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Congrats Kabu, at least you finally acknowledge that PFS might not be doing so well and that OS is the gold standard (which is what naysayers have been saying many yrs ago.) Also, you shouldn't be so negative. There was some chance of stopping for efficacy early on using OS- ASSUMING that it is highly SS with a huge separation as some modeled here. Waiting for two more events shouldn't change such great results and this could have been revealed in the early IA that should have been preplanned and executed by the DMC for the primary endpoint of PFS (or at least when the 248 FINAL PFS events was hit sometime in 2016) Would NWBO be stupid enough to NOT to take advantage of a positive IA of the OS if it was positive to hype it and PR it to hook another NW with a massive financing at soaring sp?! Of course NWBO could also have done a financing when the sp hit 12 in mid 2015, but something must have stopped them from being able to take advantage of such high prices to do a financing- what could that be? Maybe you are right and I along with rest of WS are being ignorant and DCVAX is a diamond in the rough and not a dung beetle pellet. But my post was for JJ to clarify his model. I'm confused as to why he would show Leprocon's KM curve to be the same as Brandes et al and to try using the assumption that cross-over has no effect because those who try to claim otherwise is IMO just trying to find an excuse for a failure. So I believe the best statement is to say that all patients are living longer due to SOC 2017.
JMHO
Congrats JJ, you just showed that Leprocon's curve is about the same as Brandes et al for OS. BTW you really should try to keep the survival times to be on the X-axis and the percentage survival on the y- axis as that is the norm. As for any cross-over effect, I would assume zero cross-over effect based on the Liau and Prins papers (despite her new claims in her "hopeful" presentations that are now removed from youtube). This would imply that DCVAX-L does not meaningfully work in rGBM which is the conclusion from Liau from her earlier work though it sort of changed in a later poster which had possible dubious math utilized which AVII caught. If the survival curve is supposedly great and shows such a highly SS separation, then I guess NWBO should also be highly motivated to end this trial and PR the amazing results asap. That was what IA was for- to stop a trial early for efficacy. There is nothing "early" about this trial- just delay after delay- which really portends to an utterly disastrous failure.
JMHO
The way this company operates, we could have reached 233 OS events already but the company may not even bother reporting it on time as a material event just like they never reported when the 248PFS events occurred nor whether any IA occurred for their primary endpoint. That is the funny and ironic FACT that contradicts all those who claim their models show a SS results in the PFS or even OS. If those models were accurate, then the FACTS should confirm it but unfortunately reality seems to indicate that those model predictions are as dependable as the company releasing material updates on this p3 trial in a timely manner.
JMHO
"Basic knowledge to anyone who has read the 10k is that: the dedicated suites are sitting there (and billed to NWBO at ~$450k/month) whether in use or not." AVII
Assuming you are correct regarding the fee/mth, it comes out to about $5.4mil/yr. How does it explain why Cognate charged NWBO in 2016 for $34.6 million for services compared to $37.7mil in 2015? What services was Cognate offering during a partial clinical hold where no more vaccines should have been made for trial patients from either Direct or p3 trial?
It would have been nice to have a forensic accountant head up the investigation instead of whoever it was chosen by LP. BTW where exactly is that investigation report?
JMHO
"I would like to think you've cleared this argument up, RK, but I feel certain the bears will continue to argue it, despite the evidence otherwise." Bear
Yup. You are absolutely correct. Until the company states publicly and not just to supposed few investors when that PFS 248 events was hit, then Exwannabee's guess is IMO fits my own projections. The company could have clarified this whole issue but they chose not to.
Also, I'd still like to hear from MD/Chris how he KNOWS for a fact that an IA was not conducted in 2015.
JMHO
"What do you think is the significance of the fact that the FDA lifted the partial hold in february when 248 Progression events had been reached?" JJ
What makes you think that reaching the 248PFS events is the reason for lifting of the partial clinical hold? Also, I really hope you don't believe that the 248 was reached around the time of the announcement? The company chose not to release the timing of when that event was reached so IMO it could have been reached anytime in 2016 (IMO most likely middle of 2016). The company should know this but appears to have chosen not to share it for now.
