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Demystifying Clone-Censor-Weight Method in Target Trial Emulation: A Real-World Study of HPV Vaccination Strategies

Lin, T.; Li, Y.; Huang, Z.; Gui, T. T.; Wang, W.; Guo, Y.

2026-04-22 health informatics
10.64898/2026.04.21.26351413 medRxiv
Show abstract

Target trial emulation (TTE) offers a principled way to estimate treatment effects using real-world observational data, but analyses of time-varying treatment strategies remain vulnerable to immortal time bias. The clone-censor-weight (CCW) approach is increasingly used to address this problem, yet key aspects of its causal interpretation and implementation remain unclear. In this work, we emulate a target trial using electronic health records (EHRs) to compare completion of a 3-dose 9-valent human papillomavirus vaccination (HPV) series within 12 months versus remaining partially vaccinated among vaccine initiators. We link CCW to the classic potential outcome framework in causal inference, evaluate the role of different weighting mechanisms, and account for within-subject correlation induced by cloning using cluster-robust variance estimation. Our study provides practical guidance for applying CCW in real-world comparative effectiveness studies to address immortal time bias and supports more rigorous and interpretable treatment effect estimation in TTE.

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