比较两种模型在临床试验中的生存预测表现,发现评估指标选择影响结论可靠性。
Comparison of the Cox proportional hazards model and Random Survival Forest algorithm for predicting patient-specific survival probabilities in clinical trial data
- 基于真实临床数据模拟,对比Cox模型与随机生存森林的预测能力。
- 标准log-rank分割规则在非比例风险下表现不如替代方案。
- 当存在治疗-协变量交互时,随机生存森林性能更稳定,适合复杂数据。
Cox比例风险模型常用于分析具有生存时间结果的随机对照试验(RCT)数据。随机生存森林(RSF)是一种机器学习算法,以高预测性能著称。本文基于两个来自RCT的真实参考数据集,开展全面中立的比较研究,评估Cox回归与RSF在多种模拟场景下的表现。研究动机是根据TRIPOD指南,从多个维度识别哪种方法在不同情境下更优。结果显示,仅依赖广泛使用的C指数(尤其在真实世界观察数据中)得出的结论可能不具普适性;整体性能度量通常提供更合理的判断。此外,标准log-rank分割规则在非比例风险设定下表现不佳,可被其他分割策略超越。在存在治疗-协变量交互的数据中,RSF表现优于无交互情形,而Cox-PH模型则受比例风险假设违背的影响。
原文摘要 · Abstract (English)
The Cox proportional hazards model is often used to analyze data from Randomized Controlled Trials (RCT) with time-to-event outcomes. Random survival forest (RSF) is a machine-learning algorithm known for its high predictive performance. We conduct a comprehensive neutral comparison study to compare the performance of Cox regression and RSF in various simulation scenarios based on two reference datasets from RCTs. The motivation is to identify settings in which one method is preferable over the other when comparing different aspects of performance using measures according to the TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis) recommendations. Our results show that conclusions solely based on the C index, a performance measure that has been predominantly used in previous studies comparing predictive accuracy of the Cox-PH and RSF model based on real-world observational time-to-event data and that has been criticized by methodologists, may not be generalizable to other aspects of predictive performance. We found that measures of overall performance may generally give more reasonable results, and that the standard log-rank splitting rule used for the RSF may be outperformed by alternative splitting rules, in particular in nonproportional hazards settings. In our simulations, performance of the RSF suffers less in data with treatment-covariate interactions compared to data where these are absent. Performance of the Cox-PH model is affected by the violation of the proportional hazards assumption.
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