Replies to post #471830 on NorthWest Biotherapeutics Inc (NWBO)

[pgsd]

Very interesting, thanks for sharing :-)

[eagle8]

Thank you H2R !

GLTU

[KIPK]

Thanks H2R & totally agree with the fact that the external control groups not being followed long enough to know the true numbers of "lost-to-follow-up" patients & counting them is as "surviving". completely over estimates the control group survival cure. And as such, make the performance of DCVax treated patients ARTIFICIALLY poorer than the Excellent results reported!!!!

Also, I am happy that you you put a light on that critical observation, although as its very clear in the response to you, Dr. Bosch, thus all regulatory agencies and the oncology community are full aware off,
Adding more power to DCVax !!

Very long NWBO!!

[hoffmann6383]

thanks for sharing h2r

[exwannabe]

H2R, there is good reason why clinical trial survival analysis is done this way, and it is not biased as you think. That is why LL reports 13% alive at 5 years, while the actual number known alive at 5 years was only 10.8%.

Trials will almost always have incomplete data. Not just LTFU, but patients who were still alive at the end of the trial but had not been in the trial long enough to have complete data.

You do now want to assume they died or taht they lived the full 60 months. Nor do you want to throw them away as that creates a time bias where the median (and tail) will increase if you wait.

The K/M curve is nearly universally used to handle this. It provides the best estimate of what the real numbers would be if you had the full data.

The curve is very simple and does not rely on any magic to create. Every month the curve drops by a percent that is the same percent as died out of the then at risk population,.

The assumption you are making in graphing at risk over time is that every patient who was not measured alive at 5 years was dead. Yet not all the trials in question even reported 5 year data.

[ATLnsider]

Thanks for sharing your analysis H2R

[sentiment_stocks]

Thanks for sharing H2R. Very interesting observation. And it’s logical to think that of the lost to follow up, most of those ECA patients did not go off to live long lives, made even more likely due to the fact they were in the control arm of these trials, without even access to the treatment being tested.

[sukus]

Great analysis H2R. I was wondering too about that external control % there why it shows 15% at 3 years. Seems that number was an inflated number from my first impression. I agree with your friend who put the SOC number at 5% at 3 years.

Thanks to you. You explained that numbers included the loss to follow up patients. That answered my questions. If loss to follow up was not included, it would be very likely to reach 5% at 3 years.

Looks to me NWBO puts very conservative estimates so no one can blame NWBO.

Too conservative I think. NWBO might have a very good reason. I trust them that they have a strong reason to do it that way.

[sukus]

At 5 years, the external control numbers shows at 5.7% that included the loss to follow up patients. This number too is inflated I think. We all know at 5 years, most GBM patients did not survive unfortunately. I agree with your friend the number is most likely a lot lower than 5.7% at 5 years. Your friend puts 1% at 5 years for SOC.

If we used 1%, then we would see dramatic improvements from DCVax-L.

1% compared to 13%.

1300% improvements at 5 years??

NWBO is very conservative announcing this numbers. I trust them that they have strong reasons to do it that way.

[CherryTree1]

So let me make sure I understand H2R.
Are you saying that for the external control group that any patient lost-to-follow-up is assumed to still be alive and that some of these trials didn't even track patients to 5 years or more whereas DCVAX had very few lost-to-follow-up?
That is ultraconservative and would clearly make DCVAX not look as good. It seems like the should have plotted the min and max line showing it assuming the lost-to-follow-up's are all alive and then assuming none are still alive. They could then show both graphs. Perhaps this will be discussed in detail in the journal article. I hope so. Even with the ultraconservative approach DCVAX is still clearly much than the historical SOC.
Thanks for posting this - GLTU.

[dmb2]

H2R, thx for this analysis, it is the type of simulated analysis NWBO may carefully utilize when appropriate in RA discussions. It certainly shows valuable treatment perspective that logically overcomes trial control data limitations and is supportive to the study conclusions.

[Hopeforthefuture3]

HR2, I'm confused by your second graph. The first one mgmt methylated matches the presented slide deck except for the addition of the blue line (I find that interesting).
The second graph labeled minimal residual disease does not remotely match the slide that I have from the presentation. Your slide shows at the median 16.5 vs 19.3 months advantage to dcvax and p value of 0.002 hr of 0.80 (not looking at the blue line)
If I look at the presentation slide on nGBM for minimal residual disease I see at the median months of survival at 20.3 vs 20.4 months, p value of 0.524 and hazard ratio of 1.01. Vastly different, what am I missing or do I have the wrong slide? Your slide on minimal residual disease is showing very favorable impact from dcvax, the one I'm looking at shows no impact (all just at the median)
Can you explain or am I just looking at it wrong?