" why would the FDA have any problem allowing earlier termination and the filing of a BLA /NDA due to an unexpectedly efficacious treatment effect?"
If I understand correctly, FDA agreed with the pixantrone EXTEND adaptive trial design which allows the sponsor the potential to not only terminate early due to exceptional efficacy (should any of the 2 interim analyses have been wildly significant), but also the added flexibility of adjusting sample size (or size of the primary analysis set) for the final analysis. Today's release indicate that CTIC had good interim efficacy data, while not sufficient for declaration of statistical significance, likely due to low power (because only 100 subjects were analyzed?), but did allow them to reduce the final analysis set from 320 to a smaller number, so they can get the final result slightly earlier than if all 320 subjects had to be followed to become eligible for analysis of the primary endpoint - response rate.
Regarding the second question:
" how would a statistician decide whether the standalone use of Provenge in asymptomatic AIPC/HRPC would be approved by the FDA vs. the combination therapy of Provenge plus Taxotere, or both or neither? Could this have been one of the reasons for the FDA approvable letter".
FDA seems to be perfectly happy with the fact that secondary treatment with docetaxel was relatively balanced between the two treatment arms from 9901. So no, this did not contribute to the approvable letter.
If 9902b is successful and provenge is approved as monotherapy, then a possible design would be to compare provenge vs provenge+taxotere vs taxotere would answer the above question. If 9902b fails, then further provenge prostate trial almost has no choice but to do either a head to head provenge vs docetaxel (like vital-1), or a combo study provenge+docetaxel vs docetaxel alone (like vital-2).
AI
