Replies to post #3851 on Dendreon Corp fka DNDNQ

[DewDiligence]

>I am actually thinking that it may be better for DNDN to allocate a very LOW alpha for this look, for example, a threashold of p=0.0001, thus keeping the entire 0.05 alpha for the final look. Obviously, in this case, the interim look will NOT be stat-sig, but the major merit here is that we minimize the risk that Provenge will not be stat-sig at the final look (2010) while we obtain an "official observation" at the data.<

Ordinarily, a trial protocol does not allow the DSMB to reveal the statistics of an interim analysis to the sponsor other than to say whether the analysis met the threshold for halting the study. However, if the interim look occurs after all patients have been treated and are merely being followed to measure survival, it’s more likely that the SPA would allow for the statistics to be disclosed.

[mouton29]

Isn't the question whether the FDA would be willing to aprove a "free" look to allow the company to raise funds? Presumably, the FDA is not clueless and they understand that if permit an alpha allocation that is highly unlikely to be acheived -- presumably lower than the current "very highly powered" allocation -- they will be under pressure to approve. Why not face the issue now and allow a free look, with the idea being that if it meets some reasonble threshhold, say, .03, the FDA approves conditonally with the explicit understanding the drug is pulled if the final p-value is less than .05? Since, at the time of the interim look, the trial would not only be fully enrolled, but presumably all placebo patients would have progressed and crossed over or not, I don't see that the look or conditional approval would affect the remainder of the trial and its statistical validity.

[Notabaer]

Re: Interim Look Strategy

I like this. There is a real chance that whatever alpha is allocated to the interim will be wasted, reducing the value of the final reading.

The real benefit of the interim may be its effect on negotiations. If it's supportive (let's hope strongly supportive) the FDA has to fear that a further wait of two years could finally produce some hostile scrutiny. And as you say it will send a signal to the various players who are able to provide financing, via partnership, acquisition, or lending. So it makes sense to play it your way, saving the alpha for the final look, while using the interim to affect the psychological game.