How can we design a trial to test efficacy of the surgery?

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

How can we design a trial to test efficacy of the surgery?

Postby fogdweller » Mon May 10, 2010 12:35 pm

I am not a professional at designing medical trials, and if some reader is, please step up.

In my unexpert opinon, there are two ways you could go. First, you need some objective and measurable thing to test ... e.g. fatigue level if you can figure out how to measure it, or walking ability, or the 6 pin hand coordination method.) I really don't want to test Relapse Rate. That is what all the drug trials did, and none of the drugs slowed progression, and since I have PPMS and have never had a Relapse in my life, this is not attractive to me.)

Then you take a bunch of test subjects and divide them randomly into test or control arms, treat the test arm and do not treat the control arm, and follow them long enough to comare the effect on whatever the measurable thing is.

Or you can treat everyone, and compare wilth historical data.

However, you are going to have some placebo effect on the treatment group, so they can be expected to do better than the untreated/historical group regardless, and I do not know what the placebo effect is. We might have a good number from all the drug tests, I don't know if that would translate over to a surgical procedure.

These are just my quick ideas. What else might we try? Does anyone know what the proposed trials are doing?
User avatar
fogdweller
Family Elder
 
Posts: 412
Joined: Tue Dec 08, 2009 4:00 pm

Advertisement

Postby 1eye » Mon May 10, 2010 12:48 pm

See Dr. Sclafani's topic. He has been wrestling with this, and some good ideas have been suggested. I'm sure yours would be welcomed too. I think he is trying to take the CCSVI victim's point of view into account in his study design. He is doing this on-line dialogue while he waits for IRB approval of his trial.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2920
Joined: Wed Mar 17, 2010 4:00 pm
Location: Kanata, Ontario, Canada

Use restenosis as controls

Postby frodo » Mon May 10, 2010 2:51 pm

I have already written this in other threads, but I think is a good idea, and I try to spread it... So sorry for repeating.

The only ethically possible way to have controls is to use the restenosis cases as such.

How to perform a clinical trial? Let's take a groupe of people. Perform angioplasty and then, measure EDSS or other semi-objective scale. Repeat measurements of EDSS periodically while testing their veins. Of course, do not tell them the status of their veins.

After a given amount of time you only have to compare their reported EDSS with their restenosis. You will not prove that CCSVI is the cause of MS, but you will prove that blood flow affects the EDSS of MS patients. Enough to request the therapy for everybody.

Besides, you will also get an estimation of the time that a restenosis takes to create problems.
User avatar
frodo
Family Elder
 
Posts: 616
Joined: Wed Dec 02, 2009 4:00 pm

Postby Billmeik » Mon May 10, 2010 3:00 pm

di you guys see the scientific american article on ccsvi?

They proposed a trial like : 100 patients
50 get liberated
50 get a placebo liberation. or some kind of incision that does nothing.

they are followed and reported on.

I think canadians should volunteer for it.May be the only way to move forward.
User avatar
Billmeik
Family Elder
 
Posts: 694
Joined: Fri Nov 27, 2009 4:00 pm

Re: Use restenosis as controls

Postby Cece » Mon May 10, 2010 4:13 pm

frodo wrote:The only ethically possible way to have controls is to use the restenosis cases as such.

I think however that everyone who feels better and then restenoses is immediately aware of feeling worse and quite desperate to get the procedure done again.
Billmeik wrote:They proposed a trial like : 100 patients
50 get liberated
50 get a placebo liberation. or some kind of incision that does nothing.

I will look for this, I love Scientific American.
"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
Cece
Family Elder
 
Posts: 9018
Joined: Mon Jan 04, 2010 4:00 pm

Postby fogdweller » Mon May 10, 2010 4:52 pm

Billmeik wrote:di you guys see the scientific american article on ccsvi?

They proposed a trial like : 100 patients
50 get liberated
50 get a placebo liberation. or some kind of incision that does nothing.

they are followed and reported on.

I think canadians should volunteer for it.May be the only way to move forward.


I read SciAm every month, generallhy cover to cover and do not remember seeing it. What month, and what section of the magazine?

By the way, 1eye is right, that is an issue DrScalfini has been struggling with while awaiting IRB approval. His thread is somewhat daunting for those of us that have not been following it all along. I may go back and try to synthasize the entries on this subject.

I personally think this is VERY IMPORTANT. The righ test done as soon as possible will either unleash the flood gates or put this very hot issue to bed if it is not the real deal.
User avatar
fogdweller
Family Elder
 
Posts: 412
Joined: Tue Dec 08, 2009 4:00 pm

Postby TFau » Mon May 10, 2010 5:50 pm

I agree with you, Fogdweller, about the importance of the design. I was recently speaking with a vascular surgeon (who refused to treat CCSVI for lack of evidence) about a trial design. He thought that the only way to do it, and how they've done things in the past, is to have an independent 3rd party observer examine patients. The observer would observe them before and after the treatment, but he wouldn't no who had actually been treated.

I think a problem with this is, again, how to measure subjectively reported improvements, such as fatigue and cogfog improvements. With a 3rd party observer, subjective reports of improvement would be meaningless.

I was really worried that this would be accepted as the test and, since the majority of previously reported improvements would not be caught, the treatment would fail for lack of efficacy.

