Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2023 Apr;128(8):1521-1528.
doi: 10.1038/s41416-023-02187-0. Epub 2023 Feb 9.

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

Sophie Pilleron  1   2 , Camille Maringe  3 , Eva J A Morris  4 , Clémence Leyrat  5
Affiliations
Comparative Study

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

Sophie Pilleron et al. Br J Cancer. 2023 Apr.

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

Methods: 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.

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 a smaller effect of surgery 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 exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Scenarios used in simulations.
Fig. 2
Fig. 2
Overall survival estimated using the time-fixed exposure method based on the four scenarios in young and old groups.
Fig. 3
Fig. 3. Bias of the difference in 1-year overall survival (OS) based on the four scenarios.
TF time-fixed exposure method, DE delayed entry method, L landmark method, TV time-varying exposure method. Note: a difference of 0 indicates there is no immortal-time bias.
See this image and copyright information in PMC

References

    1. Hernán MA, Sauer BC, Hernández-Díaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016;79:70–75. doi: 10.1016/j.jclinepi.2016.04.014. - DOI - PMC - PubMed
    1. Hanley JA, Foster BJ. Avoiding blunders involving ‘immortal time’. Int J Epidemiol. 2014;43:949–61. doi: 10.1093/ije/dyu105. - DOI - PMC - PubMed
    1. Shariff SZ, Cuerden MS, Jain AK, Garg AX. The secret of immortal time bias in epidemiologic studies. J Am Soc Nephrol. 2008;19:841–3. doi: 10.1681/ASN.2007121354. - DOI - PubMed
    1. Agarwal P, Moshier E, Ru M, Ohri N, Ennis R, Rosenzweig K, et al. Immortal time bias in observational studies of time-to-event outcomes: assessing effects of postmastectomy radiation therapy using the national cancer database. Cancer Control. 2018;25:1073274818789355. doi: 10.1177/1073274818789355. - DOI - PMC - PubMed
    1. Ho AM-H, Dion PW, Ng CSH, Karmakar MK. Understanding immortal time bias in observational cohort studies. Anaesthesia. 2013;68:126–30. doi: 10.1111/anae.12120. - DOI - PubMed

Publication types