
• Determination

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Reporting

• Administrative system for obtaining reports of
  investigators financial interests in research
• Integration, communication between
  grants/contracts office, IRB, COI office, etc.
• Educate faculty and staff

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Review (1)
COI committee must define and address risks
Are the risks different in human subject research?
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Review (2)

• Understand the research project
• In what ways is it susceptible to conscious or
  unconscious bias?
• Understand the financial interests and
  relationships
• How large are they? Are they fixed or contingent?
  How closely do they relate to the research?

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Review (3)

• Study design may skew to show desired outcome
• (HSR) Subject recruitment may stretch
  inclusion criteria
• (HSR) Consent process may understate risks of
  participation
• (HSR) Intervention
• Data analysis may be shaded to favor desired
  outcome, esp. if endpoints are subjective
• Publication/Presentation may overstate results
  or omit unfavorable data
• Use of resources/grant may redirect resources
  to projects with personal gain

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Case 1a Dr. Apple

• Dr. Apple conducts NIH-funded lab research in
  genetics. He consults for Genlabs on assay
  development and earns 10,000/year. Genlabs is
  developing diagnostic kits to detect inherited
  molecular markers that have been identified in
  colon cancer. Dr. Apple does not use Genlabs
  assays in his research. Is there a COI?

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Case 1b and 1c Dr. Apple

• 1b Same as 1a, except Dr. Apple earns
  30,000/year as a consultant.
• 1c Same as 1a, except Dr. Apple invented the
  assay used in Genlabs diagnostic kit and
  receives royalties.

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Case 1d Dr. Apple

• 1d Same as 1c, except the diagnostic kit is not
  on the market, so no royalties are flowing yet.
• Dr. Apple proposes to test the efficacy of the
  assay he invented in a clinical study. He is a
  co-investigator on the IRB protocol, but has no
  contact with patients. Clinicians will take
  blood samples and, using the assay in his lab,
  Dr. Apple will run the samples. His findings
  will be correlated with clinical information at 1
  and 3 years. Can he participate in the study? If
  its a pilot study? If its a definitive study?

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Case 2 Dr. Giannini

• 2a Dr. Giannini, a psychiatrist, is an expert
  in anxiety and depression in adolescents. She is
  PI of a 3-center, Phase II, NIH-sponsored trial
  comparing MegaPharms antidepressant to cognitive
  therapy in adolescents with anxiety. The drug has
  been approved for adults but not for pediatric
  use.
• Dr. Gianninis father died and left 200,000
  worth of MegaPharm stock to her 6-year old son.
  The stock is worth much less than when her father
  bought it. Can she conduct the study while her
  son owns MegaPharm stock?

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Case 2b Dr. Giannini

• 2b Dr. Gianninis son does not own MegaPharm
  stock. However, Dr. Giannini was a frequent
  speaker for MegaPharm in the year before the
  study was proposed, and she earned 40,000. She
  stopped speaking for the company when her
  institution banned speaking for industry. Can
  she be PI of the study?

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Case 2c Dr. Giannini

• 2c Dr. Giannini and her family own no MegaPharm
  stock and she never served as a speaker for the
  company. However, MegaPharm is in discussions
  with her department chair to endow an institute
  for the study of adolescent mental health, and
  she would be a member of the institute. Can she
  be PI of the study?

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Determination (1)

• The COI management arsenal
• Disclosure to research subjects, colleagues, in
  publications, presentations
• Reduce or eliminate financial interest, place
  stock in escrow
• Limit role of the conflicted investigator
• Oversight of research by disinterested expert(s)
• Establish safe haven for subordinates, students
• (for institutional leaders) evaluate
  decision-making

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Determination (2)

• Enforce compliance with management decisions
• Do spot audits
• Specify sanctions

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In closing

• Strive for culture of integrity do the right
  thing
• Questions?

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Contact Information

• Julie Gottlieb
• Assistant Dean, Policy Coordination
• Johns Hopkins University School of Medicine
• http//www.hopkinsmedicine.org/Research/OPC/
• jgottlie_at_jhmi.edu
• 410-516-5560