has not been a value in the context of other large cardiovascular outcomes trials where
they have been prospectively evaluated for cardiovascular endpoints. If I can take a
moment to just clarify and answer to Dr. Flegal earlier, as to how the agency came up
with custom MACE and the broad SMQ MACE, part of it was as the applicant had
presented that when they, I believe it was in December, you provided to us your MACE
analysis, and the agency did ask both applicants to provide their MACE analysis and was
a recognition that these two applications had very different approaches to providing a
MACE analysis to us. Recognizing that if we are now holding this guidance, let's call
them the guideposts for ruling out a cardiovascular risk, it was important that we apply
some sort of uniform approach. That is why the custom MACE analysis the definition
was established and applied equally to both companies.
there are large databases of clinical outcome trials I am sure the FDA has, where there
has been CEC adjudicated not simply investigated reported events, has there been any
look at how predictive, what's the sensitivity and specificity of this custom MACE
definition in those types of databases to kind of get some comfort as to how reliable,
because it seems as though the primary MACE is done by the Sponsor and the custom
MACE is done by the FDA, are very similar, basically point estimate and upward
Scribes, LLC Toll Free 1-800-675-8846 www.scribesllc.com
DR. PARKS: To answer your specific question, no, the custom MACE
those events were albeit there weren't as many as for whatever reason, population,
length of duration of followup etcetera.
DR. BURMAN: Thank you for the explanation. Any other questions
from the Committee?
So, a custom MACE algorithm was developed and my question is since