Orthopaedic surgeons want what is best for their patients. Determining best
practice, however, is not always straightforward. Clinicians use many sources
of information to determine treatment options for their patients. Surgeons
rely in large part on their training. As surgeons progress through their
careers, practice learned through training is influenced by their own
experience, the advice of colleagues, and their personal learning, including
continuing medical education and the use of texts or the surgical literature.
One of the more powerful forces in shaping best practice is, and should be,
the surgical literature. The literature, however, is often contradictory.
Contradictory literature leads to conflicting treatment recommendations for
many conditions, and, in some situations, to a complacency among surgeons that
anything goes (as surgeons can find some support for just about anything in
the literature). Varying treatment recommendations in the literature and
subsequent variation in practice may be acceptable if different treatments
address different clinical situations, if different treatments have similar
outcomes, or if different treatments address the variation in patient
preferences. Barring these circumstances, if different treatments have
meaningful differences in outcome, then practice variation may adversely
affect patient outcomes.
Why do the recommendations for treatment reported in the literature vary
for many conditions? At least some of the variation in the surgical literature
reflects the variation in study quality. Surgeons intuitively recognize that a
more rigorous research design provides more convincing and dependable results.
Study design is the basis for levels of evidence. Although critical appraisal
is required to determine the merit of an individual study, according to the
Levels of Evidence in The Journal of Bone and Joint
Surgery1,
randomized trials (Level I) are considered the highest quality research.
Although the case series (Level IV), the predominant form of orthopaedic
research, are considered a less rigorous research design, it is important to
recognize that, despite their limitations, case series have made tremendous
contributions to orthopaedic surgery in the past. For example, the case series
reported by John Charnley in 1972 had a failure rate of only 1.3% in 210
patients at four to seven years after total hip
arthroplasty2.
Charnley was clearly a pioneer, and this case series heralded the modern era
of joint arthroplasty. His report was such an innovative leap that a
randomized trial was not required to demonstrate the superiority of the
Charnley arthroplasty compared with its predecessors. Most case series,
however, are more limited in their impact. When comparing different case
series, surgeons are often encumbered by the uncertainty of whether the
patients in the different reports are similar, whether the outcomes were
evaluated in a similar manner, whether the outcomes were established in a
consistent fashion, and any number of other biases that makes the
determination of the best practice almost impossible. The heavy reliance on
uncontrolled case series in orthopaedics has led to many unresolved clinical
dilemmas that, in general, do not seem solvable by studying more case
series.
Are there alternative paradigms for establishing the best practice? One
possible alternative for orthopaedics would be evidence-based practice.
Evidence-based practice, described in more detail
elsewhere3,
emphasizes the importance of randomized clinical trials. No surgeon would
argue against random treatment allocation (when possible) with clinically
meaningful outcomes performed at consistent times and in a consistent fashion.
Although more randomized trials are needed in surgery, not all orthopaedic
treatments are amenable to randomization. For example, a randomized clinical
trial comparing Van Nes rotationplasty with limb salvage or amputation for the
treatment of musculoskeletal tumors seems unlikely to be successful.
Randomized clinical trials are also not feasible if outcome rates are
infrequent or too far in the distant future. Finally, surgical trials present
important challenges in design, including the difficulty of blinding,
comparing operative and nonoperative treatments, the ethical concerns related
to surgical placebos, and the effect of learning curves and surgical
expertise4,5.
Despite these caveats, for most orthopaedic dilemmas, randomized trials are
needed.
Before completely adopting a paradigm of best practice based predominantly
on randomized clinical trials, it is important to consider the value of such
an approach. The most compelling example of the value of randomized clinical
trials comes from pediatric oncology. Thirty years ago, the treatment of
malignant tumors in children was based largely on case series and the personal
preferences of pediatric oncologists. At about that time, several
collaborative research groups, now united as the Children's Oncology Group,
began to perform multicenter randomized clinical trials. During the past
thirty years, the mortality associated with malignant tumors in children has
dropped from 90% to 10%. This improvement in outcome has been largely
attributed to the clinical trials arising out of these collaborative
groups6-10.
The Children's Oncology Group has approximately fifty ongoing studies, and it
has been estimated that between 75% and 90% of children with a malignant tumor
in North America are approached for enrollment in a clinical trial. This
initiative, led by a specialty society, is a compelling example of the
potential power of randomized clinical trials.
Despite these important advances, however, there have been relatively few
studies relative to the surgical treatment of childhood sarcomas from the
Children's Oncology Group. In the past, the main reason was that there was a
compelling systemic control question (i.e., is one chemotherapy regimen
superior to another?). However, other important questions remained unanswered.
For example, what is the relative benefit of radiation compared with resection
in the local control of Ewing sarcoma/primitive neuroectodermal tumor? Do
endoprostheses or allografts offer better function as limb reconstruction
after sarcoma resections (few authors have provided studies that even address
this issue)?11 It
is not even clear that limb salvage offers a better quality of life or
functional outcome compared with
amputation12,13.
Clinical trials could begin to address these issues outside the context of a
randomized clinical trial, but, with the exception of the treatment of primary
tumors of the rib in Ewing sarcoma/primitive neuroectodermal tumor, this has
not been
done14,15.
Part of the reason that there are few randomized clinical trials in
orthopaedics is that orthopaedists are not as facile with the performance of
these types of studies and it is not part of our education and culture.
Fortunately, however, this is changing.
