Embry: Actual data from PREMiSe suggests CCSVI is of value

[MrSuccess]

let's keep the ball in the air in this conversation. I certainly am enjoying the exchange of information . And learning a few new things , to boot.

for what it's worth ...... I think the results are produced with more than you know ...in mind.


Always look for the Truth in the Lie ...... and at the same time .... The Lie in the Truth.


Yeah , I don't like it either .... but there i$ a hell of a lot at $take.




....put your head on my chest , 'cause I'm .....



MrSuccess

[NZer1]

ScutFarkus I see you use the mindset to discredit anything that I ask rather than see that there is logic in what I ask.

OK, fine, I give up. I was sincerely trying to be helpful in my reply to your post, and I thought the tone was friendly, but it's clear that what we have here is a failure to communicate.

/Scut

Thanks,
I appreciate you realising what you are doing!


N

[centenarian100]

I think Dr. Embry's anger may come from the fact his charity gave $125,000 to PREMiSe

Whoah!

[centenarian100]

Interesting. So, had the results been positive, I assume we'd have to accuse the researchers of blatant pro-CCSVI bias due to all that cash from "big-CCSVI". I jest, of course!

I guarantee that people would make this accusation.

Funding bias is important to consider, but it can't be avoided in most cases.

Who is going to fund a new drug or device trial with a cost on the order of millions of dollars other than the companies which stand to profit from a positive trial?

A lot of older off-patent drugs never get adequate testing.

For instance, azathiaprine may have comparable efficacy to first line MS drugs but is uncommonly used.

Sources:

1) azathiaprine vs placebo: http://www.ncbi.nlm.nih.gov/pubmed/17943809
2) meta analysis of 7 trials: http://www.thelancet.com/journals/lance ... E/abstract
3) German poster at AAN on rebif vs. azathiaprine for RRMS with equality with trend toward superiority for azathiprine

In fact, azathiaprine is somewhat mechanistically similar to teriflunamide (purine and pyrimidine metabolism inhibitors respectively) and may have comparable efficacy and safety.

Doctors, drug companies, and device companies want to make money. It doesn't make them bad people; it's just a fact of life.

[centenarian100]

lfor what it's worth ...... I think the results are produced with more than you know ...in mind.

Care to elaborate on this remark?

[ttucker3]

You are a perceptive lot. I would like to add that man’s execution of scientific endeavor may be driven by my more than scientific curiosity alone. Other human factors, such as greed, wrath, envy and pride (acedia and vainglory?) may also, conceivably, be motivators. I would like also to quote American author, Upton Sinclair who said that, "It is difficult to get a man to understand something, when his salary depends upon his not understanding it!" (http://en.wikiquote.org/wiki/Upton_Sinclair).

Trev. Tucker

[Cece]

Further, I wonder what throwing out the one outlier who had 8 new lesions would do to Dr. Zivadinov's statement? There seem to be two key differences between the treated and sham group. The first is that the treated group had more active disease in terms of an average of 1 previous relapse compared with only 0.4 for the sham group, half the number, and that one person in the treated group had 8 new lesions

I've been thinking about that outlier. I looked up the previous study:
http://www.thisisms.com/forum/chronic-c ... ml#p173450
In that one (a joint Ferrara/Buffalo treatment trial, with one group treated immediately and the other group delayed), there was one patient in the treated group whose MS had a recurrence and worsening on the MRI. That might be similar to this outlier. It's not outside the realm of possibility that improved blood flow is good for the majority of people who get the procedure but not good at least in the short-term for a minority percentage who respond with an immune attack when blood flow is restored.

[cheerleader]

If we remove all claims of bias, all insinuations, all MS outliers, everything...all the word salad.
We're still left with this fact.

Phase 2 patients did not have their CCSVI corrected any better than the placebo patients.
The Venous Insufficiency Severity Scores were the same for treated and untreated patients!!

This is called a treatment failure. PREMiSe was a failure. Patients did not have their CCSVI corrected.
All results after treatment are invalid.

It would be like trialing carotid endarterectomy and leaving the artery closed. You wouldn't blame the patient for having a blocked carotid artery and seeing no benefit...you would ask the treating doctors WHY they did not fix the problem.

