BACKGROUND:When there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision-making. For example, trials of intrapartum anti-bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi-state model. This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent. RESULTS:Overall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002-0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04-0.14). Node-splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p = 0.15). The findings accorded with previously published separate meta-analyses of the different outcomes, once these are re-analysed correctly accounting for zero cells. CONCLUSION:Multiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta-analyses of each outcome have none of these properties.

译文

背景:当在不同试验中报告的结果之间存在结构关系时,对每个结果的单独分析不会提供决策所需的单个连贯分析。例如,为防止早发性B组链球菌(EOGBS)疾病而进行的产前抗菌预防(IAP)试验可以报告三种治疗效果:对新生儿细菌定植的影响,对EOGBS的影响以及对有条件的EOGBS的影响在新生儿殖民地。这些结果在多状态模型中有条件地关联或嵌套。本文展示了如何利用这些结构关系,对所有可用数据进行单一连贯的综合,同时检查以确保不同证据来源是一致的。
结果:总体而言,IAP的使用降低了EOGBS的风险(RR:0.03; 95%可信区间(CrI):0.002-0.13)。大多数治疗效果归因于对定植母亲的新生儿定植的预防(RR:0.08,95%CrI:0.04-0.14)。淋巴结清扫显示仅使用直接证据计算的治疗效果与根据其余证据预测的效果一致(p = 0.15)。一旦正确地重新分析了零细胞,这些结果就与先前发表的不同结果的单独荟萃分析相符。
结论:在可能的情况下,应综合多种结果,并考虑其结构关系。这会产生适合决策的内部连贯分析,其中对每种治疗效果的估计均基于所有可用证据(直接和间接)。每个结果的单独荟萃分析均不具备这些属性。

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