Correction to my last post:


The sentence in bold was pasted after the wrong paragraph in the last post.


This is the correct version,

IMHO, there was a degree of timing placed into the trial.

The timing is a bit off, so the world has to wait.

If the Pseudo-progression enrollment didn't start until 2011 or so, then it may be the 72 spaces they added to the trial are for the them.

Do some very simple math.

Ultimately 240 in the main body.
Ultimately 112 events required for final analysis
66 required for 1st interim analysis.

72 in the alternative group (pseudo-progression)
Ultimately 33 events "desired" for final analysis.
19 "desired" for 1st interim analysis.

If you met the primary endpoint in the main body, the pseudo-progression group is not an afterthought. They are just as important, and you would want to analyze the results before you unblind the trial. You would not want to neglect this very important group, and even though they are analyzed separately, ultimately you would want to also determine how both groups did as a whole.

If you were simply going to continue the main body of the trial, you could simply do that and analyze the pseudo-progression group at the second interim analysis for the primary group. You would not wait for the pseudo-progression minimum events at the 1st interim analysis in this situation.

This would explain why they are telling us efficacy data analysis is pending.

Finally, there would be simply no reason to halt the trial for futility at the 1st interim unless the results on the primary group were showing a statistical detriment (which would be a safety issue) to the patients. Thus the safety continuation is more meaningful at the 1st interim than perhaps any other time when you have a very safe treatment.

By the way, I don't want to leave people hanging.

If this hypothesis turns out to be correct, I see it as
a positive development.

See you all in a while.

I have an idea.

According to clinical trials.gov, the pseudo-progression group is analyzed separately.

When you fully contemplate what that may mean, you will conclude that the p.s. group also needs some basic number of events to occur for statistical analysis. (This would not be a primary endpoint event trigger.)

I could ramble on until I am blue in the face with hypothetical numbers, but I think we may want to consider the fact that the pseudo-progression enrollment probably did not start until 2011 or sometime shortly thereafter.

Think hard about that. Really hard.

Ultimately, we may be waiting on a number of events in a separate group all together (or maybe they just recently reached that number). I do not think that number of events would be very large. Even though the p.s. group is not used for the primary endpoint, it would be really important to have enough powering in this separately analyzed subtype.

That may explain the delay and why efficacy is still under review.

Before you make such strong statements, you may want to make certain you know what group is responsible for conducting and issuing the interim review decision.

I'll let somebody else speak to New Link.

Nice Ou,


Thanks. This will be the third day in a row that I am adding.

Not quite.

IMHO, the data safety monitoring board still has the 1st interim analysis under review for efficacy. They can't take a look at any new data for probability until the 2nd interim analysis. Therefore, they are still reviewing efficacy with the data they have. This is the way sequential analysis works. You cannot peak at probability data inbetween the 1st and 2nd analysis.

Consequently, if you take the PR at face value, they are still considering efficacy with the present (66 events) data set.
"Review of the efficacy data is still pending"

Not just lip service.


Considering Marnix Bosch's position in this trial, I think his comment in the press release carries additional weight.

True. Unless volume skyrockets.

I agree, but I think it will take some further PR to move PPS significantly. IMHO

Dok said:

Yes. That was required by Germany.

I agree, I think that's the correct general take, but I think it's also a green light to the clinics in Germany.

I think this is a green light to proceed with clinical enrollment in Germany so NWBO can get more data to ensure eventual passage with FDA and EMA. If we halted for efficacy right now, Germany would be switching over to full on compassionate use, and they'd probably lose enrollment capacity in the trial, which would mean we go with the enrollment we have. There is still a chance we will here something on efficacy soon regarding the group Germany is not including in their enrollment -- (pseudo-progression) IMHO.

Good question.

I go back to the fact that it takes more extensive deliberations to determine if they are going to stop for efficacy. This initial decision (continuance for safety) gives the DMC (and possibly CRO) breathing room to perhaps follow the path Ou and f3tt3f suggested, which is to wait for the 88th event. This allows more data for any eventual presentation to the FDA.

This may mean our next "glimpse" on anything DCVAX related will be a "shout from the rooftops" at ASCO in May on DCVAX-Direct.

Still, I expect some announcements on Germany (reimbursement?) and DCVAX Direct clinic expansion in the meantime.

Its kind of a continue….


"The DSMB’s review of the efficacy data is still pending."

Brilliant.

I agree that this is an important factor. I also agree with your analysis. I also think the chronology of this trial reduces the burden on the d.m.c and nwbo regarding p.f.s v. o.s. endpoints.

