An empirical comparison of time-to-event models to analyse a composite outcome in the presence of death as a competing risk
Date
2020
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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.
Description
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
Keywords
Accelerated failure time, Cause-specific hazard, Competing risks, Composite endpoint, Sub-distribution hazard