26: Impacts of Immortal Time Bias on Assessing the Effects of Immune-related Adverse Events on Survival

Music City Center 

Despite advancements in immune checkpoint inhibitors (ICIs) for cancer, ICIs can trigger immune syndromes called immune-related adverse events (irAEs), often linked with survival. However, many time-to-event studies overlook immortal time bias. We examined this bias using time-naïve, time-dependent, and landmark analyses in 3343 cancer patients at OSU CCC. Incident irAEs were defined as any gastrointestinal, pulmonary, dermatological, endocrine, or hepatobiliary AEs post-ICI infusion. Kaplan-Meier and Simon-Makuch methods calculated cumulative incidence, and Cox models evaluated survival with and without time dependence. A total of 1739 patients died, and 48.5% experienced irAEs. Median survival was 10.2 months, with a median time to first irAE of 1.4 months. Time-naïve analysis showed irAEs were associated with significantly lower mortality (P <0.01) while time-dependent analysis showed higher mortality (P <0.01). Cox models yielded HR 1.41 (95% CI: 1.27-1.55) with time dependence and HR 0.86 (95% CI: 0.78-0.94) without. Using different landmark values did not mitigate bias. Accounting for time dependence is needed to avoid biased interpretations of irAEs effects on survival.

Immortal time bias

irAE

ICI

Time-Dependent 

Section on Statistics in Epidemiology