There seems 2b a guiding hand.

P.S. You brought to mind that gifted actor from England. When he used the word "Guinea Pig" to describe his situation..... I knew nwbo had more to contribute than a cancer breakthrough. I think this trial will b seen by future historians as step toward the end of placebo trials.

Maybe,

but I think if that were the case, they'd just announce a continue. No harm in that, and it avoids driving everybody nuts. I just don't think they'd wait for 22 more events without announcing a continuance in the meantime. This theory would also be outside the standard prearranged structure.

IMHO, I think there is a different reason.

Dunno. My thought is they are too smart not to have one.

Yes. That is the one I am referring to.

Alternative uptick rule in effect all day tomorrow.

Your humor won't be lost or misconstrued….

I'll repeat myself, at the risk of being crude….

It follows that if the company is going to share the DMC recommendation right when they get it, there must be a steering committee beforehand engaging with the DMC in more extensive interactions while any early halt is considered.

Otherwise it would cause complete chaos to announce a decision and then contact all the clinics, countries, etc.

Jim's correspondence with public relations helps us discern this process from a more sophisticated perspective. IMHO

Steering Committee and Firewalls.

Actually, there may be conversations going on between a steering committee and the DMC.

Doc Logic.

Larry Smith reprinted Doc Logic's statement on January 28, 2014. It's so enlightening, I thought I would also reprint it.

On it.

Red.


I added today and yesterday.

Other than the prospectus, I wonder if there is a way to determine the estimated number of total shareholders? Back in November 2013, it was about 2200.

Thanks Hodge -- it is a very hopeful post.


I hope all is well.

Well, maybe that's a famous interview. But I feel like I just watched a vampire detail how he sucks the life out of someone. Jim Cramer's voice would give life to a wonderful number of animated characters for childrens' feature films, but his heart is clearly insatiably connected toward burning those who are naive and/or not as smart. What a terrible conundrum. I almost respect the competitive spirit in him until I come to terms with the fact he destroys well meaning innocent investors on a daily basis. Those innocent investors expect the United States SEC to be smarter and more scrupulous than affable wolves, seductive vampires and grim reapers of innocence. I despise him, but I can't help pray for his soul.

We are close.

I think you are over thinking this minor article. There is only one interesting thing in it. Oppenheimer states it is "make or break." Well guess what? It isn't. Under the highly unlikely circumstances DCVAX-L is a bust, DCVAX-Direct is waiting in the wings. Oppenheimer knows this better than any other large investment company, and of course, they were the same ones that gave FOX viewers the head and shoulders back in November. So take everything with a grain of salt. There really is a very large Phoenix waiting in the wings if things go south. Want to know a 'secret'? Direct is not simply for inoperable cancer.

Occam's razor. Paperwork is always the simplest explanation.

I think looking at the international implications and clues helps keep us sharp. I also look forward to examining our correct and incorrect understandings once the trials and other processes run their course. I think there is a great deal all of us can learn that can be applied to future investments.

I definitely think it would reduce the concerns floating around about delay that might be caused by potential subtype divisional trial powering deescalation. This in turn may make the international response/decision to a halt in one or both groups much less bureaucratically delicate.

Clearly Adam navigated a quick back pedal on his positions regarding NWBO. Good Points Pip.

Welcome back Dok! I Look forward to hearing your thoughts in the coming days and weeks.

Here's a very enticing theory.


Germany does not want the pseudo progression group in the trial because they already know those patients respond exceptionally well to DCVAX-L, and more importantly, the efficacy can be determined exceptionally fast (see posts by doc, flipper and others). Thus, they are anticipating the pseudo-progression group will be halted before they start their enrollment.

Why would Germany know this? I think you can start with the clinical experiences in Cologne Germany and in the compassionate use cases in Israel and Great Britain. John has a lot of information he found in his internet research on the Cologne program.

It makes a great deal of sense to me, but I'm probably not taking enough time to lay it out based upon the other factors making this likely.

I'll just mention one. Germany is the toughest Country in Europe for a company to receive manufacturing approval, clinical trial approval and compassionate use reimbursement. In accomplishing this, they check every nut and bolt before giving the go ahead. One of the only things they required was that NWBO not include the pseudo progression enrollment and separate analysis in their part of the enrollment program. Think about that. They would not want to start enrolling people who might tomorrow be eligible for commercially approved (through Germany's expansive compassionate use program) DCVAX-L's treatment. Thus saving some patients from the placebo.

(Of course, imho any possible divided halt and continuance between the 2 groups could happen in reverse order, possibly due to the trial chronology)