I wrote a pretty thorough reply to G1945V on Stockhouse, and thought readers here might enjoy as well. Bolding additions below are edits from the original post that appeared on Stockhouse.

G1945V,

It helps to think about BETonMACE not only in terms of when first dosing took place, but how many patients have been enrolled at certain timepoints/updates. In this simple way, one can look at groups/waves of patients and approximate how long they have been dosed. You can't just look at the current ~1750 enrollment number and assume that all have been dosed for almost 22 months.

Here are my notes from news releases/presentations on the BETonMACE enrollment:

11/11/15: 0 patients, start of first patient dosing

9/12/16: 600 patients (this was the first official update)

12/15/16: 800 patients (200 added since last update)

3/17/17: 1200 patients (400 added since last update)

6/28/17: 1600 patients (400 added since last update)

8/29/17: 1750 patients (150 added since last update)

If one looks at the EXAMINE trial graph (see Figure 2A from this article), one can approximate the 3-point MACE event rates. Now, we don't know how much apabetalone is going to lower the apabetalone arm, and we don't know how much the additional low-HDL requirement is going to increase the event rates. But for approximations, it is easy to assume that the average event rates for all patients in BETonMACE will be similar to EXAMINE. These are my eye-balling approximates from the published EXAMINE trial:

3 months: 2.5%

6 months: 5%

9 months: 8%

12 months: 9%

15 months: 10%

18 months: 11%

21 months: 12%

24 months: 13%

So if you match up the "waves" of patients with the appropriate event rate from above, one can arrive at the anticipated # of MACE events that each group has experienced. This is a somewhat subjective process, since not all patients in each individual "wave" started on the same day or even month. But it works for approximation purposes. For example, let's assume that the first 600 patients to enter the trial have been dosed an average of 15 months. At 15 months in EXAMINE, about 10% of patients had experienced a 3-point MACE event. So this first wave of 600 patients would have contributed 60 3-point MACE events by this approximation method. One also has to get a little creative and project future enrollment numbers.

As you can also appreciate from the above EXAMINE event rates, the risk of experience a 3-point MACE event is highest during the first several months of follow up. In other words, if a patient is going to have a 3-point MACE event during their time being dosed in BETonMACE, it is more likely to occur during the first 9 months of follow up and less likely to occur in the follow up period beyond 9 months. Therefore, those patients that started dosing in 2017, and especially those enrolled in the past few months, will likley contribute the most number of new 3-point MACE events. Those patients that were enrolled and started dosing prior to 2017 will still contribute some new 3-point MACE events, but will experience this at lower rates than patients in the first 9 months of follow up.

Another way to do this is to calculate patient years, which is a product of the number of patients X length of time in the study. Patients are dosed for up to 24 months, and last patients enrolled are planned to be dosed for 12 months. Average dosing period is projected to be 18 months. So 2400 patients, with an average dosing period of 18 months, using the EXAMINE 18 month event rate of 11%, gives 264 MACE events. 2400 patients X 18 months = 3600 patient years. So one can also look at the "waves" of patients and use the # patients in each wave multiplied by the approximate length of time in study for each wave. Then add these up and see where we are. 1800 patient years would be the halfway point. 

Using either method, I project that we are very close to 125 and I still stand by my September (maybe October) 2017 timeline for hitting 125 MACE events. Assuming enrollment of the 2400 patients is completed by December 2017 and assuming that the 125 MACE event futility analysis is announced between now and the fall, then I still see us on track to hit the 250 MACE events by H2 2017. Of course, keep in mind that the goal posts (# patients, # target MACE events) might change. The news release regarding USA patients suggested that the BETonMACE protocol would be amended but didn't go into changes. And there is supposed to be a 175 event sample size estimate analysis. So the 2400 patient, 250 MACE event target for trial completion may still be subject to change.

I hope this helps!!!! 

BearDownAZ