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arXiv 2008.10109stat.MEcs.LGstat.AP
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在因果研究中通过校准稳定发现可解释的亚组

Stable discovery of interpretable subgroups via calibration in causal studies

University of California, Berkeley(加州大学伯克利分校);Northeastern University(东北大学);Protypia Inc(Protypia公司);Chan Zuckerberg Biohub(陈-扎克伯格生物中心)

Raaz Dwivedi, Yan Shuo Tan, Briton Park, Mian Wei, Kevin Horgan, David Madigan, Bin Yu

摘要:

基于Yu和Kumbier的PCS框架和随机实验,我们引入了一种新的方法,通过校准稳定发现可解释的亚组(StaDISC),具有大的异质性处理效应。StaDISC是在我们对1999-2000年VIGOR研究的重新分析中开发的,该研究是一项8076例患者的随机对照试验(RCT),比较了当时新批准的药物罗非考昔(万络)与较老的药物萘普生的不良事件风险。平均而言,与萘普生相比,万络可降低胃肠道(GI)事件的风险,但增加血栓性心血管(CVT)事件的风险。应用StaDISC,我们适合18个流行的条件平均处理效应(CATE)估计的结果和使用校准,以证明其较差的全球性能。但是,它们在局部校准良好且稳定,能够识别出具有大于(估计)平均处理效应的患者组。事实上,StaDISC发现了三个临床可解释的亚组,每个亚组的GI结局(总计占研究规模的29.4%)和CVT结局(总计11.0%)。使用2001-2004年APPROVe研究对发现的亚组进行补充分析,该研究是一项单独独立进行的RCT,纳入2587例患者,为StaDISC的前景提供了进一步的支持证据。

英文摘要:

Building on Yu and Kumbier's PCS framework and for randomized 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 randomized controlled trial (RCT), that compared the risk of adverse events from a then newly approved drug, Rofecoxib (Vioxx), to that from an older drug Naproxen. Vioxx was found to, on average and in comparison to Naproxen, reduce the risk of gastrointestinal (GI) events but increase the risk of thrombotic cardiovascular (CVT) 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 GI outcome (totaling 29.4% of the study size) and the CVT outcome (totaling 11.0%). Complementary analyses of the found subgroups using the 2001-2004 APPROVe study, a separate independently conducted RCT with 2587 patients, provides further supporting evidence for the promise of StaDISC.

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