Structural Limitations of Early–Late Treatment Comparisons Under Target Trial Emulation: A Simulation Study

Clicks: 28
ID: 326600
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #34 of 314 articles by views in american journal of epidemiology

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 314 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Early versus Late (E-L) treatment initiation comparisons, which are prone to immortal time bias, are widely considered amenable to causal inference through target trial emulation (TTE) using clone-censor-weighting (CCW). However, whether standard CCW yields a well-defined causal estimand for the E-L comparison under ideal implementation conditions has not been formally examined. We conducted a structural simulation study to evaluate CCW-based TTE for E-L comparisons. The design varied along three dimensions: treatment-initiation mechanisms (random versus baseline-confounded timing), benefit-harm structures governing delayed-treatment harm and post-treatment benefit, and five distinct E-L initiation-window configurations. We implemented CCW as conventionally recommended and summarized estimated 12-month marginal risk ratios across settings. Depending on the placement and structure of the initiation windows, estimated risk ratios exhibited systematic window-dependent variation, including direction reversals across window specifications, even in settings where the true marginal causal contrast was 1 by design. These patterns were not consistently explained by weight instability or lack of support overlap. Our findings indicate that, in E-L comparisons, the window-defined strategy contrast estimated using CCW-based TTE can be strongly shaped by risk accumulated before treatment initiation under the specified windows, underscoring the need for caution when interpreting E-L analyses.
Reference Key
openalex_W7204560498 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Atsushi Takayama, Shiro Tanaka, Koji Kawakami
Journal american journal of epidemiology
Year 2026
DOI
10.1093/aje/kwag208
URL
https://doi.org/10.1093/aje/kwag208
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.