Interim Monitoring for Futility in Clinical Trials With Two Co-Primary Endpoints Using Prediction

We discuss using prediction as a flexible and practical approach for monitoring futility in clinical trials with two co-primary endpoints (CPE). This approach is appealing in that it provides quantitative evaluation of potential effect sizes and associated precision, and can be combined with flexible error-spending strategies. We extend prediction of effect size estimates and the construction of predicted intervals to the two CPE case, and illustrate interim futility monitoring of treatment effects using prediction with an example. We also discuss alternative approaches based on the conditional and predictive powers, compare these methods and provide some guidance on the use of prediction for better decision in clinical trials with CPE.我们探讨了将预测作为一种灵活实用的方法，用于存在双共同主要终点（Co-Primary Endpoints, CPE）的临床试验的无效性监测。该方法的优势在于可对潜在效应量及其关联精度开展定量评估，且可与灵活的误差消耗策略相结合。我们将效应量估计的预测方法与预测区间构建方法拓展至双共同主要终点场景，并通过实例演示了基于预测的治疗效果中期无效性监测流程。此外，我们还探讨了基于条件检验效能（Conditional Power）与预测检验效能（Predictive Power）的替代分析方法，对上述方法进行了对比，并为在双共同主要终点临床试验中应用预测方法以做出更优决策提供了指导建议。