论文标题

使用基于模型的递归分配的单个患者数据荟萃分析中的亚组识别

Subgroup identification in individual patient data meta-analysis using model-based recursive partitioning

论文作者

Huber, Cynthia, Benda, Norbert, Friede, Tim

论文摘要

基于模型的递归分配(MOB)可用于识别具有不同治疗效果的亚组。逐个治疗相互作用的检测率以及使用MOB确定的亚组的准确性很大程度上取决于样本量。使用来自多个随机对照临床试验的数据可以克服太小样品的问题。但是,来自多个试验的天真汇总数据可能会导致虚假亚组的鉴定,因为研究设计,受试者选择和其他试验中异质性的来源的差异被忽略。为了说明单个参与者数据(IPD)荟萃分析随机效应模型的试验间异质性。通常,治疗效果中的异质性是使用随机效应建模的,而基线风险中的异质性是由固定效应或随机效应建模的。在本文中,我们提出了MetAmob,该过程使用通用的混合效应模型树(GLMM树)算法进行IPD荟萃分析中的亚组识别。尽管Metamob的应用可能更广泛,例如与社会科学或生命科学临床前实验的参与者进行的随机实验,我们专注于随机对照临床试验。在一项模拟研究中,Metamob的表现优于GLMM树,假设仅随机截距和基于模型的递归分区(MOB),其算法是GLMM树的基础,就错误发现率,确定的亚组的准确性和估计治疗效应的准确性而言。因此,最强大,最有前途的方法是metamob,具有对基线风险中试验中异质性进行建模的固定效果。

Model-based recursive partitioning (MOB) can be used to identify subgroups with differing treatment effects. The detection rate of treatment-by-covariate interactions and the accuracy of identified subgroups using MOB depend strongly on the sample size. Using data from multiple randomized controlled clinical trials can overcome the problem of too small samples. However, naively pooling data from multiple trials may result in the identification of spurious subgroups as differences in study design, subject selection and other sources of between-trial heterogeneity are ignored. In order to account for between-trial heterogeneity in individual participant data (IPD) meta-analysis random-effect models are frequently used. Commonly, heterogeneity in the treatment effect is modelled using random effects whereas heterogeneity in the baseline risks is modelled by either fixed effects or random effects. In this article, we propose metaMOB, a procedure using the generalized mixed-effects model tree (GLMM tree) algorithm for subgroup identification in IPD meta-analysis. Although the application of metaMOB is potentially wider, e.g. randomized experiments with participants in social sciences or preclinical experiments in life sciences, we focus on randomized controlled clinical trials. In a simulation study, metaMOB outperformed GLMM trees assuming a random intercept only and model-based recursive partitioning (MOB), whose algorithm is the basis for GLMM trees, with respect to the false discovery rates, accuracy of identified subgroups and accuracy of estimated treatment effect. The most robust and therefore most promising method is metaMOB with fixed effects for modelling the between-trial heterogeneity in the baseline risks.

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