Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint

Abstract

An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

Key Word:

• Decision-making
• Inverse normal test statistic
• Optimal design
• Predictive probability of success
• Time-to-event.