A Bayesian Exposure-Time Method for Clinical Trial Safety Monitoring With Blinded Data:

The FDA safety reporting Final Rule requires an expedited safety report whenever aggregate analysis indicates a clinically meaningful imbalance with an adverse event occurring more frequently in the drug treatment group than in a concurrent or historic control group. We introduce a safety monitoring procedure for two-arm blinded clinical trials that can be used to help address new requirements from the recent FDA safety reporting Final Rule. This procedure incorporates a Bayesian hierarchical exposure-time model for using prior information and blinded event data to make inferences on the rate of adverse events of special interest in the test treatment arm. We describe a collaborative process and provide free software for eliciting the required prior information and calibrating operating characteristics through simulation. We illustrate the use of our procedure with a case study composed of a combination of real and simulated data. Our procedure provides good operating characteristics for detecting higher ...