io_io:
1.p3analyze responded to my intial question in Ivillage about a Cox regression analysis being the primary statistical anaysis method in 9902b rather than Kaplan Meier, and the impact on his projection regarding the number of events required to reach a p value on the basis of Cox regression analysis results equivalent to that of the combined 9901/9902a integrated as follows:
Re: 9902b event target and timing
Thank Rancherho - yes - the Cox regression adjusted hazard ratio is 1.8, ie 80% prolongation of median OS, or close to 50% reduction in risk of death, powering the study at 90% would only require 1definitely will require only 122 events (scary thought - I have to go back to my event curve to find where they are at - I wouldn't be surprised that can be reached at in early 2007).
But for practical consideration, the more events, the higher the likelihood of success. If I were designing the trial, I would probably stick with 1.5 to be conservative. But one efficacy interim anlaysis at the end of accrual should have a good chance of success, if one could assume a hazard ratio of 1.8. Prod me more, so I could think more. Thanks.
His comment signing off on IHub today that DNDN seems to have positioned itself well with 9902b seems right on. The Provenge BLA skeptics including UBS's Maged Shenouda and a couple of notable IHub posters believe that statistically significant efficacy results of 9902b will be required for FDA Regular approval of Provenge and that the FDA will only issue an approvable letter on the the present BLA. UBS's further assumption was that 9902b results would not be mature until 2009 justifying its $3 target. Earlier this year, Gold projected that 9902b enrollment would be completed by the projected FDA approval in 1H07, and that based on unblinding upon reaching its projected number of events, it would be unblinded in 1H08. It would seem that if statistical significance using the Cox regression analysis is likely to be achieved in 9902b in 1H07, and the FDA was actually considering only issuing an approvable letter, they would allow DNDN to unblind 9902b upon full enrollment, and if it achieved statistical significance, grant immediate Regular approval. Therefore, the implicit assumption for those believing that only an approvable letter will be issued in response to the submission of the BLA, would seem to be that the Cox regression results of the integrated 225 patient 9901/9902a database are bogus since the smaller 127 patient size of the 9901 trial alone or concerns about TTP being the initial 9901 trial primary endpoint would be irrelevant.JMHO.
Good luck to all DNDN longs.
