What to watch out for: placebo-controlled trials

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby eric593 » Tue Jun 08, 2010 9:05 am

Well, you can't double blind it unless neuro's are blinded but not IR's since obviously IR's know who was ballooned ans who wasn't.

But the point is to assess the neurological impact of ballooning versus those who only think they were ballooned.

Does the ballooned group improve neurologically in terms of existing symptom improvement or less relapses or worsening over the placebo group? Does ballooning have a significant impact on MS over the placebo group?
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Postby Fernie12 » Tue Jun 08, 2010 9:13 am

Leonard wrote:Zamboni treated 120 patients.
All of them must have had expectations, and I guess most of them improved.
After a while, some got worse.
Tests then revealed that they had restenosed.
They were treated again and improved (e.g. the heart surgeon from Northern Ireland).

What else do "they" want?
This is not a test of the effectiveness of one or the other molecule.
The rules for mechanical surgery are at least here in Europe very different.
Treat a person with a broken leg through sham surgery?
Hope that the placebo effect will then heal his leg?
They ought to be deeply ashame.

It is unethical and I can only hope that doctors will not cooperate.
Apart from that, what if the patient later on finds out that he was not helped and has detoriated further? Who can be held liable?
Will "they" let you sign a declaration with so many small letters, cleverly drafted by lawfirm?
This is unfiar, unethical etc.

The practices for testing MS medication can not be simply carried over like that.
They should think first and then speak.


I totally agree with your post. All of it.
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Postby Cece » Tue Jun 08, 2010 9:14 am

Leonard wrote:It is unethical and I can only hope that doctors will not cooperate.
Apart from that, what if the patient later on finds out that he was not helped and has detoriated further? Who can be held liable?

I don't think anyone gets held liable...you sign it away when you join the trial. Remember those college students in the UK who took an immunosuppressive drug that had worked in animals...and ended up in the hospital in critical condition? Now that is a situation where I wonder if they had any recourse...not in this one, where the control group will be getting the standard treatment.

And the hope that doctors will not cooperate is unfounded: there are three separate trials, in IRB stages or in the case of Buffalo possibly further, that have a randomized placebo-controlled component.
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Postby Cece » Tue Jun 08, 2010 9:16 am

I completely agree that people who join research trials are to be commended...just as we should "support the troops"...but same as for troops there may be personal sacrifice involved that pits your own best self-interest against the good of the many...and honestly when it comes to health, what MSer has not already sacrificed too much?

eric593 wrote:Well, you can't double blind it unless neuro's are blinded but not IR's since obviously IR's know who was ballooned ans who wasn't.

You just need two IRs: IR#1 performs the surgery on IR#1's patients, then sees only IR#2's patients for blinded follow-up. IR#2, meanwhile, performs the procedure on IR#2's patients but sees IR#1's patients for blinded follow-up.
eric593 wrote:Cece,

If you are so convinced of the treatment of CCSVI ameliorating MS, then you shouldn"t have any problem being in a blinded trial. If the results of the CCSVI treated arm are overwhelmingly superior to the placebo arm, the trial will be halted in short order with everyone receiving treatment, as happens in trials where efficacy is so demonstrably superior to placebo. So you'd be treated rather soon anyway if the treatment is obviously far and away beneficial. So you shouldn't have to wait long anyway even if you get the initial placebo if treatment is as amazing as is being expressed by some.

This is why I asked if Dr. Zamboni's results would've been considered so blow-away good that they'd have stopped a trial and given the treatment to the control group, had there been a control group.

There were people in his group who relapsed. There were the primary progressives, who did not show much change. Some of the significant effects are in cog-fog reduction and fatigue reduction, which are hard to measure. I think they'd have seen the trial out, I would not go into a trial with the expectation that it would end early.
BooBear wrote:Do surgical procedures go through the same process as drugs do? I am not sure that is the case, but I welcome thoughts here.

Twenty years ago they didn't, but now they do. The recent health care bill that was passed also has some initiatives to test current practices to see if they are worth their salt also.
"However, the truth in science ultimately emerges, although sometimes it takes a very long time," Arthur Silverstein, Autoimmunity: A History of the Early Struggle for Recognition
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Postby 1eye » Tue Jun 08, 2010 9:48 am

Leonard wrote:
Zamboni treated 120 patients.
All of them must have had expectations, and I guess most of them improved.
After a while, some got worse.
Tests then revealed that they had restenosed.
They were treated again and improved (e.g. the heart surgeon from Northern Ireland).

