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You really have a learning disorder or something. My first post pointed you to the JAMA paper, for the answer. I presumed you could find it but apparently you could not, so you begged me for it, but I don’t do work for shorts. Your short pal brought it up and you pretended that I did not know about it, but that plus the case, which gives background on why such IA’s do not unblind, and that the IA found safety and the DSMB recommended continuation of the trial. It also explained why they did not have to and often do not disclose such IA information beyond the general.
I can’t help it that you keep playing dense. Or is it that you’re playing? You seem not to know very much that is very basic and that has been discussed over many years. I pointed you to it. I wasn’t initially going to break it down for you. But the post to which you responded is ONLY in reference to the disclosure of that information in the JAMA paper, the one I pointed to and the one you keep claiming I did not point to…
So here is a simplified explanation from ChatGPT about what the ancillary document reporting those details on the IA means... again, implying bad things for an unsophisticated audience is what shorts do.
"In this study, the researchers wanted to be very careful about making sure their results were truly meaningful and not just due to chance. To do this, they used a special process to control the risk of falsely claiming that DCVax-L was effective when it might not be. Here’s how they did it and what it means:
Setting the Stage
Goal: The main goal was to see if DCVax-L could help patients with glioblastoma live longer.
Caution: They needed to make sure any claims of success were genuine and not due to random luck. This is known as controlling the “Type I error” (the risk of a false positive).
Breaking Down the Risk
Overall Risk Limit: They set a strict limit on this risk at 2.5%. This means they wanted to keep the chance of making a false claim very low.
Interim Check: Halfway through the study, they did a preliminary check to see if they were on the right track. They adjusted their calculations to account for this, making sure the final results would still be trustworthy.
Sharing the Risk
To carefully manage their overall risk, they divided it among different parts of the study:
Main Survival Measure (Overall Survival or OS):
Risk Share: 2% was dedicated to checking if DCVax-L helps patients live longer overall.
Special Survival Measure (Conditional Survival or CS):
Risk Share: 0.309% was set aside for looking at long-term survivors specifically.
Detailed Subgroup Analysis:
Risk Share: 0.1% was used to analyze specific groups of patients, like those with certain genetic traits.
How It Worked in Practice
Main Measure (OS): They found that the median overall survival for patients receiving DCVax-L was 19.3 months compared to 16.5 months for those on standard treatment.
Long-Term Survival (CS): They noted that 13% of DCVax-L patients were alive after 5 years, compared to only 5.7% in the control group.
Subgroup Findings: They also looked at specific groups of patients, like those with certain genetic markers, to see if the treatment worked better for them.
Why This Matters
By splitting up the risk and being careful with their calculations, the researchers made sure that their findings were solid. They didn’t want to make false claims about DCVax-L’s effectiveness. This careful approach means we can trust the results they reported:
Extended Survival: DCVax-L significantly extended the life of patients with glioblastoma.
Long-Term Benefits: Some patients lived much longer than expected, especially those with certain genetic markers.
Trustworthy Results: The rigorous method used ensures these results are reliable and not just due to chance.
Conclusion
The detailed approach used in this study helps us be confident that DCVax-L is genuinely beneficial for patients with glioblastoma. By carefully managing the risk of false claims, the researchers provided strong, trustworthy evidence of the treatment’s effectiveness."
Detailed Explanation for a Highly Sophisticated Audience
The DCVax-L trial employed rigorous statistical methodologies to ensure the integrity and reliability of its results, particularly in controlling the Type I error rate across multiple primary and secondary endpoints. Here’s a detailed breakdown:
Context and Objectives
Primary Objective: To assess the efficacy of DCVax-L in extending overall survival (OS) in patients with newly diagnosed and recurrent glioblastoma.
Secondary Objectives: To evaluate conditional survival (CS) and OS within pre-specified subgroups, among other endpoints.
Type I Error Control
To maintain the overall one-sided Type I error rate at 2.5%, the study employed a combination of interim analysis adjustments and alpha allocation strategies, specifically using the O’Brien-Fleming method and an alpha-exhaustive fallback procedure.
Interim Analysis and O’Brien-Fleming Method
Interim Analysis: Conducted in March 2015 after 56.4% of subjects had completed 6 months of follow-up.
