A structural description of biases that generate immortal time.

Abstract

Immortal time arises when individuals in the analysis are either selected based on post-assignment eligibility criteria or assigned to treatment strategies based on post-eligibility information. Explicit target trial emulation prevents the introduction of immortal time in survival analyses of observational data because it synchronizes eligibility and treatment assignment at the start of follow-up. Describing the structure of the biases that generate immortal time is facilitated by specifying the target trial so that the procedures to determine eligibility and assignment can be appropriately evaluated. Selection based on eligibility criteria applied after treatment assignment at the start of follow-up results in immortal time when the analysis starts the follow-up at assignment. Misclassification of assignment to treatment strategies based on treatment received after the start of follow-up results in immortal time when the treatment strategies are not distinguishable at the start of follow-up. The above selection and misclassification can be represented using causal diagrams. We summarize analytic approaches that prevent immortal time when longitudinal data are available from the time of treatment assignment. The term "immortal time bias" suggests that the source of the bias is the immortal time, but it is selection or misclassification that generates the immortal time, leading to bias.