look at this, that, you know, you have a point estimate that happens to look really good in
one direction, you have certain confidence around that. You really need to widen what
you think the real confidence intervals are around that because you haven’t really done it
the way you like to do it. You don’t have adjudication, you don’t have pre-specification.
Now that doesn’t make it no data; these are real events that were really reported, that
were of concern to the investigators, that were adjudicated as best we could post-hoc. It
just makes the estimate of it much more difficult.
that the absence of adjudication and pre-specification are substantial limitations. There is
no doubt about it, which is why I think the guidance document was written as it was. I
guess the way I look at this is as a clinician that sometimes practices statistics at risk.
You know, I guess the issue really is for us, what is the true confidence around the
estimate? I guess in some way that we have no way to quantify. You know, when you
don’t have adjudication and you don’t have pre-specification, these are things that make
the confidence around a statistical test questionable, and make you need to widen the
confidence around whatever, something that I’ll call ‘the true estimate’ in some
immeasurable way is.
like to re-emphasize the last part of this Question 2, which is, this isn’t, I suspect, the
only time we will be discussing this, or the FDA will be discussing this. What other
suggestions do we have for improvements to present and future endpoints and analysis
that may be applied to other diabetic programs that have already been completed or have
ongoing phase 3 programs at the time the final guidance was issued. A difficult question,
What is reality? I guess sort of that, for what it’s worth, that’s the way I
DR. BURMAN: Other comments on those issues? Because I would also
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DR. KONSTAM: Yeah, you know, I think you’re very right. I think