Alpha Spending Function: The O’Brien-Fleming method adjusted the alpha levels to ensure that the cumulative Type I error rate remained within the pre-specified limit. For the final analysis, the one-sided alpha was set at 2.409%.
Alpha-Exhaustive Fallback Procedure
The overall alpha of 2.409% was distributed among the primary and secondary analyses to preserve the family-wise error rate:
Overall Survival (OS):
Alpha Level: 2% allocated to the primary endpoint of overall survival.
Rationale: OS is the primary endpoint, thus receiving the largest portion of the alpha to ensure robust statistical power.
Conditional Survival (CS):
Alpha Level: 0.309% allocated to conditional survival, focusing on the “long tail” of survival.
Rationale: CS assesses extended survival beyond a specific threshold, important for immunotherapies where long-term survivors are critical.
Subgroup Analysis of OS:
Alpha Level: 0.1% allocated for pre-specified subgroup analyses (e.g., MGMT methylation status, extent of resection, age).
Rationale: Subgroup analyses are exploratory but crucial for understanding differential efficacy across patient populations.
Implementation and Impact
Primary Endpoint (OS):
Results: Median OS for DCVax-L was 19.3 months from randomization (22.4 months from surgery), compared to 16.5 months for the external control group (HR = 0.80).
Significance: The allocated 2% alpha ensured that this finding is statistically robust, reducing the likelihood of a Type I error.
Conditional Survival (CS):
Results: At 60 months, 13.0% of DCVax-L patients were alive compared to 5.7% in the control group.
Significance: The 0.309% alpha level for CS ensured rigorous testing of long-term survival benefits, critical for immunotherapies.
Subgroup Analyses:
Results: Significant survival benefits were observed in subgroups such as patients with methylated MGMT (HR = 0.67).
Significance: The 0.1% alpha allocation enabled detailed exploration of subgroup efficacy while controlling the overall Type I error rate.
Conclusion
By employing the O’Brien-Fleming method and an alpha-exhaustive fallback procedure, the DCVax-L trial effectively managed the Type I error rate across multiple endpoints. This rigorous statistical approach ensured the reliability and robustness of the trial’s conclusions:
Extended Overall Survival: Demonstrated significant OS benefits, providing strong evidence for the efficacy of DCVax-L.
Long-Term Survival: Highlighted the potential for long-term survival in a subset of patients, critical for immunotherapy evaluation.
Subgroup Insights: Provided valuable data on differential efficacy, informing personalized treatment strategies.
Overall, this sophisticated statistical methodology underpins the trial’s compelling evidence for DCVax-L as a promising therapeutic option for glioblastoma patients"
"ChatGPT
The approach used in the DCVax-L trial to test the results appears to be appropriate and well-founded based on established statistical methodologies for clinical trials. Here's why the approach is sound:
Key Components of the Approach
Control of Type I Error Rate:
Setting the overall one-sided Type I error rate at 2.5% is standard practice in clinical trials to control for false positives.
The use of the O’Brien-Fleming method for interim analysis is a robust approach to adjust the significance levels at different stages of the trial, ensuring that the overall Type I error rate is preserved.
Alpha-Exhaustive Fallback Procedure:
Allocating portions of the alpha to different analyses (OS, CS, and subgroup analyses) allows for multiple hypotheses to be tested while maintaining the family-wise error rate.
This hierarchical testing strategy ensures that the primary endpoint is prioritized, and secondary endpoints are tested rigorously within the remaining alpha.
Interim Analysis:
Conducting interim analyses with adjusted alpha levels using the O’Brien-Fleming method provides a way to monitor the trial's progress and make informed decisions about continuing or stopping the trial early.
This is a conservative and widely accepted method to manage the risk of Type I errors in sequential testing.
Application to the DCVax-L Trial
Primary Endpoint (OS):
Focusing the largest portion of the alpha (2%) on the primary endpoint of overall survival (OS) reflects its importance and ensures robust testing.
The results showing a significant extension in OS for the DCVax-L group (19.3 months vs. 16.5 months) were evaluated with this allocated alpha, providing strong evidence for efficacy.
Conditional Survival (CS):
Allocating 0.309% of the alpha to conditional survival allows for a focused evaluation of long-term survival, which is particularly relevant for immunotherapies like DCVax-L.
