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随机效应荟萃分析检验和预测模型的临床实用性。

Random-effects meta-analysis of the clinical utility of tests and prediction models.

机构信息

Department of Development and Regeneration, KU Leuven, Leuven, Belgium.

Research Institute for Primary Care and Health Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK.

出版信息

Stat Med. 2018 May 30;37(12):2034-2052. doi: 10.1002/sim.7653. Epub 2018 Mar 25.

Abstract

The use of data from multiple studies or centers for the validation of a clinical test or a multivariable prediction model allows researchers to investigate the test's/model's performance in multiple settings and populations. Recently, meta-analytic techniques have been proposed to summarize discrimination and calibration across study populations. Here, we rather consider performance in terms of net benefit, which is a measure of clinical utility that weighs the benefits of true positive classifications against the harms of false positives. We posit that it is important to examine clinical utility across multiple settings of interest. This requires a suitable meta-analysis method, and we propose a Bayesian trivariate random-effects meta-analysis of sensitivity, specificity, and prevalence. Across a range of chosen harm-to-benefit ratios, this provides a summary measure of net benefit, a prediction interval, and an estimate of the probability that the test/model is clinically useful in a new setting. In addition, the prediction interval and probability of usefulness can be calculated conditional on the known prevalence in a new setting. The proposed methods are illustrated by 2 case studies: one on the meta-analysis of published studies on ear thermometry to diagnose fever in children and one on the validation of a multivariable clinical risk prediction model for the diagnosis of ovarian cancer in a multicenter dataset. Crucially, in both case studies the clinical utility of the test/model was heterogeneous across settings, limiting its usefulness in practice. This emphasizes that heterogeneity in clinical utility should be assessed before a test/model is routinely implemented.

摘要

使用来自多个研究或中心的数据来验证临床检验或多变量预测模型,可以使研究人员在多个环境和人群中研究检验/模型的性能。最近,提出了荟萃分析技术来总结研究人群之间的区分度和校准度。在这里,我们考虑的是净收益的性能,这是衡量临床实用性的一个指标,它权衡了真阳性分类的益处与假阳性的危害。我们认为,重要的是在多个感兴趣的环境中检查临床实用性。这需要一种合适的荟萃分析方法,我们提出了一种基于贝叶斯三变量随机效应的敏感性、特异性和患病率的荟萃分析。在选择的危害-收益比范围内,它提供了净收益的综合衡量指标、预测区间以及检验/模型在新环境中具有临床实用性的概率估计。此外,可以根据新环境中的已知患病率来计算预测区间和有用性的概率。通过 2 个案例研究说明了所提出的方法:一个是关于耳温计诊断儿童发热的发表研究的荟萃分析,另一个是在多中心数据集上验证多变量临床风险预测模型用于诊断卵巢癌的案例。至关重要的是,在这两个案例研究中,检验/模型的临床实用性在不同环境中存在异质性,限制了其在实践中的实用性。这强调了在常规实施检验/模型之前,应该评估其在临床实用性方面的异质性。

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