The data and safety monitoring board in sponsored pediatric clinical trials: practical applications

The Data and Safety Monitoring Board (DSMB) monitors the progress of clinical trials for safety and implements stopping rules as needed. Although NIH and FDA guidelines recommend the use of a DSMB for phase I, II, and III pediatric clinical trials, the manner in which the DSMB is constituted has received little attention. In this study we reviewed the Institutional Review Board (IRB) applications submitted between 2008 and 2012 at our institution (Children’s Hospital Los Angeles) for phase I, II and III studies which were multi-site, sponsored and performed under a sponsor’s Investigation New Drug Application (IND) for the type of data and safety monitoring that was being used. Our results indicate that approximately two-third of the studies used an independent DSMB, 10% utilized a sponsor’s DSMB and the remaining studies (25%) did not utilize a DSMB and relied instead on safety monitoring by the Principal Investigator (PI) and the medical monitor/director. This pattern was observed across all study phases and for blinded as well as unblinded studies. Our result suggests that a Data and Safety Monitoring Plan (DSMP), although required by the IRB, is rarely submitted by the sponsor at the time of application. Instead the DSMP is submitted to the IRB by the PI on IRB supplied templates. IRB review of these completed templates were critical to ensuring DSMB related compliance. Additionally, a significant percent of sponsored clinical trials used the PI or an individual designated as medical director/monitor, rather than constituting a DSMB.