Abstract:Interim monitoring in time-to-event trials must balance inferential maturity with operationally meaningful timing. Event-driven designs align analyses with event accumulation but can produce substantial and unpredictable calendar delays, whereas enrollment-driven designs provide predictable timing but may rely on immature follow-up. We propose the Window-Cohort with Calibrated Follow-Up Requirement (WCR) framework, which directly parameterizes follow-up maturity through a locked cohort size and a post-lock follow-up requirement. The interim analysis is conducted after the prespecified cohort has accrued the calibrated minimum follow-up, while enrollment may continue and later patients are reserved for the final analysis. The framework distinguishes restricted follow-up for landmark survival estimands from unrestricted follow-up for proportional hazards estimands, thereby linking the effective information horizon to the estimand. Design parameters and decision thresholds are jointly calibrated through constrained optimization to control type I error and power while balancing calendar time, interim maturity, and decision-lag burden. Simulation studies motivated by a rare pediatric oncology trial show that WCR attains target operating characteristics under the calibration model and offers more stable and interpretable interim timing than conventional event-driven and enrollment-driven approaches. The methodology is implemented in the open-source R package WCRBayesDesign, available on CRAN. WCR reframes interim monitoring as an information-time alignment problem and provides a practical design strategy for single-arm trials with sparse events, slow accrual, and long-horizon endpoints.
From: Haitao Pan [view email]
[v1]
Sat, 13 Jun 2026 19:33:11 UTC (70 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。