Adverse Effects of Observational Studies When Examining Adverse Outcomes of Drugs
 Dr Peter C. Austin,
 Muhammad Mamdani,
 Ivan J. Williams
 … show all 3 hide
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Objectives: The casecontrol study is commonly used to examine adverse drug events, in which prevalence of exposure in the source population is frequently very low. The objective of the current study was to examine the bias inherent in the odds ratio assessing the association between exposure and an adverse outcome when prevalence of exposure in the source population is extremely low.
Design: Monte Carlo simulations examined the effect of sample size, exposure prevalence, and magnitude of the underlying odds ratio on the bias of the estimated risk ratio, and the power to detect a nonzero risk ratio.
Results: Once the underlying odds ratio was at least four, the adverse effects of low prevalence of exposure was minimal. Studies with small sample sizes and low prevalence of exposure, coupled with small to moderate effect sizes, can result in biased estimates of association between exposure and disease status. With a sample size of 200 and an exposure prevalence of 0.5% in the control population, the bias in the estimated odds ratio can be as large as 115%. However, bias becomes negligible as sample size becomes large (n ≥ 2000), even when prevalence of exposure is very low. Once the expected number of exposed controls is at least eight, the bias in the estimated odds ratio was no more than 5%.
Conclusions: Studies with small sample sizes and low prevalence of exposure, coupled with small to moderate effect sizes can result in biased estimates of association between exposure status and adverse drug effects. However, bias becomes negligible as sample size becomes large.
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 Title
 Adverse Effects of Observational Studies When Examining Adverse Outcomes of Drugs
 Journal

Drug Safety
Volume 25, Issue 9 , pp 677687
 Cover Date
 20020801
 DOI
 10.2165/0000201820022509000006
 Print ISSN
 01145916
 Online ISSN
 11791942
 Publisher
 Springer International Publishing
 Additional Links
 Topics
 Industry Sectors
 Authors

 Dr Peter C. Austin ^{(1)} ^{(2)}
 Muhammad Mamdani ^{(1)} ^{(3)}
 Ivan J. Williams ^{(1)} ^{(2)}
 Author Affiliations

 1. Institute for Clinical Evaluative Sciences, North York, Ontario, 2075 Bayview Avenue, Toronto, G160, M4N 3M5, Canada
 2. Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada
 3. Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada