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One thing came to my mind with PREMISE study; plasebo effect. If I understood correctly, researchers didn't notice changes in baseline and after PTA.. So, did they show that plasebo has very little to do with PTA?

"Besides relapses, Siddiqui and colleagues examined other clinical outcomes including EDSS score, 6-minute walk distances, and Multiple Sclerosis Functional Composite score.

None of these measures changed significantly from baseline in either group, and there were no between-group differences, the researchers indicated"

They also didnt find positive demodynamic changes, so if PTA should fix flow, and they didn't notice plasebo effect.. then it's no wonder about study result.

Thank you, Dr. Hubbard! He provides the complete information off of the poster at AAN.
http://www.hubbardfoundation.org/CCSVI_ ... apers.html

Dr. Hubbard responds to the PREMiSe study also.

March 29, 2013

Editor

Neurology

201 Chicago Ave.

Minneapolis, MN 55415

Response to:

Siddiqui A, Zivadinov R, Benedict R, Karmon Y et al. 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, shame-controlled, prospective, randomized endovascular therapy in MS (PREMiSe) trial. Poster presented at the annual meeting of the American Academy of Neurology, March, 2013.

As the first trial of venoplasty in MS that was randomized and double-blinded including sham treatment, it is important to analyze whether the method and analysis justify the conclusions. Several questions arise that hopefully will be clarified when Dr. Siddiqui submits the study for journal publication:

1) How was the sham procedure done? Presumably a catheter was inserted, but how far was it advanced, through the internal jugular valves, into the azygos vein? How long was it left in place?

2) The inclusion criteria for pre-venoplasty diameter measured by IVUS was a reduction of ≥50%. Post-venoplasty diameter restored to at least 50% of normal proximal venous diameter. . A table should provide the actual diameters and an analysis of whether the restorations were significant, e.g. is a change from 49% to 51 % meaningful?

3) A venous hemodynamic insufficiency severity score was calculated to determine flow change over time and between groups. How was this calculated? A table presenting this data would be helpful. A statistically significant (p<0.0001) improvement from baseline to 1,3, and 6 months (combined) was found for the open-label group, but not for the treatment and sham groups (p=0.894). It would be interesting to know whether the change in vein diameter measured by IVUS correlated with the change in flow measured by the flow change score. Why was flow restoration in the open-label group successful but not in the treatment and sham groups? Were the operators and venoplasty method the same?

4) There were no statistically significant differences between the treatment and sham groups in MS relapses (p=0.389) and MRI lesion counts (p=0.81,0.5 and 0.079, Fig. 2). These results do not justify the conclusion the venoplasty “may increase MS disease activity in the short term.” No data is presented to support the conclusion that “more sizable change in venous outflow was associated with increased disease activity primarily noted on MRI.”

5) The poster concluded that venoplasty “failed to provide any sustained improvement in venous outflow as measured through duplex and/or clinical and MRI outcomes.” Since the study’s objective hypothesized that correction of venous flow would improve MS, why would MS improvements be expected if venous flow was not?

David Hubbard, MD

Academy of Neurology member

a "shame-controlled" study?

They'll never get, and no Dr's or studies are following this path, that stenoses are variable.

And as such, such studies are doomed from the start. While we argue internet wide ( I read comments posted on blogs all over the place), this and that minutae of the study (ies), whether it's a neuro running things, blah blah blah, never once does anyone ask, "hmm, what if these damn narrowings come, and go, move around, up and down, hither and yon", ( which can ONLY be ascertained by FREQUENT testing and irrespective of any "gold" standard designations, ), no, we settle for one, two, three distant moments in time, treat based on the first, then evaluate results of that moment in time,
and wonder why the results are not matching the testing?

Who cares about prevalence, or rather why do we care?

It's about X percentages of flow over X time and sprinkle in a crapload of
other variables, enviro, genetics diet etc.