This helps to confirm the durability of the treatment effect in a specific subset of patients who survive beyond a certain threshold.
Subgroup Analyses:
Using the remaining 0.1% of the alpha for subgroup analyses ensures that these exploratory findings are still rigorously tested, adding depth to the understanding of treatment effects across different patient populations.
This approach supports personalized medicine by identifying which subgroups benefit most from the treatment.
Validity of the Approach
Statistical Rigor: The methods used (O’Brien-Fleming, alpha-exhaustive fallback) are well-established in the field of clinical trials and are designed to rigorously control for Type I errors.
Regulatory Acceptance: These methods are aligned with regulatory guidance from agencies such as the FDA and EMA, which advocate for robust statistical controls in clinical trials.
Clinical Relevance: By focusing on OS as the primary endpoint and ensuring stringent control over the error rate, the trial provides clinically meaningful and statistically reliable results.
Conclusion
Yes, this is the correct approach to test the results. The statistical methodologies employed in the DCVax-L trial are appropriate for the study's design and objectives. They ensure that the findings are robust, reliable, and minimize the risk of false positive conclusions. The use of these rigorous methods supports the credibility of the trial outcomes, providing strong evidence for the efficacy of DCVax-L in treating glioblastoma.
For heaven's sake, read the post. I said it was in the JAMA article you DUNCE.
The only lie is your inability to accept that I pointed to the truth and your false allegation that I didn't actually point you right there. I do not even think that you remembered it was there until I said it. Are you so insecure in your understanding and belief that you need to falsely claim such things? Obviously so. LOL.
I said to read the JAMA paper and I said UP TO THAT POINT in my post. I guess you failed reading comprehension.
You're so deluded you can't read what people;post. You come back as if you discovered something when I pointed you right there to it in my previous post. When did that get published? After the Court Case. The court case explains that they are not unblinded by IA's, and that the DSMB found no safety issues. You really didn't prove anything since it is posted right there in the JAMA article which still concludes as it concluded. It did not undo or disprove anything. Just another implied bit of nonsense from shorts who have NOTHING.
Yeah, you can pay people on the internet to do just about anything. Global economy and all, you can pay very little for very intelligent people in other countries to do this kind of awful work, I have no doubt. Hedge funds have so much money, I have no doubt that some traders even individually can contract to ensure they make their numbers and not tell a soul. Plausible deniability. And with Crypto, it made it all that much easier.
That’s the common approach. And a safety review. There are no safety issues. Disclosed numerous times, like every time they discuss the treatment. They can’t make that up if the IA said something else. Again, is your short fund intern posting or is this really you?
That’s not the discussion we’re having at the moment. Like I said, you seem way out of your depth at the moment. Is your intern posting at this point?
Exactly, they do not care. It is all implication and distracting nonsense to keep people from seeing the positive and buying shares. They manufacture FUD, as we all know. That is their pointless, destructive job.
I am not here to educate you. It explains the nature of IA’s and no, they do not have to disclose results. That also has been discussed in depth here over the years. The court case explains that they are not unblinded. That the DSMB chose to continue the trial, NOT HALT it. You just have to learn to read, develop reading comprehension, just the basics.
Agreed. I do not expect these numbskulls to move on. And you have to wonder about people whose entire livelihood depends on posting false information on social media, about companies that other people invest in for the common good and to advance science. What kind of people would willingly have such careers for not just a year or two, many have done this for a decade and more. What kind of people are these? What are their morals? What kind of values do they have? Why can’t they do positive things for themselves and for others? They clearly cannot. This destructive behavior is literally ALL THEY HAVE in their empty, pointless lives.
No, that’s not what I said. I said it is all documented in the ruling I gave you and the JAMA paper and all you need to do is actually act diligently to know the facts rather than believing everything posted by shorts.
I provided you with a link to the ruling related to that matter through 2017. You also have the JAMA article.
That you agree with false notions promoted by a short is no surprise, but given how often this matter has been discussed and given my just previous post… which covers points you asked about, you might try to read stuff before agreeing.
Except UCLA says right here in this press release that their vaccine IS DCVax-L
Lies are lies… and facts are facts.
https://www.uclahealth.org/news/article/fda-approval-brain-cancer-alzheimers
No, it was a safety IA, but more importantly and more critical, the results and changes were made by an external, completely blinded, expert team of epidemiologists abd statisticians who created the new protocol and ECA. There was a very meticulous effort to exclude any bias. It was clearly, very painstakingly done and took considerable time.
