Not sure Smith (on stocks) fully explained DCVax trial.
He kind of gave the impression we are not going to know the anything except the safety and most effective dose.
Here is why I think this explanation is insufficient.
Phase 1 and Phase 2 are combined. Check.
Phase 1 will determine the most efficacious dose. Check.
Phase 2 will follow phase 1 without further FDA approval needed. Check
MISSING from explanation.
Emphasis that BOTH PHASES are UNBLINDED (not just phase 1)
Because it is an unblinded study, the dosing findings for each dose will be released.
Because of this, we will know the exact efficacy for the separate doses immediately upon completion of patients through phase 1.
Here is why. Unlike many medicines, this biologic works so fast that the "correctly" dosed patients, who will be included in the phase 2 trial statistics, will immediately be placed in phase 2, and because their tumor sufficiently regressed or disappeared, we will be notified immediately, not in the middle of 2014 as Smith and some contend. Again, because the results of BOTH phases are UNBLINDED, and patients who are already disease free will be included immediately into phase 2 statistics.
This is why phase 1 and phase 2 are described as combined.
If the results really cause 80% to 100% of tumors to regress and disappear, there is likely no "correct" dose, only completely effective doses at all ranges.
I do not think Smith intentionally misstated this. I simply think he has been at it so long and seen so many disappointing results, that this didn't occur to him when he wrote the article.
In other words, we won't simply get the standard line "the trial will continue." Instead, we will know the doses that worked the best and we will immediately know if this resulted in total tumor regression. Get It?
The best I can tell is that phase 2 starts when the first 36 patients from phase 1 demonstrate levels of response. Fortunately for the patients, if this is going to happen, it happens very very fast. The results are not blinded so NWBO can literally start talking about response level to dose amount a few patients at a time. Not mentioning the patient's names of course.
Phase 2 is also unblinded, and this phase measures safety and efficacy to compare it with its effects on other cancer types in the same study. Here, the results will already be known for 36 out of the 60 patients in phase 2 before the trial even begins. Again, this is unblinded, and 36 ongoing results will likely be announced at the front end of this trial.
If 12 of those 36 patients have significant tumor regression in phase 1 , which again happens very, very fast, then NWBO met its basic threshold allowance (this would slow down the process as the number of treatments. However, if significant tumor regression occurs in 100% of patients, then phase 2 will start and end immediately on those 36 patients. The new 24 patients will be given the best doses for their cancer as determined in phase 1. Again, the results are unblinded and likely will be announced a few at a time.
The delay from phase 1 will simply be due to when the remaining trial sites start (or potentially from disappointing results if multiple treatments over months becomes necessary.)
The key is that this treatment works very very fast. So we will know the initial results from the patients at Anderson MD very soon if they are positive.
I am an optimist regarding this company, but I think the results will be in days to a few weeks, not months. The detail we get from the first few patient results will let us know the level of transparency allowed to the public.
Smith might be able to comment on the exact statements/details likely to be made in hypothetical results.
You have to be careful, however. The phase one trial is spread out over numerous different cancers, which means drawing statistical conclusions about any of them is not going to be practical (you might get something from the gestalt, especially if the results are really good or really bad, but that's about the limit).
The phase two trial is only going to be carried forward on a limited number of cancers. That means that the total number of people transferring from Phase one to two is going to be vanishingly small (maybe 3-4 if that). So definitely not enough to draw a reasonable conclusion. You need the more expanded cohorts from the phase two before it's reasonable to draw real conclusions.
I'll just emphasize a phrase from your reply. "[E]specially if the results are really good...."
You can call it Gestalting, schmalting or pole-vaulting, but with 80-100% (hopefully) significant regression across many different types of cancer tumors, it would be statistically significant in my book -- even though I understand the trial size is wanting. The added challenge from various cancers multiplies the difficulty in obtaining consistent results from one type of treatment, and therefore, challenges normal statistical analysis.