Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 22 - Evidence - October 18, 2012
OTTAWA, Thursday, October 18, 2012
The Standing Senate Committee on Social Affairs, Science and Technology, to which was referred Bill S-204, An Act to establish a national strategy for chronic cerebrospinal venous insufficiency (CCSVI), met this day at 10:29 a.m. to give consideration to the bill.
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
[English]
The Chair: We are continuing our study of Bill S-204, An Act to establish a national strategy for chronic cerebrospinal venous insufficiency, better known as CCSVI.
Welcome to everyone. I will welcome our witnesses in a moment. I am Kelvin Ogilvie, chair of the committee. I am a senator from Nova Scotia. I will invite my colleagues to introduce themselves, starting on my right.
Senator Seidman: Judith Seidman, from Montreal, Quebec.
Senator Unger: Betty Unger, from Edmonton.
Senator Seth: Asha Seth, from Toronto, Ontario.
Senator Verner: Josée Verner, Quebec.
Senator Enverga: Tobias Enverga, from Ontario.
Senator Buth: JoAnne Buth, from Manitoba.
Senator Dyck: Lillian Dyck, Saskatoon, Saskatchewan.
Senator Munson: Jim Munson from Ontario, but my heart is always in New Brunswick.
Senator Merchant: Pana Merchant, Saskatchewan.
Senator Cordy: Jane Cordy, from Nova Scotia.
Senator Eggleton: Art Eggleton, from Toronto, and deputy chair of the committee.
The Chair: I want to welcome our witnesses today. We have, from the National CCSVI Society, Bernhard Juurlink, Director; and appearing as an individual is Dr. Barry Rubin, Medical Director, Peter Munk Cardiac Centre, University Health Network. Unfortunately, from the College of Physicians and Surgeons of Alberta, Dr. Trevor Theman, who is the registrar, who was going to appear by conference, had to withdraw because of an urgent situation but has submitted a report to us.
I did not myself determine from the witnesses if they had arm-wrestled to see who would go first, so I will follow the order they appear on my list, if that is acceptable to you.
That would mean, Mr. Juurlink, that you will go first.
Bernhard Juurlink, Director, National CCSVI Society: This is a committee on post-angioplasty treatment, I gather. Is that correct?
The Chair: We are the Standing Senate Committee on Social Affairs, Science and Technology, which is currently charged with reviewing a bill that is before the Senate dealing with proposed legislation with regard to the CCSVI procedure.
Mr. Juurlink: I am a director of the National CCSVI Society, but previously I was an academic at the University of Saskatchewan and a founding faculty member at Alfaisal University. As a background, I have spent over 30 years teaching, and teaching medical students, amongst other students, and in a variety of subjects. I have had quite extensive research experience, mostly in neuroscience but also cardiovascular. I am reasonably familiar with pathologies associated with stroke and MS, spinal cord injury, et cetera.
I do not know if CCSVI plays a causal role in MS. Only properly controlled clinical trials will establish that, but I do know that I have met many people who have had had the angioplasty and they have claimed it had many positive effects. Four of the directors of this society have had angioplasty with positive results, or so they say.
One of those is Bill Code, a colleague of mine at the University of Saskatchewan. He and I were members of the Saskatchewan School of Research Centre and we carried research together. Bill tells me that his migraines have disappeared; his brain fog has disappeared; his bladder control is back and he has more energy. If this is placebo effect, then we should make use of the placebo effect.
One of the adverse side effects with angioplasty and with venous angioplasty is thrombosis. In the published literature it is somewhere between 1 and 1.5 per cent of individuals develop thrombosis. You can have worse problems such as rupture of the vein, but thrombosis is the most common adverse side effect. The incidence of thrombosis I believe is greater if you have a stent in place.
I will leave it to my clinical colleague how to deal with thrombosis, but I would like to bring up an issue of MS patients who have had the angioplasty and then were refused treatment when they came back to Canada. I have mentioned several in my written submission, but I will just stick with Mahir Mostic, who went to Costa Rica for angioplasty. Symptoms he claimed improved. He came back to Canada and he developed thrombotic problems. The health care system refused to treat him. He did not have money to go back to Costa Rica immediately, and his friends fundraised. He went back to Costa Rica and, unfortunately, he died there. If he had been treated by the health care system promptly in Canada, he likely would be alive.
My message is that these individuals who go abroad for angioplasty are not criminals; they are doing nothing illegal. The health care system in this country treats vicious murderers and people who engage in dangerous physical activities without hesitation, but people who have had angioplasty and their physicians hear about that, many of them have had difficulties. Many people with MS have approached me and had complaints.