"I know NWBO said they weren't going to recruit any more patients but in theory if they wanted they could recruit 17 patients tomorrow if they were available." JJ
Excuse me but when did the company state that they could in theory recruit 17 more patients? Are you stating that the FDA allowed NWBO to continue to finish enrollment but the company CHOSE not to finish enrollment?
JMHO
Here's an encouragement. OS might show something positive like maybe txt arm has 24+mth medOS. I doubt it but at least I believe there is a slight chance of 2ndry endpoint success. But the primary endpoint of PFS seems like a total bust. In fact, the good news might be that the HR is something like 1.25 which would indicate indirectly that DCVAX-L is causing more pseudoprogression. I wouldn't underestimate LP's ability to pump any positives from this trial which MAY cause a surge in the sp- temporarily.
GL to you and JMHO
I would agree with Avii's assessment regarding this topic and endorse his views. If it is true that most pseudoprogression occurs within 3mth after the chemo/rad regimen (and some papers state as high as 6+mth), then this DCVAX-L p3 trial that has baseline 1 MRI scan done at 2wks AFTER the chemo/rad regimen will miss MANY psPD patients. If RK was correct and this trial used RANO, then many of those missed psPD patients would be caught and corrected, but if AVII is correct then those psPD patients will "wreak havoc to this trial" as Bosch sort of alluded to in his general comments awhile back by lowering the over-all medPFS numbers ESPECIALLY IF DCVAX-L caused some of that pseudoprogression (good thing for patients but bad for the primary endpoint). What does the evidence in how things are unfolding point to who is most likely correct? AVII or RK?
BTW Read this article regarding psPD in GBM:
http://www.ascopost.com/issues/august-15-2012/understanding-and-managing-pseudoprogression-in-glioblastoma-patients/
"The incidence of tumor pseudoprogression ranges from 28% to 66% in all glioblastoma patients undergoing chemoradiation and typically occurs within 3 months after the completion of concurrent radiation and temozolomide.1 Glioblastoma patients with promoter methylation of the repair enzyme 06-methyl guanine DNA methyltransferase (MGMT) may be at a higher risk of tumor pseudoprogression, with 91% (21 of 23 patients) of such patients developing early radiographic changes in one study.2"
For those who think that this p3 DCVAX-L is catching most of the psPD patients at baseline 1 is fooling themselves. There will be a percentage of those who pass baseline one and gets randomized into the main arm but will be ruled to have progression even if it is a pseudoprogression (thus psPD is wreaking havoc on trials as Bosch stated). Depending on the size of that percentage, this would tend to lower the blended medPFS so I'm not surprised that after the actual enrollment curve was shared, that my original guess on medPFS to be around 12mth went down to closer to 9mth. And also consider that they only randomized 32 psPD patients. That just seems too few from this trial screening numbers so I'm assuming that many others were "missed" at baseline 1 scan.
Again JMHO
Regarding Liau's slide that seems to indicate that she has access to blinded data (which should not be the case), there has to be a mistake on that slide unless her claims of being blinded to data was false. As Exwannabe pointed out, there is absolutely no way she could know how many placebo progressed without having access to unblinded data. So those who think that based on her presentation that 100% of the 110 placebo patients had progressed is probably a wrong assumption. She of course should be able to know how many entered the cross-over arm while still being blind to patient assignment. That to me makes more sense in regards to the 86 and now 90% numbers being thrown out there. Of course Bosch could have clarified that issue as well and specifying that those numbers represent the percentage who crossed over.
As for the 2 OS/mth correlating to 2 PFS/mth, if you look at the KM curve for PFS and OS, there may be a correlation early on and in the middle of the curve. But toward the latter curve, the correlation disappears because the OS curve tend to show a long tail whereas the PFS pretty much goes to zero. In otherwords, OS events rate will tend to slow down but PFS event rate will IMO not slow down as much as OS. So I am not surprised that the 86% (or about 285 PFS events) went up to 90% (298 PFS events) or 13 PFS events since Liau's presentation to Bosch's presentation. If this was true, then this would imply that there are only 33 patients who may have not progressed yet and that break down to placebo or treatment is blinded and cannot be known by Bosch or Liau. Thus one can project blended data but trying to break it further down to placebo or txt is more closer to guessing.
