Subcommittee on Neurological Disease Committee on Dec. 7th, 2010

[Dr. Alain Beaudet]

There's a procedure. The procedure is a diagnostic procedure, and that's a very important one because it's another major issue. We really don't know what the best approach is to diagnose this condition. Is it, as Dr. Zamboni claims, ultrasound imaging? Is it venography? Is it nuclear magnetic resonance imaging?

What these projects are doing is comparing the various techniques. Most of them use, as a baseline, the ultrasound approach done by Dr. Zamboni to try to at least reproduce these results. Most of them, actually, have sent their technicians to Buffalo to get the proper training to read these Dopplers in the same way as Zamboni did, and that's their baseline. They're comparing that with venographic studies, and in some cases NMR studies.

We want to establish the best possible approach to diagnose the condition, so when there's a trial in phase two we know exactly what the perfect, true inclusion criterion is and what the standard used in terms of diagnosis will be.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Beaudet.

[Dr. Alain Beaudet]

Sorry, it's a bit technical.

[The Chair, Conservative, Joy Smith]

That's okay. Don't apologize. This is what you're here for. Thank you so much.

Dr. Carrie.

[Colin Carrie, Conservative, Oshawa, ON]

Thank you very much, Madam Chair.

Thank you very much, Dr. Beaudet, for being here today.

As you know, in another life I actually treated people who had MS, and for me and so many people it's about real people, real families. I was wondering if you could take a moment and discuss the importance of ensuring that the science is sound before moving ahead with these clinical trials, and maybe explain to people who might be listening or might read this what the risks are of not waiting for the signs.

[Dr. Alain Beaudet]

It's very clear. The risk of not waiting for the signs is subjecting patients to a treatment that is not innocuous--and we have proof of this--and that could have a number of complications, without having the proof that we're actually improving their condition. Some of these complications could be serious.

We're talking about blood clotting. We're talking about internal bleeding, because in most of these patients there are thinning agents that are used as drugs before the procedure and after the procedure. In the case of a stent insertion, indeed the safety is probably even less because stents, as you know, are meant for arteries. The wall of the vein is really thinner, and the danger, of course, is that the blood flow is not as rapid and there's a danger of clotting.

All of these things are serious, and we don't have a real appreciation because it's not very common to do angioplasty of veins and to put stents into veins. We don't have a good idea of the incidence of complications and negative events. There's no question that a good clinical trial will have to include, either as a phase one or into the trial, a measurement of the safety component.

[Colin Carrie, Conservative, Oshawa, ON]

All right.

You also mentioned the research associations in your opening statement--and you've been in touch and in good communication with the different associations. I was wondering if you could let the committee know what the positions of the different physician associations, the MS associations, and other stakeholders is on the need.... You mentioned that you're working to try to demonstrate the link between CCSVI and MS before conducting these clinical trials.

What are the experts saying in these different associations?

[Dr. Alain Beaudet]

By and large, it's really the position of most MS societies. And it is certainly the position of the U.S. and the Canadian MS society. The German MS society had a very harsh statement. On the other hand, the international MS society had a more balanced statement, stating the importance of furthering clinical trials, clinical research, to establish the validity of the procedure.

I think it's important to note that in Italy the MS society is sponsoring a very large study on several thousands of patients, involving a large number of sites in the country, to do exactly what the seven studies are attempting to do here. It's association studies to try to demonstrate whether there's a link between patients with MS and this entity called CCSVI. So we're in contact, and we'll be monitoring the results of that very large study, as we're monitoring the ones from the studies carried out in Canada and the U.S.

[Colin Carrie, Conservative, Oshawa, ON]

Because you mentioned Italy, I was just curious. Dr. Zamboni came up with this procedure, so has he received authorization to proceed with it? If he has not, why hasn't he?

[Dr. Alain Beaudet]

I think this is an important point. First of all, Dr. Zamboni was originally part of the very large association studies that involved I think around 20 sites in Italy, and he withdrew from the study. The scientific director of the Italian MS Society told us that he withdrew because he asked that all the images from all the sites be vetted by his own laboratory, which obviously the committee didn't feel was appropriate. Dr. Zamboni, however, is also applying for a therapeutic trial, a trial this time to investigate the treatment. As far as I know, the study doesn't have all the funds necessary to be fully carried out. He did receive a bit of money from the province where his lab is, but I don't know about the status of the ethical approval of this study. He was supposed to receive ethical approval at the beginning of December. I don't know whether he did receive it.

Do you know? We don't know.

The last time we spoke to Dr. Battaglia, the scientific director of the Italian MS Society, Dr. Zamboni still hadn't received the ethical approval for his studies. It was pending, and we were told the beginning of December. What we know, however, is that right now the funding from the province that he's receiving for that study is not sufficient to carry out the type of study that would be necessary to prove or disprove the efficacy of the treatment.

