Instrumental variable methods in comparative safety and effectiveness research

Authors

  • M. Alan Brookhart PhD,

    Corresponding author
    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA
    2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    • Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg CB#7435, Chapel Hill, NC, 27599-7435, USA.
    Search for more papers by this author
  • Jeremy A. Rassen ScD,

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Sebastian Schneeweiss MD, ScD

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA
    Search for more papers by this author

  • The authors declare no conflict of interest.

Abstract

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. Copyright © 2010 John Wiley & Sons, Ltd.

Ancillary