considered: the endpoints, the treatment periods, and the methods. You have already
heard a lot of information about these issues. I am going to mention a few statistical
aspects. You have heard from several speakers detailing about the two endpoints defined
by FDA. Because these endpoints were not adjudicated, and were defined post talk, there
was an effort to capture any cardiovascular signal by including a broad endpoint. With
the SMQ endpoint, we are aiming to show consistency of a fact with the custom
endpoint. Adjusting from multiple endpoints though is not an issue because it is the
“Custom MACE” endpoint, which is of primary concern.
you some of the issues we considered when planning the MACE analyses, including
the choice of statistical methods. Then I will present the results starting with an overview
followed by some specifics about the SMQ in “Custom MACE” results. At the end of
my talk I will show some sub group results.
impact of the use of open label rescue medication. About one-third of the patients in
these trials entered the long-term period on rescue medication and rescue was generally
higher in the placebo groups. So, we wondered about the influence of rescue on
followup. The addition of low dose rescue medication in the long-term period may or
may not bias towards the alternative hypothesis that of showing non inferiority when
looking at these cardiovascular endpoints. So, we decided we should look at both the
short-term period where no events on rescue medication are captured and also look at the
short-term plus long-term period.
When planning the MACE analyses, there were three issues we
With regard to the time period to use in our analyses, we considered the
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About 85% of the patients continue to be followed on double-blind
treatment into the long-term period and so the randomized groups were largely preserved.