JMHO
First of all, you should check your assumptions. Your assumption that having 2 OS/mth should equate to 2 PFS/mth makes no sense at all. Also, you are assuming that Liau's slide regarding the break down of who got DCVAX-L did not have a mistake.
The most likely answer is that there were placebo patients who did not progress back in Dec 2016 who ended up progressing and getting DCVAX-L. That 86% went up to 90% and probably still going up IMO.
JMHO
"If the NWBO DCVAX-L PH3 read out is positive then we will proceed with having her vaccine made after the chemo and radiation treatments." NWDR
Couldn't you just go ahead and get the vaccine made through Cognate and the compassion program without having to wait for the results of this p3 trial? If KAT from the UK was able to do this in the US, then I don't see why you being in the US can't get it done here as well?
JMHO
"The bad dosing for DCVax and in only one tumor is surely the fault of the FDA. People died who might have benefitted from DCVax Direct. " Happy
Seriously, why would you try to blame the FDA for the design of the Direct earlier trials? It seems like you are one of the few who is finally acknowledging that possibly NWBO is responsible for the current sp and not some outside forces. Direct may have had some positive impact on patients but the onus of proving efficacy lies on NWBO and not the FDA. If direct had shown some ORR positive results, then the scientific community might have been more excited about its prospects. and IMO it made total sense to only inject a single tumor and it makes no sense at all to try to inject more than one tumor.
JMHO
market makers
"But, that 10 or 11 months doesn't fit with 248 events hitting late 2016. So something doesn't "fit"." AVII
Real simple. Maybe the 248 PFS events was hit mid 2016. There must be a reason why the company is so hush about when that was hit. BTW I thought JML did incorporate the 66PFS event timing for his modeling because I did the same and got what he did - around 12 mth medPFS blended. Now adjusting for the actual enrollment curve, I'm guessing that number drops closer to 9mths but your 10-11 mth is just as good. My model predicted that the 60% would be hit mid 2015, 80% around end of 2015, and 100% around mid 2016. Of course this wasn't taking into acct the actual enrollment curve to predict the timing.
JMHO since this is just a model prediction. The company I'm sure could/did something similar but won't disclose it.
"I understand that and I don't know why but I noted that more than 50% of patients in the Argos ph 3 trial were censored and that scared me a bit. I sure hope the number is much lower in this trial." Kab
Not to worry. The maximum censoring for the DCVAX-L p3 nGBM trial is around 30% for the combined cohort when that 233 OS event occurs(ed) and data lock is initiated. There is nothing to get scared about ARGOS trial having 50% censoring. If I remember correctly, they stopped at an IA for futility so it should be no surprised that the censoring would be that high. The real worry is if ARGOS could determine a futility boundary being crossed after a 50% OS eventing, then couldn't NWBO also do a futility analysis at an IA for OS, but that is assuming that there is even an IA planned for a secondary OS endpoint. That is the bigger issue, that the OS secondary endpoint may be moot at best in this trial in regards to FDA approval. Kind of unfair when a game is rigged with the company giving "hints" of hope when there is IMO none at all for approval.
JMHO
Kab, with all due respect, when you state 1 out of 93 patients are alive at month 60 time point, you are not clarifying the number of censored patients that play a significant role in generating the KM graph which must be seen as an ESTIMATE. This is why the very far right side of the KM graph is not a very good ESTIMATE. I guess I will state it again, the KM graph is an ESTIMATE that takes into account the censored data (censored for either good or bad reason like end of trial, missing with no chance of follow thru, etc. BUT for an overall survival KM graph, progression as an excuse for censoring does not exist as far as I know). You are right though regarding how KM graphs and this supposed long tail survival means to uninformed readers, they will put too much emphasis on that far right of that KM graph and put too much significance on it. I guess I can't blame anyone for doing that considering that even Dr. Liau is trying to make a big deal out of it. The FEW examples out there including the one that AVII posted where the long tail did affect the over-all HR positively is a unique situation and if one were to carefully look at those situations I would think that there were a good number of events in that later time points (and that is the key, a large collection of long term survival data is needed to make that far right portion of the KM graph to be more accurate- but this is a rather VERY expensive endeavor especially for NWBO and even at this point in time, not enough time has lapsed IMO for this collection to occur so far. Maybe by next yr, but IMO it will be moot at best because I don't think that there will be much of a SIGNIFANT difference between the two grps.