What else do "they" want?
This is not a test of the effectiveness of one or the other molecule.
The rules for mechanical surgery are at least here in Europe very different.
Treat a person with a broken leg through sham surgery?
Hope that the placebo effect will then heal his leg?
They ought to be deeply ashame.

It is unethical and I can only hope that doctors will not cooperate.
Apart from that, what if the patient later on finds out that he was not helped and has detoriated further? Who can be held liable?
Will "they" let you sign a declaration with so many small letters, cleverly drafted by lawfirm?
This is unfiar, unethical etc.

The practices for testing MS medication can not be simply carried over like that.
They should think first and then speak.

I can agree with this post. The truth is, this is an unsolved ethical dilemma along similar lines to the problem of euthanasia. The difference is, a lot of 'MS' patients, and a lot of doctors, do not understand or have sympathy for people with progressive 'MS'. I know, because I used to be one of these. It is very hard (it was impossible for me) for a person who is able-bodied and healthy to even suspect what life wiould be like when they have lost all their health, all their dignity, and even their abilites to think.

This whatever it is, this problem with what we have circulating in our brains, will not go away. There are always those who will promise you health. But after a while you get very cynical about such offers. Especially because they never seem to get the success you know they would if they were any good. Eventually, even your life will fall apart. Because the promise is, that most RRMS becomes SPMS.

I did not admit it to myself for a long time. When I safely held down a high-paying job, I even interviewed for a job at a similar high level. At the time, I still had my driver's license, could still play the guitar, and still walk reasonably well. The guy might even have been able to do the job, somewhat. But he had SPMS. I could see that unlike myself, then only RRMS, he was not a very good risk. In a few years' time, I was punished for that crime. But I cannot even convince you with that. All I can do is say: remember the day you found out about your MS. SPMS may surprise you like that. SPMS may sneak up on you.

Or you may deny it, like I did. Denial is good. Keeps you in shape. But accepting bruises, gooseggs, hematomas, etcetera, will be necessary, if you are lucky.

I used to tell myself this was all hogwash, it's not a different disease, I just won't let myself get so sick. I had always succeeded, more or less. I was unable to put myself into the shoes of the disabled. I had no empathy. But that is a perilous state for a person who is RRMS. Because the odds are not with you. You may think you have everything under control, but the day you realize you are not going to get any mor remissions..

It's sometimes, still, less gradual. Sometimes it attacks, but much less frequently. Like the day I realized I couldn't play guitar anymore. Oh I still play with the piano, because I was never any good anyway, so I can't disappoint myself. But the guitar, I could never compromise with. Now it's nothing but. So I don't go near it.

But eventually, though you can't imagine it now, you will only have progression. Like getting old, but faster. Because there are limits to the number of times and ways your systems can fail. But symptoms which seem tolerable now, can sometimes get much worse. After a while, even if you have saved some money and would like to use it, for example for an elevator because you can't use stairs, you just can't get your mind around taking even more of a footprint and denying your family what they need to be successful and happy in this world. Stuff like art supplies; skateboards, trips. You can't take trips much because they are so much work. For you and even more for your companions.

I'm not trying to give you a sob story. Nor am I trying to be negative, though I know this can be, especially to those who have not yet had to live it. You cannot possibly imagine. You can wander around YouTube but you will not see MS at it's worst, or even close.

I guess I am saying don't play lightly with the idea of placebo, because this disease can be not very pardoning. During placebo, especially with progressive MS, you may lose something that never comes back. Or you may cross the line and realize you can't do something anymore. Like react quickly enough to drive. Or like be legally sighted. You won't really care that you have less lesions on your MRI. Or you may only have slow progression, which just takes you closer to those nadirs, on a track you are well familiar with.

Notice nowhere above did I mention despair or desperation. If you did not have hope, you would not be in a trial. But pity the poor soul who's on the cusp of both major new disability, and going on placebo. Sure, they can always withdraw. Some consolation. Just don't tell them that they were better off on placebo than no treatment at all. You're not likely to stay friendly that way. Then again maybe you'll see what a fool all this voodoo pseudo-science has made you, and the world will be a slightly older but wiser place.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Postby NZer1 » Tue Jun 08, 2010 1:47 pm

I'm enjoying this thread, I have PPMS.
Treatment is currently available. Two problems so to say 1.Cost 2.waiting lists.
In time to come the situation will change, there will still be two problems 1. Cost 2. waiting lists.
The thing that will change will be where treatment is available, and there will be even bigger waiting lists as more people enroll.
There is safety to be resolved and there is benefit to MSers to be proven. The question of quality of life improvements has the greatest power in the equation.
If we can't afford treatment now why are we beating ourselves up. Hope is vitally important and it needs a degree of reality so that it doesn't destroy itself.
Time is the denominator that we will have to surrender to. Trust the process.
Some very skillful people are working on this whole issue, they need our support and they need us not to whip this into a frenzy and cause backward steps.
It would be very easy to create more harm than good.
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Postby JCB » Tue Jun 08, 2010 3:18 pm

I too have PPMS, and would be willing to be in a controlled study. Not because I'm such a great guy (I'm not), but because I would hopefully either not be in the placebo group, or would get treated faster. I am on a few lists now playing the waiting game.

