Smith Catrin Tudur, Williamson Paula R, Marson Anthony G
Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool L69 3BX, UK.
Stat Med. 2005 May 15;24(9):1307-19. doi: 10.1002/sim.2050.
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.
不同研究在设计特点、方法学、临床程序和患者特征方面存在差异,这些因素可能导致荟萃分析中各研究间治疗效果的变异性(统计学异质性)。回归建模可用于检验治疗效果与协变量之间的关系,目的是从临床、方法学或其他因素方面解释这种变异性。此类调查可使用汇总数据或个体患者数据进行。汇总数据方法可能存在问题,因为很少能获得足够的数据,而且将汇总效应转化为个体患者的情况往往会产生误导。个体患者数据方法虽然通常对资源要求更高,但能更全面地调查异质性的潜在来源,并能在荟萃分析中更充分地分析事件发生时间结局。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,并在此背景下检验协变量与删失失败时间数据之间的关系。该模型有其他形式,并使用来自五项比较两种治疗癫痫药物的随机对照试验的荟萃分析中的个体患者数据进行了说明。这些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大小有所不同。探索并比较了每种情况下每个模型的行为。
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