Replies to post #5535 on Dendreon Corp fka DNDNQ

[iwfal]

Some 200 events were required for the Vital 1 interim; more than the total number of events in the combined 9901 and 9902a Ph3 trials.

Tax327 had a p value of 0.009 for 367 events. At only 200 events it would have had a p value nearer to 0.10 (above p=0.05). DSMB's typically stop for safety (i.e. not something the company gets to weigh in on) only when p value is a lot lower than that.

My limited understanding of the O'Brien Fleming method of allocating alphas lead me to believe that it also provides some sort of horizontal funnel plot that can be used to set some outer limits for futility and any stopping test for unexpected overwhelmingly positive results.

OF does not require futility testing per se. And many companies choose not to use futility testing - to be Dew-class cynical I would suggest a reason is that the companies need the trial as much as they need success. (and to be less cynical, many trials are done enrolling by the time the interim is performed so it doesn't cost too much to keep the trial going even if it is long odds.)


BTW - I believe a common futility test is if given the results actually seen plus assuming that the remainder of the trial goes the way you expected initially (i.e. using what HR you assumed before the first patient enrolled) then if you have less than 20% chance of stat sig the trial is halted for futility. I suspect that is a fairly high alpha for futility but I haven't done the math.

[ocyanblue]

The below paragraph from the CEGE 07/10/2007 PR gave a hint of why Vital-1 might be turning out not as CEGE expected. The phase 2 data were based on rather healthy patients as predicted by nomograms. Vital-1 patients might track the normal HRPC population with nomogram-predicted survival time below 20 months. Who knows whether or not the high medians would hold up in that case.

Cell Genesys' ongoing Phase 3 GVAX immunotherapy for prostate cancer program is supported by the median survival results from two, independent, multi-center Phase 2 clinical trials in approximately 115 patients. The subset of patients in these two trials who received the doses comparable to the Phase 3 dose showed median survival of 34.9 months and 35.0 months, respectively. These results also exceeded the predicted survival of 22.5 months and 22.0 months, respectively, as determined by a seven point patient disease characteristic nomogram. The results of the first trial were published in the July 1 issue of Clinical Cancer Research. Results from both studies compare favorably to the previously published median survival of 18.9 months for metastatic HRPC patients treated with Taxotere chemotherapy plus prednisone, the current standard of care.

Also note the bogus comparison of the benefit of GVAX shown in the phase-2 data vs. that of Taxotere shown in a much sicker population. The predicted survival time of patients before GVAX treatment was already better than the actual survival time of patients treated with Taxotere. Should that not tell them that the comparison was invalid due to wildly different patient populations? If this sort of sloppy thinking was a part of the trial design process...

[p3analyze]

>>BTW, does anyone know if 9902b uses the same Haybittle Peto method of allocating an interim alpha as was used in 9901 and 9902a<<
We could probably ask Dew to set up a poll:
<0.005
0.005 to 0.01
0.01 to 0.015
0.015 to 0.025
>0.025

[eagle-eye]

9902B used the O'Brien-Fleming method.