"I was wondering if you factored in the fact that only one of the four arms, the Reo + Crestor, would actually demonstrate what we would expect as an outcome and could have a significant statistical say 50% cylincal improvement.  Or for 25% of the patients, 50% of them would not become statistics as soon as predicted.  Is this not what we are all hoping for (a new an improved Crestor 2).  Seems this would add another 12.5% to your projections.  My point, did I get this right?"

First of all, there is no fact in what you stated. I believe you are extrapolating from plaque data from the ASSURE trial showing that rosuvastatin + apabetalone was superior to atorvastatin + apabetalone. While that is a fact, it is unproven and therefore just speculation that one statin will prove superior to the other in combination with apabetalone for the BETonMACE MACE data (CVD death, myocardial infarction, stroke). 

Second, my point of making this 3600 patient year post was to focus on the predicted patient years and get away from event rates. Yes, the two are related in the sense that a lower overall event rate will require a larger number of total patient years to achieve a given number of MACE events. Conversely, a higher overall event rate will require less patient years to achieve the same number of MACE events. There are still a lot of unknows with the event rates. However, the tracking of patient years over time will help give us a sense of where we stand relative to the original goal by using the number of patients enrolled and how long each wave of patients has been enrolled.

"Given all this, I do not see the point of this statistical 188 milestone.  If the 2400 patients is enough statistally, then we just have to wait until the trial ends.  If not, then we have to wait another 6 months for more Americans and others to be enrolled."

I don't claim to be an expert, but in my opinion the point of sample size re-estimation analysis at 188 events is to determine if the 2400 patients is enough to provide a statistically sound conclusion. If the results look statistically sound with projections for 2400 patients, then maybe no changes. But if the sample size re-estimation analysis shows that data with 2400 patients is insufficient to make a sound statistical conclusion, then this affords an opportunity to adapt the trial at this point to add more patients to improve the confidence in the final conclusion, whatever it may be. 

"The stock price would drop.  I think this is all a slight of the hand by DM  and the US FDA to not do the FA until all of the American patients have been enrolled for at least 6 months.  Does anyone recall Don actually saying they would do the FA or just replace it with the statistical analysis?  Only hope is that if the 188 milestone is OK, that the Europe, China, and Isreal proceed with sales.  We could use some good news.  So, do they slip in new financing before or after good news.  I think they are walking it down for new financing first."

A lot of conjecture there Absolutely. Many of us, including myself are somewhat skeptical of the logic behind only having one or two hundred US patients in the trial for less than a year (assuming trial ends Q4 2018) while there are over 2000 patients from non-US sites in the trial for up to 2 years. I don't recall Don ever explicitly describing what will and will not happen at the sample size re-estimation analysis. My opinion is that this analysis will serve the dual purpose of providing a futility check and allowing for sample size re-estimation, if necessary. It won't be long now until this 188 event trigger occurs, so we'll find out soon for better or for worse.

One last side note.....slide 15 of the latest slide deck entitled "BETonMACE Current Highlights" made that statement "Projected primary MACE rate still 8.0 per 100 patient years on top of aggressive standard of care = strong unmet need." I'm not sure if that is projecting based on original trial design or making a statement from observed BETonMACE event rates. If the latter, it is not clear if this is ALL patients (placebo and apabetalone treated) or just the placebo group. I sent an inquiry to the company this morning so hopefully they will clarify this.

Have a good weekend,

BearDownAZ