• Adriani Nikolakopoulou, Dimitris Mavridis, Toshi A Furukawa, Andrea Cipriani, Andrea C Tricco, Sharon E Straus, Siontis George C M GCM Department of Cardiology, Bern University Hospital, Bern, Switzerland., Matthias Egger, and Georgia Salanti.
• Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
• BMJ. 2018 Feb 28; 360: k585.

ObjectiveTo examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) ("living" network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis.DesignEmpirical study of the accumulating evidence about the comparative effectiveness of clinical interventions.Data SourcesDatabase of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015.Eligibility Criteria For Study SelectionNetwork meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (P<0.10).Outcomes And AnalysisCumulative pairwise and network meta-analyses were performed for each selected comparison. Monitoring boundaries of statistical significance were constructed and the evidence against the null hypothesis was considered to be strong when the monitoring boundaries were crossed. A significance level was defined as α=5%, power of 90% (β=10%), and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses.Results49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78, 95% confidence interval 1.00 to 7.72, P=0.05). Studies directly comparing the treatments of interest continued to be published for eight comparisons after strong evidence had become evident in network meta-analysis.ConclusionsIn comparative effectiveness research, prospectively planned living network meta-analyses produced strong evidence against the null hypothesis more often and earlier than conventional, pairwise meta-analyses.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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