[Colin Carrie, Conservative, Oshawa, ON]

Do I have time for a little more here?

[The Chair, Conservative, Joy Smith]

Yes, you do.

[Colin Carrie, Conservative, Oshawa, ON]

I believe there was a study done in Sweden, and I was wondering if you were familiar with that and are able to elaborate on the process there and the results of that study.

[Dr. Alain Beaudet]

Yes, there were studies in Sweden and Germany that actually showed very different--as, Kirsty, you know--results from those of Dr. Zamboni. Actually, essentially, they found no difference between the venous anatomy of patients with MS and that of normal controls.

[Colin Carrie, Conservative, Oshawa, ON]

How many people did they do that study on? Do you remember, off the top of your head?

[Dr. Alain Beaudet]

I don't remember. I don't want to venture a number. I'm not good at remembering numbers. I can't remember my phone number, so I won't go there.

But that's why we're doing these studies. When you have a controversy like this, and you have one group finding one thing and another group finding the other thing, you have to try to devise a very strict protocol. What's really great about these studies is the use of several diagnostic approaches that will be compared to determine whether (a) there's a problem with the anatomy, and (b) there's a problem with the blood flow, and trying to associate that with MS.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Beaudet.

We'll now go into our five-minute rounds of questions and answers, beginning with Dr. Duncan.

[Kirsty Duncan, Liberal, Etobicoke North, ON]

Thank you, Madam Chair.

And thank you to Dr. Beaudet for coming.

I want to pick up on a couple of things. There really has been follow-up missing. I gave one example; I can give many examples of where patient appointments have been cancelled and then they were told they would no longer have their specialist. There have been tests that are repeated every six months for drugs that have been cancelled, and people who have had clotting issues are being refused treatment.

I want to pick up on the expert panel that was talked about for the August 26 decision. If you're going to have an expert panel, I would like to see people who've actually been involved in the imaging and done the procedure be involved. I know there was fear of biasing the sample. Having said that, there were people on that panel who had actively spoken out against the procedure for over six months. We absolutely must have evidence-based medicine here in Canada. We have to. We do need to establish protocols around imaging, whether it's ultrasound, whether it's MRI. We need to know if we are going to be using stents. We need to establish these protocols.

As you know, I have concerns because I do think we're doing replication work, work that's been done elsewhere. If people had gone to the international conferences...Bulgaria, Canada, Italy, Kuwait, and the United States are all presenting the same data. That data is as follows: 87% to 90% of MS patients show one or more venous problems if ultrasound or MRI is used. Now the outlier to that was in Buffalo, and you have to look at those results. How was the study undertaken? Did you have someone who was trained in the operations? They also looked at first-degree relatives, and we know that venous problems may run in families. So there were issues.

Dr. Carrie brought up the Doepp and the Sundström papers. You have to look at the history of that. Those papers were published in six weeks. That's highly unusual in science. Dr. Simka's work out of Poland has done angioplasty on 381 patients, which people would describe as the gold standard; 97.1% showed one or more venous problems.

I'm going to hand that over.

[Dr. Alain Beaudet]

There are several elements to your questions. I'll try to go through them rapidly.

First, I want to tell you how important it is that MPs care and how important is your statement about the need for evidence-based practice.

[Kirsty Duncan, Liberal, Etobicoke North, ON]

We have to.

[Dr. Alain Beaudet]

It's the basis of our medical practice in this country, and at times it's tough to follow. You feel for those patients who have very few options right now. Quite frankly, the last thing I want to do is blame the patients, because I understand that. We have a role to explain to them why we believe they shouldn't go abroad at this point to get a treatment.

I really do believe that the majority of physicians will never refuse to see a patient who is sick and wants to see them, whether they've been—

[Kirsty Duncan, Liberal, Etobicoke North, ON]

I can give you case after case after case.

[Dr. Alain Beaudet]

You may well be right, but I can tell you that it's not acceptable; we will not condone it, and we'll try to, as I said, by working with the professional associations and colleges, impress upon these groups the importance that patients are seen and are treated. The only thing I can tell you is that the working group—as I said, most of them were actually physicians—said they would never refuse to see patients, and a lot of their patients had actually undergone treatment abroad. But it's an issue. We don't accept it. We have to try to change that, and there's a message that must be sent.

The other thing is the composition of the August working group. I don't really want to go back to that, but since you bring it up again, our criterion was very simple. We invited physician scientists that were funded either by CIHR or by the U.S. NIH. That was simple, clear. They're all—

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Beaudet.

We'll now go to Dr. Carrie.

[Colin Carrie, Conservative, Oshawa, ON]

There has been a lot of attention given to chronic cerebrospinal venous insufficiency. I was reading in the paper today--I get up really early, and I'm one of those strange people who actually reads the paper before I get to work--that there is a new drug out, and I believe it's called RXR-gamma.

Could you bring us up to date on what else is going on in MS research around the world?