Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA 27599-7435, USA.
Pharmacoepidemiol Drug Saf. 2010 Jun;19(6):537-54. doi: 10.1002/pds.1908.
Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial.
工具变量（IV）方法已被提议作为解决医学干预比较研究中普遍存在的未控制混杂问题的一种潜在方法，但许多研究人员对 IV 方法并不熟悉。本文的目的是为比较安全性和有效性研究提供一种非技术性的实用 IV 方法介绍。我们概述了有效 IV 估计所需的原则和基本假设，讨论了如何解释 IV 研究的结果，回顾了在比较有效性研究中使用的工具，并为 IV 分析提出了一些最低报告标准。最后，我们提供了我们对基于暴露或结果的统计建模的更传统方法的观点，以及基于 IV 估计的作用的观点。我们预计，对于非常罕见结果的药物安全性研究，IV 方法通常功效不足，但在可能存在大量未控制混杂的预期效果研究中可能具有潜在用途。
