Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg.
Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
BMC Med Res Methodol. 2018 Jun 28;18(1):66. doi: 10.1186/s12874-018-0509-7.
Network meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma.
Randomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other's control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches.
Twenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average.
The analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.
网络荟萃分析（NMA）允许估计未在头对头试验中研究过的治疗方法的相对有效性；然而，只有在现有证据形成一个连接的网络的情况下，才能得出所有干预措施的相对治疗效果。在许多疾病领域，头对头证据有限，经常导致证据结构不连贯，有大量的治疗方法可用。在复发性或难治性多发性骨髓瘤治疗证据中也是如此。
系统文献综述中确定的随机对照试验（RCT）形成了两个不连续的证据网络。拟合标准贝叶斯 NMA 模型以获得每个网络内相对效果的估计值。确定观察性证据以填补证据空白。根据协变量信息得出的距离度量标准，将单臂试验匹配为彼此的对照组。通过分析可能匹配的空间，将包含此证据产生的不确定性纳入分析。
25 项随机对照试验形成了两个不连续的证据网络；考虑了 12 项单臂观察性研究来桥接两个网络。选择了 5 个匹配项来桥接网络。虽然观察到排名存在显著差异，但达雷木单抗联合地塞米松和来那度胺或硼替佐米，以及卡非佐米、伊沙佐米和埃洛佐米联合来那度胺和地塞米松的三联疗法，在无进展生存期方面显示出最高的效果，平均而言。
该分析展示了如何使用观察数据来填补 RCT 证据现有网络中的空白；允许对大量无法进行直接比较的治疗方法进行间接比较。通过情景分析来考虑额外的不确定性，降低了对结果解释过度自信的风险。
