Case 1. An orthopaedic surgeon publishes a paper featuring a
positive evaluation of a new medication to prevent deep venous thrombosis. The
surgeon serves as a paid consultant to the drug manufacturer.
Case 2. An orthopaedic surgeon is asked by a medical device
company to conduct a study evaluating a novel total hip prosthesis. The device
manufacturer assumes responsibility for funding the study and publishing the
results.
Case 3. An orthopaedic surgeon has developed a novel synthetic
tendon graft, which she hopes to market after obtaining approval from the
United States Food and Drug Administration (FDA). She seeks to enroll one of
her patients in a clinical trial of the graft.
Conflict of interest has been defined as "a set of conditions in
which professional judgment concerning a primary interest (such as a patient's
welfare or the validity of research) tends to be unduly influenced by a
secondary interest (such as financial
gain)."1
Within the field of medicine, financial conflict of interest may play a role
in clinical practice, continuing medical education, or academic research. This
article focuses on conflict of interest in orthopaedic research.
In the research setting, financial conflict of interest may occur when an
investigator conducts research that is related to the interests of a company
from which he or she receives funding, or a company in which he or she has
stock or ownership interest. The subject has attracted substantial media
attention in recent years, due in part to
scandal2-5
and tragedy6.
Conflict of interest as it relates to medical research has also received
considerable attention in the medical
literature7-15,
and with good reason. Industry provides 60% of all funding for biomedical
research16 and 70%
of the money required for clinical drug
trials8.
Furthermore, fully one-quarter of all biomedical investigators receive
research funding from for-profit
companies17. Among
the orthopaedists who presented research at the 2002 Annual Meeting of the
American Academy of Orthopaedic Surgeons (AAOS), 32% had a financial conflict
of interest to
report18.
This high prevalence of corporate funding in orthopaedic research is not
inconsequential. Studies have shown that industry-funded research is more
likely to result in positive
findings17,19-23,
more likely to restrict investigator
behavior17, and
less likely to result in negative
findings20. In
addition to compromising the integrity of academic medicine, conflicts of
interest may also threaten the welfare of clinical research
subjects24.
Government and professional organizations have responded with laws and
guidelines to address conflict of interest in biomedical research.
Medical journals were perhaps the first to develop specific policies to
address conflict of interest in medical research. The New England Journal
of Medicine began requiring disclosure of funding sources in
198440, and The
Journal of Bone and Joint Surgery followed one year
later41. Recently,
medical journals have also taken steps to address industry suppression of
negative results. In particular, the International Committee of Medical
Journal Editors has mandate that all clinical trials be registered with an
approved entity (such as
)
at the time of study inception to be eligible for
publication42. It
is believed that prospective registration of clinical studies will make it
more difficult for industry to suppress negative results.
Professional organizations have also sought to address financial conflict
of interest in medical research. The AAOS, for example, promotes a policy that
centers on disclosure:
"An orthopaedic surgeon reporting on clinical research or experience
with a given procedure or device must disclose any financial interest in that
procedure or device if the orthopaedic surgeon or any institution with which
that orthopaedic surgeon is connected has received anything of value from its
inventor or
manufacturer."43
"An orthopaedic surgeon reporting on clinical research or experience
with a given procedure or device must disclose any financial interest in that
procedure or device if the orthopaedic surgeon or any institution with which
that orthopaedic surgeon is connected has received anything of value from its
inventor or
manufacturer."43
The American Medical Association (AMA), in addition to requiring
disclosure, prohibits remuneration not "commensurate with the efforts of
the researcher" as well as the purchase or sale of stock belonging to
the company for whom the investigator is performing research. The policy also
recommends that individual medical centers take the initiative to develop
"specific guidelines for their clinical
staff."44
Guidelines for ethical conduct have also been proposed by representatives
of the drug and device
industries45,46.
In 2004, for example, the Advanced Medical Technology Association (AdvaMed)
issued a "Code of Ethics on Interaction with Health Care
Professionals."45
While the document focuses primarily on interactions between physicians and
industry in the clinical realm, interactions in the research setting are
considered as well. In particular, agreements with clinical investigators are
described as being subject to guidelines governing arrangements with
consultants. The selection of research partners by industry should be on the
basis of "qualifications and expertise," and not the volume of
business that is generated. Also, contracts should include a written research
protocol, and compensation should be "consistent with fair market value
for the services provided."
