Transcript Conflict of Interest: - University of South Florida

Fundamentals of
Conflict of Interest in
Research
By
Camille A. McWhirter, J.D.
Director, Research Compliance
USF Health
Learning Objectives
Generally:
 Define a conflict of interest (COI)
 Recognize different types of “self-interest”
that can create a conflict of interest
 Recognize the various ways a conflict of
interest can occur in the research context
Learning Objectives (cont)
Regulatory Context:
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Understand the difference between the state’s
interest in regulating COI and the federal
government’s interest in regulating COI
Identify the three federal government agencies
who have rules regulating COI in research
Understand when each agency’s rules apply
Learning Objectives (cont)
Practical Application:
Identify the different types of conflicts of
interest in a given scenario
 Perform a COI review and develop a
management plan

“Working” Definitions
Conflict of Interest
A conflict of interest exists when an
individual’s professional or ethical obligations
might be compromised by self-interest.
Conflicts of Interest and Commitment
w/ University Employment
(Excessive time spent on external endeavors,
use of USF resources/name/students
in furtherance of private interests,
waiver of USF IP rights in private agreements)
Conflicts of Interest
in Research
(Personal financial interests
that may bias the design,
conduct or reporting
of USF Research)
General Conflicts of Interest
(Nepotism, Doing Business w/USF
in Private Capacity,
Board/Committee Membership,
Purchasing Decisions)
“Working” Definitions
Conflict of Interest in Research
A conflict of interest in research exists when an
investigator’s self-interests may compromise, or
have the appearance of compromising, an
investigator's professional judgment in the
design, conduct or reporting of research.
Investigator
Any person responsible for the design, conduct
or reporting of research.
COI =
Individual +
Self-Interest +
An Ethical or
Professional Duty
COI in Research =
Investigator +
Self-Interest +
Objectivity in the
Design/Conduct/Reporting of
Research
HINT: The management goal
is to protect the integrity of
the research
Hypothetical: COI in Research?
Dr. Needbucks of Public University invented a
drug to prevent Alzheimer’s disease.
DevicesRUs, wants to sponsor a study with Dr. N
as the PI to develop and test a device that will
deliver Dr. N’s drug directly to the brain.
Dr. N’s spouse is the president of Lab Solutions,
Inc. that manufactures lab supplies and
equipment.
Dr. N and her staff purchase all of their basic
supplies and equipment from Lab Solutions.
Ask:
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Investigator? Yes. The individual is an investigator on a
research study.
Self-Interest? Yes, financial interest of spouse in a company
that sells research products.
What is the professional/ethical obligation that is
compromised? The duty potentially compromised by this
self-interest is the duty of public stewardship--to refrain from
using one’s public position to enhance one’s private interests.
Conclusion: This is a conflict of interest in a research setting,
but not a “COI in Research” as we have defined it because
the investigator’s self-dealing, while perhaps a conflict with
her public position, does not compromise the integrity of the
research results.
What if during the course of the
study…
Dr. Needbucks purchases $30,000 worth of
stock in DevicesRUs?
Repeat the analysis:
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Investigator? Yes. The individual is an investigator on a
research study.
Self-Interest? Yes, Dr. N’s financial investment in the
sponsor/manufacturer of the device being tested.
What is the professional/ethical obligation that is
compromised? The duty potentially compromised by this
self-interest is the duty of objectivity in the design, conduct, or
reporting of the research study.
Conclusion: This is a “COI in Research” as we have defined
it. Note that there may be more than one type of conflict of
interest at work in the research context—multiple avenues of
self-interest and multiple professional or ethical duties.
Types of Self-Interest
Self-interest can manifest in the form of
 A financial benefit
 Enhanced reputation
 Personal relationships
 Professional relationships
 Other interests (personal, political,
religious, or intellectual beliefs)
What type of self-interest is
represented by these examples?
Dr. Warren is an investigator for a study testing a
new medical device. Dr. Snyder’s brother is one
of the owners of the company developing the
device.
