NorthWest Biotherapeutics Inc (NWBO)

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CherryTree1

Re: Johnni post# 539265

Sunday, November 27, 2022 8:28:49 AM

Post#
539326
of 539379
Thanks for posting this.
I sent this email to them per their request at the end of the article:
Dear Ms Houser,

There are important allegations in your article that are wrong.
Namely when you state:

"When the terms of an analysis are defined after results have already been seen, it’s called a “post-hoc analysis,” and it’s a controversial way to assess a treatment’s efficacy. “The more analyses that are done post-hoc, the greater chance of finding results by chance — meaning that they are not true results"

Post-hoc analysis is defined as: "Post hoc in Latin means 'after this'. Simply put, a post-hoc analysis refers to a statistical analysis specified after a study has been concluded and the data collected. A post-hoc test is done to identify exactly which groups differ from each other. Therefore, such tests are also called multiple comparison tests." Post-hoc analysis is also at times called Data dredging -- sometimes referred to as data fishing -- is a data mining practice in which large data volumes are analyzed to find any possible relationships between the data. Data scientists can then form hypotheses about why these relationships exist. That did not happen here.

The analysis for the DCVAX-L Phase-3 trial was not "post-hoc" because the SAP (Statistical Analysis Plan) was updated and submitted before the trial data was unblinded. Updating the SAP is common before unblinding as stated here: "The plan should be reviewed and possibly updated as a result of the blind review of the data and should be finalized before breaking the blind." http://onbiostatistics.blogspot.com/2020/01/pre-specification-and-statistical.html

If you do you Due Diligence you will find your allegation that the SAP was done after data lock is completely incorrect If you review the their October 2020 NWBO press release:

https://nwbio.com/northwest-biotherapeutics-announces-data-lock-of-phase-iii-trial/

Northwest Biotherapeutics Announces Data Lock of Phase III Trial
05 OCT 2020
FOR IMMEDIATE RELEASE

CONTACTS
Dave Innes
804-513-4758
[e-mail]

Les Goldman
240-234-0059
[e-mail]

BETHESDA, Md., October 5, 2020 – Northwest Biotherapeutics (OTCQB: NWBO) (“NW Bio”), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the database for the Phase III trial of DCVax®-L for Gliobastoma has been locked.

With the database now locked, the independent service firms managing the Clinical Trial are arranging for the independent statisticians to have access to the unblinded raw data from the Trial. Neither the Company nor any party other than the independent statisticians will have access to any unblinded data at this stage.

The statisticians will proceed as quickly as possible with analyses of the raw data and prepare summaries of the Trial results for review by the Company, the Principal Investigator, the Steering Committee of the Trial, the Scientific Advisory Board, and a panel of independent brain cancer experts, who will analyze the data with the statisticians in preparation for public announcement and scientific publication.

“We are excited to be so close to the finish line now, after such a long road” commented Linda Powers, the Company’s CEO. “We are hopeful that DCVax®-L can become an important new treatment option for patients who urgently need more and better treatments for Glioblastoma brain cancer.”

“We are grateful to the independent service firms and the clinical trial sites who have worked so hard to complete the data collection and confirmation during many months of COVID restrictions and challenges,” Ms. Powers continued. “We are also very grateful to our shareholders for their patience and support, which has made all this possible.”


How could the statisticians proceed with analyses of the raw data and prepare summaries of the Trial results without the final SAP?
They couldn't.
. . . and the Principal Investigator, the Steering Committee of the Trial, the Scientific Advisory Board, and a panel of independent brain cancer experts, who analyze the data with the statisticians in preparation for public announcement and scientific publication would not let them change SAP after all this is done . . . and even if NWBO tried to do that do you think they would remain silent. These panels, boards and committees are put in place to ensure nothing untort/nefarious like data dredging happens. That could happen for even a microsecond. That is why these people were put in place.

I hope you find my comments and feedback helpful

Bullish
BULLISH
Men who are occupied in the restoration of health to other men, by the joint exertion of skill and humanity, are above all the great of the earth. They even partake of divinity, since to preserve and renew is almost as noble as to create.


