title: Impact of immortal person-time and time scale in comparative effectiveness research for medical devices: a case for implantable cardioverter-defibrillators.
abstract: OBJECTIVE
  To assess the extent of immortal time bias in estimating the clinical effectiveness of implantable cardioverter-defibrillators (ICDs) and the impact of methods of handling immortal time bias.
  
  
  METHODS
  Retrospective population-based cohort study of patients with heart failure in a national registry linked to Medicare claims (2003-2008). We compared three methods of handling immortal time bias, namely the Mantel-Byar (or time-dependent exposure assignment), the landmark, and the exclusion methods.
  
  
  RESULTS
  Of the 5,226 study patients, 1,274 (24.4%) received ICD therapy. Total person-years in the Mantel-Byar method were 2,639, or 490 more than that in the exclusion method, reflecting potential immortal time in the study. The exclusion method yielded a hazard ratio of 0.71 (95% confidence interval [CI]: 0.63-0.80), which was 16% lower than the Mantel-Byar method (0.84; 95% CI: 0.75-0.95). The 120-day landmark method yielded similar results to those produced by the Mantel-Byar method (0.82; 95% CI: 0.72-0.95).
  
  
  CONCLUSIONS
  Immortal time bias was detected in the ICD clinical effectiveness study, which might have led to substantial bias overestimating the treatment effect if handled by exclusion. When an appropriate landmark was selected, that method yielded similar hazard ratios to those obtained by the Mantel-Byar method, supporting the validity of the landmark method.
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC 27715, USA.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Mi
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Hammill
authors.forename: Lesley H
authors.initials: LH
authors.lastname: Curtis
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Greiner
authors.forename: Soko
authors.initials: S
authors.lastname: Setoguchi
mesh_terms: D000368:Aged; D015982:Bias; D057186:Comparative Effectiveness Research / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D006278:Medicare; D011336:Probability; D012042:Registries; D013997:Time Factors; D061665:Time-to-Treatment / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology
keywords: Bias (epidemiology); Defibrillators, implantable; Heart failure; Immortal time; Landmark method; Mantel-Byar method; Propensity score; Regression analysis; Time scale