论文标题
强大的因果关系推断药物相互作用
Robust Causal Inference of Drug-drug Interactions
论文作者
论文摘要
人们对开发因果推断方法的多价处理方法的兴趣越来越大,重点是成对平均治疗效果。在这里,我们专注于一个临床上重要但不足的估计:因果药物 - 药物相互作用(DDIS),量化药物A的因果效应的程度因存在与不存在药物的存在而改变的程度。治疗。但是,当倾向得分模型被弄清楚时,这种方法通常会产生偏见的结果。我们提出了两种基于经验可能性的加权方法,允许指定一组倾向得分模型,第二种方法通过结合其他非参数约束,将第二种方法平衡。当假定的倾向分数模型包含正确的估计值时,这两种方法的估计器都是一致的。该属性被称为多种鲁棒性。然后,我们通过模拟评估其有限样本性能。结果表明,根据鲁棒性和效率,所提出的估计器的表现优于标准IPTW方法。最后,我们采用了提出的方法来评估肾素 - 血管紧张素系统抑制剂(RAS-I)对使用从电子医疗记录中从大型多生育健康系统的电子病历中得出的数据,对非甾体类抗炎药(NSAID)和阿片类药物的比较肾毒性的影响。
There is growing interest in developing causal inference methods for multi-valued treatments with a focus on pairwise average treatment effects. Here we focus on a clinically important, yet less-studied estimand: causal drug-drug interactions (DDIs), which quantifies the degree to which the causal effect of drug A is altered by the presence versus the absence of drug B. Confounding adjustment when studying the effects of DDIs can be accomplished via inverse probability of treatment weighting (IPTW), a standard approach originally developed for binary treatments and later generalized to multi-valued treatments. However, this approach generally results in biased results when the propensity score model is misspecified. Motivated by the need for more robust techniques, we propose two empirical likelihood-based weighting approaches that allow for specifying a set of propensity score models, with the second method balancing user-specified covariates directly, by incorporating additional, nonparametric constraints. The resulting estimators from both methods are consistent when the postulated set of propensity score models contains a correct one; this property has been termed multiple robustness. We then evaluate their finite sample performance through simulation. The results demonstrate that the proposed estimators outperform the standard IPTW method in terms of both robustness and efficiency. Finally, we apply the proposed methods to evaluate the impact of renin-angiotensin system inhibitors (RAS-I) on the comparative nephrotoxicity of nonsteroidal anti-inflammatory drugs (NSAID) and opioids, using data derived from electronic medical records from a large multi-hospital health system.