To The Editor:
We enjoyed the recent Current Concepts Review "The Use
of Low-Intensity Ultrasound to Accelerate the Healing of Fractures" (83-A:
259-70, Feb. 2001), by Rubin et al. It sounds like ultrasound is
the best thing since sliced bread—and it may be, but we were
a little disappointed with the references.
The section entitled "The Ability of Ultrasound to Accelerate
Fracture-Healing in the Clinical Setting" cited twelve
sources. Two of these were articles published in The Journal
of Bone and Joint Surgery. The first, by Heckman, Ryaby, McCabe,
Frey, and Kilcoyne1, found that
ultrasound made tibial fractures heal faster. The second, by Kristiansen,
Ryaby, McCabe, Frey, and Roe2,
found that ultrasound made distal radial fractures heal faster.
Since The Journal requires disclosure of potential
conflicts of interest, the reader is told that for both papers, "One
or more of the authors have received or will receive benefits for
personal or professional use from a commercial party related directly
or indirectly to the subject of this article. Funds were received
in total or partial support of the research or clinical study presented
in this article. The funding source was Exogen, Incorporated."1,2 The articles also show that Ryaby
and McCabe are employees of Exogen and that Frey is an employee
of Health Products Development, Inc. The reader is not told what
form of support Exogen gave, how much support, or to whom it was
given.
A third article, published in Clinical Orthopaedics and
Related Research, by Cook, Ryaby, McCabe, Frey, Heckman,
and Kristiansen3 and cited in
this section, was apparently a second look at the patients from the
aforementioned two studies. Cook et al. showed that ultrasound makes fractures
in smokers heal better. Since Clinical Orthopaedics and
Related Research doesn’t require financial disclosure,
the reader cannot find out whether Exogen supported this research
as well.
In the Current Concepts Review by Rubin et al., another article
cited in the clinical section, by Mayr, Frankel, and Rüter4, apparently analyzed information
from Exogen’s database of patients who had received the
ultrasound device. This article states that "the device
. . . is provided by Exogen." So not only did Exogen provide
the devices, they provided the study data as well. No financial
disclosure was given, as Archives of Orthopaedic and Trauma Surgery does
not require it.
One reference was a case report of one patient5,
again with no financial disclosure. Another reference, published
in Clinical Orthopaedics and Related Research, by
Strauss and Gonya6, reported the
successful use of ultrasound in two patients with Charcot arthropathy
who underwent revision ankle fusion surgery. Again, no financial
disclosure was given.
Other references cited were abstracts presented at an annual
meeting of the International Society for Fracture Repair that were
later published in the Journal of Orthopaedic Trauma7,8. That journal requires financial
disclosure from its authors, but the abstracts contain no such information.
Both abstracts showed positive effects of ultrasound. Ryaby was
an author of both abstracts.
Two other studies, both by Emami et al., were cited: one was
published in the Journal of Orthopaedic Trauma9 and one, in Clinical Orthopaedics
and Related Research10.
The first states that "Exogen Inc. provided the ultrasound
devices used in this study. The authors have received nothing else
of value."9 The second
article provides no information about financial support of the study.
Both studies by Emami et al. were prospective, randomized, blinded, and
placebo-controlled. Both showed no difference in healing between
the patients who were treated with ultrasound and those who were
not.
It may be that ultrasound has an enormous beneficial effect on
fracture-healing, and we realize that industry support of research
doesn’t necessarily mean that the research is flawed or biased,
but the fact that an employee of a company that sells ultrasound
devices co-authored the Current Concepts Review raises doubt about
the potential for bias. Other investigators have shown that the
conclusions of review articles are strongly associated with the affiliations
of their authors11. It is also
possible that interactions between physicians and industry may affect
prescribing and professional behavior12.
Given the shrinking budget for research, it is inevitable that
industry will become more important in the funding of clinical studies.
It seems likely that the increasing involvement of industry in the
design, execution, analysis, and reporting of clinical research
will increase the risk that doctors will be fooled occasionally.
We need to be vigilant.
Would it have been possible for the Editorial Board of The
Journal to find a group of qualified authors who were not financially
tied to the device that they were reviewing? One would think that if
the thing worked all that well, one would be able to find a reviewer
who wasn’t beholden to the company that sells the device.
Readers rely on The Journal of Bone and Joint Surgery to
be objective. We’re not certain that this Current Concepts
Review passes muster in terms of objectivity.
T.A. Einhorn replies:
Drs. Starr, Borer, and Reinert raise important and timely issues
regarding conflict of interest in the medical literature and both
the value and the potential failure of disclosure. In this Current Concepts
Review, full disclosure by the authors is recognized, but concern
is raised regarding inclusion as an author of an individual who
is employed by the company (Exogen, Inc.) that provided research
funds for some of the studies cited in the review and the use of
references taken from sources in which there is no disclosure of
conflict of interest.
As many of the so-called cutting-edge technologies in orthopaedic
science emanate from pharmaceutical and biotechnology companies,
there is concern that the quality and reporting of new data are
potentially influenced by corporate agendas. Indeed, some of the most
critically reviewed clinical and basic-science journals consistently
publish articles written exclusively by authors who are employed
by such companies. The Journal of Bone and Joint Surgery is
not alone in its ongoing need to address conflict of interest.
Most of the time, when an article reports the results of a clinical
or basic-science research study, one can carefully examine the experimental
design, the methods used for reducing bias, the statistical methods
used for analyzing data, and the conclusions as supported by those
data. However, with a review article, the ability to use these criteria
is limited. Indeed, many of the references cited in the review by
Rubin et al. were from sources in which conflict of interest is
not policed. This point, I believe, is particularly important. While
I believe it is necessary for editors and readers to rely on disclosure
of conflict of interest in published articles, our lack of attention
to the use of sources in which conflict of interest is not disclosed
requires reexamination, although exploring this would add a layer
of complexity to the editorial review process.
One of the suggestions made by Drs. Starr, Borer, and Reinert
is that the Editorial Board seek authors who do not have any conflict
of interest and therefore could be more objective in writing an
article such as the one in question. I disagree with this recommendation. Frequently
the so-called thought leaders in our field are called upon to provide
critically important information to companies developing our next
generation of advanced technologies, and these individuals have
every right to be compensated for their time and expertise, as well
as to be permitted to pursue their academic goals without a penalty for
contributing to a corporate or commercial process. This is where
honesty and trust among clinicians and scientists are required.
As new advances in orthopaedic care continue to evolve, the issue
of conflict of interest in the reporting of the results of basic-science
studies and clinical trials published in The Journal will
continue to be reevaluated and redefined. As the Deputy Editor responsible
for the editorial preparation of the Current Concepts Review in
question, I can assure our readers that exceptional attention was
paid to issues of bias in this article. I do not believe that exclusion
of an author because he or she is associated with a company is fair
or appropriate. On the other hand, I do agree that we and the editors
of other journals can and should do a better job of establishing
policies on the use of reference materials taken from sources that
do not require conflict-of-interest disclosure. On that particular
point, I wish to thank Drs. Starr, Borer, and Reinert for their
concerns and for making an excellent suggestion for the ongoing
reevaluation of the editorial process at The Journal.