was for developing the custom MACE. It wasn't clear to me whether this was done
before looking at the data or whether there was some feature of the data that led to the
development of the custom MACE, and a sort of related question maybe, is this idea of a
reassuring point estimate, I wasn’t sure what was actually meant by that?
CLARIFYING QUESTIONS FROM THE
COMMITTEE TO FDA
custom MACE endpoint and the broad SMQ MACE endpoint were both defined before
looking at any of the data. The broad SMQ endpoint used standard SMQs for myocardial
infarction, the central nervous system hemorrhages and infarctions and cardiovascular
death, but there was concern when looking just at the broad SMQ MACE that some of
the events that are included in that standard endpoint, although they could be consistent
with an acute important cardiovascular event, they may not necessarily represent such an
event in some patients. So to try and pair that down, three clinical reviewers came up
with, they looked through all those preferred terms and picked out the ones that they
DR. JOFFE: Let me speak first to those custom MACE endpoint. The
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Finally, analyses of all endpoints yielded estimates of common odds ratio less than one,
and upper bounds for the 95% confidence interval of less than 1.8. Thank you.
floor up now for discussion by the committee and specifically questions to any of the
members of the FDA who presented this morning, including Dr. Joffe.
DR. BURMAN: Thank you both very much. We would like to open the
DR. FLEGAL: I would like to understand a little better what the reason
increased CPK. Short-term and long-term results including the followup of rescued
subjects were consistent with the short-term results.
The MACE results were not dependent on the statistical method used.