(Personal Relationship)
Dr. Mercer sits on the IACUC and reviews a study
about cloning.
Dr. Mercer thinks cloning is
immoral and unethical.
(Personal Belief)
What type of self-interest is
represented by these examples?
Dr. O’Connor owns significant stock in a biotech company.
The company approaches him about conducting research
on the viability of a new genetics test.
(Financial Interest)
Dr. Tate is the co-founder of a new method of behavioral
therapy for which he has received worldwide recognition.
He is approached about conducting a study for another
form of therapy which, if effective, would render his form of
therapy obsolete.
(Reputation )
What type of self-interest is
represented by these examples?
Dr. Markham sits on the board of directors of Company X.
Company X is developing a new piece of equipment and
they ask Dr. Markham to conduct a study on the safety and
efficacy of the equipment.
(Professional Relationship)
State Regulations (Code of Conduct of
Public Officers and Employees)
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The state regulations only address general COI of public
officers and employees and are designed to prohibit
and/or manage conflicts between a public employee’s
duties to the state employer and the employee’s
personal interests
Example: A public employee acting in a private
capacity, may not sell goods to his or her own agency.
Example: A public employee may not have an ongoing
or regularly recurring conflict with his or her public
employment (catch-all provision).
What interests are the state COI regulations designed to
protect?
Federal Regulations (NSF/PHS and
Food & Drug Administration)
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The federal regulations only address financial interests
and relationships in research (COI in Research)
Example: Universities receiving federal funds to conduct
research must have policies to manage bias in the
design, conduct or reporting of research funded with
federal dollars (PHS/NSF).
Example: A sponsor of a new drug/device must certify
that COI of investigators in studies supporting the FDA
approval of the drug/device either does not exist or is
adequately managed
What interests are the federal regulations designed to
protect?
Federal Regulations
The federal regulations only address one
type of “self-interest”:
FINANCIAL INTERESTS
(Why?)
Federal Regulations
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Food and Drug Administration
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Applies in research involving a drug, device
or biologic.
Requires disclosure at the time of application
for approval of a drug device or biologic.
Evaluates the impact of the researcher’s
financial interests on the reliability of the
study.
Federal Regulations
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Public Health Service (PHS) & National
Science Foundation (NSF)
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Applies to institutions receiving grants from these
agencies
Requires development of a COI policy that meets
certain minimum requirements
Deliberately vague to permit flexibility in the
administration of policy
PHS and NSF regulations were developed
cooperatively to make the regulations consistent.
FDA Regulations
“Anyone who submits a marketing
application of any drug, biological product
or device must submit certain information
concerning compensation to, and financial
interests of, any clinical investigator
conducting studies covered by this rule.”
21 CFR Part 54
What is the “certain information”?
Applicant must EITHER certify that:
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No financial arrangements have been made with
an INV where study outcome could affect
compensation.
INV has no proprietary interest in the tested
product.
INV does not have significant equity in sponsor
and has not received other payment
OR
Disclose the specified financial arrangement and
any steps taken to minimize the potential for bias.
Then, FDA will determine whether conflicting
interest could jeopardize the integrity of the study.
Such a determination can result in severe delays
and significant financial losses. So….institutions
are doing it for themselves.
Potential FDA Actions
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If the FDA is concerned about the conflict,
the FDA can:
Audit the data derived from the INV in
question
Request further data analysis to evaluate
the effect of the INV data on overall results
Request additional independent studies
Refuse to use the data to support an FDA
action
PHS/NSF COI Regulations
Investigator Responsibilities:
Must report any significant financial
interests (including those of spouse and
dependent children) to a designated
institutional official.
Significant Financial Interests
Anything of monetary value, including
salary, consulting fees or honoraria,
equity interests (stock, ownership
interests) and intellectual property
rights.