New brain cancer vaccine completes clinical trial
Northwest Biotherapeutics reports that its new brain cancer vaccine can extend glioblastoma patients’ lives by months or even years.
By Kristin Houser
November 26, 2022
A new brain cancer vaccine can extend some glioblastoma patients’ lives by months or even years, according to its maker — but the design of the company’s trial has some questioning the claims.
The challenge: The standard treatment for glioblastoma — the most aggressive form of brain cancer — starts with surgery to remove as much of the tumor as possible. After that, patients typically undergo chemotherapy and radiation therapy to kill lingering cancer cells.
But even with treatment, the prognosis for glioblastoma isn’t great — the cancer almost always comes back, and patients live an average of just 12 to 18 months after diagnosis.
A brain cancer vaccine: US biotech company Northwest Biotherapeutics has developed a brain cancer vaccine, called DCVax, that’s designed to help a patient’s own immune system target their tumor.
“The vaccine … provides a personalized solution, working with a patient’s immune system.”
Keyoumars Ashkan
To deliver the treatment, doctors remove a special type of immune system cells, called dendritic cells, from a patient’s blood sample. The cells are then mixed with antigens taken from a sample of the patient’s own tumor.
When the dendritic cells are injected back into the patient, they teach the rest of the immune system to recognize and attack the tumor cells.
“The vaccine … provides a personalized solution, working with a patient’s immune system, which is the most intelligent system known to man,” Keyoumars Ashkan, the European chief investigator of a phase 3 DCVax trial, told the Guardian.
The trial: For the trial, more than 300 newly diagnosed glioblastoma patients were treated with either the brain cancer vaccine or a placebo after standard treatment (surgery to remove their tumor, when possible, followed by radiotherapy and chemotherapy).
That is a very typical trial design. But placebo group members whose cancer returned during the course of the trial were also given the option to receive the vaccine. 
When the vast majority of the placebo group chose to get the treatment, the researchers had to find a different comparison group, which wasn’t part of the study.
In the end, 13% of all trial participants treated with DCVax lived for more than five years after diagnosis, compared to 5.7% in the comparison group used for the study, which consisted of more than 1,300 patients from the control groups in other, previous glioblastoma trials.
One trial participant lived for more than 8 years after diagnosis.
According to Ashkan, DCVax produced “clear benefits” in patients who typically have a poorer prognosis, such as older people, and it was well-tolerated, too — just five trial participants reported significant adverse effects that might have been related to the treatment.
“The total results are astonishing,” said Ashkan. “The final results of this phase three trial … offer fresh hope to patients battling with glioblastoma.”
The controversy: Not everyone agrees with that assessment — Donald O’Rourke, a professor of neurosurgery at the University of Pennsylvania, who wasn’t involved with the trial, told STAT he found the data to be “unpersuasive,” in part due to how the study was conducted.
Before Northwest Bio decided to offer the treatment to people in their placebo group, it found that the median time it took for tumors to return was 6.2 months in treated trial participants and 7.6 months in untreated participants.
That means tumors came back sooner in people who received the brain cancer vaccine than those who received the placebo.
“The more analyses that are done post-hoc, the greater chance of finding results by chance.”
Merit Cudkowicz
The decision to compare the trial data to external controls wasn’t made until after the trial had already started. When the terms of an analysis are defined after results have already been seen, it’s called a “post-hoc analysis,” and it’s a controversial way to assess a treatment’s efficacy.
“The more analyses that are done post-hoc, the greater chance of finding results by chance — meaning that they are not true results,” Merit Cudkowicz, the chief of neurology at Mass General Hospital, who wasn’t involved in the study, told the ALS Therapy Development Institute.
Linda Liau, principal investigator of the DCVax study, defended the decision to STAT, noting that, because two-thirds of the people in the placebo arm eventually opted to received DCVax, researchers didn’t have enough people left in that group to conduct a traditional, randomized clinical trial.
“Many clinical trials reported in the literature use external case controls, which is just a different level of evidence than the traditional, randomized controlled trials,” she said.
The bottom line: By giving people in the placebo group an opportunity to receive DCVax when their cancer came back, the trial researchers gave them another shot at fighting their deadly disease — but in doing so, the trial ceased to be a simple comparison of treatment and placebo, muddying the results.
Despite the initial results — that showed tumors returned sooner with DCVax — the brain cancer vaccine could still be a worthwhile glioblastoma treatment. It might lead to better outcomes when paired with another treatment, for example, or work particularly well in certain types of cancer patients.
To find out, though, Northwest Bio will need more trials, designed in such a way that the results are indisputable.
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NWBO
Northwest Biotherapeutics Inc (QB)
0.895
0.04295 (5.04%)
Volume: 2,843,315
Day Range: 0.855 - 0.927
Bid: 0.865
Ask: There are multiple 10 year survivors in the DCVax trial. The actual doctors that participated in the study have confirmed this. I don’t know exactly how many, but I remember a bare minimum of 5 individuals that have personally expressed this testimony on social media. I would wager it’s around ~20 people if I had to guess.

And by the way, this is utterly unheard of in GBM
Larppis

Re: biosectinvestor post# 538531

Sunday, November 27, 2022 3:29:57 AM

Post#
539311
of 539375
Hey Bio,
Could it be that the Poly-ICLC used in this DCVax+Keytruda+Poly-ICLC combo trial ( https://clinicaltrials.gov/ct2/show/NCT04201873 ) actually is Hiltonol as under the 'Intervention/treatment' section it says;

Drug: Poly ICLC
Given IM
Other Names:
Hiltonol
Poly I:Poly C with Poly-L-Lysine Stabilizer
poly-ICLC
PolyI:PolyC with Poly-L-Lysine Stabilizer
Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
Stabilized Polyriboinosinic/Polyribocytidylic Acid

Maybe not any significance in that even if it really is Hiltonol. But anyways I found it even somewhat interesting bit


Re: ATLnsider post# 539290

Sunday, November 27, 2022 1:50:05 AM

Post#
539299
of 539376
Yes she does say that this new SPORE project is with BMS.
Also I thought I had seen these same slides somewhere and, yes it was in this video where LL also presents the Poly-ICLC combo survival data;



At about 6:45 mark she first talks about BMS failed GBM trials.
Then after the Poly-ICLC data (at about 25:55 mark) she goes into those BMS slides from the Mount Sinai video (this WCM video is a more recent one). And at 31:30 she talks about this future combo trial of DC vaccine+Poly-ICLC+PD-1 mAb+CSFi. It would seem that this trial will be with BMS, too.

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