论文标题

使用一致权重的多组观测研究中多元结果的无不满的荟萃分析框架

Unconfounded Meta-analytical Frameworks for Multivariate Outcomes in Multigroup Observational Studies using Concordant Weights

论文作者

Guha, Subharup, Christiani, David C., Subramanian, S. V., Li, Yi

论文摘要

虽然荟萃分析回顾性癌症患者人群,但对癌症亚型靶向癌基因表达的差异的研究具有很大的兴趣,因为结果可能会发现新颖的肿瘤发生机制并改善筛查和治疗策略。加权方法促进了多个观察性研究中多群势结果的无关比较。例如,Guha等人。 (2022)引入了一致的权重,从而通过最大化有效的样本量来允许对生存结果进行综合分析。但是,尚不清楚如何使用这种或其他加权方法来分析各种连续,分类,序数或多元结果,尤其是当研究利益优先级不常见或未计划的估计值时;示例包括百分位数和群体潜在结果的力矩以及多元结果的成对相关性。本文提出了一种统一的荟萃分析方法,可容纳各种类型的端点,并培养与大多数加权框架兼容的新估计器。在温和的假设下研究了估计量的渐近特性。对于采样群,我们设计了小样本程序来量化估计不确定性。我们将多站点的TCGA乳腺癌数据进行荟萃分析,阐明了亚型浸润导管癌和浸润小叶癌的八个靶向基因的差异mRNA表达模式。

While meta-analyzing retrospective cancer patient cohorts, an investigation of differences in the expressions of target oncogenes across cancer subtypes is of substantial interest because the results may uncover novel tumorigenesis mechanisms and improve screening and treatment strategies. Weighting methods facilitate unconfounded comparisons of multigroup potential outcomes in multiple observational studies. For example, Guha et al. (2022) introduced concordant weights, allowing integrative analyses of survival outcomes by maximizing the effective sample size. However, it remains unclear how to use this or other weighting approaches to analyze a variety of continuous, categorical, ordinal, or multivariate outcomes, especially when research interests prioritize uncommon or unplanned estimands suggested by post hoc analyses; examples include percentiles and moments of group potential outcomes and pairwise correlations of multivariate outcomes. This paper proposes a unified meta-analytical approach accommodating various types of endpoints and fosters new estimators compatible with most weighting frameworks. Asymptotic properties of the estimators are investigated under mild assumptions. For undersampled groups, we devise small-sample procedures for quantifying estimation uncertainty. We meta-analyze multi-site TCGA breast cancer data, shedding light on the differential mRNA expression patterns of eight targeted genes for the subtypes infiltrating ductal carcinoma and infiltrating lobular carcinoma.

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