Performance of instrumental variable methods in cohort and nested case-control studies: a simulation study

• Published in: Pharmacoepidemiology and drug safety 2014-02, Vol.23 (2), p.165-177
• Main Authors: Uddin, Md. Jamal, Groenwold, Rolf H. H., de Boer, Anthonius, Belitser, Svetlana V., Roes, Kit C. B., Hoes, Arno W., Klungel, Olaf H.
• Format: Article
• Language: English
• Subjects: Bias; Biological and medical sciences; Case-Control Studies; Clinical trial. Drug monitoring; cohort; Cohort Studies; Computer Simulation; confounding in epidemiology; Economic models; Epidemiologic Methods; Epidemiology; General pharmacology; Humans; instrumental variable; Medical sciences; nested case-control; pharmacoepidemiology; Pharmacoepidemiology - methods; Pharmacology; Pharmacology. Drug treatments; rare outcome; Research Design; simulation; variability; weak IV
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.3555

ABSTRACT Purpose Instrumental variable (IV) analysis is becoming increasingly popular to adjust for confounding in observational pharmacoepidemiologic research. One of the prerequisites of an IV is that it is strongly associated with exposure; if it is weakly associated with exposure, IV estimates are reported to be biased. We aimed to assess the performance of IV estimates in various (pharmaco‐)epidemiologic settings. Methods Data were simulated for continuous/binary exposure, outcome and IV in cohort and nested case–control (NCC) designs with different incidences of the outcome. Pearson's correlation, point bi‐serial correlation, odds ratio (OR), and F‐statistic were used to assess the IV‐exposure association. Two‐stage analysis was performed to estimate the exposure effect. Results For all types of IV and exposure in the cohort and NCC designs, IV estimates were extremely unstable and biased when the IV was very weakly associated with exposure (e.g. Pearson's correlation