Novel and Rigorous Statistical Learning and Inference for Comparative Effectiveness Research with Complex Data

项目摘要 医学中的比较有效性研究(CER)通常是为了发现和提供信息。 关于替代药物或治疗方法在有效性和安全性方面可能存在的差异的通知。是这样的 如果信息可靠和准确，可以帮助患者、临床医生和其他医疗保健利益相关者做出 更知情的医疗决策，并改善医疗服务的提供和结果。但是，图形有效 而来自观察性研究的关于治疗效果的相关推断涉及到来自 无论是主题研究人员还是统计学家。一方面，因果推理依赖于结构假设-- 特兹。这类假设的两个突出类别是无混性或工具变量(IV)假设： 特兹。另一方面，假设存在结构性假设，因果推断也需要统计建模 以及从经验数据估计总体属性和关联性。统计学习的问题 而推理可能是具有挑战性的，同时允许大量候选回归变量，如主效应 以及协变量之间的相互作用。我们研究的目标是开发、评估和传播一种新的 一套理论上严格的、数值自动化的、实用的统计学习方法和方法 用复杂、高维数据估计CER治疗效果的推论。三个具体目标 主要结果如下：(1)UNCON下群体和亚群体平均处理效应的高维推断。 多值处理的基础；(2)局部平均处理效果的高维推断 和IV依赖的平均处理效果对使用多值仪器和治疗的受试者，以及 (3)对平均治疗效果的高维推断，如生存和危险之间的对比 纵向数据和生存数据的概率。我们将研究新方法在以下几个方面的应用 比较有效性和安全性研究，包括最近一项关于 精神分裂症和一个正在进行的评估同类药物治疗互换性的项目，用于前- 房颤或心房扑动或二肽基肽酶-4患者服用充足、直接的口服抗凝剂 在2型糖尿病患者中使用抑制剂，同时利用由Medicare Pre-Rate设计创建的静脉输液 手写药品福利。我们将开发和公开发布用户友好的计算机软件，包括透明 直接实施新方法的文档。

Project Summary Comparative effectiveness research (CER) in medicine is commonly conducted to discover and provide infor- mation on possible differences between alternative drugs or treatments in their effectiveness and safety. Such information, if reliable and accurate, can help patients, clinicians, and other healthcare stakeholders to make better-informed healthcare decisions and improve healthcare delivery and outcomes. However, drawing valid and relevant inferences about treatment effects from observational studies involves effort and expertise from both subject-matter researchers and statisticians. On one hand, causal inference relies on structural assump- tions. Two prominent classes of such assumptions are unconfoundedness or instrument variable (IV) assump- tions. On the other hand, granted the structural assumptions, causal inference also requires statistical modeling and estimation of population properties and associations from empirical data. The problem of statistical learning and inference can be challenging, while allowing a large number of candidate regressors such as main effects and interactions of covariates. The objective of our research is to develop, evaluate, and disseminate a new set of theoretically rigorous, numerically automated, and practically useful methods of statistical learning and inference for estimating treatment effects in CER with complex, high-dimensional data. Three specific aims are (1) high-dimensional inference about population and subpopulation average treatment effects under uncon- foundedness with multi-valued treatments, (2) high-dimensional inference about local average treatment effects and IV-dependent average treatment effects on the treated with multi-valued instruments and treatments, and (3) high-dimensional inference about average treatment effects such as contrasts between survival and hazard probabilities with longitudinal and survival data. We will investigate applications of the new methods to several comparative effectiveness and safety studies including a recent study on comparative treatment strategies in schizophrenia and an ongoing project to evaluate the therapeutic exchangeability of same-class drugs, for ex- ample, direct oral anticoagulants among patients with atrial fibrillation or atrial flutter or dipeptidyl peptidase-4 inhibitors among patients with type 2 diabetes, while exploiting IVs created by the design of the Medicare pre- scription drug benefit. We will develop and publicly release user-friendly computer software including transparent documentation for direct implementation of the new methods.