JMHO
"I did email Dr Stupp a while back to clarify how the KM analysis was done and to try and get more explicit data for the 2005 (NEJM) and 2015 (JAMA) publications. Specifically I was after the number of patients censored at each time point and for what reason when they did their KM analysis. However I never got a reply. " james
Seriously, do you really think that Dr. Stupps has the time to go back and find that information for you especially considering that what you are proposing is rather ridiculous assumption regarding censoring. Reading some of the other poster's understanding of censoring shows that they don't understand the role of censoring in generating a KM graph ESTIMATE for survival. Dealing with censoring is a MUST for generating the size of each drop by adjusting the denominator. I really don't think that there is that much of a variability in defining the criteria for censoring- rather it is cut and dry when to censor a data- and what you propose that Stupp et al censored upon progression for an overall survival KM graph simply does not make any sense at all from any angle. Also, regarding the interpretation of the far right of a KM graph that some posters are trying to make sense of, they don't seem to understand that portion of the KM graph is not very dependable ESTIMATE due to the very fact that there are less patients which means less accuracy.
JMHO and correct me if I misunderstood your assumption regarding Stupp et al.
JMHO
Avii, Flipper is correct. Looking at your KM graph of OS in that link, if you look real carefully at the 60mth point, you can barely see that the line for the total resection is slightly below that of the partial resection line. It helps to zoom in 500x. Of course, just ignore the rest of the graph where total resection is clearly shown to improve survival compared to partial resection. I particularly like that the long tail is around 10%- 20% range. Makes me wonder where DCVAX-L will fall within that range.
Great question Afford. I'd also like to know how he came up with 70million shares.
Here's what I saw only:
https://www.nwbio.com/nasdaq-accepts-nw-bio-remediation-plan-for-shares-and-warrants-previously-issued-to-cognate-bioservices/
"After lengthy discussions with Nasdaq and extensive negotiations with Cognate, the matter has been resolved with Nasdaq’s acceptance of a remediation plan under which:
(a) Cognate will return and the Company will cancel 8,052,092 restricted shares previously issued to Cognate under the MFN provisions of the 2014 and 2013 Agreements, and the MFN provisions will be deleted from those Agreements;
(b) Cognate will return and the Company will cancel warrants for 6,880,574 shares issued under the 2014 Agreements and the Company will issue to Cognate new warrants for 4,305,772 shares at a higher exercise price (resulting in a net reduction of 2,574,802 warrants held by Cognate); and
(c) Cognate will return and the Company will cancel 731,980 of the total of 5,101,330 restricted shares initially issued under the 2014 Agreements, so that the effective issuance price of the remaining shares will be adjusted to the market price on the date of those Agreements, as measured using Nasdaq’s criteria.
The Company will proceed with the registration of all shares and warrants held by Cognate, as was already required under the 2014 and 2013 Agreements for all securities issued thereunder.
The remaining portions of the multi-year lock-up periods relating to shares and warrants held by Cognate will be cancelled. Most of the lock-up periods have already taken place, with Cognate having been locked up during those times.
As a result of the foregoing, overall Cognate will return and the Company will cancel a total of 8,784,072 shares, and the warrants held by Cognate will be reduced by 2,574,802
The Nasdaq settlement does not affect other obligations of the Company to Cognate, including for existing unpaid invoices."
Note that those numbers are NO WHERE near 70million shares. Of course most people probably know this by now despite what is being touted on MBs.
JMHO
http://www.mdedge.com/rheumatologynews/article/104503/rheumatoid-arthritis/baricitinib-shows-encouraging-phase-iii-results
There were four cases of malignancy reported in the baricitinib group and none in the adalimumab group in weeks 0-24. Two deaths were reported in the baricitinib group and none in the other two groups.
FDA must be focusing along the lines of this safety signal. Otherwise, this drug should have been a clear cut approval. We're back to the risk-averse FDA.
JMHO
SGEN deal is halted by judge according to twitter. Getting interesting.
