TL20: Safety Monitoring of Events of Interest in Placebo-Controlled Clinical Trials
*Bradley McEvoy, CDER, FDA  *Elena Polverejan, Johnson & Johnson 

Keywords: safety monitoring, stopping rules

Unblinded safety monitoring of events of interest could be performed by a Data Monitoring Committee (DMC), as well as a regulatory agency. Stopping rules based on events of interest are sometimes pre-specified in trial protocols. In placebo-controlled clinical trials, the comparison of the occurrence of events of interest in the active arms versus placebo is of particular interest. The applied statistical methods include odds ratio, methods taking into account differences in treatment duration between arms (hazard ratio, incidence rate ratio) or various Bayesian methods. If the pre-specified stopping rules are met or some concern threshold is met then the DMC, the sponsor or a regulatory agency could decide at some time point during the study to stop an active arm, a study or all the studies within a project. The participants will share their views and experience on this topic. Key Discussion Questions: 1. What statistical methods could be applied for comparisons versus placebo, stopping rules, identification of a vulnerable patient subgroup? Any preference? 2. What stopping rules don’t involve statistical methods? 3. When is safety monitoring of events of interest not a statistical issue?