论文标题

在一致性概率估计的荟萃分析中考虑时间依赖性

Accounting for Time Dependency in Meta-Analyses of Concordance Probability Estimates

论文作者

Schmid, Matthias, Friede, Tim, Klein, Nadja, Weinhold, Leonie

论文摘要

近年来,已经开发了许多新颖的疾病预后评分工具。要被接受用于临床应用,必须在外部数据上验证这些工具。实际上,验证通常受到后勤问题的阻碍,从而导致多个小型验证研究。因此,有必要使用荟萃分析技术合成这些研究的结果。在这里,我们考虑了荟萃分析事件数据(“ C-Index”)的一致性概率的策略,该概率已成为评估预测模型的歧视力量的流行工具。我们表明,C-指数的标准荟萃分析可能会导致偏差结果,因为一致性概率的幅度取决于用于评估的时间间隔的时间长度(例如,通过随访时间定义,这在研究之间可能有很大差异)。为了解决这个问题,我们提出了一组随机效应元回归的方法,这些方法将时间直接作为模型方程中的协变量。除了通过分数多项式,样条和指数衰减模型分析非线性时间趋势外,我们还提供有关在元回归之前C-指数转换的建议。我们的结果表明,使用logit转换的c-index值使用分数多项式元回归,最好将C-指数分析。当随访时间很小时,经典的随机效应荟萃分析(不将时间视为协变量)被证明是合适的替代方法。我们的发现对未来研究中C-指数值的报告具有影响,该研究应包括有关计算基础时间间隔的信息。

Recent years have seen the development of many novel scoring tools for disease prognosis and prediction. To become accepted for use in clinical applications, these tools have to be validated on external data. In practice, validation is often hampered by logistical issues, resulting in multiple small-sized validation studies. It is therefore necessary to synthesize the results of these studies using techniques for meta-analysis. Here we consider strategies for meta-analyzing the concordance probability for time-to-event data ("C-index"), which has become a popular tool to evaluate the discriminatory power of prediction models with a right-censored outcome. We show that standard meta-analysis of the C-index may lead to biased results, as the magnitude of the concordance probability depends on the length of the time interval used for evaluation (defined e.g. by the follow-up time, which might differ considerably between studies). To address this issue, we propose a set of methods for random-effects meta-regression that incorporate time directly as covariate in the model equation. In addition to analyzing nonlinear time trends via fractional polynomial, spline, and exponential decay models, we provide recommendations on suitable transformations of the C-index before meta-regression. Our results suggest that the C-index is best meta-analyzed using fractional polynomial meta-regression with logit-transformed C-index values. Classical random-effects meta-analysis (not considering time as covariate) is demonstrated to be a suitable alternative when follow-up times are small. Our findings have implications for the reporting of C-index values in future studies, which should include information on the length of the time interval underlying the calculations.

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