Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database

Cancer Control : Journal of the Moffitt Cancer Center
Parul AgarwalMadhu Mazumdar

Abstract

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was pres...Continue Reading

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Citations

Mar 10, 2020·Diseases of the Colon and Rectum·Sunil V PatelTimothy Hanna
Apr 3, 2020·Journal of the National Cancer Institute·Rikki A CanniotoChristine B Ambrosone
Aug 25, 2020·International Journal of Cancer. Journal International Du Cancer·Fei WangXiao-Ou Shu
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May 27, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Abdel Aziz ShaheenMark G Swain
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