Objective To 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.
Design Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions.
Data sources Database 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 selection Network 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 analysis Cumulative 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.
Results 49 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.
Conclusions In 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.

中文翻译：

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比较有效性研究中的生活网络荟萃分析与成对荟萃分析的比较：实证研究


目的检验前瞻性计划的随机对照试验（RCT）（“活”网络荟萃分析）网络的持续更新是否比更新传统的成对荟萃分析更早地提供了反对医疗干预比较有效性零假设的有力证据。分析。

设计对有关临床干预措施比较有效性的积累证据进行实证研究。

数据来源通过检索 Medline、Embase 和 Cochrane 系统评价数据库（截至 2015 年 4 月 14 日）确定的 RCT 网络荟萃分析数据库。

研究选择的资格标准2012 年 1 月后发表的网络荟萃分析，比较了至少五种治疗方法，并包括至少 20 项随机对照试验。临床专家被要求确定每个网络中临床最感兴趣的治疗比较。排除基于侧面或节点分裂测试的直接和间接证据不一致的比较（P<0.10）。

结果和分析对每个选定的比较进行累积配对和网络荟萃分析。构建了统计显着性的监测边界，并且当跨越监测边界时，反对零假设的证据被认为是强有力的。显着性水平定义为 α=5%，功效为 90%（β=10%），检测的预期治疗效果等于网络荟萃分析的最终估计。将获得强有力证据的频率和时间与成对和网络荟萃分析之间的原假设进行比较。

结果纳入了来自 44 个网络的 49 个感兴趣的比较；大多数（n=39，80%）是在活性药物之间，主要来自心脏病学、内分泌学、精神病学和风湿病学专业。 29 项比较同时采用直接和间接证据 (59%)，13 项比较采用间接证据 (27%)，7 项比较采用直接证据 (14%)。网络和成对荟萃分析都为 7 次比较提供了反对原假设的有力证据，但对于另外 10 次比较，只有网络荟萃分析提供了反对原假设的有力证据 (P=0.002)。获得反对原假设的强有力证据的中位时间在活网络荟萃分析中为 19 年，在活配对荟萃分析中为 23 年（风险比 2.78，95% 置信区间 1.00 至 7.72，P=0.05）。在网络荟萃分析中出现强有力的证据后，继续发表直接比较感兴趣的治疗方法的研究，进行八次比较。

结论在比较有效性研究中，前瞻性计划的生活网络荟萃分析比传统的成对荟萃分析更频繁、更早地产生了反对原假设的有力证据。