EXCEPTIONS:
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Salary from your own institution
Ownership interest in an institution applying
for an SBIR grant
Income from speaking engagements
sponsored by government or non-profit
Income from advisory boards of G or NP
Equity interest < $10,000 or 5%
Annual payments < $10,000
PHS/NSF COI Regulations
Institutional Responsibilities:
Written enforced policies on COI
Designated institutional official
Ensure that each investigator submits a disclosure form for
PHS and NSF research annually
Provide guidelines for review of COI and manage COI
Maintain records for 3 years
Establish enforcement mechanisms and sanctions
Report failures to comply to awarding agency
Problem for Institutions
COI can be subtle and complex, often involving
ethical issues beyond the scope of regulation.
Also, the regulations that do exist are
purposefully flexible in order to allow the
institutions to apply them in the way that best
suits the institution. So the regulations can
often seem vague and open to interpretation.
Solution: Guidance Documents
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Consequently, a number of federal government
agencies and national professional associations
have published guidance documents to help
individuals and institutions cope with COI in
research issues regulated by the federal
government.
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Among these organizations are the American
Medical Association (AMA), the Association of
American Universities (AAU), and the Association
of American Medical Colleges (AAMC).
Conflict of Interest Committee
Many of the guidance documents
recommend that institutions create a
Conflict of Interest Committee (COIC) to
evaluate, manage COI resulting from
external financial interests in research, and
to ensure that the institution’s COI policies
and procedures and applicable COI
regulations are met.
General Principles
in Dealing with COI in Research
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COI is virtually unavoidable.
COI does not preclude participation of an
investigator in a project.
Must have a culture of honest and full disclosure
so that steps can be taken to manage conflicts
effectively
Not all COI can be managed.
COI Committee Review
MOTIVATION
How much incentive does the INV have to
bias the design, conduct or reporting of the
research?
OPPORTUNITY
Is the INV in a position to bias the design,
conduct or reporting of the research?
Possible Steps to Manage COI
Elimination of the conflicting interest (e.g.,
divestiture of financial interest or removal from
project)
Substitution of non-interested personnel on the
project
Public disclosure of the financial interests (journals,
research subjects, collaborators, etc.)
Monitoring of research by independent reviewers
Look for inherent management controls (e.g., the
research has objective endpoints that are not
subject to manipulation by the investigator)
COI Committee: Hypothetical
Investigator Scully has regular and ongoing
consulting agreements with various
sponsors of clinical trials on which he
conducts studies.
The aggregate of income for any one
sponsor can be anywhere from $8,000 $30,000 per year.
COI Committee: Hypothetical
Investigator Scully is approached to conduct a study for
Company X and files a financial disclosure stating that
he anticipates receiving $9,999 in income from
Company X over the next 12 months.
Scully also served on the advisory board of Company X
to assist with the study design and analysis on the study
that he has been asked to conduct for Company X.
Scully might receive more $$$ from Company X if he is
asked to give lectures on the study during the year.
COI Committee: Hypothetical
Additional facts:
The study in question is a multi-center trial that will
obtain data from 10 different sites aggregate. Scully is
the PI for one of the sites.
Data analysis is externally conducted—i.e., Scully is not
involved in the analysis of study data
The COI is disclosed in manuscripts submitted for
publication per journal requirements.
COI Committee: Hypothetical
The research subjects’ informed consent will outline
Scully’s interests related to Company X.
There are other investigators on the study who do not
have an interest in Company X.
Some Issues to Consider
What information do you need from INV
Scully?
How would you handle the “uncertain”
amount of income that may be received
annually?
Is there sufficient motivation to be concerned
about bias in the design, conduct or
reporting of the study?
Some Issues to Consider
Is there sufficient opportunity?
Is this conflict manageable?
How does the involvement of human subjects
influence your decision?
Would your opinion change if the amount of
annual consulting compensation was
$100,000?
For further consideration…
A colleague reports that Scully is diverting
the best grad students to work on the
Company X project to the detriment of
other unfunded research projects in the
Department.
Should this issue be addressed in your
review?
Other types of conflicts of interest that
occur in the research context:
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Nepotism (hiring relatives to work on your
grant)
Use of university resources to benefit a
private entity
Excessive time spent on external
endeavors
Waiver of University patent rights in a
private consulting agreement