RE:Q: Still dosing?"question tho... are we still dosing? Last visit or treatment visit? So we are still accumulating patient years and events? I don’t see any statements saying dosing stops. Is that how we get the additional events?"
I was wondering the same thing. The news release didn't explicitly say that dosing had ended. However, the news release did indicate that "Those sites with the most patients enrolled will commence [Last Study Visits] first, followed by the others. This will allow additional time to build the overall MACE events to about 260 or greater while not slowing down the trial’s move towards final database lock." There was always a safety follow up period built into BETonMACE. Every single BETonMACE design slide has shown a 4-16 week safety follow up period. Definitely some ambiguity in the news release today though about dosing. One possibility is that dosing will stop in all patients immediately, but the actual LSV date will vary over a 4-16 week period. Alternatively, patients may stay on drug until they schedule and/or complete their LSV over the 4-16 week period......kind of a rolling/progressive end of dosing. Great question to follow up with IR.
"one thing I never fully grasped. Wasnt the trial designed for 250 events, then modified to 250+, so say 260. That’s 10 more events than designed, which is 10/250 = 4%, so if all those events fit in say one side, the good side, we have the ability to sway rrr by up to 4% in either direction?
if so, is that good trial design/standard clinical practice or an act of desperation?"
250 events was always the target number of events. However, as in most, if not all, cardiovascular outcomes trials, the target number of events isn't necessarily the final number of events. Sometimes higher, sometimes lower. BETonMACE is a relatively small CVOT trial from the perspective of number of patients and number of target events. Resverlogix had options as to how to wind down the trial, since it is an adaptive trial. They had to reach 250 events, but they had some flexibility as to how they arrived at 250. Recall at the Sept 2018 AGM, Resverlogix stated that they could end dosing before 250 events and then during the final adjudication of the previously unconfirmed/unudjudicated events reach an eventual ~250 events. Or they could dose until 250 events had been reached, and then during the final adjudication of the previously unconfirmed/unudjudicated events reach an eventual number of events "250+", which may end up being more or less than 260. They chose the latter option as Resverlogix stated at and since the AGM. No reason to suspect poor design or desperation. It's actually a good thing from a safety, efficacy and statistical viewpoint to choose the adaptive path they chose.
BearDownAZ