Recognizing the heightened risk of harm in research dealing with human
subjects, some organizations have also developed specific policies to address
conflict of interest in clinical research. The AMA, for example, requires that
investigators disclose all conflicts of interest to potential research
subjects as part of the informed consent process. Furthermore, to properly
differentiate between the role of a physician as a clinician and the role of a
physician as an investigator, the informed consent of the subject is to be
obtained by someone other than the treating physician. Physicians must ensure
that the sponsoring company will not obstruct the presentation or publication
of results, and that financial compensation is "commensurate" with
research efforts. The policy also notes that it is "unethical for
physicians to accept payment solely for referring patients to research
studies."47
The most far-reaching guidelines published to date, however, have been
those of the Association of American Medical Colleges
(AAMC)48. The six
main principles of this policy can be summarized as follows:
With regard to research done on human subjects, all significant financial
interests are potentially problematic and require close scrutiny.Researchers with significant financial interests may be permitted to
conduct research on human subjects under "compelling
circumstances," subject to conditions imposed by a conflict-of-interest
committee.Significant financial interests should be fully disclosed to the
institutional conflict-of-interest committee and updated regularly.Institutional policies should be "comprehensive, unambiguous,
well-publicized, consistently applied, and enforced through effective
sanctions."When compelling circumstances permit a researcher with financial interests
to conduct clinical research, "rigorous, effective and disinterested
monitoring" is crucial.Individuals conducting research on human subjects must know the
conflict-of-interest guidelines of their institution and must "act
diligently" to fulfill the requirements.
With regard to research done on human subjects, all significant financial
interests are potentially problematic and require close scrutiny.
Researchers with significant financial interests may be permitted to
conduct research on human subjects under "compelling
circumstances," subject to conditions imposed by a conflict-of-interest
committee.
Significant financial interests should be fully disclosed to the
institutional conflict-of-interest committee and updated regularly.
Institutional policies should be "comprehensive, unambiguous,
well-publicized, consistently applied, and enforced through effective
sanctions."
When compelling circumstances permit a researcher with financial interests
to conduct clinical research, "rigorous, effective and disinterested
monitoring" is crucial.
Individuals conducting research on human subjects must know the
conflict-of-interest guidelines of their institution and must "act
diligently" to fulfill the requirements.
While the policy defines "signiicant financial interests" in a
manner similar to the 1995 PHS guidelines (see above, under "Legal
Implications"), what is meant by "compelling circumstances"
is left to the interpretation of the individual university. It is worth noting
that "full disclosure...to research subjects and others" is listed
as a possible requirement to be imposed by the conflict of interest
committee.
Conflict of interest is common in orthopaedic research. The prioritization
of financial interests over patient welfare or scientific objectivity is
clearly objectionable. Ethical considerations require full disclosure of
financial conflict of interest to research subjects, journals, and others and
also require appropriate management of such conflicts by the institution.
However, only disclosure is required by law. No attempts have been made to
restrict the type or amount of financial conflict of interest that an
individual researcher may have.
With regard to Case 1, an investigator may publish a positive evaluation of
a drug manufactured by a company for which he or she serves as a paid
consultant. However, this financial conflict of interest, as well as any
others, should be fully disclosed when submitting the research for publication
or presentation. When reading the resultant article, orthopaedic surgeons
should bear in mind that the results of such studies are more likely to be
positive regarding the item being evaluated.
With regard to Case 2, an orthopaedic surgeon may contract with a medical
device company to conduct a study evaluating a novel prosthesis. The device
manufacturer may provide funding for the research as long as it is
consistent with fair market value and commensurate with the
efforts of the researcher. The study should be registered at the time of
its inception at
or another similar registry. Finally, the investigator should not allow the
device manufacturer to assume responsibility for reporting the findings, as
this may allow the company to obstruct or unreasonably delay the presentation
or publication of results (especially if they are unfavorable).
With regard to Case 3, the orthopaedic surgeon will have a significant
conflict of interest in a clinical trial of the synthetic tendon graft that
she has developed. According to AAMC guidelines, individuals with significant
financial interests should not conduct clinical research unless
"compelling circumstances" prevail. While this approach certainly
represents a laudable goal, it may not be feasible at the current time. As
such, the situation should be regarded as potentially problematic and should
be closely scrutinized by the surgeon's institution. When seeking
institutional review board approval, the conflict should be disclosed fully.
One or more of the surgeon's patients may be enrolled in the trial, but the
conflict should be fully disclosed to them and informed consent should be
obtained by someone other than the surgeon (to differentiate between her role
as a clinician and her role as an investigator).