Moreover, that court case you hate said two important things, that up to the time you always claimed there had already been such an IA, there had not been, it was for safety. Up to that point. Further, and MORE importantly, such an IA would not unblind.
https://casetext.com/case/lerner-v-nw-biotherapeutics
“It first bears noting that Plaintiffs cite to a December 13, 2013 press release which explicitly states, "The Company does not participate in the interim analysis process or the assessment, and both the Company and the clinical trial sites remain completely blinded." ECF No. 26–6 at 5. Thus, it is unclear from the Complaint how Plaintiffs attribute the alleged shortcomings of the safety board review to Defendants given their stated lack of involvement.”
All one has to do is to thoroughly read that case to see how absolutely nuts, bat s/it crazy shorts were to make all manner of false and misleading assertions that had zero basis in fact but they had just enough to IMPLY bad faith. Heck, filing the lawsuit and waiting for it to resolve allowed them to go on for YEARS implying false and misleading and nasty things about the company, management and DCVax-L as well as about Dr. Liau, and get away with it.
Shorts are, and if it is not obvious to observers, it should be by now, filled with crazy hot air because as success becomes more and more apparent, they realize that they literally have nothing BUT hot air and implied allegations without basis in substantial truth. Implied allegations always rely on some nut of fact, not necessarily proving the claim, but something upon which they can IMPLY something nasty or unpleasant.
But time and time again. Shorts are wrong.
https://wapo.st/3Ke1J1g
https://www.uclahealth.org/news/article/fda-approval-brain-cancer-alzheimers
No idea. I don’t want to say something I have possible lack of visibility to know. We have an update up to the end of 1st Q. And then Les’ statement. We know when, absent requests for information and click off, the 150 day period is expected to be. But regulators are difficult to predict in these circumstances, in terms of timing and requests for information and other aspects. We’re not the ones talking to them. I think the effort to decipher too deeply, without real information, can be counterproductive and cause people to mislead themselves.
I generally agree with this though not with the point that it’s not relatively typical of a microcap development stage biotech without an approved product yet to warn that changing to a commercial company, including sales staff, and the lack thereof is a risk factor. Many of these companies are merged are bought, so yeah, not atypical, IMHO.
But your point that its removal suggests something significant has likely occurred of which we have not been made aware is a good insight.
The start date for the 150 day countdown is the first validation date. I have very little doubt about it. Clock off after that is for requests for information and the answer period.
Yeah, that’s why top institutions around the world and top researchers signed off on it… because they don’t know as much about it as anonymous posters on the internet…
No, they are deep in a regulatory process. So your notion seems to not understand that and no, this is a single product company at this stage. They PR what they can, but there is not a lot they can do at this stage.
As for the UK Specials program, there is a lot I have said previously, that addresses the issue, to some degree. But I am not here to feed shorts. Less is more.
I am fairly certain the 150 day count starts in Jan, not March. The issue will only be, requests for information stopping the clock. Last we knew, that had not happened but of course it doesn’t mean it did not happen subsequently.
As for Les’ prediction, I believe they took my advice after the last two times where MHRA was late and shorts and a strange number of longs turned it into a false debacle. You take the expected time and double it and still communicate some uncertainty. If you come out earlier, you’re a hero, not a bum.
The reality is, if they say, June and approval comes in July or August, the response is always, “Those bums! They lied.” Even though it virtually is always the regulator taking their sweet time.
I did not suggest any sales number. I have no idea. But the way the UK Psecials program is set-up by the regulator, for payment, after some due diligence I believe that it is not intended for us as investors or anyone else to know much about what is happening before they are approved.
Moreover, as you know, it is all OUT-OF-POCKET, the UK is a relatively small jurisdiction in terms of potential cases in any one year and the treatment is not approved yet, so not everyone’s personal doctor is going to know about it. So that demand, whatever it is, is not likely a determinant of anything at this stage.
Unfortunately, the way the UK specials program works, it keeps both the sales and distribution and the bulk of the money at the local manufacturing company. It is all local, and it is all kept between that company and the local regulator.
