Overcoming the Challenges of Randomized Orthopedic Clinical Trials
BY LAUREN UZDIENSKI, AUGUST 14, 2007
Despite randomized clinical trials' status as the most scientifically rigorous of potential research designs, RCTs make up a relatively small percentage of published orthopedics research. More randomized trials are being conducted now than in the past, but ongoing concerns about how to design, implement and manage orthopedic randomized studies remain. This month in JBJS, Dr. Stephen Trippel et al argue that the challenges of RCTs in orthopedic surgery are surmountable and that patient care advances in orthopedic surgery hinge on successful RCTs.
The paper highlights issues unique to orthopedics and advises potential investigators on how to overcome them. Among the points discussed are the importance of the research question, which should be evaluated with questions like, "Does the project address an unsolved problem?" and "Does the hypothesis survive the 'who cares' question?" Alongside defining the primary value of the study, the paper's authors advise against cluttering the research with subhypotheses and encourages researchers to stay focused on the principal question.
Contemplating feasibility is a key phase in developing a study; timing and extended follow-up could lengthen a trial to ten years. Additionally, challenges of patient recruitment necessitate having multiple investigators at multiple sites to ensure enough participants. When recruitment is difficult, the authors recommend relaxing the eligibility criteria, improving the consent rate, prolonging the trial or recruiting at multiple sites.
The authors emphasize teamwork and state that an orthopedic surgeon should partner with a Ph.D. epidemiologist or research methodologist to provide a strong infrastructure for the study. Dr. Trippel adds that young investigators should not be excluded, as they could bring enthusiasm, fewer biases and less cynicism relative to older colleagues. Additionally, each site should have dedicated research personnel to recruit patients, organize patient visits and collect trial data.
Surgical study design poses unique challenges, namely the issue of blinding. Sham surgery can control for the placebo effect, but the practice is laden with ethical concerns. The authors suggest that despite limitations on surgeon and patient blinding, an appraiser can be blinded; one example involves comparing a minimally invasive and a standard hip replacement, whereby the outcomes were evaluated with the incisions covered by bandages so neither the participants nor the evaluator knew whether participants had the minimally invasive or standard procedure.
Gaining approval for a study requires collaboration with a site's institutional review board. The IRB's main role is protecting patient populations, which includes ensuring that written informed consent has been obtained and overseeing the creation of a data safety monitoring board. The IRB must also approve the marketing used to solicit patients for the trial. Additionally, the IRB oversees patient reimbursement.
A study's execution depends on communication between investigators and sites, randomization to prevent bias and data management software emphasizing sanity and security.
Finally, surgeon culture can be an obstacle for orthopedic trials. Widely divergent treatment paths can be taken for the same condition, and a lack of robust data for many orthopedic procedures could limit identifying an optimal treatment. The paper acknowledges that this is changing, and surgeons will be held accountable for their treatment decisions by such programs as pay-for-performance. Still, a study cited by Trippel shows that surgeons may fail to acknowledge their uncertainty about treatment, while another study shows that surgeon opinion about the efficacy of a particular procedure can change week-to-week.
According to Trippel, evidence-based medicine represents a new era for healthcare, the start of a "culture of progress." Orthopedics, for all its challenges, will be included in this culture shift; as healthcare begins to rely increasingly on robust data, RCTs will have a more prominent role in orthopedic research, to the benefit of patients and surgeons.
