Immortal time bias in older vs younger age groups: a simulation study with application to a population-based cohort of patients with colon cancer

Abstract

Background: In observational studies, the risk of immortal time bias (ITB) increases with the likelihood of early death, itself increasing with age. We investigated how age impacts the magnitude of ITB when estimating the effect of surgery on one-year overall survival (OS) in patients with stage IV colon cancer aged 50-74 and 75-99 in England. Method: Using simulations, we compared estimates from a time-fixed exposure model to three methods addressing ITB: time-varying exposure, delayed entry, and landmark methods. We then estimated the effect of surgery on one-year OS using a national population-based cohort of patients derived from the CORECT-R resource. Results: In simulations, the magnitude of ITB was larger among older patients when their probability of early death increased or treatment was delayed. The bias was corrected using the methods addressing ITB. When applied to CORECT-R data, these methods yielded smaller effects than the time-fixed exposure approach but effects were similar in both age groups. Conclusion: ITB must be addressed in all longitudinal studies, particularly, when investigating the effect of an exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.

Persistent High Long-term Excess Mortality after Elective AAA Repair Especially in Women

“…Older patients have a higher a priori risk of death. Therefore, comparing overall crude survival differences between younger and older patients introduces bias (immortal time bias) 30 . Relative survival analysis, which corrects for age differences in (a priori) life expectancy, overcomes this.…”

“…Therefore, comparing overall crude survival differences between younger and older patients introduces bias (immortal time bias). 30 Relative survival analysis, which corrects for age differences in (a priori) life expectancy, overcomes this. Furthermore, to the best of our knowledge, this is the first study to apply a competing risk analysis for CV mortality in AAA patients.…”