RE:Ramblings on BETonMACEHi BearDownAZ and others.
I've been looking at the start of trial time series graph Don presented recently and last fall based on the combined ASSURE/SUSTAIN trials and there are a few things that struck me beyond just the end point RRR of 77% (p=.01) in the sub-group with diabetes mellitus and RRR=55% (p=.02) in the full sample.
What struck from the graph are the following:
- From almost day one, in both the DM(diabetes mellitus) cell and the total sample MACE was higher in the control group and there was not 1 point where the paths crossed. In fact the paths continued to diverge.
- At the 4.5 month period MACE began to accelerate in the control group(DM, low HDL, treated with just Crestor) at an exponential rate and this acceleration continued until day 210.
- In the test group (DM, low HDL, Crestor plus rvx-208) the MACE rate was much lower and grew at a much slower, somewhat linear rate, until about 3.5 months and then MACE rates were almost flat (barely increasing) up to until 6.5 months.
To me, it seems quite remarkable because it says something about Crestor's inability (or at least reduced ability) past 4.5 months to impact MACE. Of course my statement is not completely accurate because we are not able to have data on a population of DM, low HDL with no treatment. What we do know is that Crestor + Rex-208 makes a huge potential difference in reducing MACE events in DM low HDL populations.
Also, the
test group MACE curve has a diminishing returns pattern (used by economists) until the last data point AND what it means in this case is that as each 15 day measurement progressed the
rate of increase in MACE in the test group
diminished to the point where it was almost flat at just above 3% until the 210 day end point (vs control moving from 6.1% at day 60 to 21% at day 210) where there was a slight jump.
I'm sure everyone reading these posts understands that statistical extrapolation (as in forecasting) into the future usually is associated with
high statistical variation. For example, a regression curve could be fitted to the test and control groups for MACE and projected out to, for example, 1 year based on the 7 month trial data. I have not run any regressions (because I don't have the actual data points, nor time to do it) but it looks like that if projected out to one year the
test group MACE might be in the 8% range (just an eyeball guess) and we already know that MACE in the
control is 21% at 7 months. So even if control group MACE remained at 21% after a year (the probability of which would almost be zero based on the data we already have) then the RRR would be 62%.
So now imagine if the
control group MACE continued to
accelerate at even a modest exponential rate of increase for a year. Who knows where the 21% would go in the 5 months beyond the 7 months of data we have. I'm almost feeling that Don has been very cautious in not blowing these findings out to what they really imply (once bit and twice shy) but on the serious side, if these results hold up it is one hell of an important issue in health! Think about the strokes, heart attacks, heart failure, death levels, etc in the group only treated with Crestor. I think sometimes as I think about this as an investor I lose sight of how serious the health issues are. It is important to step back and put a human perspective on MACE and the patient and family impact.
Of course there could be many complications such as unknown interactions, statistical variations etc that would yield very different data but we've got to work with the data we have.
So here is my question to the scientific, research and medical posters and anyone who can provide insight. These reason I wrote this note is that it struck me while I was out jogging this morning that there must be a huge amount of scientific data available regarding MACE statistics on people with diabetes mellitus and CVD. AZ must have data for their Crestor patients but there must be published statistics.
- Do these stats exist and are they accessible?
- Do any posters have easy access to the data?
- Is 6 month, 1 year, 2 year data available?
- If so why hasn't RVX communications published it?
I'd like to know if there is any comparison in broad populations comparable to the SUSTAIN/ASSURE control groups for MACE. I've been reading a book that referred to high MACE in DM patients but with no specifics. Even mortality rate data would be of value.
If statistics beyond the SUSTAIN/ASSURE trial support the 21% MACE at 210 days as in the control group then at least that component of statistical variability is stabilized.
Anyway, at the end of the day it's all about the BETonMACE trial. Science must be replicated.
So of course...IMHO....DYOD.....GLTA
Happy Valentines Day to all.
Cheers
Toinv