JMHO
"When an open-label trial has clinical responses (i.e. tumor shrinkage) measured by the investigators themselves, rather than by central adjudication, there is so much inherent bias in the measurement that it makes for a low-quality dataset. It’s doubtful, IMO, that such a trial would be sufficient for FDA approval in an indication (second-line CLL) where there are multiple approved treatments." DewD
I like to read negative posts because usually it has some substance. But to contradict your statements, this company PR stated the following:
"All responses were assessed by independent blinded central review using the iwCLL 2008 guidelines. Per iwCLL guidelines, responders require confirmation of response for a minimum duration of 2 months. As of the date of the analysis, each arm had responders that were awaiting confirmation visits which are scheduled to occur over the next two months."
We'll have to see in two months if there will be any surprises, but your comment is totally irrelevant to TGTX's Genuine trial. Also, what current approved treatments are you referring to in the second line CCL?
As for Exwannabee's comments regarding the changes to this trial, it doesn't hold water. Not that it isn't a risk factor but we will soon find out if the FDA will allow a BLA to be submitted or not. I'm guessing they will allow it.
JMHO
"It is curious also that Hopefulsurgeon reports the Chairman of the DSMB resigned. Just another data point here as we try to connect the dots. " AVII
I'm not too surprised that Dr. Furberg decided to resign considering how long this trial is taking to report the finish. In fact, I'm afraid that while we are trying to connect the dots, these dots will go on and on and outlive all of us before we get the completed picture.
JMHO
"Companies often have "Filing Teams" or they establish "Steering Committees". In the case of a stop rec (for futility or efficacy) these compartmentalized teams, if they exist, are consulted first.
Maintaining the blind protects the sponsor from disclosure responsibility.
"In particular, remaining blinded to interim results “protects the sponsor (and thus the trial) from pressure towards premature disclosure of results due to SEC [the Securities and Exchange Commission] requirements, fiduciary responsibility, or other business considerations."
https://researchonline.lshtm.ac.uk/13859/1/FullReport-hta9070.pdf
© 2017 InvestorsHub.Com, Inc.
" AVII
The above quote of yours refers to the DMC and not a TSC. The independent members of the TSC can see the unblinded data from the DMC reports but the sponsor representatives will only see the open portion of the DMC reports to remain blinded. BUT that would NOT be an excuse for the sponsor to fail to disclose that DMC recommendation in an 8K filing. The TSC will report to the sponsor while keeping the sponsor blinded to the interim data. BTW I highly doubt that NWBO created a TSC for this p3 trial.
Also, not sure how that Contrave OREX fiasco has anything to do with this disconnect between the TSC and the sponsor in regards to SEC disclosure requirements. In fact, the example seems to support the failure of the management to disclose the findings/recommendations of the TSC. IMO there is no good reason for the TSC to NOT communicate a DMC recommendation to the sponsor. In fact, it is almost impossible not to considering that the TSC usually has a sponsor rep in it.
JMHO
"Regarding the recent claim the "the company has never received a futility rec":
A Steering Committee, if in place here, can shield the sponsor from disclosure requirements.
" AVII
CAn you clarify this statement of yours or give an example? Very highly unlikely IMO that LP and the sponsor here would not be involved in the ultimate decision especially based on the PR's that this company has released so far.
JMHO
Yeah, I was "sure" because I trusted an SA analyst to do a thorough DD, but not anymore which would include SOS as well. That partial clinical hold made me curious enough to do my own modeling which confirmed your own DD as well as confirming Pyrr's numbers on how the PFS was trending. That is why I "flipped" my opinion late in 2015. Until then, I thought that maybe the company was trying to get another "enhancement" thru the FDA. But that CLDX conference call made me even more sure that there had to be an IA done sometime before that halt to screening of new patients occurred in Aug 2015.
I'm not sure how you could have flipped your opinion based on Liau's Oct 2015 removed youtube video considering that it wasn't posted on youtube and found by AVII until early 2016. Also, relying on Liau's statement about all patients living longer to mean that PFS is taking longer to event is to assume that PFS and OS correlates which is not accepted by the FDA and many other scientists in the GBM field. It might change once the iRANO criteria is fully adopted in these current CI trials, but won't help the older trials.
