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

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 1-year overall survival (OS) in patients with Stage IV colon cancer aged 50-74 and 75-84 in England.

Using simulations, we compared estimates from a time-fixed exposure model to three statistical methods addressing ITB: time-varying exposure, delayed entry and landmark methods. We then estimated the effect of surgery on OS using a population-based cohort of patients from the CORECT-R resource and conducted the analysis using the emulated target trial framework.

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 a smaller effect of surgery than the time-fixed exposure approach but effects were similar in both age groups.

ITB must be addressed in all longitudinal studies, particularly, when investigating the effect of exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.