论文标题
在观察性研究中具有多价处理的目标学习:抗精神病药治疗安全的评估
Targeted learning in observational studies with multi-valued treatments: An evaluation of antipsychotic drug treatment safety
论文作者
论文摘要
我们研究了在没有随机分组的情况下多种竞争(多价)处理的因果关系的估计。我们的工作是由对六种常规处方抗精神病药在近39,000名患有严重精神疾病的成年人组成的六种普通抗精神病药中的分配的相对心脏代谢风险的意向性研究的动机。双重稳定估计器,例如有针对性的最小损失估计(TMLE),需要正确规范治疗模型或结果模型,以确保一致的估计;但是,通用TMLE实施使用多个二项式回归而不是多项式回归估算治疗概率。我们实施了使用多项式治疗分配和集成机器学习来估计平均治疗效果的TMLE估计器。我们的多项式实施改善了覆盖范围,但不一定会减少与二项式实施相对于具有不同治疗倾向重叠和事件速率的二项式实施的偏见。评估抗精神病药对三年糖尿病风险或死亡的因果关系,我们发现安全益处是从被认为是第二代药物中最安全的第二代药物转变为以低心脏代谢风险而闻名的不经常开处方的第一代药物。
We investigate estimation of causal effects of multiple competing (multi-valued) treatments in the absence of randomization. Our work is motivated by an intention-to-treat study of the relative cardiometabolic risk of assignment to one of six commonly prescribed antipsychotic drugs in a cohort of nearly 39,000 adults with serious mental illnesses. Doubly-robust estimators, such as targeted minimum loss-based estimation (TMLE), require correct specification of either the treatment model or outcome model to ensure consistent estimation; however, common TMLE implementations estimate treatment probabilities using multiple binomial regressions rather than multinomial regression. We implement a TMLE estimator that uses multinomial treatment assignment and ensemble machine learning to estimate average treatment effects. Our multinomial implementation improves coverage, but does not necessarily reduce bias, relative to the binomial implementation in simulation experiments with varying treatment propensity overlap and event rates. Evaluating the causal effects of the antipsychotics on three-year diabetes risk or death, we find a safety benefit of moving from a second-generation drug considered among the safest of the second-generation drugs to an infrequently prescribed first-generation drug known for having low cardiometabolic risk.