JMHO
Okay Flipper. I do remember us "flipping" our position on the timing of the IA. My original anticipation was purely based on Grant Z.'s analysis on SA (that was a mistake) and the company claiming to be blinded to the trial data. I don't recall LLiau's video from 2015 stating about not reaching whatever endpoint events etc. and can't confirm because THAT video was removed as well. I do recall LP stating "months" which would translate to sometime mid 2015 from my POV. But I also remember how "Sure" you were about an IA occurring in 2015 before we flip flopped on our opinions later. Anyway, thanks for your DD and GL with the rest of your portfolio.
JMHO
HappyLib, when did NWBO state that the IA was "pending"? I'm pretty sure it wasn't after mid 2015 when this company after they were caught hiding the suspension in patient enrollment by the public went into a carefully controlled silence mode.
As for your analogy, IMO I don't think you understand that the conducting of the PREPLANNED interim analysis is done by the INDEPENDENT DMC and NOT by the company. It is NOT a choice that a DMC will just decide to NOT do it on a whim. It would take something major like getting a major "enhancement" thru the FDA to stop the DMC from conducting that pre-planned IA. I wouldn't quite use the word "charge" because I mainly like to deal with probabilities: and IMO I SPECULATE that most likely there should have been an IA conducted back in around mid 2015 and the very FACT that there was no disclosure of the results of that anticipated IA means logically IMO that the results must have been bad.
BTW thanks to Flipper for helping me even realize that the company gave the guidance for when to anticipate the first IA. Also, Happy, I'm sure you were part of that conversation about that IA back in 2015.
JMHO
Boy Flipper, how ironic that you ask this question. I'd love to give a link but NWBO deleted that LP presentation. How convenient. Instead, I'll just repost one of your post. In Fact, I believe that is how I first even figured out that the management gave guidelines on when they expected the first IA. Thanks so much for your DD.
"flipper44 Member Level Thursday, 05/07/15 11:25:48 PM
Re: None
Post #
34366
of 105159 Go
Quote:
Linda Powers interrupts: No, no, no, no. No, well, if you know if the patients, umm, depending on the patients, of course. No, we think it is more like close
to the turn of the year. Like the beginning of 2016, not the middle. -- RK quoting LP from earlier in the year
Exactly.
The subtle powerful message is not slow enrollment, but that events keep taking longer than anticipated. First Les thought 1st IA in March of this year. Then LP thought Final IA by January 2016. Now they think First IA in June or later 2015, and the Final IA by June or maybe September 2016.
If one appreciates the clinics are opening quite fast while these predictions changed, I might surmise that patient "events" are not occurring so quickly, which is a powerfully positive subtle message that builds and builds.
Seize Opportunity. Trade at E*TRADE.Advertisement
Which insider are you referring to who bought half million dollar worht of shares recently?
Sure there is a chance that an approval could be done based on a VERY positive secondary endpoint of OS. It's just that IMO that chance is VERY slim in general. Personally I give that chance practically zero based on the hints given by their PI in her presentations- which is awful. No one IMO should be able to offer up any hints without a clear proper disclosure by the company in a proper 8K SEC disclosure.
That is JMHO
Sorry vator, you are referring to their ORIGINAL 1st IA when the 66 PFS events was declared by NWBO. I'm referring to the missing 149PFS NEW 1st IA that the management was anticipating sometime mid 2015. Did you not realize that? It is very irregular IMO to not disclose an IA that is supposedly preplanned in a trial protocol.
JMHO
Bravo! I applaud your persistence in argument. Yes, this is why the FDA does NOT recognize PFS (yet) as correlating to survival in GBM. It is IMO a design flaw in this p3 trial to seek regular approval with a primary endpoint of PFS. I can understand that it might be acceptable for seeking AA and using the OS as a confirmatory endpoint within the same trial. But what happens if the primary fails? Will that make a confirmatory secondary endpoint pointless? I can only make an educated guess that this would be the case and the FDA will IMO most likely not consider the OS data for approval UNLESS it is an amazingly huge difference. But LLiau put that likelihood as slim to none IMO with her statement that all patients living longer is NOT helping the trial but it is great for the patients (something to that effect).
Maybe that is why some really want to believe that there will be a confirmatory scan to correct for psPD- so to support their hope that the primary endpoint of PFS can show a SS difference.