Like all of these early access programs, it is still replete with challenges. They are just less obvious to the outside. It’s still good and more practical than some other programs, but it also still is not all one would hope for it to be.
I expect that is true too, but likely not always the same issues and people involved, not the same part of the process. But yes, I expect they have developed new expertise as part of their work validating and licensing Sawston and Advent.
Yes, but they need shares. They do not want to be buying and chasing this thing up before news. Then it will just go higher. They are hoping they can bottle it up not just until the news, but even after.
As persons involved in the trial. Not the experts a regulator needs. They know those “experts” are ready at any time. That’s not what I was talking about. That’s obvious, and no, Dr. Ashkan and Dr. Liau are not just partisans, they are clinicians. Regulators are concerned with much larger commercial and manufacturing issues as well and they are not experts for those conversations, besides being on team applicant, so not a consultant for the MHRA at all.
That is often not possible at a price that would justify the wait of shareholders. Bad actors often do their bad acts through third parties and pretend to be cheap saviors.
If you don’t like it, invest somewhere else. For heaven’s sake. Be responsible for yourself and your investments and quit faking being some sort of “victim”. You knew the deal. You’ve been told the deal by all kinds of people every day. The company is silent. They have not misled you either. They hardly say anything. Just the minimum, because it is impossible to know how long a lot of this will take. And at any moment, the partner you claim would help, might act, but they haven’t. So you can take from that what you want but why hang around here a/it posting day after day, under different ID’s, when there is a large market available with all kinds of opportunities. It’s YOUR choice and your disposition.
They hardly ever say anything. Your claims are utter nonsense as I said, unless you’re naive. You can’t time these small biotechs and anyone who knows anything, knows that, yes, even when you go in only in the phase stage. It is exceptionally difficult and you knew there was a partial halt and all kinds of other potential issues. Making this kind of noise just before approval is completely and utterly disingenuous.
No, it’s validation, and the first validation that is relevant. But yes, regulators can take longer for new kinds of complex drugs like this one. So I would not assume they won’t have questions or won’t take their time if they feel it is worthwhile. Secondly, they may not have a lot of expertise in this particular field and so they may seek advice and they also have complained they are understaffed.
So we’ll just have to see.
Not true. I recognize this is biotech, not Tech, and it’s highly regulated and this is a new product. The person who claims to have invested here is the one who doesn’t understand time and money, since it is up to you to measure your timeline and what you need money and how much risk to take with your money. So don’t be a moron and blame other people like longs invested here, for your poor management of your money by not deciding what your timeline required. The victim card!? I am not at all playing victim. That is ALL for the morons who falsely claim they did not know this takes a long time and were not told, as I have said many times, do not bet it all on one stock.
But the reality is, I do not believe people who post nonstop nonsense and moreover, we had what amounted to a huge return from under .20, .17 to $2.51, so those in a hurry, should have taken some money off the table and let their risk be subsidized.
But no, ignore the process, the reality of what you invested in and make stupid claims as if this was Amazon, not a microcap biotechs with a new, personalized medical product like nothing ever before… OK. Yeah, 6 months, and you’re out. So why are you not out?
This is false.
People who come here to “complain”, are here for specific purposes and to taunt and talk the price down, generally speaking. There are people who are clear investors and certainly there are legitimate issues to discuss, of course. But mostly it’s a pitched battle of people and shorts come here to affect sentiment, generally. It’s their job.
They may have believed that PFS would work out, despite crossover and pseudoprogression. I am not surprised and in fact I have seen the exact same overly optimistic views expressed at every small biotech in the market. And sometimes they are luckily, correct.
What were they supposed to think and tell you? Hey, this is going to be extremely difficult, there are unforeseeable challenges ahead and we have no idea when this will be completed, it could be another 10 years or more, but we’d really like you to invest?
They’d be out the door. And the reality is, they told you that negative story every quarter and in every single regulatory filing. Things don’t go as planned in this space and things that can go wrong, frequently do go wrong and then they were deprived of capital by shorts for most of that time.
