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个体水平数据的荟萃分析能在多大程度上实现个体化治疗?一项荟萃流行病学研究。

How often can meta-analyses of individual-level data individualize treatment? A meta-epidemiologic study.

机构信息

Departments of Medicine, of Health Research and Policy, of Biomedical Data Science and of Statistics, Stanford University, Stanford, CA, USA.

Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.

出版信息

Int J Epidemiol. 2019 Apr 1;48(2):596-608. doi: 10.1093/ije/dyy239.


DOI:10.1093/ije/dyy239
PMID:30445577
Abstract

BACKGROUND: One of the claimed main advantages of individual participant data meta-analysis (IPDMA) is that it allows assessment of subgroup effects based on individual-level participant characteristics, and eventually stratified medicine. In this study, we evaluated the conduct and results of subgroup analyses in IPDMA. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to 31 December 2014. We included papers if they described an IPDMA based on randomized clinical trials that investigated a therapeutic intervention on human subjects and in which the meta-analysis was preceded by a systematic literature search. We extracted data items related to subgroup analysis and subgroup differences (subgroup-treatment interaction p < 0.05). RESULTS: Overall, 327 IPDMAs were eligible. A statistically significant subgroup-treatment interaction for the primary outcome was reported in 102 (36.6%) of 279 IPDMAs that reported at least one subgroup analysis. This corresponded to 187 different statistically significant subgroup-treatment interactions: 124 for an individual-level subgrouping variable (in 76 IPDMAs) and 63 for a group-level subgrouping variable (in 36 IPDMAs). Of the 187, only 7 (3.7%; 6 individual and 1 group-level subgrouping variables) had a large difference between strata (standardized effect difference d  ≥  0.8). Among the 124 individual-level statistically significant subgroup differences, the IPDMA authors claimed that 42 (in 21 IPDMAs) should lead to treating the subgroups differently. None of these 42 had d  ≥  0.8. CONCLUSIONS: Availability of individual-level data provides statistically significant interactions for relative treatment effects in about a third of IPDMAs. A modest number of these interactions may offer opportunities for stratified medicine decisions.

摘要

背景:个体参与者数据荟萃分析(IPDMA)的一个声称的主要优势是,它允许根据个体参与者特征评估亚组效应,并最终实现分层医学。在这项研究中,我们评估了 IPDMA 中亚组分析的实施和结果。

方法:我们从 1966 年 1 月 1 日至 2014 年 12 月 31 日在 PubMed、EMBASE 和 Cochrane Library 进行了检索。如果文献描述了基于随机对照试验的 IPDMA,该试验调查了人类受试者的治疗干预措施,并且荟萃分析之前进行了系统的文献检索,则纳入研究。我们提取了与亚组分析和亚组差异(亚组-治疗相互作用 p<0.05)相关的数据项。

结果:共有 327 项 IPDMA 符合纳入标准。在报告了至少一次亚组分析的 279 项 IPDMA 中,有 102 项(36.6%)报告了主要结局的统计学显著亚组-治疗相互作用。这相当于 187 个不同的统计学显著亚组-治疗相互作用:124 个为个体水平的亚组变量(在 76 项 IPDMA 中),63 个为群体水平的亚组变量(在 36 项 IPDMA 中)。在这 187 个中,只有 7 个(3.7%;6 个个体和 1 个群体亚组变量)在分层之间有较大差异(标准化效应差异 d≥0.8)。在 124 个个体水平的统计学显著亚组差异中,IPDMA 作者声称 42 个(在 21 项 IPDMA 中)应该导致对亚组进行不同的治疗。这些亚组中没有一个 d≥0.8。

结论:个体水平数据的可用性为 IPDMA 中约三分之一的相对治疗效果提供了统计学显著的相互作用。这些相互作用中有相当数量可能为分层医学决策提供机会。

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[7]
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[9]
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