JMHO
Diver, I respect that you have done your DD on this. Whether you believe it or not I have done a rather too extensive DD on this company along with many others in this particular niche in immuno-oncology. I acknowledge that there are potential changes (both good and bad) that are occurring in the regulatory field along with very fast paced changes in I-O. The criticisms against this company and their p3 trial are not just by some anonymous naysayers on a MB or a PhaseV blogger or even by NWBO's largest holder NW. It spreads to the scientific community involved in GBM research as expressed by the Dr. Weller presentation that AVII found. Many are interested in learning more from this p3 DCVAX-L trial and are deeply concerned by the delay in having the results publicized as well as the abnormal behavior of a company that is so reticent to being transparent. There should be a lot to be learned from that p3 trial to guide this field for the future. That being said, IMO it would be foolish to expect an approval based on this single p3 trial considering how things have evolved especially IMO when a missing IA from mid 2015 was never disclosed by the company. You claim to talk to the management. Have you ever asked them if they conducted an IA in 2015 and if they received a recommendation from the DMC?
JMHO
Serious, all that stuff is just details details. Who here or any MB other than scienceforums.net will be able to understand even the median amt of all that stuff let alone the mean. Come on, them MB longs are smarter than the FDA and still believe that PFS should be the prinary end point.
http://www.bmj.com/rapid-response/2011/10/28/method-prinary-screening.
NWBO's got the secret sauce baby! Try some n u will believe!
JMHO
RK with all due respect, I really don't understand your post. What does iRANO or even RANO have ANYTHING to do with this p3 DCVAX trial that was designed and started recruiting before either standards were formally recommended and implemented as the standard for clinical trials (not as standard of care). This "problem of pseudoprogression" is great for patients in this trial but sucks for the trial itself since PFS is the primary endpoint. Maybe the FDA understands this and that is why they tell all the other companies to choose OS as the primary endpoint for GBM p3 registrational trials.
"Why would a doctor, in giving the current standard of care, be required to give a premature determination. It doesn't make sense. And I don't think there are any indications yet that this is the case." biosect
Real simple. If the doctors have as much confirmation bias as those who are long on NWBO, then it is a no brainer to choose to get their patients on the "REAL" DCVAX vaccine ASAP by crossing them over as soon as there is ANY indication or suspicion of progression. Who cares about pseudoprogression- that's a problem for clinical trials and not for patients who will get the "real" vaccine sooner because of that "problem". As for whether this is all pure speculation, there are PLENTY of evidence that AVII has already pointed out MANY times: patient blogs, NWBO scientists and PI making public statements concerning the problem with pseudoprogression, the whole GBM society concurring with this issue of pseudoprogression, and the very fact that iRANO was recommended and is NOW being followed in the CURRENT designed GBM trials. DCVAX-L p2/p3 trial ABSOLUTELY CANNOT utilize the latest iRANO changes to correct for pseudoprogression without making their previous PFS data totally useless for comparison purposes.
No AVII, You are just plain wrong because I said so. Here's the proof:
https://academic.oup.com/asj/article-abstract/36/10/1198/2664529/What-is-Wrong-With-Systematic-Reviews-and-Meta?redirectedFrom=fulltext
What is Wrong With Systematic Reviews and Meta-Analyses: If You Want the Right Answer, Ask the Right Question!
Achilleas Thoma, MD, MSC, FRCS(C), FACS Felmont F. Eaves, III, MD, FACS
Aesthet Surg J (2016) 36 (10): 1198-1201. DOI: https://doi.org/10.1093/asj/sjw172
Published: 18 October 2016 Article history
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We see more and more systematic reviews (qualitative pooling) and their variant meta-analyses (quantitative pooling) being published in the Aesthetic Surgery Journal. Systematic reviews and meta-analyses are on the top of the hierarchy of evidence; hence their impact in practice can be quite large if done correctly.1 Unfortunately the current quality of published systematic reviews in plastic surgery is poor.2 The statistical jargon that is presented in most systematic reviews and meta-analyses seems impressive for the naïve reader who may unwittingly accept their conclusions.