I think that this just shows the importance of having neurologists involved. They know the full range of debilitating effects of MS (the good neurologists, anyway).
User avatar
TFau
Family Elder
 
Posts: 222
Joined: Tue Nov 24, 2009 4:00 pm

Postby Billmeik » Mon May 10, 2010 6:35 pm

there is sure a lot of talk about symptom reports..what about mri comparisons over time? Software can do the comparison and so there is no subjectivity at all.
User avatar
Billmeik
Family Elder
 
Posts: 694
Joined: Fri Nov 27, 2009 4:00 pm

Postby Billmeik » Mon May 10, 2010 6:50 pm

User avatar
Billmeik
Family Elder
 
Posts: 694
Joined: Fri Nov 27, 2009 4:00 pm

Postby mrhodes40 » Mon May 10, 2010 9:09 pm

He thought that the only way to do it, and how they've done things in the past, is to have an independent 3rd party observer examine patients


The campath trials have been done this way--

http://www.ncbi.nlm.nih.gov/pubmed/18946064

--334 patients with EDSS less than 3 in open label treatment of Campath or Beta interferon

--blinded neuro doing assessment

the patient knows what they got but they are testing for lesion burden and relapses and edss so it is thought that the blinded neuro can be objective without a placebo control.
marie
I'm not offering medical advice, I am just a patient too! Talk to your doctor about what is best for you...
http://www.thisisms.com/ftopic-7318-0.html This is my regimen thread
http://www.ccsvibook.com Read my book published by McFarland Health topics
User avatar
mrhodes40
Family Elder
 
Posts: 2066
Joined: Thu Sep 23, 2004 3:00 pm
Location: USA

Postby Billmeik » Mon May 10, 2010 9:09 pm

I guess if the patients were under full sedation during the angio?
User avatar
Billmeik
Family Elder
 
Posts: 694
Joined: Fri Nov 27, 2009 4:00 pm

Postby fogdweller » Tue May 11, 2010 10:22 am



Found it too. It is on the web site and not in the magazine, I guess. Not a bad article. However, it says they need to do a study where both patients and doctors are unaware of who has had the treatment. It gives no idea of how to do that. I still do not think it is possible.

I think with surgey (or IR intervention) it is not possible for the patient to not know who has been treated. I think the sugesstion above, that observers that are unaware of the who was treated or not do the scoring on improvement may be the best we can do.

That is sort of what Zamboni did with the CCSVI veionograms. He had them read by third parties that did not know who had MS and who did not, and thus his determination that the CCSVI was mostlly present in the MS patients had some real weight with me. However, in that case the people taking the veinograms knew. In Buffalo they made an effort to hide this as well, so the results were even more legiltimate.

The placebo effect, which is real, means that those MS patinets who are treated will improve even if the tester does not know which ones were treated. And I think this is not just a subjective matter but will also affect even the objective factors like MRIs. I am not real sure of this last issue. I hope someone a bit more informed of the placebo effect will chime in, but we shouls be able to account for that effect in analyzing the results.
User avatar
fogdweller
Family Elder
 
Posts: 412
Joined: Tue Dec 08, 2009 4:00 pm

Postby Cece » Tue May 11, 2010 11:26 am

This is from a meta-analysis of studies using placebos on people with MS:

research wrote:Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature.
La Mantia L, Eoli M, Salmaggi A, Milanese C.

Istituto Neurologico C. Besta, Milano, Italy.
Abstract
To verify whether the outcome in placebo-treated MS patients actually corresponds to that expected on the basis of the natural history and pretrial evolution of the disease, we here review the results of clinical trials conducted according to a placebo-controlled, randomized design, regardless of the experimental therapy used. The frequency of relapse in remitting-relapsing patients decreases during follow-up, and disability in progressive cases increases more slowly than before enrollment. These data should be borne in mind when evaluating the impact of experimental drugs on the natural course of the disease.

http://www.ncbi.nlm.nih.gov/pubmed/8797067
Decrease of relapses and disability both sound like objectively measured things, so we're not just talking placebo/not real but placebo/has an objective effect, I think.
"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
Cece
Family Elder
 
Posts: 9018
Joined: Mon Jan 04, 2010 4:00 pm

Postby fogdweller » Tue May 11, 2010 12:25 pm

Cece wrote:This is from a meta-analysis of studies using placebos on people with MS:

research wrote:Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature.
La Mantia L, Eoli M, Salmaggi A, Milanese C.

Istituto Neurologico C. Besta, Milano, Italy.
Abstract
To verify whether the outcome in placebo-treated MS patients actually corresponds to that expected on the basis of the natural history and pretrial evolution of the disease, we here review the results of clinical trials conducted according to a placebo-controlled, randomized design, regardless of the experimental therapy used. The frequency of relapse in remitting-relapsing patients decreases during follow-up, and disability in progressive cases increases more slowly than before enrollment. These data should be borne in mind when evaluating the impact of experimental drugs on the natural course of the disease.

http://www.ncbi.nlm.nih.gov/pubmed/8797067

Good find. My point, even objective factors are decreased per placebo. I was talking to a neuro who said that all the drug trials seemed to be about 35-40% reduction and he thought that might not be real. However those were double blind studies, so whatever their placebo effect, that could give us a number to use. (a placebo effect.)
Decrease of relapses and disability both sound like objectively measured things, so we're not just talking placebo/not real but placebo/has an objective effect, I think.
User avatar
fogdweller
Family Elder
 
Posts: 412
Joined: Tue Dec 08, 2009 4:00 pm

Postby fogdweller » Tue May 11, 2010 12:28 pm

Billmeik wrote:I guess if the patients were under full sedation during the angio?


You would also have to make an incision. I think the risk, even slight, of placing a patient under anesthesia and making an incision when you know you are not going to treat would be unethical.

However, I am not sure. Could informed consent allow this? If so that could be an anwer!!
User avatar
fogdweller
Family Elder
 
Posts: 412
Joined: Tue Dec 08, 2009 4:00 pm

Next

Return to Chronic Cerebrospinal Venous Insufficiency (CCSVI)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service