Many who go abroad for angioplasty do not dare tell their own physicians they have done so because they are scared if they do they will not get health care treatment.
I can have other comments. I can comment on plausible mechanisms, why pain blockage may result in MS or MS-like symptoms. I can comment on some of the irrationalities with current therapeutic treatments as well, but I will stop here.
Dr. Barry Rubin, Medical Director, Peter Munk Cardiac Centre, University Health Network, as an individual: It is my pleasure to appear before this committee. I have some comments, which I have submitted in writing in advance of this presentation. As we have not met before, I thought it would be appropriate to outline some of my qualifications. I am a full professor of surgery at the University of Toronto. I have a certificate of special competence in vascular surgery from the Royal College of Physicians and Surgeons of Canada. I have a doctorate in experimental medicine from the University of Toronto.
I am currently the Medical Director of the Peter Munk Cardiac Centre, responsible for cardiac surgery, cardiology, vascular surgery and medical imaging activities at University Health Network. I was previously head of vascular surgery at that institution for nine years.
I have treated patients with narrowed arteries and veins and run a peer-reviewed molecular biology research laboratory for 18 years at Toronto General. I am also a member of the CIHR MS Expert Working Group, and I am a member of the Health Canada Scientific Advisory Committee on Medical Devices used in the Cardiovascular System. I gave a presentation on CCSVI to that panel on June 1, 2012, and I believe the record of that is publicly available.
I was also Co-chair of the Ontario MS Expert Advisory Group that developed guidelines for the care of patients that undergo vein dilation procedures, and I submitted reports that we developed, one for patients and one for physicians to this committee in advance of this appearance.
I will migrate from my prepared remarks and say that I could not agree with Mr. Juurlink more; I think it is unconscionable that any patient who goes outside of Canada and has any therapy would be denied therapy when they return to Canada. That is just an abrogation of a physician's responsibility to their patients and should never be condoned.
I have never had a consulting relationship with a pharmaceutical or medical device company during my career. The comments I make today represent my own opinions based on my review of the literature and my experience as both a vascular surgeon and a career research scientist.
For clarity, I am not an expert in the diagnosis and management of patients with MS, and I have no clinical experience managing patients with MS. The only patients with MS that I have met are the ones that have come to my clinic over the last couple of years seeking advice on balloon dilation therapy for multiple sclerosis.
As a result of meeting these patients and the people with MS and their families who asked me questions about vein dilation therapy when I discussed this issue in a public forum in Toronto a couple of years ago, I am deeply sympathetic to the pain and suffering that MS causes these frequently young and otherwise healthy patients. I know that patients with MS are aware of a new way to treat this disease that they have heard could change their lives. I have told each one of these patients with MS the same thing. Treatment should be evidence-based; complications of any procedure must be clearly identified; and to proceed with therapy, there should be a demonstration that the risks outweigh the benefits.
Like all of you, I would like nothing more than to be able to tell MS patients that a relatively simple procedure with a balloon that could be done on a day basis could improve their lives.
As you know, Dr. Zamboni proposed that patients with MS have narrowed or blocked veins that drain the brain or spinal cord, that this condition may cause some forms of MS, and that dilating these diseased veins with a balloon improves the quality of life of some patients with the relapsing and remitting form of MS. Other investigators have made similar claims. Indeed, I have spoken directly with patients who told me that brain fog is better, that bladder function is better. One patient who is a lawyer said that he can now write his own opinions, where he used to not be able to. There is no doubt that I have heard these stories as well.
A few facts: The human brain and spinal cord have many veins through which blood can leave these organs. If one of these veins is narrowed or blocked by disease, other veins can take over, thereby maintaining the ability of the brain or spinal cord to drain blood and to let these organs continue to function. This redundant system of veins exists in most every organ system in the human body.
While fascinating, there are some theoretical problems with Dr. Zamboni's suggestion that narrowed or blocked veins could cause MS. If the veins leading out of the brain or spinal cord in patients with MS were narrowed or blocked, one would expect that the pressure in the veins in the brain or spinal cord would be elevated because it would be harder for the blood to get out of those organs. However, there is no evidence that patients with MS have elevated pressure in their brain or spinal cord by clinical exam; you can look at the retina with an ophthalmoscope and see the veins, CT scan or MRI studies.
