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.