Bayesian efficient safety monitoring: a simple and well-performing framework to continuous safety monitoring of adverse events in randomized clinical trials.

Abstract

During randomized controlled trials, it is critical to remain vigilant in safety monitoring. A common approach is to present information over time, such as frequency tables and graphs, when analyzing adverse events. Nevertheless, there is still a need for developing statistical methods for analyzing safety data of a dynamic nature. The process is typically challenging due to small sample sizes, a lack of observational data sources, difficulties in false-positive control, and the necessity for early detection of serious adverse events. In this article, we propose a simple and effective framework called Bayesian Efficient sAfety Monitoring (BEAM) to analyze evidence aggregation of potentially serious adverse events that may arise during the trial, as well as a timeline for when concrete evidence for safety concerns of unlikely outcomes becomes available. BEAM can be easily tabulated and visualized before the trial starts, making evaluations transparent and easy to use in practice, while maintaining flexibility when the underlying adverse event rate varies. Simulation studies have shown that BEAM supports continuous monitoring, can incorporate external information, and demonstrates good operating characteristics across various scenarios. In most practical situations, it has a reasonable likelihood of detecting elevated risks and identifying safety signals early on when safety concerns arise regarding the investigational drug.