If narrowed or blocked veins cause MS, one might expect that patients who develop narrowed or blocked veins in the neck would be at risk to develop MS, but this is not the case, and we have a lot of experience in this area. Intravenous catheters that are used for dialysis and pacemaker wires that are used to control the heart rate can cause narrowing or blockage of veins in the neck, and the main veins in the neck are frequently removed in their entirety during the course of surgery for head and neck cancers. They are not just narrowed; they are taken out as a whole structure. There has never been a report of a patient with these kinds of narrowed, blocked or removed veins developing multiple sclerosis. It may be argued that patients with dialysis catheters and pacemaker wires do not live long enough to develop multiple sclerosis, but that is at odds with the observation that children can develop multiple sclerosis.
Narrowed veins have scar tissues that have elastic properties. If you take out a narrowed vein and look at it under the microscope, you see elastic fibres. This is important because after you treat a narrowed or blocked vein with a balloon, as reported in the studies by Dr. Zamboni and others, the elastic properties of the scar tissue frequently cause the narrowing in the vein to recur.
Think about it this way. If you took an elastic band and put it on a balloon and you inflated the balloon, the elastic band would enlarge, but when you deflate the balloon the elastic band will contract back to its original size. That is exactly what happens in veins.
Through clinical experience and published studies, we know that balloon dilation of large veins is associated with a high rate of recurrent narrowing or blockage, so even if CCSVI exists, as proposed by Dr. Zamboni, one can predict that the impact of dilating narrowed veins on the ability of blood to drain from the brain or spinal cord would not be sustained as these veins would likely re-narrow over time. That is certainly exactly what we see in patients with vein narrowing because of dialysis catheters or because of pacemaker wires. You do the balloon and the narrowing comes back.
We are also quite concerned about putting stents into dilated veins because, as opposed to arteries, which they are designed to go into, veins have a pressure that is about one fifteenth of that in an artery and the combination of injuring the endothelial surface or the lining of the vein with the low-flow state and low pressure in a vein makes clotting much more likely in that setting. That is why stents are generally not approved for use in veins, and we only use them as an extreme last measure in those circumstances.
In its initial meetings, the CIHR MS Expert Working Group considered these issues, evaluated the relationship between the CCSVI criteria proposed by Dr. Zamboni and MS, and carefully reviewed available reports on the safety and efficacy of vein dilation therapy in patients with MS. As some groups reported a relationship between CCSVI and MS while others did not, the working group endorsed the conduct of seven observational studies that you are aware of, four in Canada and three in the United States, to further assess this potential relationship. I anticipate that we will be hearing results of those seven trials at the next meeting of the working group in November in Toronto. Having said that, two of the groups have already reported their results.
As the relationship between CCSVI and MS was not clear, and because the intervention study reported by Dr. Zamboni's group was not blinded and was not randomized, features of clinical research that make results more likely to be valid and reproducible, the working group did not recommend a trial of balloon therapy for patients with MS at that time.
At its next meeting, the working group was informed of two new facts, and this caused the working group to change its opinion. A meta-analysis of imaging studies of MS patients carried out by Canadian researchers identified an association between MS and CCSVI criteria, and importantly, a post-mortem study done at the Cleveland Clinic of patients with multiple sclerosis and healthy controls identified an increased frequency of vein narrowing in the patients with MS. This was not based on an imaging study. You are looking at the vein and seeing that it is abnormal. Those results were convincing.
With those two new pieces of information in hand, the working group changed direction and recommended the conduct of a Phase I/II trial of balloon dilation therapy for patients with MS.
Unfortunately, dilating neck veins has led to the death of at least four patients that I am aware of and has caused serious complications in others, such as stroke, nerve injury and bleeding. We reported some of those complications. This caused the U.S. Food and Drug Administration to issue a safety communication on May 10, 2012, which alerted people with MS to the risks of serious injury and death associated with procedures to treat multiple sclerosis.
I went to medical school at McGill. On the first day of medical school, the dean walked into the auditorium, said hello and said, ``Do no harm.'' That is the first principle in medicine. I did not see him again until the fourth year, but that is a different story.
While vein dilation is relatively simple and usually a safe procedure, there can be no doubt that it has and will continue to harm patients.
However, it is absolutely axiomatic that some patients will be harmed when new therapies are deployed. We would not have low-risk coronary angioplasty or heart bypass surgery if pioneers in those fields had not treated and, in some cases, inadvertently caused the death of some patients. The onus is on the medical community to ensure, to the best of its ability, that the benefits of a given therapy outweigh the risks. The frequency of adverse outcomes after vein dilation therapy in MS patients appears to be low in some published studies, but the interpretation of these studies in some cases is complicated by short follow-up times, lack of blinding and potential conflicts of interest.
