A lesson on futility analyses from the CETP inhibitors
posted on
May 10, 2017 02:47PM
As we wait for the apabetalone futility analysis, here are some sobering stories from the CETP inhibitor family. Here's a nice summary presentation too. Long story short, passing the first futility analysis in a Phase 3 cardiovascular outcomes trial is no guarantee that the trial will succeed.
Torcetrapib: Never made it to the DSMB futility analysis at 50% of anticipated MACE events. Stopped prematurely due to safety.
Dalcetrapib: Made it past the first futility analysis at 50% of anticipated MACE events but terminated at second futility analysis (after 70% of anticipated events) due to futility. From the NEJM article: "At the second prespecified interim analysis, which included 1135 primary end-point events (71% of those projected), the independent data and safety monitoring board recommended termination of the trial for futility, in accordance with prespecified criteria (see the Supplementary Appendix)"
Evacetrapib: Made it past futility analysis on July 27, 2015 but then trial terminated for inusfficient efficacy 2 1/2 months later on October 12, 2015.
Anacetrapib: Passed futility analysis in November 2015. Follow up ongoing. No additional interim efficacy analyses are planned. The main study results are anticipated later in 2017. "In November 2015, the DMC considered the guidelines for premature stopping (see Supplementary Material) and recommended that the study continue as planned."