"That's really interesting. So even though several of the sub-group analyses (pre-specified I think) showed positive results in plaque reduction, the ASSURE trial was still deemed a failure."

I looked further at the ASSURE study document and realize that there were 3 patient populations used for endpoint analysis: Modified Intent-to-Treat (mITT), Full Analysis Set (FAS) and Per Protocol (PP) Population, as well as the safety population. Importantly, the primary efficacy analysis was performed for the mITT Population and the subgroup analyses were done for the FAS and PP Populations. So not exactly an apples to apples comparison. I wonder if a similar population distinction will be done for BETonMACE subgroup analyses?

"This study used three analysis sets, referred to as populations, to carry out the planned analyses: Modified Intent-to-Treat (mITT), Full Analysis Set (FAS) and Per Protocol (PP) Population. The Safety Population was used for all safety analyses; mITT, FAS, and PP Populations were used for the efficacy analyses.

Modified Intent-to-Treat: A mITT population was used for both primary and secondary endpoint analyses. This consisted of all randomized patients who had received at least 1 dose of study drug. A patient was considered randomized as soon as a treatment number was assigned by the interactive voice response system. Patients were analyzed according to the treatment to which they were randomized regardless of whether or not the study drug was prematurely discontinued or dose lowered due to an adverse event (AE). The mITT Population was the primary efficacy analysis population.

Full Analysis Set: The FAS population was used for the primary and secondary endpoint analyses. The FAS consisted of all randomized patients who have received at least 1 dose of study drug and completed both the baseline (Visit 1) and Week 26 (Visit 12) intravascular ultrasound (IVUS).

Per Protocol Population: All patients who completed all protocol-specified dosing days (active or control), and who had completed both a baseline and follow-up IVUS procedure between Week 17 and Week 30, had a study drug compliance rate of 80%, and had no major protocol violations were included in the PP Population. The PP Population was defined after a review of the blinded data and protocol deviations prior to unblinding the data. The PP Population was used to assess the effect of treatment in completers who had no substantial protocol deviations.

Safety Population: All patients who received at least 1 dose of study drug (active or control) were included in the Safety Population and were analyzed based on the actual treatment received. The Safety Population was used for all safety summaries."