Replies to post #520513 on NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

Yes, FDA has been crucial and has approved multiple DCVax studies and they have approved the current Keytruda combo study. I also agree that SNO is significant, but don’t forget all the other institutions that were involved leading up to SNO 2022 and the forthcoming peer-reviewed publication: NIH, King’s College, UCLA, MHRA, and the Nobel Prize-winning discovery of the dendritic cell that led to the landmark development of the DCVax platform technology…

These and so many more..





https://www.livescience.com/16354-nobel-prize-medicine-2011-immune-research.html

https://virtualtrials.org/dcvax.cfm

[Roman516]

You can infer or imply an adaptive trial based on the methods used within the trial. You don't have to mention the trial is adaptive either, case closed.

[pgsd]

The FDA's position is very supportive of adaptive trial designs for rare diseases (GBM is an Orphan disease).

You might want to take note of the following including FDA guidance below. Note GBM is an orphan disease

Trial Design and Statistical Considerations in
Rare Disease Clinical Trials
[FDA - September 6, 2019)

Conclusions:
To overcome significant challenges in designing and conducting adequate and well controlled rare disease trials, we support innovative trial designs and analyses provided they are well thought through, justified, and able to

“distinguish the effect of a drug from other influences,
such as spontaneous change in the course of the disease,
placebo effect, or biased observation.”

Adaptive Designs and Orphan Diseases: Building a Bridge of Innovation

For example, the 2010 FDA guidance on adaptive study designs classified designs into “generally well-understood adaptive designs with valid approaches to implementation” or “adaptive study designs whose properties are less well understood”

https://www.worldwide.com/blog/2018/04/adaptive-designs-orphan-diseases-building-bridge-innovation/

GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.”

https://nwbio.com/nw-bio-confirms-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer-is-ongoing/
Link to 'Trial Design and Statistical Considerations in
Rare Disease Clinical Trials' FDA

https://www.fda.gov/media/131882/download

[RPD60]

No. The FDA document on Adaptive Trials clearly states that it is a “guidance document and not a regulatory requirement.” How convenient you left out that important fact.

Furthermore, and most importantly, the primary purpose behind “prespecifying” the trial design (per the FDA document) is to avoid arriving at erroneous conclusions from the data. However, there is no way to fake, mathematically or otherwise, the extraordinary OS data.

Personally I think adding the external controls makes a stronger statistical case as to the potency of the result…..unless, of course, the external controls were cherry picked…..which I don’t think they were because those external controls are the same or worse than the Stupp data, which is exactly what you expect if Stupp is the SOC.

[pgsd]

"You can't "infer or imply" adaptive trials. Read the FDA Adaptive Trial Guidance -- the NWBO trial doesn't meet any of the requirements"

You are 'cherry picking' which particular FDA guidance suits your flawed narrative. Whether you like it or not the FDA has official guidance on 'Rare Disease clinical trials' (as referenced below and numerous other times). Simply ignoring this guidance which applies to NWBO by virtue of the fact GBM is an orphan disease and by definition a Rare Disease is flawed, it is clear for anybody who reads the FDA guidance provided that the FDA's position is very supportive of adaptive trial designs for rare diseases (GBM is an Orphan disease) :-)

Trial Design and Statistical Considerations in
Rare Disease Clinical Trials
[FDA - September 6, 2019)

[color=red][Conclusions:
To overcome significant challenges in designing and conducting adequate and well controlled rare disease trials, we support innovative trial designs and analyses provided they are well thought through, justified, and able to

“distinguish the effect of a drug from other influences,
such as spontaneous change in the course of the disease,
placebo effect, or biased observation.”[/color]

The FDA's position is very supportive of adaptive trial designs for rare diseases (GBM is an Orphan disease).

You might want to take note of the following including FDA guidance below. Note GBM is an orphan disease

Trial Design and Statistical Considerations in
Rare Disease Clinical Trials
[FDA - September 6, 2019)

Adaptive Designs and Orphan Diseases: Building a Bridge of Innovation

For example, the 2010 FDA guidance on adaptive study designs classified designs into “generally well-understood adaptive designs with valid approaches to implementation” or “adaptive study designs whose properties are less well understood”

https://www.worldwide.com/blog/2018/04/adaptive-designs-orphan-diseases-building-bridge-innovation/

GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.”

https://nwbio.com/nw-bio-confirms-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer-is-ongoing/
Link to 'Trial Design and Statistical Considerations in
Rare Disease Clinical Trials' FDA

https://www.fda.gov/media/131882/download