Are large clinical trials in orthopaedic trauma justified?

Abstract

BackgroundThe objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data.MethodsThe FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study.ResultsThe pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75–3.04; RR: 1.39, 95% CI: 0.60–3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81–1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50–1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04–1.57).ConclusionsOur findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds.Trial registrationNCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

CORR Insights®: Discordance Abounds in Minimum Clinically Important Differences in THA: A Systematic Review

“…For example, if a previous study showed a particular difference between groups, there is no reason to believe this difference is clinically meaningful unless patients specifically help us make that determination, and an anchor-based MCID is the best tool we have for this job [6]. Pilot trials (and small trials in general) are known to have spuriously high or low point estimates with wide confidence intervals that can be misleading; in fact, previous orthopaedic studies have shown that pilot trials may even show the opposite result of a larger, more-definitive trial [7, 8]. Therefore, differences found in pilot studies are unreliable estimates on which to base a sample size calculation for a larger trial.…”

Evolution in the Acute Management of Open Fracture Treatment? Part 2

“…The authors such as Bhandari, Sprague, and Ioannidis have investigated the mass production of redundant, misleading, and conflicted systemic reviews and metaanalyses in numerous medical fields and commented on how these instruments often serve as easily produced publishable units or marketing tools, instead of promoting evidence-based medicine and health care. [77][78][79][80] The majority of the literature from 1970 to 2010 that has driven the various standards of care and recommendations in the treatment of open fracture can be cast in this same light, but some general statements can be made with relative confidence: 1. Increasing severity of the soft-tissue injury in open fractures is associated with a higher infection rate, particularly for the tibia.…”

“…The authors such as Bhandari, Sprague, and Ioannidis have investigated the mass production of redundant, misleading, and conflicted systemic reviews and meta-analyses in numerous medical fields and commented on how these instruments often serve as easily produced publishable units or marketing tools, instead of promoting evidence-based medicine and health care. 77–80…”

Vitamin D Status and Patient Outcomes after Knee or Hip Surgery: A Meta-Analysis

“…Recently, a study that evaluated the health outcomes with the use of vitamin D after hip fracture surgery, found that the use of vitamin D was associated with a statistically significant but not clinically significant improvement in health-related quality of life [20]. Several studies have indicated a link between vitamin D deficiency and poorer outcomes and suboptimal functional recovery after joint surgery, but the outcomes are not always consistent.…”