Abstract:Externally controlled trials compare outcomes from a single-arm trial with external controls drawn from historical trials, registries, or observational studies. For time-to-event endpoints, a key challenge arises when follow-up is indexed at treatment initiation in the single-arm trial, but the external-control data are indexed at an earlier clinical milestone, such as diagnosis or relapse. This misalignment can induce immortal time bias, distort risk sets, and complicate the interpretation of survival comparisons. We propose Index Date Imputation (IDI), a truncation-aware approach for imputing comparable index dates for external-control patients in settings with delayed treatment initiation. IDI estimates the marginal distribution of treatment-initiation times in the target single-arm population while accounting for the fact that initiation times are observed only among patients who survive long enough to initiate treatment. The imputed index dates are then used to align follow-up and enforce comparable truncation conditions in the external-control cohort. Because temporal alignment alone does not address population-level confounding, IDI is combined with propensity score weighting or matching to improve covariate comparability between cohorts. We evaluate the finite-sample performance of the proposed approach through Monte Carlo simulation studies. Using data from a randomized oncology trial, we emulate an externally controlled analysis with induced index-date misalignment and show that IDI reduces discrepancy from the randomized trial benchmark. IDI provides a practical strategy for index-date alignment in survival analyses involving delayed treatment initiation and can be integrated with standard covariate-adjustment methods when suitable external controls are available.
From: Quentin Le Coënt [view email]
[v1]
Wed, 17 Sep 2025 17:16:57 UTC (713 KB)
[v2]
Tue, 16 Jun 2026 18:01:25 UTC (1,609 KB)
此内容由惯性聚合(RSS阅读器)自动聚合整理，仅供阅读参考。 原文来自 — 版权归原作者所有。