I can’t figure out if you really are this naive or you’re just larding it on for bulletin board drama to get that price down as low as possible. This is THE game when companies are coming up on approvals or big, major turning points. Swing traders especially when anticipating approval will sell their shares and then s/it talk a company to get those shares as close to zero as they possibly can, so that on the event, assuming it goes well, they can buy back in at dirt cheap prices just before the stock, presumably, takes off from the low low price they talked it down to…
I agree with your description that the two drugs are coadministered. I do not think that means that it is a “maturation agent” in this context. I think that is back to the notion that it’s one drug. I do agree that it makes sense for the company to find a way, as soon as possible, to work with Oncovir to ensure that patients, going forward, not just in trials, can access and have Poly-ICLC, specifically Hiltonol, with their DCVax-L injections, as an adjuvant treatment that stimulates the immune system broadly, not just the dendritic cells in the vaccine. It does so by pretending to be viral DNA. It would be good if the companies find ways to collaborate, work together and commercialize in a manner that provides patients with the best possible solution, as well as positions both companies to prosper from the collaboration.
No cult. I just recognize the reality. And I would not have invested much 12 years ago because honestly, I’ve known enough bios to know that they had a long way to go. I was watching them then.
I don’t disagree with the notion that it has taken an ungodly amount of time to get to where they are, but I also recognize and understand what it is they are trying to do, how challenging that is and that they have unnecessary hurdles being put in their way. I also recognize that most persons that I have seen in this field, with phenomenal resumes and previous accomplishments that take over such companies inevitably fail because they do not have the time, or patience or desire to invest their lives in a new technology like this team has. So most often they either bankrupt the company or sell it for cheap so they can move on. THOSE guys are loved by shorts and tend to fail upward. So I agree with you that this teams determined and long effort will typically be portrayed as “failure” and that persons who invested early, not really understanding what they were doing, may sometimes be disgruntled. They can also often be swing traders.
By the way, the markets are large, you claim to be a long, you’re here 24/7, but you have only had mostly negative things to say. Are you dispositionally challenged in that you can only invest in companies and management teams that you apparently hate with passion? Why don’t you go out and buy some NVIDIA or some company you like rather than spitting all over long investors in this company, claiming to be another “long”. I would not be surprised if you do own shares, but most such people are SWING traders and for swing traders, in the lead up to an approval, they think their job is to get the stock price as LOW as possible by bashing the crap out of the companies so that they can buy again very low, and swing their profits high on an approval.
Whatever the case, manipulating stocks is problematic.
Not a revelation of anything new for small biotechs. That is literally their job to be constantly believing and hoping that some key event will open up market interest and if you take a moment and read that Washington Post article about the company and AF, it’s quite obvious there have been many times such incidents and continue to be such incidents, but it’s a tiny company, they are limited by a variety of circumstances and they are overwhelmed by an ant farm of short posters who seem to be part of an ongoing, compensated effort to keep the price low. We also know that larger entities appear to have enabled manipulation of the stock price, though we do not yet know if they can be held to account over their activities.
No they haven’t. This is typical of shorted small microcap bios at this time. They have taken the company to the edge and they have a single product. That shorts have been, for years now building in an expectation that they will be rejected is also quite common.
They are set for a moderate commercial launch and we do not know yet if they have any possible deals in the wings, but quite frequently, a company will wait until they have a reasonable valuation to accept such deals.
We’ll see what happens next, but the notion that, given where they are, they have “failed” is nonsense. The reality is far from that. That it’s a small company and a few entities or personalities with deep pockets can manipulate the price is no revelation in our modern markets.
Oh nonsense. Total garbage swing trade crap.
It’s an adjuvant treatment. I didn’t say I am certain one way or the other, only that anonymous posters are not the best source, as was proven by the claim that it was fully approved. But adjuvant use is not the same as a standalone approval and it may be that the CRI is correct and we see, in fact, that the combination trial with Keytruda allows for DCVax-L and Poly-ICLC as the standard of care. Meanwhile, Keytruda, in that mix, is the only standalone drug of the 3 that is approved as a standalone drug.
Things are not always absolute, in the way we might expect. But as I said, I am not claiming it is a standalone approval. It’s an immuno-stimulant and it would make sense if, having so much data that indicates it is not a risk for safety, regulators were OK with it when it’s addition to a therapy performed as expected, as an immune stimulant and PAMP.
But I’m no ideologue. I also said I do not think it matters at the moment. DCVax-L is seeking approval as its own treatment that is part of the SOC. Their application does not require poly-iclc to be approvable.
Yes. Only NWBO.