The Predictive Approaches to Treatment Effect Heterogeneity statement focused on baseline risk as a robust predictor of treatment effect and provided guidance on risk-based assessment of treatment effect heterogeneity in the RCT setting. The aim of this study was to extend this approach to the observational setting using a standardized scalable framework. The proposed framework consists of five steps: 1) definition of the research aim, i.e., the population, the treatment, the comparator and the outcome(s) of interest; 2) identification of relevant databases; 3) development of a prediction model for the outcome(s) of interest; 4) estimation of relative and absolute treatment effect within strata of predicted risk, after adjusting for observed confounding; 5) presentation of the results. We demonstrate our framework by evaluating heterogeneity of the effect of angiotensin-converting enzyme (ACE) inhibitors versus beta blockers on three efficacy and six safety outcomes across three observational databases. The proposed framework can supplement any comparative effectiveness study. We provide a publicly available R software package for applying this framework to any database mapped to the Observational Medical Outcomes Partnership Common Data Model. In our demonstration, patients at low risk of acute myocardial infarction received negligible absolute benefits for all three efficacy outcomes, though they were more pronounced in the highest risk quarter, especially for hospitalization with heart failure. However, failing diagnostics showed evidence of residual imbalances even after adjustment for observed confounding. Our framework allows for the evaluation of differential treatment effects across risk strata, which offers the opportunity to consider the benefit-harm trade-off between alternative treatments.
翻译:治疗效果异质性说明侧重于基线风险,作为治疗效果的可靠预测,并为基于风险的治疗效果评估提供了指导。这项研究的目的是利用标准化的可缩放框架将这一方法扩大到观察环境。拟议框架包括五个步骤:1) 界定研究目标,即人口、治疗、参照方和感兴趣的结果;2) 确定相关数据库;3) 为相关结果开发一个预测模型;4) 对预测风险层的相对和绝对治疗效果进行基于风险的评估,然后根据观察到的混杂情况进行调整;5) 介绍结果。我们通过评估Angiostensin enverval enzyme(ACE)抑制剂和乙型阻塞在三个观测数据库中的三种功效和六项安全结果的异质性性。拟议框架可以补充任何比较性残余研究;3) 为将这一框架应用于在预测风险层的预测风险层中的相对和绝对治疗效果;4) 估算结果的估算结果的相对和绝对效果;5) 介绍结果。我们展示了我们的框架,通过评估Andenen en en enevent enal enal adal Ex Procialal Exal Exal Exalalalalalal 结果结果,我们的所有演示患者都展示了我们所观察到的诊断性结果。