This article focuses on an important practical barrier to carrying out more
randomized clinical trials in orthopaedic surgery: who will organize them? One
common mechanism is for a single investigator to create the necessary local or
national collaborations. This approach has the disadvantage of needing to
recruit collaborators and develop infrastructure for every trial. A second
mechanism has been for groups of surgeons to form collaborative networks
supporting one or more trials. Again, this has the disadvantage of providing
little permanent infrastructure, and it runs the risk of dissolution with gaps
in funding or investigator interest. A third mechanism would be national
leadership from organizations such as the American Academy of Orthopaedic
Surgeons or the American Orthopaedic Association to facilitate such research.
Such organizations, however, have broad mandates, and it is not clear that
there are sufficiently shared interests among the members to make such
organizations successful in facilitating randomized clinical trials. Finally,
the more logical groups with the potential to facilitate randomized clinical
trials are the musculoskeletal specialty societies. Specialty societies have
the necessary shared interest to promote trials. Although major funding of
trials is an important consideration for those specialties with limited
financial resources, specialty societies could still play several important
functions. First, societies should form Clinical Trials Committees with
responsibilities such as championing the cause of multicenter trials,
determining minimum standards for trials, providing education on randomized
clinical trials and evidence-based practice, and communicating information
about potential and ongoing trials to their membership. Second, specialty
societies should encourage specific randomized clinical trials through seed
grant support. Specialty societies either have or should consider having small
granting programs that could provide pilot funds to initiate randomized
clinical trials. Third, the annual meetings of the societies could be the
natural forum for investigators to meet, consider educational initiatives, and
provide information on randomized clinical trials to society members. Finally,
societies could provide permanent minimum infrastructure for trials such as a
clinical trials web site. Clinical trial web sites, which should ideally be
hosted on specialty society web sites, could educate members, create a
mechanism for surgeons to sign onto and to monitor trials, and be used to
manage such elements as online data entry. The specific roles of the Council
of Musculoskeletal Specialty Societies could be to share experience among
specialty societies; provide joint purchasing power, such as web-site
development; and, finally, encourage industry funding of randomized
trials.
One important additional barrier to multicenter randomized trials in
orthopaedics is the cost. Trials often involve a relatively small number of
centers with high volumes of patients and dedicated study personnel. These
trials are generally quite expensive. An alternative, less expensive, model
would be the involvement of many centers with a few patients. This model
reduces costs by not requiring study personnel at each center, but it requires
more dedicated site investigators. In either case, investigators will have to
seek funding from agencies such as the National Institutes of Health or the
Orthopaedic Research and Education Foundation. The National Institutes of
Arthritis and Musculoskeletal and Skin Diseases, in addition to funding
clinical trials, provides planning grants of $75,000 for one year.
Philanthropic agencies may also be able to fund trials. Finally, industry may
have a role.
The Pediatric Orthopaedic Society of North America (POSNA) has supported
clinical trials for more than five years. First, POSNA established a Clinical
Trials Committee. Second, POSNA encouraged investigators to compete for a
one-year grant of up to $30,000. Third, the POSNA annual meeting has been the
site of two instructional courses, has provided annual reports from the
Clinical Trials Committee, and has served as a venue for the presentation of
research results. Fourth, the society developed the POSNA Clinical Trials
Network web site. Initially, this web site was hosted through a commercial
vendor, but it is currently linked to the POSNA web site. The POSNA web site
provides guidelines for developing a randomized clinical trial, has an example
of a funded multicenter randomized clinical trial, has links to potential
funding agencies, allows surgeons to monitor the progress of randomized
clinical trials, and allows online data entry for surgeons participating in
randomized clinical trials. POSNA paid the initial development costs for the
web site. Since the initial development in 1999, the costs of developing such
web sites have dropped dramatically. POSNA also supports the annual web-site
maintenance fees. However, each new trial added to the web site involves
development costs, which in the case of the POSNA web site, are borne by the
investigators. POSNA has sponsored three multicenter clinical trials, with one
involving thirty-four investigators at twenty-three sites. Although the number
of trials has been less than some would wish, when one considers the fact that
the pediatric oncologists needed at least thirty years to organize, POSNA has
made remarkable gains in a short time.
Many key lessons were learned by the POSNA Clinical Trials Network, and
several are worth mentioning. First, early trials should investigate
conditions for which the diagnosis, treatment, and outcome are relatively
straightforward. Second, as previously discussed, having a few patients in
many centers makes trials feasible, as surgeons can handle that patient load
without stressing their individual practices. Third, trials with low budgets
that cannot afford study personnel at each site need to identify either a
secretary or nurse who will ensure that patients are seen at the appropriate
time and that surgeons complete the forms. Finally, centralizing ethical
approval at the site of the principal investigator substantially increases the
number of participating centers.
In summary, randomized clinical trials should play a major role in
determining best practices for orthopaedics. One of the limitations to
carrying out more trials is the need for the support of professional
organizations. The musculoskeletal specialty societies, which are linked by
common clinical interests, may be that champion. It is logical that the
American Academy of Orthopaedic Surgeons through its Council of
Musculoskeletal Specialty Societies (COMSS) could foster this initiative. This
would provide a meaningful role for COMSS and would serve as a stimulus to the
specialty societies to carry out these studies. The clinical questions abound.
We, as orthopaedists, need to change our culture and to be more proactive in
carrying out randomized clinical trials and other studies to increase the
availability of evidence-based research to guide our clinical care.
Orthopaedics, through its specialty societies, should establish Clinical
Trials Committees and consider developing infrastructure support, such as seed
grants and web sites, to promote randomized clinical trials. Donations to the
Orthopaedic Research and Education Foundation can be directed to an
individual's specialty society interest, and such funding is desperately
needed to conduct evidence-based research. Everyone can contribute in this way
whether they actually conduct the research or not. As the number of randomized
clinical trials in orthopaedics increases, the outcome of patients with
musculoskeletal disease will improve. This research will not only help us as a
specialty but, more importantly, will ensure that our patients receive the
best possible care.