Objective It is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact on effect estimates of selecting different treatment combinations (ie, network geometries) for inclusion in NMAs. Design Multiverse analysis, covering all possible NMAs on different combinations of treatments. Setting Data from a previously published NMA exploring the comparative effectiveness of 22 treatments (21 antidepressants and a placebo) for the treatment of acute major depressive disorder. Participants Cipriani et al explored a dataset of 116 477 patients included in 522 randomised controlled trials. Main outcome measures For each possible treatment selection, we performed an NMA to estimate comparative effectiveness on treatment response and treatment discontinuation for the treatments included (231 between-treatment comparisons). The distribution of effect estimates of between-treatment comparisons across NMAs was computed, and the direction, magnitude and statistical significance of the 1st and 99th percentiles were compared. Results 4 116 254 different NMAs concerned treatment response. Among possible network geometries, 172/231 (74%) pairwise comparisons exhibited opposite effects between the 1st and 99th percentiles, 57/231 (25%) comparisons exhibited statistically significant results in opposite directions, 118 of 231 (51%) comparisons derived results that were both significant and non-significant at 5% risk and 56/231 (24%) treatment pairs obtained consistent results with only significant differences (or only non-significant differences) at 5% risk. Comparisons based on indirect evidence only were associated with greater variability in effect estimates. Comparisons with small absolute values observed in the complete NMA more frequently obtained statistically significant results in opposite directions. Similar results were observed for treatment discontinuation. Conclusion In this multiverse analysis, we observed that the selection of treatments to be included in an NMA could have considerable consequences on treatment effect estimations. Trial registration . Data are available in a public, open access repository. The data and code are openly shared on the OSF () and the dataset is shared by the original authors on Mendeley ().

中文翻译：

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混合治疗比较中治疗选择导致的效果振动：重度抑郁症中抗抑郁药网络荟萃分析的多元宇宙分析


目的 经常发现关于同一主题的重叠网络荟萃分析 （NMA），在纳入的两种治疗和效果估计方面存在差异。我们旨在评估选择不同治疗组合 （即网络几何形状） 以纳入 NMA 对效果估计的影响。设计多元宇宙分析，涵盖不同治疗组合上所有可能的 NMA。设定 来自先前发表的 NMA 的数据，探索了 22 种治疗方法（21 种抗抑郁药和一种安慰剂）治疗急性重度抑郁症的比较效果。参与者 Cipriani 等人探索了 116 477 名患者的数据集，这些患者包含在 522 项随机对照试验中。主要结局指标 对于每种可能的治疗选择，我们进行了 NMA 以估计所纳入治疗的治疗反应和治疗中断的比较有效性（231 次治疗间比较）。计算 NMA 之间治疗间比较的效果估计分布，并比较第 1 个和第 99 个百分位数的方向、幅度和统计显着性。结果 4 116 254 个不同的 NMA 涉及治疗反应。在可能的网络几何中，172/231 （74%） 成对比较在第 1 个和第 99 个百分位数之间表现出相反的效果，57/231 （25%） 比较在相反方向上表现出统计学显着结果，231 个比较中有 118 个 （51%） 得出的结果在 5% 风险下既显著又不显著，56/231 （24%） 治疗对获得一致的结果，在 5% 风险下只有显着差异（或仅非显着差异）。仅基于间接证据的比较与效果估计的较大变异性相关。 与在完整 NMA 中观察到的小绝对值的比较更频繁地获得相反方向的统计学显着结果。在治疗中断时观察到类似的结果。结论在这项多元宇宙分析中，我们观察到选择要包含在 NMA 中的治疗可能会对治疗效果估计产生相当大的影响。试用注册 .数据在公共、开放访问存储库中可用。数据和代码在 OSF （） 上公开共享，数据集由 Mendeley （） 上的原作者共享。