Abstract
Effective monitoring of event rates is essential for maintaining statistical power and study integrity in clinical trials, particularly when the primary endpoint involves time-to-event outcomes. We propose Sequential Event Rate Monitoring (SERM), a new and innovative approach for continuous monitoring of event rates. SERM leverages the Sequential Probability Ratio Test (SPRT) with improved boundaries derived from the nonlinear renewal theorem by Kim and Woodroofe (2003). This method represents the first practical implementation of their theoretical work in this area. SERM offers several tangible benefits, including ease of implementation, efficient use of data, and broad applicability to trials. Decision boundaries can be directly obtained from simple formula. A detailed illustration of the method using real-world data from a large Phase III clinical trial demonstrates its potential for rapid assessment. SERM operates on blinded data so it can be used in tandem with a broad range of study designs while preserving study integrity. Although slow patient accrual lengthens the time needed to reach a conclusion, it does not significantly affect type I or type II errors associated with the decision. This new method provides a robust tool for enhancing trial monitoring, enabling timely and informed decision-making in diverse clinical settings.