Let's prove this thing once and for all.

I am also a type 1 diabetic and have done countless studies in the hopes that if a cure is found I would be further up the list. Either way science is moved forward. I am all about progression except when it comes to my MS. Whatever I can do to speed up this entire process, I'm ready to get in line. I do not think double blind placebo controlled group studies are required with this procedure. I don't even think they are ethical, but again "they" aren't asking my opinion.

So... where do I sign
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Postby mshusband » Tue Jun 08, 2010 6:03 pm

Again I'm going to say it ... and if anyone wants to take me up on this bet I'll more than willing put down any amount you want.

Hopefully one day we all look back and be like ... man that MSHusband guy was right.

It doesn't matter what your neurologist calls your disease course anymore ... CCSVI IS going to be what it's called in the future.

What is going to be important for CCSVI are the following 3 things.

1. Which vein(s) is(are) stenosed
2. Time
3. How bad is the stenosis

That explains all the following of MS ... type/symptoms/progression and more

PPMS (azygous vein stenosis = spine lesions)
RRMS (jugular vein stenosis = brain lesions)
SPMS (jugular vein stenosis + time, azygous stenosis = brain and spine lesions)
RPMS (jugular and azygous stenosis = brain and spine lesions)
Let's remember ALL MS is progressive (remember 50% go from RRMS to SPMS in 10 years (azygous anyone?) and 90% in 30 years ... so really are you primary progressive all along (just azygous stenosis isn't that bad in that group?)??? Think about it.


Thus:
someone with VERY bad azygous stenosis will be in a wheelchair quickly.
someone with moderate azygous stenosis will take longer.
someone with light jugular stenosis (and no azygous involvement) will likely never progress much at all (and may just have optic neuritis and fatigue)


Symptoms will even start to be figured out (based on lesions and vein stenosis)...

fatigue = in everyone because the body gets worn out from fighting itself all the time

numb hands = stenosis higher up - in the cervical spine (jugular veins putting pressure on the vertebral veins)

numb feet = stenosis lower down - in the thoracic spine (azygous vein) ... left side because the hemi-azygous and accessory hemi-azygous is getting reflux
right side because the azygous is taking the reflux back through

speech issues = stenosis in the jugulars causing brain activity (which part of the brain affects speech)

walking troubles = azygous stenosis (again left side vs. right side as above)

l'hermittes = stenosis in the jugulars putting pressure on the vertebral veins (lesion in the cervical spine)

urinary/bowel problems = brain involvement (which part of the brain affects those controls)

IT ALL MAKES SENES FOLKS. TELL ME WHAT I SAY ABOVE THERE DOESN'T MAKE SENSE?

IN 20 YEARS OR HOWEVER LONG IT WILL BE MEDICALLY 'PROVEN' BUT I THINK DOCTORS WILL HAVE FIGURED THIS OUT LONG BEFORE THEN (IN FACT I BELIEVE SOME HAVE ALREADY).

Again, if anyone wants to bet me ... I'll take that bet right now.

If you really don't believe me ... google the nerve responders for different parts of the brain and spine and where they control) then compare it to your symptoms and where your lesions are ... and when you have CCSVI treatment, compare that to where you had stenosis.

You're all going to see this makes too much sense. It's all ENGINEERING, it's simple. The human body is very complex, but at it's core very simple.

Unfortunately some damage currently in persons with MS for a long time won't be able to be healed, but in the future when people get CCSVI treatment as soon as they present an MS symptom ... it's going to be able to ALL be healed.

But those of you newly diagnosed or without bad symptoms right now ... GO GET CCSVI TREATMENT IMMEDIATELY.

AND ... if they don't find stenosis in your azygous ... don't settle for it. Dr. Zamboni found azygous stenosis in 86% of his patients (and 91% in the jugulars). From what I read about people being treated in Poland, they're not even finding close to those percents. Dr. Sclafani had started to find a lot more azygous stenosis right before he was shut down ... that azygous vein is going to be the KEY. Don't leave the doctor until they are 100% sure they either find stenosis in the azygous ... or can guarantee there is nothing there.