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In this edition of the Hub we will use the published meta-analysis by Carloni et al, “Are There Factors Predictive of Postoperative Complications in Circumferential Contouring of the Lower Trunk? A Meta-Analysis”3 as a springboard to highlight some basic concepts of systematic review and meta-analysis. We also explain...
https://academic.oup.com/asj/article-abstract/37/2/NP22/2798667/Comments-on-What-is-Wrong-With-Systematic-Reviews?redirectedFrom=fulltext
Comments on “What is Wrong With Systematic Reviews and Meta-Analyses: If You Want the Right Answer, Ask the Right Question!”
Raphael Carloni, MD Florian Naudet, PhD Eric Watier, PhD Nicolas Bertheuil, MD
Aesthet Surg J (2017) 37 (2): NP22-NP23. DOI: https://doi.org/10.1093/asj/sjw230
Published: 03 January 2017
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We read with great interest the recently published Evidence Based Medicine (EBM) Hub article entitled “What is Wrong With Systematic Reviews and Meta-Analyses: If You Want the Right Answer, Ask the Right Question!” by Thoma and Eaves.1 We agree with most of the comments on the limitations of our study.2 Indeed, their didactic article drew attention to important methodologies that need to be adopted when appraising systematic reviews and meta-analyses. These methodologies allow non-statisticians to become more familiar with such papers, which are being published with increasing frequency in plastic surgery journals. For every scientific paper, it is important to be able to understand the research question, and to identify shortcomings in the methods used to generate the results; doing so might be useful for clinical practice or further research.
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Thoma and Eaves1...
JMHO
Is there such a thing as timely death? Also, these quotes are from dead guys? Semantics. Who says they're dead? Also, humanity being slowed down?! IMO it is humanity that is slowing itself down and we are witnessing it being played right now with this NWBO saga.
JMHO and GL and have a great day regardless of how the stock market is doing (or not doing)
Flip, GL to you too and best regards.
I disagree with you obviously but that is moot at this point. I just found out someone I know has cancer- and they are seeking alternative treatment. If one thinks the controversy around NWBO is serious, IMO what is worse is that concerning the quackery surrounding alternative medicine. Best regards to Liau and LP as well. I don't really care whether LP made tons of money from these related party transactions, but I do care to have them release ALL the data from this p3 trial for the benefit of future trials and GBM patients.
Some quotes:
“The statistics on death have not changed. One out of one person dies." George Bernard Shaw
"Some people die at 25, and aren't buried until 75"
Benjamin Franklin
"Live as if you were to die tomorrow. Learn as if you were to live forever."
Mahatma Gandhi
"Death is nothing, but to live defeated and inglorious is to die daily." Napoleon Bonaparte
JMHO
"I use many assessment criteria for tumors and even though they are meant to be objective, they rarely can be. At the end of the day it's a subjective decision many times." Reef
So it must suck to use PFS which is so SUBJECTIVE as this trial's primary endpoint according to your experience?!
"The other issue is that there is much more to lose by calling progression than by saying "attention in follow up" or "equivocal" or "indeterminate". In fact the word progression is frowned upon by oncologists unless it is 100% unequivocal" Reef
Sure, I'd agree with that. What NO likes to tell their patient that their last MRI scan showed a POSSIBLE progression despite the patient doing physically and mentally well (and these NO probably wouldn't bring this up unless the scans met the criteria based on the protocol to call it progression). At this point what can the NO tell these patients on this trial? Sure, the scan shows a possible progression but it could also be just pseudoprogression and let's wait for the next scan in 2mths to confirm. OR maybe the NO will advise the patient that he/she can cross over to make sure they get the REAL vaccine and not jsut placebo. Which scenario do you think patients and their NO will most likely choose for the BENEFIT of the patient?! AVII already showed at least one patient example of the latter scenario being played out.
And the interesting thing about the cross-over whether it was due to progression or pseudoprogression, the NO and the patient will be able to find out whether they were on the placebo or the TXT arm by either asking for the info or simply running out of vaccine. The blind is pretty much useless after cross-over and if the PI or the Sponsor is really inquisitive and seek out this information (which they shouldn't) then they would be able to get a better picture of how this trial is performing (this would be frowned upon by the FDA due to the introduction of bias).
JMHO