American Journal of Epidemiology Advance Access originally published online on November 25, 2008
American Journal of Epidemiology 2009 169(3):273-284; doi:10.1093/aje/kwn299
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PRACTICE OF EPIDEMIOLOGY |
Instrumental Variable Analysis for Estimation of Treatment Effects With Dichotomous Outcomes
Correspondence to Dr. Jeremy A. Rassen, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120 (e-mail: jrassen{at}post.harvard.edu).
Received for publication May 5, 2008. Accepted for publication August 26, 2008.
Instrumental variable analyses are increasingly used in epidemiologic studies. For dichotomous exposures and outcomes, the typical 2-stage least squares approach produces risk difference estimates rather than relative risk estimates and is criticized for assuming normally distributed errors. Using 2 example drug safety studies evaluated in 3 cohorts from Pennsylvania (1994–2003) and British Columbia, Canada (1996–2004), the authors compared instrumental variable techniques that yield relative risk and risk difference estimates and that are appropriate for dichotomous exposures and outcomes. Methods considered include probit structural equation models, 2-stage logistic models, and generalized method of moments estimators. Employing these methods, in the first study the authors observed relative risks ranging from 0.41 to 0.58 and risk differences ranging from –1.41 per 100 to –1.28 per 100; in the second, they observed relative risks of 1.38–2.07 and risk differences of 7.53–8.94; and in the third, they observed relative risks of 1.45–1.59 and risk differences of 3.88–4.84. The 2-stage logistic models showed standard errors up to 40% larger than those of the instrumental variable probit model. Generalized method of moments estimation produced substantially the same results as the 2-stage logistic method. Few substantive differences among the methods were observed, despite their reliance on distinct assumptions.
antipsychotic agents; confounding factors (epidemiology); instrumental variable; pharmacoepidemiology
Abbreviations: APM, antipsychotic medication; COX-2, cyclooxygenase 2; GMM, generalized method of moments; NSAID, nonsteroidal antiinflammatory drug; PACE, Pharmaceutical Assistance Contract for the Elderly
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