Please, join me in asking BNAC WHY they did not successfully treat CCSVI, yet chose to publicize their "results" of a failed treatment. If they want to use YouTube, Facebook and the press to spread their "results"--we can ask them questions publicly, using the same medium.


cheer

[ScutFarkus]

If we remove all claims of bias, all insinuations, all MS outliers, everything...all the word salad.
We're still left with this fact.

Phase 2 patients did not have their CCSVI corrected any better than the placebo patients.
The Venous Insufficiency Severity Scores were the same for treated and untreated patients!!
This is called a treatment failure.

This is true, and is indeed a big mystery.

PREMiSe was a failure. Patients did not have their CCSVI corrected.
All results after treatment are invalid.

This is where I disagree. The stated objective of the study was "To investigate the safety and efficacy of percutaneous transluminal venous angioplasty (PTVA) for correcting CCSVI in MS in the setting of a prospective, double-blind, sham-controlled, randomized pilot trial". Specifically, the goal of the trial was to test a procedure, PTVA, not to test what happens when you correct CCSVI. The results show that this procedure wasn't effective in the effectiveness part of the trial, and might be associated with worsening of symptoms. This is a valid result.

Again, if you're testing whether or not a procedure is effective in achieving some goal, and your test results suggest it's not effective, this is still a valid test of the procedure.

It would be like trialing carotid endarterectomy and leaving the artery closed. You wouldn't blame the patient for having a blocked carotid artery and seeing no benefit...you would ask the treating doctors WHY they did not fix the problem.

You're too focused in the secondary (non-goal) objective of measuring patient improvement when their CCSVI is corrected. We were all hopeful this trial would yield results on that question, but sadly it didn't for the reasons you specify. But since that wasn't the primary goal, you cannot reasonably claim the trial was invalid for not hitting that goal.

Please, join me in asking BNAC WHY they did not successfully treat CCSVI, yet chose to publicize their "results" of a failed treatment.

I feel that only the first part of your question (why the procedure wasn't effective) is a valid question.

The trial as a whole was valid and has valid results, even if they're disappointing and don't answer the "real" question on all of our minds (of whether or not correcting CCSVI improves MS).

/Scut

[NZer1]

Further, I wonder what throwing out the one outlier who had 8 new lesions would do to Dr. Zivadinov's statement? There seem to be two key differences between the treated and sham group. The first is that the treated group had more active disease in terms of an average of 1 previous relapse compared with only 0.4 for the sham group, half the number, and that one person in the treated group had 8 new lesions

I've been thinking about that outlier. I looked up the previous study:
http://www.thisisms.com/forum/chronic-c ... ml#p173450
In that one (a joint Ferrara/Buffalo treatment trial, with one group treated immediately and the other group delayed), there was one patient in the treated group whose MS had a recurrence and worsening on the MRI. That might be similar to this outlier. It's not outside the realm of possibility that improved blood flow is good for the majority of people who get the procedure but not good at least in the short-term for a minority percentage who respond with an immune attack when blood flow is restored.

Way to many assumptions from this one example of how unpredictable 'MS' is.

If the person was thoroughly tested and answers were sort as to why a person for no apparant reason has a flare in the disease then some indications would be interesting.

No-one, I'll repeat that again, No-one knows what MS is caused by, and no-one knows what connection MRI findings have to MS. That has been established, yet we are not taking notice of this fact!

I TOTALLY agree with Joan that trial was a failure! The purpose was to test CCSVI PTA treatment and use listed methodology to gauge the effects of treatment.

So why would you target less than 50% improvement as the benchmark for assessments!

All that can be said is that for XYZ amount of Time and Money, patients were put through a stressful process by BNAC who 'did' a Trial, which was dragged out into two parts that were disconnected from each other, and they chose to test how CCSVI undertreatment would perform!

If I was a Sponsor I would be asking for my money back because I was mislead by BNAC!

Thanks Trev, good to hear from you!

;)
Nigel

[NZer1]

Quote;
"centenarian100 wrote:
NZer1 wrote:
Who looked comfortable and who looked very uncomfortable and was cut short in the staged PR interview, WHY?