This is why I feel like certain clinics are straight up RIPPING OFF
MS patients and taking advantage of their desperate need to try anything.

Since the so-called patient advocates wont stand up and say a damn thing after three years, I will:

People are getting ripped off. Period. Why? Because they are treated as a "snapshot in time" insofar
as the pathologies go, with zero pre-op other than day before, zero post op other than day after, and a big big BILL for anything that pops up later.

One day, when the medical and patient community understands that these
little stenoses CAN come and go, then we will stop this whack-a-mole approach
to treatment of narrowings, and get to the SOURCE.

Until then, all these ridiculous studies, imaging, treating or otherwise, are a waste of money, unless they incorporate imaging FREQUENTLY enough to show what I've already said, it is variable. Or better put, can be. Obviously not in all people, some were successfully treated PTA one shot done.

They are the exception and good for them. Good for us that did stents right out the door.
Variabilty not too much of an issue for us. Stents guard (but dont guarantee) against variabilities. Mine have kicked ass and taken names for four years, I spent 12 hours today in the hot sun, ensuring that Valero refinery got their precious money making gas line back in service tonight. They did.

I blame my stents for keeping the blood lines of communication open, but they are not the answer.

We need to get down to the nitty gritty why the narrowings happen when they happen, where they happen, and why they can vary and move around.

Until then, we are wasting millions of dollars studying the unstudyable.

When I see A**** defenders jousting to the death on FB like he's some god, it absolutely
sickens me. And they havent even been treated yet!. Or experienced failed treatment. Cult
of personality has replaced reason, if you make a good FB post you are golden.

I feel sorry for the newbies, just for the fact there is so much crap and personal
agendas to wade through, which are undetectable unless you know
the history, and background.

11:22 and I am off to another hot day at 5 AM. Have a great week.

Mark Miller

http://www.thebarrieexaminer.com/2013/0 ... -procedure

In 2011, a similar surgery called Prospective Randomized Endovascular Therapy in MS (PREMiSe) ran trials in Buffalo.

The researchers recently released results indicating only 11 of the 19 people saw improved conditions after PREMiSe surgery. (Arata points out one of the doctors involved in the research also suggested the autonomic system — not the veins — was benefiting from the procedure).

However, the study’s findings determined that while the treatment is safe, it didn’t provide sustained improvement for the patients.

Is that true? Eleven out of nineteen people treated in PREMiSe got improvements but because they weren't sustained they don't count?

“I was positive I was one of the ones who had the real liberation surgery,” Budd said, who travelled to Buffalo for the trials for a year beginning in Nov. 2011.

“I didn’t know until two weeks ago that I was right.”

Budd said she’s seen a significant improvement in both her fatigue and brain fog symptoms in the last year.

But perhaps the biggest improvement is her left eye where she’d lost vision and can now see again.

“You’re going to get varying results because not everyone got MS seven years ago and had all the same symptoms. But I don’t understand why they didn’t look at the successes of each person who had it, instead of the average improvement. My improvements were remarkable,” she said.

They have to look at the average because relapsing remitting MS goes up and down.
Maybe RCTs could ask the question: do you feel that you've had remarkable improvements? yes/no
People with MS know their own bodies!

Cece wrote:People with MS know their own bodies!

I am not so sure personally. With such a disease with a lot of self reported symptoms (eg tingling), I think it may be a condition apt for placebo effects more than say something more easily visible or measurable by third parties.

Cece wrote:http://www.thebarrieexaminer.com/2013/0 ... -procedure

In 2011, a similar surgery called Prospective Randomized Endovascular Therapy in MS (PREMiSe) ran trials in Buffalo.

The researchers recently released results indicating only 11 of the 19 people saw improved conditions after PREMiSe surgery. (Arata points out one of the doctors involved in the research also suggested the autonomic system — not the veins — was benefiting from the procedure).

However, the study’s findings determined that while the treatment is safe, it didn’t provide sustained improvement for the patients.

