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Re: DewDiligence post# 970

Monday, 09/11/2006 8:00:11 PM

Monday, September 11, 2006 8:00:11 PM

Post# of 12660
Dew - You should reread my posts 460 and 464 on iVillage.
There was no assertion in these posts of some "FDA policy about “free” or implicit p-value for survival".

Those posts highlighted the Coreg's pivotal trial where the survival benefit was discovered unexpectedly and how the FDA treated that case. That trial missed everything including the primary surrogate endpoint (p = .27). However, its survival endpoint had p value .03. The FDA reviewers themselves discussed whether the implicit p value for survival should have been .05. So, the eventual approval of the drug did give the appearance that the FDA had reset the p-value during their evaluation. That might or might not be true as we don't know if they had other data on hand in their consideration. But that was a good counter-example to the usual bear assertion that missing the primary endpoint was fatal even with an achievement in survival.

The discussion of surrogate endpoints in the 03/2005 ODAC mentioned in my previous post shows that, at least, among the FDA advisors, there is openness in not being strictly orthodox about dividing the p-value among such endpoints. Whether or not this will apply to D9901 is yet unclear. But a change in attitude among these statisticians can only be positive for the case of Provenge.

For someone not subscribing to your naugahide theory, these events can be seen as evidence against your perma-pessimism.

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