论文标题
将纵向和事件时间数据应用于组顺序临床试验的联合建模
Joint modelling of longitudinal and time-to-event data applied to group sequential clinical trials
论文作者
论文摘要
通常在第3阶段临床试验中测量长期事件终点（例如总生存期或无进展生存）的长期临床试验，研究人员还收集了有关生物标志物的重复测量，这些措施可能可以预测主要终点。尽管这些数据可能无法直接利用来支持早期停止决策，但我们可以更多地利用这些数据来提高效率并改善临时决策？我们提出了一个用于纵向和事件时间数据的联合模型，并提出了一种在跨临时分析中建立关节模型中参数连续估计的方法。有了这一点，我们可以使用估算来定义疗效和徒劳的停止规则。使用仿真，我们评估合并生物标志物信息的好处以及对临时决策的影响。
Often in Phase 3 clinical trials measuring a long-term time-to-event endpoint, such as overall survival or progression-free survival, investigators also collect repeated measures on biomarkers which may be predictive of the primary endpoint. Although these data may not be leveraged directly to support early stopping decisions, can we make greater use of these data to increase efficiency and improve interim decision making? We present a joint model for longitudinal and time-to-event data and a method which establishes the distribution of successive estimates of parameters in the joint model across interim analyses. With this in place, we can use the estimates to define both efficacy and futility stopping rules. Using simulation, we evaluate the benefits of incorporating biomarker information and the affects on interim decision making.