Again ... make my words. TIME will tell ... but I'm usually right (at least my mom always told me growing up ... you ALWAYS think you're right - even then I usually WAS).

:D

PS I've never talked about my wife on here (but I'm going to start right now to prove a point). Her 1st symptom was depression (years ago in college). We never connected it to MS until we made the CCSVI connection - so we went and compared her brain MRI with the part of the brain that controls happiness and other emotions ... guess what? Lesion ... LIKE I SAID ... read through above. It's amazing neurologists couldn't figure this out YEARS ago ...

THANK YOU DR. ZAMBONI
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Postby scorpion » Tue Jun 08, 2010 6:13 pm

I will take that bet.
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Postby Drury » Tue Jun 08, 2010 6:15 pm

mshusband,

That was brilliant!!!

Drury
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Postby mshusband » Tue Jun 08, 2010 6:20 pm

How much scorpion ... you're on ...
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Postby JCB » Tue Jun 08, 2010 6:38 pm

mshusband,

It all makes sense to me too. If scorpion has deeper pockets than you let me know. I am willing to help out.
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Postby mshusband » Tue Jun 08, 2010 6:44 pm

Trust me ... he doesn't. (thanks for the offer though, it's very kind, if he actually does want to bet and pays up - I'll give you some of the proceeds).

I'm an engineer and my wife's a psychologist - both graduates of some of the finest schools for our degrees in the country. We've got it covered - unless he's Dr. Mark Freedman and is willing to bet all his "MS Society and government funding for his 'stem-cells' as a cure" that he wants to put down.

After all, we really don't know who HE "is".

BUT I don't want to drag this thread down, because I think the points I made are VERY important for EVERYONE to read and consider, and not get sidetracked by a "bet".
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Postby Cece » Tue Jun 08, 2010 6:49 pm

JCB wrote:I too have PPMS, and would be willing to be in a controlled study. Not because I'm such a great guy (I'm not), but because I would hopefully either not be in the placebo group, or would get treated faster. I am on a few lists now playing the waiting game.

You might be a great guy, don't sell yourself short. :)

I can see where you're coming from, my concern though is the idea that being in a controlled study will get a person treated faster. For the placebo group, it might put treatment two years into the future, going by Dr. Sclafani repeatedly saying that two years is how long a randomized trial should be. You can do much better than that on almost any waiting list.

1eye wrote: Because the odds are not with you. You may think you have everything under control, but the day you realize you are not going to get any mor remissions..

Some scary authentic truths here. As a relapsing-remitter, I have gotten used to the ebb and flow...it is hard for me to imagine what it might be like to be well and stay well, as is the hope with the venoplasty procedure... and I try not to spend much time thinking about the getting worse and staying worse either.
NZer1 wrote:Time is the denominator that we will have to surrender to. Trust the process.
Some very skillful people are working on this whole issue, they need our support and they need us not to whip this into a frenzy and cause backward steps.
It would be very easy to create more harm than good.

When I started this thread, I thought about this...I think there will still be plenty of people willing to participate in randomized trials. I don't think this thread, which will drop off into the archives within a few days, will have that much of an effect on anyone's decision. There is such difficulty in getting treated at all, that if an opportunity to be in a randomized trial came up, I think a lot of people would grab it. I just don't think they should...at least not without thinking it all the way through and being aware of any other better options that might be out there.
"However, the truth in science ultimately emerges, although sometimes it takes a very long time," Arthur Silverstein, Autoimmunity: A History of the Early Struggle for Recognition
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Postby Cece » Tue Jun 08, 2010 7:50 pm

mshusband wrote:It doesn't matter what your neurologist calls your disease course anymore ... CCSVI IS going to be what it's called in the future.

What is going to be important for CCSVI are the following 3 things.

1. Which vein(s) is(are) stenosed
2. Time
3. How bad is the stenosis

mshusband, brilliant, you break it down to exactly what it's all about. From this part in particular I take away: let go of the old ways of thinking about this disease, here are the new ways, and don't they make a helluva lot more sense.

And TIME is huge...I've lost enough of my life to this. In Budd-Chiari, when the veins that drain the liver are blocked, you end up with a liver transplant at around age thirty, because of the thirty years of slow damage. I've got thirty-five years of slow damage to the brain and, yeah, no brain transplants coming...but, oh man, to think that there is finally something I can do about it...it is too sweet a possibility, I don't want to waste a minute.
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