Study Design
Immortal time bias
Immortal time bias is a distortion in cohort studies where a span of follow-up during which the outcome cannot occur is misattributed to a treatment group. Because members must survive event-free long enough to receive the treatment, the treated group gains a spurious survival advantage built into the design.
The name captures the mechanism: a stretch of time is effectively immortal because the outcome, often death, cannot happen during it without changing the person's group assignment. If patients are classified as treated because they filled a prescription during follow-up, the time before that prescription, during which they had to stay alive and event-free, is frequently and wrongly counted as treated exposure.
The bias reliably makes treatments look protective when they are not. It has produced famous artefacts, including apparent survival benefits for Oscar winners and for patients adhering to medication, that dissolve once the immortal period is handled correctly. The fix is to define exposure using time-dependent methods or landmark analysis so that follow-up is attributed to the correct group at each moment.
For reviewers of pharmacoepidemiology and observational survival studies, the question to ask is when exposure was defined relative to the start of follow-up. If group membership depends on something that happens after baseline, immortal time bias is likely lurking.
Example
Patients counted as treated only after their first refill appeared to live longer, but that survival edge was the immortal time before the refill.
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