Estimating Relative Efficacy in Acute Postoperative Pain: Network Meta-Analysis is Consistent with Indirect Comparison to Placebo Alone.

Network meta-analysis (NMA) uses direct comparisons of interventions within randomized controlled trials and indirect comparisons across them. NMA uses more data than a series of direct comparisons with placebo, and theoretically should produce more reliable results. We used a Cochrane overview review of acute postoperative pain trials and other systematic reviews to provide data to test this hypothesis. Some 261 trials published between 1966-2016 included 39,753 patients examining 52 active drug and dose combinations (27,726 given active drug, 12,027 placebo), in any type of surgery (72% dental). Most trials were small; 42% of patients were in trials with arms <50 patients, and 27% in trials with arms ≥100 patients). Response to placebo in third molar extraction fell by half in studies over 30-40 years (171 trials, 7882 patients given placebo).NMA and Cochrane analyses provided very similar results (average difference 0.04 NNT units), with no significant difference for almost all comparisons apart from some with small patient numbers or small effect size, or both. NMA did not detect significant differences between effective analgesics. The similarity between NMA and Cochrane indirect analyses probably arose from stringent quality criteria in trials accepted in Cochrane reviews (with consequent low risk of bias), and consistency in methods and outcomes. NMA is a useful analytical tool that increases our confidence in estimates of efficacy of analgesics in acute postoperative pain, in this case by providing similar results.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.