Adam, the DMC have the power and authority to recommend to the sponsor that the trial be altered or enlarged, even while the sponsor is blinded. Remember, the sponsor is blinded to ALL PATIENT EFFICACY DATA during the trial.
Now note, a sample size re-evaluation was designed into the trial… once the trial hit 80% enrollment *** that means those patients were through the pipeline and randomized INTO the trial *** and note, the previous main arm enrollment number was 240. What do you bet they hit that 80% main trial enrollment number in the time frame, and that’s when the DMC recommended enlarging the trial.
So that means that by around the time the DMC (not the sponsor) were reviewing the data on the 66 patients (December 2013 through February 2014), the trial reached 192 patients. (240 x 80% = 192). And as we know, around that same time, they had reached 66 events. Now, they went quiet in June 2015, and no first interim analysis for efficacy had occurred prior to that because Linda was still telling us it was still coming in the May presentation. So perhaps by June 2015, they reached the NEW 1st IA number of 149 events. And I say perhaps. We really don’t know. Maybe they didn’t, and that would even be more remarkable.
But say they did… and let’s pretend for a moment that they never enrolled another patient after February 2014 and thus, had only had 192 patients enrolled. So by a full 12 months later, we still haven’t reached 149 PFS events. Huh.
And we still have to go another 4 months, or 16 total months, to reach 149 PFS events. So that means that if the trial never increased past 192 from Feb 2014, it took a full 16 months for 83 more patients from 192 “pretend enrollment” to reach the required 149 events.
Gosh, and there were even 64 of them that were placebo patients. 16 months is an awfully long time for 83 more (from 192) newly diagnosed GBM patients to just event. Maybe they actually had to add more patients just to get some more placebo patients into the mix.
Yet you think the DMC recommended Linda halt the trial for futility, and she said no way, let’s not only move forward, let’s increase the size! Well, it seems a good thing she did because it took a long time for this trial to reach just 149 events.