title: Time-window bias in case-control studies: statins and lung cancer.
abstract: Time-related biases in cohort studies can produce illusory "beneficial" effects of medications due entirely to an artifact of the analytic design. We describe "time-window bias" in the context of a case-control study, reporting that statin use was associated with a 45% reduction in the incidence of lung cancer. This bias results from the use of time-windows of different lengths between cases and controls to define time-dependent exposures. We illustrate the bias using a population of 365,467 patients from the United Kingdom's General Practice Research Database, including 1786 incident cases of lung cancer during 1998-2004. The case-control approach used in the published study yielded a rate ratio of lung cancer incidence of 0.62 with statin use (95% confidence interval = 0.55-0.71). A case-control approach that properly accounts for time produces a rate ratio of 0.99 (0.85-1.16)-suggesting no benefit of statins on lung cancer risk. We show analytically that the magnitude of the bias is proportional to the ratio of the unequal time-window lengths.
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada. samy.suissa@mcgill.ca
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.forename: Sophie
authors.initials: S
authors.lastname: Dell'aniello
authors.forename: Sarah
authors.initials: S
authors.lastname: Vahey
authors.forename: Christel
authors.initials: C
authors.lastname: Renoux
mesh_terms: D000368:Aged; D015982:Bias; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012107:Research Design; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors