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A person may find him- or herself in a situation
where two or more competing interests creates the perception
or the reality of an increased risk of bias or poor judgment.
Such challenging situations come up regularly in both our personal
and professional lives. Collectively, we refer to these as conflicts
of interest. This term has become synonymous with monetary or
personal gain. It encompasses behaviors or actions in which someone
(or a member of their immediate family or household) gains personally
or financially as the result of that person exploiting his or
her position. Conflict of effort on the other hand involves situations
where demands from separate entities jeopardize the duties and
responsibilities associated with one of more of those entities
(e.g., outside consulting activities interfering with duties
of one's primary employment). Yet a third type of conflict is
called conflict of conscience. Here the conflict is created by
having to maintain objectivity in the face of your convictions
which go against the grain of something you must act on or evaluate.
Such a conflict might emerge during peer review; e.g., being
asked to review a manuscript on fetal stem cell research, when
you believe that such research is wrong because the origin of
such cells is from aborted fetuses. Conflicts encountered in
the profession of science are not inherently bad. Indeed, they
are to be expected. It's how they are handled that can lead to
untoward, inappropriate, or bad outcomes.
Although scientists have a professional, fiduciary, and ethical interest in the
responsible conduct of research, these interests may be compromised by personal
interest. A common worry is that financial interest in the outcomes of research
can result in unethical behavior or criminal misconduct.
Discussions about conflict of interest generally focus on financial interests,
but it is equally plausible that interests other than financial could compromise
the responsible conduct of research. Examples of non-financial interests that
might conflict with the integrity of science include career advancement, publishable
results, service to patients or students, fame, power, or family and friendships.
Another potential conflict can come in the form of conscience. An individual
might suffer a conflict of interest if the mission or expectation of the institution
is not compatible with his or her personal values.
Of course, having a personal interest does not necessarily mean acting irresponsibly.
Although some might take personal interest as a motivation for misconduct, it
is obvious that not all individuals would make this choice.
Conflicts of interest are not merely a hypothetical problem. Financial conflicts
are associated with altered outcomes of research. Stelfox et al. (1998) reviewed
the literature in 1995 and 1996 for reports on the safety of calcium channel
antagonists. They classified reports as being supportive, neutral, or critical
of these drugs. They found that 100% of authors of reports supporting calcium
channel antagonists had financial relationships with drug companies, while only
43% of authors of reports critical of the drugs had such connections with drug
companies. Many different hypotheses might explain this trend, but one lesson
is that it would be valuable to know if a published study was supported by industry.
Rules and regulations
A variety of regulations and guidelines govern
the disclosure and management of conflict of interest. Although
many of the concerns addressed could be generalized to any form
of conflict of interest, the explicit problem in nearly all cases
is financial. The most relevant of these are federal regulations,
notably those of the Public Health Service (PHS) and National
Science Foundation (NSF).
PHS and NSF policies
are substantially the same regarding conflicts of interest
(PHS, 1995; NSF, 1995). Under PHS policy: '...investigators
are required to disclose to an official(s) designated by
the institution a listing of Significant Financial Interests
... that would reasonably appear to be affected by the
research proposed for funding by the PHS.' The institutional
official(s) are responsible to review 'those disclosures
and determine whether any of the reported financial interests
could directly and significantly affect the design, conduct,
or reporting of the research and, if so, the institution
must, prior to any expenditure of awarded funds, report
the existence of such conflicting interests to the PHS
Awarding Component and act to protect PHS-funded research
from bias due to the conflict of interest.' Significant
Financial Interests are defined to be: '...anything of
monetary value, including, but not limited to, salary or
other payments for services (e.g., consulting fees or honoraria);
equity interests (e.g., stocks, stock options or other
ownership interests); and intellectual property rights
(e.g., patents, copyrights and royalties from such rights).' |
Professional societies and journals are an important
source for guidance on the management of conflicts of interest.
These are quite variable in their scope and rarely enforced,
but two examples are noteworthy. The first is a policy statement
from American Society of Gene Therapy (ASGT), and the second
is the published requirements for publication in the New England
Journal of Medicine. In a statement adopted in April of 2000,
the ASGT concluded that 'investigators and team members directly
responsible for patient selection, the informed consent process
and/or clinical management in a trial must not have equity, stock
options, or comparable arrangements in companies supporting the
trial.' (Woo, 2000) As early as 1984, the New England Journal
of Medicine requested that 'all authors disclose to [the Editor]
any associations they had with businesses that could be affected
by their work -- including direct employment and consultancy,
stock ownership, and patent-licensing arrangements.' (Angell
and Kassirer, 1996).
Federal regulations defer, in part, to institutional definitions of conflicts
of interest. Not surprisingly, institutional standards vary greatly. Regarding
stock ownership, most use the federally defined threshold of $10,000 or 5%
of total shares as a definition of significant financial interest that must
be declared. However, some institutions have been somewhat stricter. For example,
Harvard scientists are prohibited from working for a company in which they
have more than $20,000 in stock (Brainard, 2000).
Principles
Perhaps the adverse consequences of conflicts
of interest will eventually be mitigated by the structure of
science-- objectivity, blinding of experimenters, repetition
of studies, peer review, disclosure, and so on. In practice,
this strategy does not address the harms to subjects in clinical
trials, misinformation entering the literature, and increased
cynicism about science.
Conflicts of interest increase the temptation
to commit misconduct.
Conflicts of interest do not necessarily amount to research misconduct. If
the potential gain is large, however, then principles that guide responsible
conduct in research may be compromised.
Conflicts of interest increase the risk of unintentional bias.
Unintentional bias can be a more serious threat than deliberate misconduct,
because even those who are biased would be unaware of the ways in which their
actions were effected.
For example: Because research is expensive,
the research interests of individual scientists are likely
to drift toward those topics, methods, and approaches for
which support is available. In the design of experiments,
scientists may be unconsciously biased to choose, or stick
with, approaches likely to provide 'marketable' findings,
rather than those designed to increase basic understanding
of mechanisms. In the collection of data, a researcher with
significant financial interests may unwittingly introduce
bias into enrollment of subjects for a clinical trial, into
evaluation of data dependent on subjective judgments, or
even into the reading of objective measurements. Finally,
unintentional bias could alter choices about data selection,
statistical methods, and presentation of results.
Conflicts of
interest can lead to harmful misperceptions of scientists
and the scientific enterprise.
When large sums of money are involved, it may be difficult for the public,
legislators, the judicial system, and even colleagues to be convinced that
results were not biased for personal gain. Perceived impropriety can result
in consequences as damaging as if intentional misconduct had been committed.
With increased media, governmental, and public scrutiny, a researcher's reputation,
research funding, and employment can depend as much on perceptions of integrity
as on integrity itself.
Guidelines
Beyond the existing rules, the following are
guidelines generally applicable to the management of conflicts
of interest and commitment:
Avoid and minimize conflicts
Everyone has different interests, and eventually these will come into conflict.
Although it is not possible to avoid all sources of conflict, it is in the
best interests of the scientific community and the individual scientist to
recognize conflicts of interest and to take steps to nullify or mitigate those
conflicts; for instance, sell shares in the company, turn down research support,
or abandon a project.
Disclose interests
If conflicts cannot be avoided, then those conflicts should be disclosed. At
minimum, the institution and any other parties with a significant interest
should be made aware of the extent and nature of the conflict. This includes
the audience at meeting presentations as well as journal editors (before submitting
or refereeing manuscripts).
| Disclosure usually occurs only
for financial interests, and such disclosure is not routine
in the biomedical literature (Krimsky et al., 1998).
In a survey of 789 scientific papers published by Massachusetts
scientists in the leading journals of cell and molecular
biology, Krimsky and his colleagues contacted the authors
and found that 34% of the articles had at least one Massachusetts
author with a significant financial interest. Despite
this high rate of financial interests, Krimsky et al.
reviewed 62,000 papers and found that only about 0.5%
included disclosure statements. Unfortunately, even as
financial conflicts and the risks for bias are increasing,
a minimal expectation that those conflicts would be disclosed
is not being met. |
Manage potential for
conflict
Disclosure is often not enough because of the risks of bias, the temptation
for irresponsible conduct, public and regulatory concerns about the possibility
of misconduct, and the appearance of impropriety. For every step of the research
process, attempts should be made to isolate the conflicted individuals from
all decisionmaking functions. For example, steps should be taken to maximize
the objectivity of patient selection, data collection, the selection of data
for publication, and interpretation of the findings. These functions should
be the responsibility of, or should at least be reviewed by, an unconflicted
individual or group.
In summary, it is important to understand that both the potential for conflicts
of interest and the strategies for dealing with those conflicts are evolving.
Considering the potential for misperceptions of a researcher's motives, it
is best to assume that good intentions are not enough.
UAF Specific Information
All UAF personnel
should be familiar with the following UAF Policy related
to Conflicts of Interest and Commitment.
A form for disclosing Significant
Financial Conflicts of Interest is available on the OSP
website. If you are uncertain about whether or not something
qualifies as a conflict of interest contact the Director,
Office of Sponsored Programs for more information. This
applies to any member of the research team, their close family
members, close friends, or business associates. If you have
a conflict of interest you are required to report it on the
OSP Routing Form and work with the Director,
Office of Sponsored Programs, to develop a plan to manage
or mitigate the conflict.
Although PI's are only required to report significant
financial conflicts of interest, they are strongly encouraged
to report and develop management plans for other types of conflicts
as well. The Director, Office of Research
Integrity, can assist PIs in developing an appropriate
management plan.
Works Cited
- Angell M, Kassirer JP (1996): Editorials
and conflicts of interest. New England Journal of Medicine
335(14): 1055-6.
- Brainard J (2000): The Ties That Blind?
(financing that might influence medical research) Chronicle
of Higher Education. Sept. 8, 2000 47(2): A31.
- NSF (1995): NSF Investigator Financial
Disclosure Policy. Federal Register July 11, 1995 60(132)
http://www.nsf.gov/pubs/stis1996/iin117/iin117.txt
- PHS (1995): PHS Policy on Objectivity
in Research. NIH Guide to Grants and Contracts July 14, 1995
24(25)
http://grants.nih.gov/grants/guide/notice-files/not95-179.html
- Stelfox HT, Chua G, O'Rourke K, Detsky
AS (1998): Conflict of interest in the debate over calcium-channel
antagonists. New Engl J Med 338(2): 101-106.
- Woo SL (2000). Policy of the American Society
of Gene Therapy on financial conflict of interest in clinical
research. Mol Ther 1(5 Pt 1): 383-4.
http://www.asgt.org/position_statements/conflict_of_interest.html
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