Stable Discovery of Interpretable Subgroups via Calibration in Causal Studies
Stable Discovery of Interpretable Subgroups via Calibration in Causal Studies
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DOI：
10.1111/insr.12427
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发表时间：
2020-12-22
影响因子：
2
通讯作者：
Yu, Bin
中科院分区：
文献类型：
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作者：
Dwivedi, Raaz;Tan, Yan Shuo;Yu, Bin
基于 Yu 和 Kumbie 的可预测性、可计算性和稳定性 (PCS) 框架以及随机实验，我们引入了一种通过校准稳定发现可解释亚组的新方法 (StaDISC)，具有较大的异质治疗效果。 StaDISC 是在我们对 1999-2000 年 VIGOR 研究进行重新分析时开发的，该研究是一项 8076 名患者的随机对照试验，比较了当时新批准的药物罗非考昔 (Vioxx) 与较旧药物萘普生的不良事件风险。研究发现，与萘普生相比，万络平均可以降低胃肠道事件的风险，但会增加血栓性心血管事件的风险。应用 StaDISC，我们针对这两种结果拟合了 18 个流行的条件平均治疗效果 (CATE) 估计器，并使用校准来证明它们较差的全局性能。然而，它们在局部经过良好校准且稳定，能够识别具有大于（估计）平均治疗效果的患者组。事实上，StaDISC 发现了三个临床可解释的亚组，每个亚组分别针对胃肠道结局（总计占研究规模的 29.4%）和血栓性心血管结局（总计 11.0%）。使用 2001-2004 年 APPROVe 研究（一项有 2587 名患者参与的独立独立随机对照试验）对发现的亚组进行补充分析，为 StaDISC 的前景提供了进一步的支持证据。
Building on Yu and Kumbier's predictability, computability and stability (PCS) framework and for randomised experiments, we introduce a novel methodology for Stable Discovery of Interpretable Subgroups via Calibration (StaDISC), with large heterogeneous treatment effects. StaDISC was developed during our re-analysis of the 1999-2000 VIGOR study, an 8076-patient randomised controlled trial that compared the risk of adverse events from a then newly approved drug, rofecoxib (Vioxx), with that from an older drug naproxen. Vioxx was found to, on average and in comparison with naproxen, reduce the risk of gastrointestinal events but increase the risk of thrombotic cardiovascular events. Applying StaDISC, we fit 18 popular conditional average treatment effect (CATE) estimators for both outcomes and use calibration to demonstrate their poor global performance. However, they are locally well-calibrated and stable, enabling the identification of patient groups with larger than (estimated) average treatment effects. In fact, StaDISC discovers three clinically interpretable subgroups each for the gastrointestinal outcome (totalling 29.4% of the study size) and the thrombotic cardiovascular outcome (totalling 11.0%). Complementary analyses of the found subgroups using the 2001-2004 APPROVe study, a separate independently conducted randomised controlled trial with 2587 patients, provide further supporting evidence for the promise of StaDISC.