Assessing the uncertainty of treatment outcomes in a previous systematic review of venous leg ulcer randomized controlled trials: Additional secondary analysis.

Abstract

In this secondary analysis of a previous systematic review, we assessed randomized controlled trials evaluating treatments of venous leg ulcers in terms of factors that affect risk of bias at the study level and thus uncertainty of outcomes obtained from the interventions. Articles that assessed the wound bed condition in venous leg ulcers and that were published in English between 1998 and May 22, 2018 were previously searched in PubMed, Embase, CINAHL, CENTRAL, Scopus, Science Direct, and Web of Science. Duplicates and retracted articles were excluded. The following data were extracted to assess the risk of bias: treatment groups; primary and secondary endpoints that were statistically tested between groups, including their results and p values; whether blinding of patients and assessors was done; whether allocation concealment was adequate; whether an intention‐to‐treat analysis was conducted; whether an appropriate power calculation was correctly done; and whether an appropriate multiplicity adjustment was made, as necessary. Pre‐ and post‐study power calculations were made. The step‐up Hochberg procedure adjusted for multiplicity. Results were analysed for all studies, pre‐2013 studies, and 2013/post‐2013 studies. We included 142 randomized controlled trials that evaluated 14,141 patients. Most studies lacked blinding (72.5–77.5%) and allocation concealment (88.7%). Only 49.3% of trials provided a power calculation, with 27.5% having an appropriate calculation correctly done. Adequate statistical power of the primary endpoint was found in 27.2% of trials. The lack of multiplicity adjustment in 98.6% of studies affected the uncertainty of outcomes in 20% of studies, with the majority of the secondary endpoints (67.7%) in those studies becoming non‐significant after multiplicity adjustment. Recent studies tended to weakly demonstrate improved certainty of outcomes. Venous leg ulcer randomized controlled trials have a high degree of uncertainty associated with treatment outcomes. Greater attention to trial design and conduct is needed to improve the evidence base.