Is someone in bed with Dr. Zivadinov?! DUN DUN DUUUUUUN! "


My reply;
I saw that Dr Z was uncomfortable and I think that was an indicator he was put in a situation by others. I personally think he is not happy with the performance of BNAC regarding this trial. Just to clarify!

;)
Nigel

[Shayk]

Cheer wrote:

Phase 2 patients did not have their CCSVI corrected any better than the placebo patients.
The Venous Insufficiency Severity Scores were the same for treated and untreated patients!!

Agreed and I think by virtue of the title of the poster from the AAN site I think some people at BNAC know this (emphasis added).

P04.273- “Percutaneous Transluminal Venous Angioplasty (PTVA) is Ineffective in Correcting Chronic Cerebrospinal Venous Insufficiency (CCSVI) and May Increase Multiple Sclerosis (MS) Disease Activity in the Short Term: Safety and Efficacy Results of the 6-Month, Double-Blinded, Sham-Controlled, Prospective, Randomized Endovascular Therapy in MS (PREMiSe) trial” - Robert Zivadinov, Buffalo, NY

I question why this wasn't highlighted or even acknowledged in the publicity. ??? if the pr folks at the university wanted to put their own spin on it--perhaps to benefit the university.

I also wonder why no one has questioned whether the difference between sham and treated was because of a failure of DMDs. I know the trial wasn't about that, but everyone (treated and sham) was required to be on a DMD and interferons are known to produce antibodies (in some people) that increase lesions, relapses and disability. Were the people with more lesions on interferons? Did they have antibodies to the interferons? Did their DMDs fail them?

Lots of questions...more research needed.

Take care all

Sharon

[MrSuccess]

make no doubt about it ..... DMD's .... play a significant role in ANY trial . They are indeed 'the devil in the details ' .

Again .... MrSuccess strongly suggests that any future CCSVI >>>> MS Trial , can only yield true results ...... when .... ALL of the Trial participants have not one drop of ANY of the DMD's , inside of them.

Take DMD's out of the equation ...... then look at THOSE results.

It can be done . I'm certain they can round up 30-50 pwMS that are on this path.



MrSuccess

[centenarian100]

This is where I disagree. The stated objective of the study was "To investigate the safety and efficacy of percutaneous transluminal venous angioplasty (PTVA) for correcting CCSVI in MS in the setting of a prospective, double-blind, sham-controlled, randomized pilot trial". Specifically, the goal of the trial was to test a procedure, PTVA, not to test what happens when you correct CCSVI. The results show that this procedure wasn't effective in the effectiveness part of the trial, and might be associated with worsening of symptoms. This is a valid result.

Again, if you're testing whether or not a procedure is effective in achieving some goal, and your test results suggest it's not effective, this is still a valid test of the procedure.

I agree with this scut, but the venous insufficiency severity scores may suggest that the lack of benefit was due to the poor correction of CCSVI rather than that correction of CCSVI does not have benefit in multiple sclerosis.

[ScutFarkus]

This is where I disagree. The stated objective of the study was "To investigate the safety and efficacy of percutaneous transluminal venous angioplasty (PTVA) for correcting CCSVI in MS in the setting of a prospective, double-blind, sham-controlled, randomized pilot trial". Specifically, the goal of the trial was to test a procedure, PTVA, not to test what happens when you correct CCSVI. The results show that this procedure wasn't effective in the effectiveness part of the trial, and might be associated with worsening of symptoms. This is a valid result.

Again, if you're testing whether or not a procedure is effective in achieving some goal, and your test results suggest it's not effective, this is still a valid test of the procedure.

I agree with this scut, but the venous insufficiency severity scores may suggest that the lack of benefit was due to the poor correction of CCSVI rather than that correction of CCSVI does not have benefit in multiple sclerosis.

Agreed completely. We were all hoping this study would provide some scientifically robust results showing whether or not CCSVI correction would improve symptoms. But since the correction itself failed, the study results don't answer that question.

However, the results do provide relevant data on a question patients should be asking, which is "if I have this procedure, will I see improvement." Failure of the treatment itself, just like restenosis following successful treatment, is a real possibility. This study suggests it may be a high probability result, but until we have more info on what went wrong here, we don't really know.

/Scut