Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes
Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes
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DOI：
10.1002/sim.2050
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发表时间：
2005-05-15
影响因子：
2
通讯作者：
Marson, AG
中科院分区：
文献类型：
--
作者：
Smith, CT;Williamson, PR;Marson, AG
研究之间在设计特征和方法、临床程序和患者特征方面的差异是导致荟萃分析中研究之间治疗效果差异的因素（统计异质性）。回归模型可用于检查治疗效果和协变量之间的关系，目的是解释临床、方法学方面的变异性。或其他因素。可以使用汇总数据或个体患者数据来进行此类调查。汇总数据方法可能存在问题，因为很少有足够的数据可用，并且将汇总效应转化为个体患者往往会产生误导。个体患者数据方法虽然通常需要更多资源，但可以更彻底地调查异质性的潜在来源，并能够在荟萃分析中对事件结果的时间进行更全面的分析。分层 Cox 回归模型用于识别和探索荟萃分析中异质性的证据，并检查协变量和审查故障时间数据之间的关系。该模型的替代表述是可能的，并使用来自五项随机对照试验的荟萃分析的个体患者数据进行说明，这些试验比较了两种治疗癫痫的药物。该模型进一步应用于模拟数据示例，其中异质性程度和治疗效果的大小各不相同。探索并比较了每种情况下每个模型的行为。版权所有 (c) 2005 John Wiley & Sons, Ltd.
Differences across Studies in terms of design features and methodology, clinical procedures, and patient characteristics, are factors that can contribute to variability in the treatment effect between studies in a meta-analysis (statistical heterogeneity). Regression modelling can be used to examine relationships between treatment effect and covariates with the aim of explaining the variability in terms of clinical, methodological. or other factors. Such an investigation can be undertaken using aggregate data or individual patient data. An aggregate data approach can be problematic as sufficient data are rarely available and translating aggregate effects to individual patients can often be misleading. An individual patient data approach, although usually more resource demanding, allows a more thorough investigation of potential Sources of heterogeneity and enables a fuller analysis of time to event outcomes in meta-analysis.Hierarchical Cox regression models are used to identify and explore the evidence for heterogeneity in meta-analysis and examine the relationship between covariates and censored failure time data in this context. Alternative formulations of the model are possible and illustrated using individual patient data from a meta-analysis of five randomized controlled trials which compare two drugs for the treatment of epilepsy. The models are further applied to simulated data examples in which the degree of heterogeneity and magnitude of treatment effect are varied. The behaviour of each model in each situation is explored and compared. Copyright (c) 2005 John Wiley & Sons, Ltd.