An empirical comparison of time-to-event models to analyse a composite outcome in the presence of death as a competing risk

Haushona, Ndamonaonghenda ; Esterhuizen, Tonya M ; Thabane, Lehana (2020)

CITATION:Haushona N, Esterhuizen TM, Thabane L, Machekano R. An empirical comparison of time-to-event models to analyse a composite outcome in the presence of death as a competing risk. Contemp Clin Trials Commun. 2020;19:100639. Published 2020 Aug 14. doi:10.1016/j.conctc.2020.100639

Article

Introduction: Competing risks arise when subjects are exposed to multiple mutually exclusive failure events, and the occurrence of one failure hinders the occurrence of other failure events. In the presence of competing risks, it is important to use methods accounting for competing events because failure to account for these events might result in misleading inferences. Methods and Objective: Using data from a multisite retrospective observational longitudinal study done in Ethiopia, we performed sensitivity analyses using Fine-Gray model, Cause-specific Cox (Cox-CSH) model, Cause-specific Accelerated Failure Time (CS-AFT) model, accounting for death as a competing risk to deter- mine baseline covariates that are associated with a composite of unfavourable retention in care outcomes in people living with Human Immune Virus who were on both Isoniazid preventive therapy (IPT) and antiretrovi- ral therapy (ART). Non-cause specific (non-CSH) model that does not account for competing risk was also per- formed. The composite outcome comprises of loss to follow-up, stopped treatment and death. Age, World Health Organisation (WHO) stage, gender, and CD4 count were the considered baseline covariates. Results: We included 3578 patients in our analysis. WHO stage III-or-IV was significantly associated with the composite of unfavourable outcomes, Sub-hazard ratio (SHR) = 1.31, 95% confidence interval (CI):1.04–1.65 for the sub-distribution hazard model, hazard ratio [HR] = 1.31, 95% CI:1.05–1.65, for the Cox-CSH model, and HR = 0.81, 95% CI:0.69–0.96, for the CS-AFT model. Gender and WHO stage were found to be signifi- cantly associated with the composite of unfavourable outcomes, HR = 1.56, 95% CI:1.27–1.90, HR = 1.28, 95% CI: 1.06–1.55 for males and WHO stage III-or-IV, respectively for the non-CSH model. Conclusions: Results show that WHO stage III-or-IV is significantly associated with unfavourable outcomes. The results from competing risk models were consistent. However, results obtained from the non-CSH model were inconsistent with those obtained from competing risk analysis models.

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