What formal steps should be made in order for the scientific community to acknowledge beyond doubt that CCSVI is real and has non-trivial consequences?
A - Take 1-2 hundred patients, half with MS and half healthy controls with no symptoms and compare their venography and IVUS blindly. if there is a difference we establish by gold standards once and for all that patients with MS have abnormal venous drainage. If there is no difference, then we go home.
B - Take 1-2 hundred patients with MS, catalog all signs and symptoms, divide them into two groups: one group receives venoplasty, or valvuloplasty using venography and IVUS to confirm successful treatment, the other group receives a sham operation. Both groups blinded to whether they have had treatment or sham. Compare improvements in symptoms for a year.Determine whether there is a benefit in the treated patients. DO NOT focus on whether there MS improves or not. That is a study for later.
That is my opinion.
I am going to try to acheive the impossible and question your trial design Dr S and stay on polite terms with TiMS posters. I hope you will take my comments as thoughts from a critical friend.
I see a flaw in the first trial (my label A) as it assumes that CCSVI is unique to MS. If CCSVI occurs in other early stage (pre-diagnosis) neurovascular diseases then you could find stenoses in healthy controls. Also as MS is a multi-factorial disease there are likely to be pwMS who do not have stenoses. If either or both of these senarios occur then the main discussion (introduced by Neuros) will be that CCSVI is not the cause of MS.
Your second trial (my label B) is too small in size to be conclusive. The MS group has too many sub-groups in it to allow statistically valid data to be generated. New MS drug trials are very large in size in order to acheive statistical significance and many barely acheive this despite their large size. In the UK, the use of complete sedation to conduct Sham Trials would probably not gain ethical approval (NICE has not demanded sham trials in IPG420).
I am tending towards a '500 controlled case study' (then group findings) as the trial method most likely to succeed for CCSVI in pwMS. I see the main problem for IRs in such a study being that the same diagnosis and treatment regime must be used (no improvements during the trial) for all 500 case studies. That is not the way IRs work in my limited knowldge, IRs tweak the method as you use it.
So my question on your trial design is 'are you sure?'
Mark, the question that was posed to me was 'what will it take to have ccsvi and its treatment accepted by neurologists"
in my opinion this is not the question that I would ask. I would do a trial, to look at symptomatic relief. But that is another story.
i also said i am ready to do a trial, but i dont have the money. The reason i am ready is that i believe that i have maximized my techniques. True there are nuances still left to study, but they are uncommon presentations and require uncommon techniques. These need to be trialed themselves. For example, does treating the C2 compression make a difference? how about the may thurner syndrome?
I would envision trials on efficacy of venoplasty for fatigue, imbalance, and other commonly improved symptoms. This make the most sense. But who had common sense on any of this stuff. As you say, trying to prove that ccsvi causes ms is not going to happen in my career.
with regard to sham trial, there is no other way to exclude placebo effect. The current trial of radiofrequency ablation of the renal sympathetic fibers for uncontrollable hypertension divides the groups in two... 2/3 of patient undergo arteriography and RFA and 1/3 undergo arteriography without RFA. After six months all those undergoing the sham operation may opt in for the procedure as well. No reason why we cannot do this for ccsvi except that no one will consent to this HIGH RISK POTENTIALLY LIFE THREATENING catheterization (sic) without having the use of the LIFE THREATENING angioplasty catheter.
I can see that you are understanding my frustrations after two years of this banter.
Hi all, I think that the issue is mostly about "what is the symptom group that PTA will change".
At this point in time MS has not been defined, so it is not going to be a case of working with just MS patients and see what happens.
It can only be test for CCSVI issues with IVUS, treat with PTA and measure the results.
It is no different, as Dr. S is saying, from when we as a group looked at a study survey of symptoms that are said to be the MS Symptoms twoish years ago.
Firstly the tests that were said to be the accepted ones by Neurology and the research people for the treatments used so far for PwMS were unusable, not accurate and relied on the patients assessment, therefore not transferable across the Globe.
The only way forward for CCSVI outcome understandings is to look at the IVUS found malformations etc and treat them, watch what happens and hope in the meantime that MS becomes a defined disease.
The "MS disease" tag as we know it, is an excuse by, particularly Neurologists, that because there are no known treatments there is no reason to define what are the parameters of MS disease are. All Autoimmune category diseases are in the same situation. Autoimmunity is blamed and therefore there is only symptom management and dollars to be made from the mostly drug treatments. Customers for life, UNTIL Dr Zamboni and the Internet came along.
So exposing what hasn't happened in the Medical world is going to have to be acknowledged before CCSVI can move ahead and help people with the condition, no matter what previous label or pigeon hole they were left to sit in.
CCSVI is crossing boundaries of Disease classification and that in itself is and issue for Mainstream Medical Professionals.
So to move ahead the way is, as Dr. S is saying IMO, treat what IVUS is finding, because low or no flow is going to have symptoms, end of story!
Regards to all,