title: Estimating risk of venous thromboembolism in patients with cancer in the presence of competing mortality.
abstract: BACKGROUND
  In studies on cancer-associated venous thromboembolism (VTE), patients not only are at risk for VTE but also may die from their underlying malignancy.
  
  
  OBJECTIVE
  In this competing-risk (CR) scenario, we systematically compared the performance of standard (Kaplan-Meier estimator [1-KM]), log-rank test, and Cox model) and specific CR methods for time-to-VTE analysis.
  
  
  METHODS
  Cancer patients (1542) were prospectively followed for a median of 24 months. VTE occurred in 112 (7.3%) patients, and 572 (37.1%) patients died.
  
  
  RESULTS
  In comparison with the CR method, 1-KM slightly overestimated the cumulative incidence of VTE (cumulative VTE incidence at 12 and 24 months [1-KM vs. CR]: 7.22% vs. 6.74%, and 8.40% vs. 7.54%, respectively). Greater bias was revealed in tumor entities with high early mortality (e.g., pancreatic cancer, n = 99, 24-month cumulative VTE incidence: 28.37% vs. 19.30%). Comparing the (subdistribution) hazard of VTE between patients with low and high baseline D-dimer, the Cox model yielded a higher estimate than the corresponding CR model (hazard vs. subdistribution hazard ratio [95% CI] 2.85 [1.92-4.21] vs. 2.47 [1.67-3.65]). For this comparison, the log-rank test yielded a higher test statistic and smaller P-value than Gray's test (χ(2) on 1 degree of freedom: 29.88 vs. 21.34).
  
  
  CONCLUSIONS
  In patients with cancer who are at risk for VTE and death, standard and CR methods for time-to-VTE analysis can generate differing results. For 1-KM, the magnitude of bias is a direct function of competing mortality. Consequently, bias tends to be negligible in cancer patient populations with low mortality but can be considerable in populations at high risk of death.
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Ay
authors.forename: F
authors.initials: F
authors.lastname: Posch
authors.forename: A
authors.initials: A
authors.lastname: Kaider
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D001317:Austria; D015982:Bias; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000401:mortality*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
keywords: bias; neoplasms; risk; thrombosis; venous thromboembolism