|I was wondering if "active, not recruiting" simply means they're temporarily halting the trial as they work the numbers in the first stage of the analysis and plot out the next stage. That wouldn't be inconsistent with how they handled TNBC. In fact, I recall that Chau believed that after the pause in TNBC accrual, and then subsequent resuming of the trial with the recommended additional patients for the second stage, that resumption (and the inferred FDA nod) would be a positive share price event. It turned out not to be but I cannot recall if that was due to a market yawn, a terrible financing, and/or the FIASCO happening concurrent with said resumption.|
In retrospect, I get the basket approach and why moving forward with the second stage of the 2-stage analysis for TNBC should have been a stock moving event. I'd be surprised to learn that IMMU didn't frame out the resumption of stage 2 for urothelial, for instance, in that context. I'm thinking it may be worthy of a press release if and when that trial resumes, signifying that stage 2 is moving forward.
Two stage approaches are common in phase II studies. You can look at a minimal patient population so as not to potentially subject a larger group to ineffective treatments, assuming the null hypothesis (drug ineffective) to be true. After all, in most cases a drug does fail in phase II. It also is a way to mitigate the financial strain of funding a larger study. I don't know how IMMU structured the 2-stage analysis, but one can contemplate that:
1. There is some threshold in terms of response rate below which the study won't move on to the second stage.
2. There is some RR above which the trial may be halted due to efficacy, which will result in going straight to the AA application.
3. I think what we're seeing here is something in between. IMMU-132 in urothelial, for instance, is seemingly active and efficacious. Given the results in the first stage of the analysis, and given a desired significance level, say 5%, and study power, how many patients do they need to accrue in the second stage for the alternative hypothesis to be borne out.. They can increase the power by raising the significance level from 5% to something larger, but by doing so, they'll increase Type 1 errors (reject null hypothesis when it was true, meaning that they move forward when the drug is really inactive.)
I don't mean to get in the weeds, but it has always been my impression that to understand how things have been moving forward over the past couple years, one would need to understand the premeditated 2-stage approach to these phase II trials. And, by the way, I do not for a second pretend to be any kind of expert in this statistical arena.