TL14: Incorporating Futility into a Phase 3 Outcomes Trial Governed by a Data Monitoring Committee
*Richard Davies, GlaxoSmithKline 

Keywords: Futility, Data Monitoring Committee

Developing futility strategies for a phase 3 trial involves the balancing of many factors, most notably the risk of making an incorrect decision such as stopping a trial that would ultimately have been successful. However, it is important that the definition of success be clearly described and agreed by both the sponsor and the Data Monitoring Committee (DMC) at the time of DMC charter finalization. While it is often the case that success is defined by the sponsor (and most DMC charters) as a statistically significant primary endpoint in the final analysis, the DMC needs to balance many more factors when making futility recommendations to the sponsor such as protecting the safety of the patients in the trial, and determining whether continuing the trial will advance important scientific understanding. In addition to ethical concerns related to continuing treatment of an apparently ineffective investigational medication, there are significant cost implications which are often not well understood by the DMC. This can result in DMC recommendations regarding futility which are consistent with charter language but not in line with sponsor expectations. It is for this reason that sponsors often propose proscriptive futility rules while the DMC may support looser language that relies in large part on DMC judgment. Specific challenges related to the monitoring of multiple trials by the same DMC will also be discussed. Real-world challenges associated with the recently published darapladib phase 3 outcome trials STABILITY and SOLID-TIMI 52 will be shared.