arXiv:2606.08305stat.MLcs.LG2026-06

用机器学习校准外部对照数据,提升治疗效果评估的准确性。

MEC-Cox: Machine-Learning-Assisted Generalized Entropy Calibration for ATT Marginal Hazard-Ratio Estimation

  • 通过机器学习校准权重,同时实现数据迁移与预后平衡。
  • 仿真显示可降低偏倚、提高效率,且置信区间覆盖更准确。
  • 适合罕见病或癌症等难做随机对照试验的研究场景。

当同期随机对照不可行时,外部控制生存试验在肿瘤学和罕见病研究中日益重要。本文聚焦于治疗组平均处理效应(ATT)型边际风险比估计,通过逆概率加权Cox回归进行估计。由于IPW-Cox依赖权重影响事件贡献和风险集均值,直接引入灵活的机器学习扰动估计存在挑战。基于李与金(2026)提出的机器学习辅助广义熵校准(MEC),本文提出MEC-Cox方法,用于ATT加权的IPW-Cox回归。该方法从标准化源倾向性得分优势权重出发,采用Bregman校准使外部对照与治疗组患者在交叉拟合的预后摘要上达到平衡,校准基础可包括控制组生存预测、Cox线性预测器、正则化生存模型预测或其他预后评分。校准后的权重兼具源转移与预后平衡双重作用。我们建立了估计量的一致性,刻画了校准带来的效率增益,并提出了堆叠式沙漏方差估计器。模拟结果表明,MEC-Cox可通过灵活的机器学习调整显著降低偏倚、提升效率并改善覆盖率。

原文摘要 · Abstract (English)

Externally controlled survival trials are increasingly used when concurrent randomized controls are infeasible, particularly in oncology and rare-disease settings with time-to-event endpoints. We target an average-treatment-effect-on-the-treated (ATT)-type marginal hazard-ratio estimand, comparing treatment with counterfactual control in the treated trial population, and estimate it using inverse-probability-weighted (IPW) Cox regression. Valid inference is challenging because IPW Cox regression depends on the weights through both event contributions and risk-set averages, making flexible machine-learning nuisance estimation difficult to incorporate directly. Building on machine-learning-assisted generalized entropy calibration (MEC) by Lee and Kim (2026), we propose MEC-Cox for ATT-weighted IPW Cox regression. The method begins with normalized source-propensity-score odds weights for external controls and then applies Bregman calibration to balance cross-fitted prognostic summaries between external controls and treated trial patients. The calibration basis may include control-survival predictions, Cox linear predictors, penalized-survival-model predictions, or other prognostic-score summaries. MEC-updated weights therefore play a dual role as source-transport and prognostic-score balancing weights. We establish consistency, characterize a calibration-induced efficiency gain, and develop a stacked sandwich variance estimator. Simulations show that MEC-Cox can reduce bias, increase efficiency, and improve coverage through flexible machine-learning-assisted adjustment.

生存分析机器学习因果推断外部对照

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