DMCs and the New Final Rule: How Will We (Should We) Respond?

• Activity Number: 235
• Type: Topic Contributed
• Date/Time: Monday, August 5, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Janet Wittes*+
• Companies: Statistics-Collaborative
• Keywords: drug safety ; FDA Final Rule ; Data Monitoring Committees ; clinical trials

Abstract

The FDA's Final Rule (FR)on safety reporting has potential major impact on how Data Monitoring Committees (DMCs) behave. The FR states that during the a clinical trial sponsors should report an unanticipated serious adverse event (SAE) promptly to the FDA if the event is reasonably likely to have been caused by the experimental therapy. To comply with the FR during masked randomized trials, Sponsors must know whether the event occurred in the treated arm; that is, an unanticipated SAE must be unmasked. DMCs traditionally report to the Sponsor only when they are almost certain that the experimental therapy caused the unanticipated SAEs. Many DMCs report such events only when the level of concern becomes high enough to warrant a change in the informed consent document. For Sponsors to comply with the FR, DMCs must define a threshold that determines its need to report. Defining such thresholds will be especially difficult when the event is noticed not because it is a single occurrence nearly unequivocally associated with the experimental therapy but because it is an increase relative to control in the rate of event. This talk proposes some approaches to setting such thresholds.