Is that true? Eleven out of nineteen people treated in PREMiSe got improvements but because they weren't sustained they don't count?

That was my point, they can't be sustained, because they are here today, gone tomorrow.
We keep desperately grasping at this study data, but the data is flawed from
the very first scan. This is like talking to a brick wall.

What I want to know is, if 11 out of 19 treated patients got improvements however temporary, did an equal percentage of shammed patients get similar temporary improvements? Or is this something that distinguishes the treated group from the shammed group?

Show me the data Cece for their conditions months prior, to months afterwards.

They don't have it, because it costs too much money. We aren't just guinea pigs,
but guinea pigs with dollar signs attached. Show me one Dr. that does regular evals
months prior to months after. We want the quick fix, or eval.

Such an animal does not exist, but WE will pay a king's ransom to hear as such.
I offered the above evals and post-evals for free, got one taker.

It is an American thing. We want to *think* that we get our money's worth.

Why get something for free, when you can spend 15k for it?

Same with these studies. There is too much money to be had doing mass
numbers of people, good bad or ugly. Zivadinov I called as a jerk from 2009, I was responded
to that he was a "friendly neuro" and we need these people to get CCSVI on
the map. And after he's spent the money, wonder of wonders.

I have no doubts from my personal experience that the procedure worked wonders for me. I see the difference every day even two years later. If this can help people, I want it to be available to the people it can help; and I want the researchers to identify who those people are so that no money is wasted, no unnecessary risk is taken, and no one lives for one moment with symptoms that could be alleviated through venoplasty.

The original idea was that by removing CCSVI, the MS progression would stop. Nobody was expecting improvements, not even in the long term, but just a delay of progression instead.

When improvements appeared it was a suprise for researchers, including Zamboni, and now we know they do not always occur.

We should not expect so much from this treatment and we should use the same evaluation criteria that we use with the other treatements.

frodo wrote:We should not expect so much from this treatment and we should use the same evaluation criteria that we use with the other treatements.

CureOrBust wrote:With such a disease with a lot of self reported symptoms (eg tingling), I think it may be a condition apt for placebo effects more than say something more easily visible or measurable by third parties.

Two very good points.

it's really unfortunate that the level of conversational respect ..... is lowering.

I have always thought of TIMS as more or less ..... a large roundtable of medical professionals ..... being observed by a large gallery of observers. A small circle surrounded by a large circle.Certainly NOT ... neutral observers . Loud and boistrous fans.

I am delighted to read of new medical professionals pulling a chair up to this table. New thoughts. Old theory's revisited . Thinking ' outside of the box ' .

At the middle of the table is something called .... MS. A complete mystery. Think of MS as a huge jumble of puzzle pieces. Do the Neurologists have some or most of the pieces in place ? Has Dr. Zamboni provided a edge of the puzzle ,or two or four ? I think he has.

The PREMISE Trial papers are now on the table for all to read.

It is most interesting to observe the comments of those sitting at the table .....

From Chaos ..... will come Order.


MrSuccess

Ernst , there is much ballyhoo [ that's also called bullshit in Finland ] about something called the Placebo Effect. In other words .... your mind CAN control your body.

I call bullshit on this.

Here is why. Try this at home. Sit in a chair . Hold your right leg straight out [ horizontal] and slowly rotate your right leg in a CLOCKWISE rotation . Without stopping .... lift your right arm straight out - [ again ... Horizontaly ] ...... now rotate your right arm in a circle COUNTER Clockwise direction ....

Your right leg will AUTOMATICALLY reverse direction and both leg and arm will rotate in the same direction - Counter Clockwise -. No matter how hard you try .... your brain will control your movements.

Maybe the sceptic anti-CCSVI Neurologists can train THEIR brains to do the impossible. Maybe a pwMS really CAN enlist mind over matter



MrSuccess

One poor example does not in invalidate a scientific belief demonstrated many times.