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Published on: June 29, 2018
Use of clone-censor-weight to avoid immortal-time bias: a systematic methodological review
Aldrine Manzanilla1, Clément Brunetta1, François Peyre-Pradat1
1Université Paris-Saclay, INSERM U1018, CESP, Oncostat, labeled Ligue Contre le Cancer, Villejuif, France, 114 rue Edouard Vaillant, 94800 Villejuif, France.
Journal of Clinical Epidemiology
|August 14, 2026
Summary
The clone-censor-weight (CCW) method helps reduce immortal-time bias in observational studies. However, inconsistent application and potential biases remain, highlighting the need for clearer methodological guidelines.
Area of Science:
- Epidemiology
- Biostatistics
- Health Services Research
Background:
- Observational studies evaluating treatment strategies are susceptible to immortal-time bias.
- The clone-censor-weight (CCW) approach is gaining traction to mitigate this bias in target trial emulation.
- This review assesses CCW implementation, immortal-time bias handling, and identifies limitations.
Purpose of the Study:
- To systematically review the implementation of the CCW approach in observational studies.
- To evaluate how CCW handles immortal-time bias.
- To identify key considerations and limitations in CCW application.
Main Methods:
- A comprehensive search of MEDLINE and Embase databases (2010-2025) was conducted.
- Manual citation searching on relevant reviews was performed.
- Two independent reviewers screened studies; data extraction and risk of bias assessment were done by one or two reviewers.
Main Results:
- 103 out of 113 studies (91.2%) implemented CCW within target trial emulation.
- Inverse probability of censoring weighting (IPCW) or treatment weighting (IPTW) were commonly used.
- Immortal-time bias persisted in 22 studies (19.5%) due to post-baseline exclusions or ill-defined time zero.
Conclusions:
- CCW implementation shows variability in statistical modeling and handling of censoring.
- Inconsistent application of CCW can still lead to immortal-time bias.
- Clarifying methodological components is crucial for consistent CCW application and improved reporting.
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