title: Selection of confounding variables should not be based on observed associations with exposure.
abstract: In observational studies, selection of confounding variables for adjustment is often based on observed baseline incomparability. The aim of this study was to evaluate this selection strategy. We used clinical data on the effects of inhaled long-acting beta-agonist (LABA) use on the risk of mortality among patients with obstructive pulmonary disease to illustrate the impact of selection of confounding variables for adjustment based on baseline comparisons. Among 2,394 asthma and COPD patients included in the analyses, the LABA ever-users were considerably older than never-users, but cardiovascular co-morbidity was equally prevalent (19.9% vs. 19.9%). Adjustment for cardiovascular co-morbidity status did not affect the crude risk ratio (RR) for mortality: crude RR 1.19 (95% CI 0.93-1.51) versus RR 1.19 (95% CI 0.94-1.50) after adjustment for cardiovascular co-morbidity. However, after adjustment for age (RR 0.95, 95% CI 0.76-1.19), additional adjustment for cardiovascular co-morbidity status did affect the association between LABA use and mortality (RR 1.01, 95% CI 0.80-1.26). Confounding variables should not be discarded based on balanced distributions among exposure groups, because residual confounding due to the omission of confounding variables from the adjustment model can be relevant.
authors.affiliation: Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, The Netherlands, r.h.h.groenwold@umcutrecht.nl
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Arno W
authors.initials: AW
authors.lastname: Hoes
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000367:Age Factors; D000368:Aged; D015986:Confounding Factors, Epidemiologic; D015340:Epidemiologic Research Design; D005260:Female; D006801:Humans; D008297:Male; D019370:Observation; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000401:mortality; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D000318:Adrenergic beta-Agonists