title: Extension of Kaplan-Meier methods in observational studies with time-varying treatment.
abstract: OBJECTIVE
  Inverse probability of treatment weighted Kaplan-Meier estimates have been developed to compare two treatments in the presence of confounders in observational studies. Recently, stabilized weights were developed to reduce the influence of extreme inverse probability of treatment-weighted weights in estimating treatment effects. The objective of this research was to use adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests to examine the effect of a treatment that varies over time in an observational study.
  
  
  METHODS
  We proposed stabilized weight adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests when the treatment was time-varying over the follow-up period. We applied these new methods in examining the effect of an anti-platelet agent, clopidogrel, on subsequent events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted into a coronary artery. In this population, clopidogrel use may change over time based on a patient's behavior (e.g., nonadherence) and physicians' recommendations (e.g., end of duration of therapy). Consequently, clopidogrel use was treated as a time-varying variable.
  
  
  RESULTS
  We demonstrate that 1) the sample sizes at three chosen time points are almost identical in the original and weighted datasets; and 2) the covariates between patients on and off clopidogrel were well balanced after stabilized weights were applied to the original samples.
  
  
  CONCLUSIONS
  The stabilized weight-adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests are useful in presenting and comparing survival functions for time-varying treatments in observational studies while adjusting for known confounders.
authors.affiliation: The Institute for Health Research, Kaiser Permanente Colorado, Denver, CO 80111, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Xu
authors.forename: Susan
authors.initials: S
authors.lastname: Shetterly
authors.forename: David
authors.initials: D
authors.lastname: Powers
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Raebel
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Tsai
authors.forename: P Michael
authors.initials: PM
authors.lastname: Ho
authors.forename: David
authors.initials: D
authors.lastname: Magid
mesh_terms: D000367:Age Factors; D000368:Aged; D000077144:Clopidogrel; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D003324:Coronary Artery Disease / Q000601:surgery; D054855:Drug-Eluting Stents; D005260:Female; D015438:Health Behavior; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine