A Structural Description of Biases That Generate Immortal Time
Miguel A. Hernán, Jonathan A C Sterne, Julian P. T. Higgins, Ian Shrier, Sonia Hernández–Dı́az
Abstract
Immortal time may arise in survival analyses when individuals are assigned to treatment strategies based on post-eligibility information or selected based on post-assignment eligibility criteria. Selection based on eligibility criteria applied after treatment assignment results in immortal time when the analysis starts the follow-up at assignment. Misclassification of assignment to treatment strategies based on treatment received after eligibility results in immortal time when the treatment strategies are not distinguishable at the start of follow-up. Target trial emulation prevents the introduction of immortal time by explicitly specifying eligibility and assignment to the treatment strategies, and by synchronizing them at the start of follow-up. We summarize analytic approaches that prevent immortal time when longitudinal data are available to emulate the target trial 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.