Confirmatory adaptive group sequential designs for single-arm phase II studies with multiple time-to-event endpoints

BIOMETRICAL JOURNAL(2022)

引用 2|浏览6
暂无评分
摘要
Existing methods concerning the assessment of long-term survival outcomes in one-armed trials are commonly restricted to one primary endpoint. Corresponding adaptive designs suffer from limitations regarding the use of information from other endpoints in interim design changes. Here we provide adaptive group sequential one-sample tests for testing hypotheses on the multivariate survival distribution derived from multi-state models, while making provision for data-dependent design modifications based on all involved time-to-event endpoints. We explicitly elaborate application of the methodology to one-sample tests for the joint distribution of (i) progression-free survival (PFS) and overall survival (OS) in the context of an illness-death model, and (ii) time to toxicity and time to progression while accounting for death as a competing event. Large sample distributions are derived using a counting process approach. Small sample properties are studied by simulation. An already established multi-state model for non-small cell lung cancer is used to illustrate the adaptive procedure.
更多
查看译文
关键词
martingale theory, multi-state models, sample size recalculation, survival analysis
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要