title: Inhaled corticosteroids in chronic obstructive pulmonary disease: results from two observational designs free of immortal time bias.
abstract: BACKGROUND
  Recent cohort studies in chronic obstructive pulmonary disease (COPD) have questioned the validity of previously reported associations between inhaled corticosteroids (ICS) and reductions in mortality and rehospitalization in observational studies. Using time-dependent versions of statistical survival models, these studies have suggested immortal time bias as responsible for the proposed beneficial association.
  
  
  OBJECTIVE
  We explored the extent of this bias in a study of patients with COPD monitored for a year from COPD discharge with two designs free of any immortal time bias in the General Practice Research Database in the United Kingdom.
  
  
  METHODS
  In Design 1, we used only patients whose treatment status was defined on the same day of discharge to obtain a matched cohort based on propensity scores, which were derived from the patient-level baseline characteristics. In Design 2, we identified all in the study cohort who experienced death or rehospitalization and then matched each case to up to four noncases by randomly sampling from the cohort risk sets without regard to treatment status.
  
  
  RESULTS
  The propensity scores matched cohort analysis of 786 patients without a wait time found a significant risk reduction associated with use of ICS: hazard ratio, 0.69 (95% confidence interval, 0.52-0.93). The matched nested case-control analysis of 2,222 patients, designed without regard to exposure status and hence free of immortal time bias, gave a similar association with exposure to ICS in the last 6-month period: hazard ratio, 0.71 (0.56-0.90).
  
  
  CONCLUSIONS
  We conclude that immortal time bias cannot account for the risk reduction associated with ICS exposure in observational studies.
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline R&D, Greenford Road, Greenford, Middlesex UB6 0HE, UK. victor.a.kiri@gsk.com
authors.forename: Victor A
authors.initials: VA
authors.lastname: Kiri
authors.forename: Neil B
authors.initials: NB
authors.lastname: Pride
authors.forename: Joan B
authors.initials: JB
authors.lastname: Soriano
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D012107:Research Design; D012306:Risk; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids