Document Sample
					University/Industry Relationships
    and Conflict of Interest
          Kelvin W. Gee Ph.D.
             May 20, 2009
      Conflict of Interest: An Issue of Ethics
Can ethics be taught?

Can a person become moral and ethical by reading moral treatises
and applying them to case histories?

Aristotle: If you need moral guidance seek out a person who has
succeeded in living a moral life rather than someone who has
succeeded in memorizing moral arguments.

You can memorize the Metaphysics of Ethics by the philosopher
Immanuel Kant and still be a moral dunce.

Kant states that our moral duties are an unconditional obligation, or
an obligation that we have regardless of our will or desires.
What is a conflict of interest?

A set of conditions in which professional
judgment (such as a patient’s welfare or the
validity of research) tends to be unduly
influenced by a secondary interest (such as
financial gain).

                           Thompson, NEJM, 1993
  Academia and the Public Trust –
           circa 1915
“All true universities, whether public or
  private, are public trusts designed to advance
  knowledge by safeguarding the free inquiry
  of impartial teachers and scholars. Their
  independence is essential because the
  university provides knowledge, not only to
  its students, but also to the public agency in
  need of expert guidance and the general
  society in need of greater knowledge.”
                  American Association of University Professors, 1915
Intellectual Honesty and the Scientific
          Method –circa 1925
“Intellectual Honesty: In the interpretation of
  observations and in the acceptance of principles a
  maximum amount of fairness and open-mindedness
  is essential. Prejudice must not enter…” Anyone
  who fails to follow these rules is not following
  the Scientific Method and is therefore not doing
  science or scientific research period. In science,
  we do not have a “science police” to report
  violators of these rules. No true scientist would
  ever voluntarily violate the rules of science. .”
                       Physics Nobel Laureate Robert Millikan, 1925
   In 2009, we live in a complex world
• Once upon a time, the rules were clear
   – Faculty worked full time in the University
   – Business was kept outside the ivory towers
• Then times changed
   – The Baby Boomers cast aside the rules
   – The Generation Xers created new rules that focus on life style
     and money
   – The Bayh Dole Act (1980) turned over technology generated
     with federal funds to the University with instructions to partner
     with industry and move it to the market place
   – Faculty entrepreneurs developed relationships with industry,
     and industry invaded the halls of academe
   – But along with the problems, more technology has been moved
     to the marketplace to better healthcare
  We Stay Awake Nights Struggling To Keep
    Up With Managing All the Changes,
      Trying To Do The Right Thing –
            But In Research . . .
• Faculty generate technology, license it from the University for their
  own start-up companies -- and want NIH grants to further develop
  the technology at the University for their companies and financial
• Faculty are paid consultants to pharmaceutical and device
  companies to design the animal and human subject research
  protocols -- and then want to be the investigators at the University
  who carry out the research proposals, sponsored by the company
• Attention should be directed to
  –   professionalism
  –   protection of human subjects
  –   protection against exploitation of students/trainees
  –   integrity of data
  –   trust
  –   setting standards in education
  –   reputations and credibility

Pharmaceutical, device, and equipment companies
• DO want to sell products that benefit patients and
• DO need and want the expertise and advice of academic
  scientists to help them

• Pharmaceutical, device, and equipment companies have a
  fiduciary duty to their shareholders to make money.
• Physicians and scientists have
   –   a fiduciary duty to their universities,
   –   a social obligation to the public,
   –   a professional obligation to their profession and societies, and
   –   a moral and ethical obligation to their patients, peers, and trainees
• Physicians and scientists have an obligation to put patient care,
  research integrity, and the education of their trainees and peers
  first, when faced with a choice between making money or doing
  their duty……….CONFLICT!
        The “Kept” University
“commercially sponsored research is putting at
risk the paramount value of higher education –
disinterested inquiry. Even more alarming……,
universities are behaving more and more like
for-profit entities.”

                          Atlantic Monthly, March 2000
What happened?
               What happened?
• DNA recombinant technology
• 1980 U.S. Supreme Court decision (Diamond vs
  Chakrabarty) allowing patenting of “anything
  under the sun that is made by man”
• 1980 Bayh-Dole Act
    Gave recipients of federal funds the right to patent
     federally funded research inventions and the obligation
     to spur the translation of those inventions into public
• Declining state support for public universities
• Deregulation of everything financial in the 1990’s
  through today where we are now reaping the
  “fruits” of deregulation
         A 1999 Snapshot
• $17.8 billion funded by NIH
• $22.7 billion funded by top 10 pharmaceutical
• 2800 gene patents (73%) awarded to
• >450 start-up companies founded
• Executed >4300 licenses (50% exclusive)
• Generated $40 billion worth of economic
• A non-trivial high stakes activity
    UC Irvine Start-up Companies
            Account For:
• 47% of UCI’s active license agreements
• Licensing 30% of UCI’s active invention
• 20% of UCI’s industry research funding
• 40% of UCI’s royalty and fee income

                Source: Start-up Companies Founded on UCI Technologies
                                                            May, 2003
What are the possible causes of
     A COI can arise because of:
•   Research funded by for-profit sponsors
•   Faculty consulting agreements
•   Patenting of academic research
•   Faculty start-up companies
•   Ownership of stock or options
•   Receipt of royalty payments
•   Receipt of research-related gifts
          Important Principles About
             Conflicts of Interest
• COIs are inevitable for faculty and institutions
  engaged in technology transfer

• COIs rarely arise from a bad person doing wrong
  (illegal, immoral, unethical, unprofessional) things.
  They usually arise from a good person who has
  two worthy objectives that conflict with one

• The faculty member or student/trainee is seldom
  consciously aware of having a COI until educated.
What are the potential risks of COI?
   Potential Risks for Academic
• Compromise of scientific integrity
• Improper direction of student or employee’s
• Inappropriate delay or restriction on
• Unbalanced allocation of faculty member’s
  time or effort
• Appearance of impropriety
 Findings of academic COI analyses

  • >25% of researchers have industry
  • >65% of academic institutions hold equity in
    start-ups that sponsor institutional research
  • Restrictions on publication and data-sharing
  • Research outcomes favor industry

Berkelman et al., JAMA, 2003
             Biased research outcomes

RCT = randomized control trials
Bekelman et al., JAMA, 2003
                Biased research outcomes

Original Article, May 11, 2009
Frequency, nature, effects, and correlates of conflicts of interest in
published clinical cancer research

Reshma Jagsi, MD, DPhil , Nathan Sheets, BS , Aleksandra Jankovic, MS, Amy R.
    Motomura, BSE , Sudha Amarnath, BS, Peter A. Ubel, MD

1.   The authors identified 1534 original oncology studies; 29% had conflicts of interest
     (including industrial funding) and 17% declared industrial funding.

2.   Randomized cancer trials that assessed survival were more likely to report positive
     survival outcomes when a conflict of interest was present (P = .04).
    Clinical Trials Case Study
• In September 2000, Immune Response, a
  biopharmaceutical company, filed a $7
  million legal action against the University
  of California at San Francisco after
  researchers published negative findings
  from a clinical trial of the company's
  experimental acquired immunodeficiency
  syndrome (AIDS) vaccine, Remune.
• The investigators had refused to allow the company to
  insert its own statistical analyses into the manuscript.

• Immune Response demanded that the researchers not
  publish the article and withheld some of the data in an
  effort to dampen their publication prospects.

• The investigators succeeded in publishing but
  subsequently faced a legal battle that ended only after
  the university filed a counterclaim alleging that the
  contract between the parties gave the researchers
  permission to publish.
       Depression Expert at Emory Pulls out of Research Projects
NIH Freezes Grant Money; Emory to begin monitoring potential conflicts of
                       By GAYLE WHITE, CRAIG SCHNEIDER
                             The Atlanta Journal-Constitution
                               Tuesday, October 14, 2008
Emory psychiatry professor Dr. Charles B. Nemeroff is stepping down from university
research projects funded by the National Institutes of Health, as the federal agency cracks
down on the school’s handling of potential conflicts of interest, university officials said.

The NIH has frozen funds for a $9.3 million project on depression led by Nemeroff,
acknowledged Ron Sauder, a university vice president. The project had been under way for
two of its proposed five years.

The NIH also has instituted tighter rules on approving grants for Emory. The new rules
demand more thorough checks and documentation on researchers’ outside activities and
potential conflicts of interest.

Nemeroff’s critics say he has collected millions (~$2.8 MM over 7 years) of dollars in
speaking and consulting fees from drug companies whose products he’s reviewed and
promoted. They even say his science has been compromised, though defenders dispute
                      Case study
Sandra was excited about being accepted as a graduate student in
the laboratory of Dr. Frederick, a leading scholar in the field, and
she embarked on her assigned research project eagerly. But after
a few months she began to have misgivings. Though part of Dr.
Frederick's work was supported by federal grants, the project on
which she was working was totally supported by a grant from a
single company. She had known this before coming to the lab
and had not thought it would be a problem. But she had not
known that Dr. Frederick also had a major consulting agreement
with the company. She also heard from other graduate students
that when it came time to publish her work, any paper would be
subject to review by the company to determine if any of her work
was patentable.
1. What are the advantages and
   disadvantages of Sandra doing research
   sponsored entirely by a single company?

2. How can she address the specific
   misgivings she has about her research?

3. If Sandra wishes to discuss her qualms
    with someone at her university, to whom
    should she turn?
                        Case study
John, a third-year graduate student, is participating in a department-
wide seminar where students, postdocs, and faculty members discuss
work in progress. An assistant professor prefaces her comments by
saying that the work she is about to discuss is sponsored by both a
federal grant and a biotechnology firm for which she consults. In
the course of the talk John realizes that he has been working on a
technique that could make a major contribution to the work being
discussed. But his faculty advisor consults for a different, and
competing, biotechnology firm.
1. How should John participate in this

2. What, if anything, should he say to his
   advisor-and when?

3. What implications does this case raise for
   the traditional openness and sharing of
   data, materials, and findings that have
   characterized modern science?
                        Case study
Professor Frost, along with postdoctoral student Cooper and graduate
student Kim, developed a novel computational methodology and mass
spec analysis to determine protein structure from amino acid
sequence. They patented this process which is very novel and a bit
controversial. There was no interest in the patent among large
companies but local venture capitalists agree to form a new startup
company (Prostruktm ) to try to exploit the discovery. Frost, Cooper
and Kim are founders and have founder stock. The company appoints
Frost to the Board of Directors and wants Cooper to be a member of
the SAB which entails 4 one-day meetings per year and $15,000 per
year of pay. They also wish to have Cooper and Kim work at the
company 4 hours a week to “help get things started”.
 Frost says that the work at the company is distinct from his 2 NIH
grants. However, both deal with protein structure and mass spec
and both are used to pay Kim and Cooper.
 Is it permissible for grad students and postdocs to be included
 in patents?

 Is it permissible for them to be founders of a company? To
 receive founders stock?

 Can students be on the SAB? Can they be consultants? If so,
 how much time do they have for this activity. Can they work at a
 company part time? Is there a difference between the graduate
 students and postdocs?

 Is it permissible for the graduate student to do work on projects
 funded by Prostruktm

How can we deal with COI?

   What can be done with Conflicts of
It is in the best interests of the community of
science and individual scientists to recognize
conflicts of interest and to:
•      Avoid
•      Minimize
•      Manage
   COI Oversight Requirements
• 1982 State of California
• 1990 House Committee on Government
• 1995 DHHS regulations
• 2000 American Society for Gene Transfer
• 2002 AAMC Task Force on Financial
  Conflicts of Interest in Clinical Research
        UCI’s COI Policy

• Disclosure of financial interests
• Review by the COIOC
• Determination whether or not conflict is
• Implementation of management plan
    Factors in Evaluating COI
•   Restrictions on dissemination
•   Student involvement
•   Separation of interests
•   Past and current funding of the PI
•   Research and/or development facilities
•   Clinical trials issues
•   Educational impact
•   Diversity of company’s product line
     Potentially Harmful COIs
• PI who is president or CEO of a for-profit sponsor
• PI who holds a non-management position with a
  for-profit sponsor (manageable)
• Clinical trials on a drug, device or patented
  procedure developed by PI (unacceptable)
• Sponsored research on PI’s own intellectual
  property not involving human subjects
• Equity (ownership) interest in a sponsor
  (potentially unmanageable)
    COI Management Strategies

•   Public disclosure
•   Monitoring by independent reviewers
•   Disqualification from project participation
•   Divestiture
•   Severance of relationships that create COI
•   Notification of sponsor (NIH, NSF, others)
        UCI Student COI Policy
• Industrial sector support found to provide significant
  opportunities for students, but also carries risks

• A possible conflict of interest arises when a thesis advisor
  has a financial interest in the outcome of a project on which
  the student is working and may exist even if the student’s
  research is not supported by the financial interest.

• New academic policy approved in Spring 2000:
    Establishes a mechanism to protect the academic interests of a
     student whose mentor may have COI relating to their project
    Process may be initiated by the student, faculty mentor,
     departmental representative or COIOC.
    Additional member (i.e., oversight member) may be added to thesis
     committee to monitor academic interests of the student
Selection of Oversight Member
The Dean of Graduate Studies shall select the Oversight Member from
a list of three nominees chosen by the departmental representative
(graduate advisor or chair) and agreed upon by the student and the
faculty research advisor.

 The request for appointment of an Oversight Member must be
submitted in writing to the Dean of Graduate Studies no less than two
weeks prior to the date of the exam but preferably as soon as the
conflict has been identified.

The request will also include background information describing the
circumstances of the possible conflict.

The Dean of Graduate Studies will retain sole authority to appoint the
Oversight Member. No exceptions to this requirement will be
    Role of the Oversight Member
The Oversight Member shall participate on all student research
advisory and/or thesis committees.
An additional role of the Oversight Member is to be fully
cognizant of the issues related to the possible COI and its
potential impact on the student, and to be fully cognizant of the
UCI resources available should a COI problem arise.
If there do not appear to be any harmful results from COI, the
Oversight Member shall sign a statement to that effect after each
committee meeting.
This statement shall be placed in the student's file as well as
forwarded to the Dean of Graduate Studies.
       Why not just ban any Conflicts of
Because…….in a capitalist society, the incentive for innovation and creativity
are rewards of which the financial type is among the most common

Practical application (i.e., commercialization) will not occur without incentives

To say that you will innovate without incentives that are financial or otherwise
would be disingenuous

Moreover universities have become dependent upon the profits flowing from
patents resulting from faculty and student research

UC patent income over the last decade has progressively increased:
•       1997: $67 MM
•       2001: $89 MM
•       2008: $129 MM

Managing the conflict, if possible, is still the pragmatic solution
   More technology has been moved to the marketplace to better
healthcare in last two decades than any other period along with more
                   conflicts of interest than ever but:

      “Without conflict, there is
            no interest”
                                            Dave Schetter, 1995
                                             Assistant Vice Chancellor
                                                       for Technology
                                                            U.C. Irvine