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A Novel Approach for Handling Immortal Time Bias in Observational Studies
  • Victor Kiri A,
  • Paolo Messina
Victor Kiri A
Labcorp Clinical Development Limited

Corresponding Author:[email protected]

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Paolo Messina
Labcorp Clinical Development Limited
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Abstract

Purpose: To propose the Entry-time Comparability Retention (ETCR) method- a novel methodology that uses propensity scores (PS) as a design tool to minimize immortal time bias- a bias that occurs when the determination of a patient’s treatment status involves a period prior to treatment initiation that is unaccounted for in the assessment of treatment effect. Methods: The treatment status of each member of a cohort is classified at cohort entry, based on whether or not the patient initiated treatment at any time during the study period- namely, as either ever-treated or never-treated. Two sets of propensity scores are derived on each patient: 1) at cohort entry to construct blocks of comparable patients by propensity scores matching each ever-treated patient to the never-treated patients who survived up to the ever-treated patient’s time of treatment initiation, which are then retained and assigned the same start of follow-up to address the immortal time bias, and 2) at treatment initiation, to derive the second set of propensity scores to address confounding. Using simulated data, the performance of a simplified form of the ETCR method, that is based on simple blocks of 1:n greedy matching, is compared with two of the leading approaches- the Landmark and time-dependent Cox methods. Results: The ETCR method consistently yielded the lowest mean percentage of residual bias across the different scenarios in our simulation. Conclusions: The ETCR results suggest the propensity scores as an effective design tool for creating and retaining comparable treatment groups to minimize immortal time bias.