As noted by the FDA, there is currently no clear diagnostic evidence that CCSVI exists as a distinct clinical disorder or is linked to MS, and the safety and efficacy of using balloon angioplasty devices or stents in neck or chest veins has not been established for any clinical indication. The seven imaging studies currently in progress will help clarify the potential link between CCSVI and MS, and the Phase I/II trials in Canada, New York and Australia will help establish the safety and efficacy of vein dilation for patients with MS.
Last week, the results of a blinded, multicentre ultrasound study was presented at ECTRIMS, which is a major multiple sclerosis meeting: 1,257 MS patients, 232 patients with other neurological diseases and 382 healthy controls were reported. The prevalence of CCSVI criteria independently evaluated was 3.2 per cent in the MS patients, 2.8 per cent in patients with other neurological diseases, and 1.98 per cent in healthy controls. The author of the study stated at ECTRIMS that given these results he felt that a trial of balloon therapy for patients with MS was unethical.
Some of my colleagues have said that it may make sense in rare cases to conduct a clinical trial before the desired weight of scientific evidence accumulates: for instance, if thousands of MS patients are exposing themselves to the risks and costs of unevaluated medical procedures. In some situations where preliminary evidence suggested that a treatment was beneficial, like bone marrow transplantation for women with metastatic breast cancer and the use of some drugs to treat patients with malignant arrhythmias or abnormal heart rhythms, the initial studies were positive and when the meta-analysis was done and bigger trials, more patients died because of the therapy than in the control groups. To avoid repeating this kind of outcome, we should proceed with caution in the evaluation of vein dilation therapy for MS, while maintaining an acute awareness of the toll this devastating disease is taking on patients and their families.
Thank you for giving me an opportunity to present my prepared remarks.
The Chair: Thank you both for your presentations.
I will now open the meeting up to questions from my colleagues. I will start with Senator Cordy, who is the proponent of this legislation.
Senator Cordy: Thank you very much to the two of you for being here today and for contributing to the discussion on the bill before us.
I was pleased, Dr. Rubin, that you talked about the need for scientific evidence because, of course, that is what everyone wants. We want evidence-based information. We want scientific evidence when we are making decisions.
You also said that we have heard stories from those who have MS but few facts. One of the things that this bill calls for is the collection of data for people who have had the procedure done outside of the country. The government did promise a registry to collect that data in March 2011, and 18 months later we still do not have a registry. That is unfortunate because we have missed out on 18 months of data that we could have used to see what happens three months after the procedure, what happens after six months, one year, two years, or 18 months in this case. We have missed out on all that data. We have missed out on saying how many people have shown substantial improvement. We do know from statistics that I have read, and they have not varied from all the documentation that I have read, that it has been one third with substantial improvement, one third with some improvement and one third with no improvement. It would be nice to see whether or not the Canadian data would substantiate those numbers.
Dr. Rubin, you said in your opening that you are a member of the expert panel but that you have had no experience dealing with MS patients and CCSVI, so I was curious to know how you got on the expert panel. Both presenters talked about the need for follow-up care, that patients in Canada should not be excluded from follow-up care.
Dr. Rubin, when the Scientific Expert Working Group was looking at it, which provincial guidelines for follow-up care did you follow? Which ones do you think we should be following in terms of follow-up care?
Dr. Rubin: To answer your first question, I was contacted by CIHR before the panel was formed because I was in their database as being both a vascular surgeon and someone who had a track record of peer-reviewed research funding. I think there are only a couple of vascular surgeons who fit into that category in the country. I felt that it was a very interesting topic, and I felt that as director of the largest cardiovascular centre in the country, if this was going to be an important therapy for MS patients, I wanted to be aware of it.
My contribution to this panel is that I have in-depth and detailed understanding of what happens when you put a tube in a vein, you put a balloon up that vein, and you blow that balloon up in both arteries and veins. It was that aspect that I was asked to comment on during the discussions. I had nothing to say about the relative merits of different drug therapists or different etiologies for multiple sclerosis.
With regard to the guidelines, I actually co-chaired the panel in Ontario that consisted of family physicians, neurologists and interventional radiologists who wrote the guidelines. We generated them de novo. We also consulted with a group of patients that had multiple sclerosis, some of whom had this procedure and some of whom had not. It is not that we followed anything because we wrote the guidelines.
Senator Cordy: The Scientific Expert Working Group stated ``media reports that have stated that Multiple Sclerosis (MS) patients who experience complications after Chronic Cerebrospinal Venous Insufficiency (CCSVI) treatment are not being seen by Canadian doctors are not justified.'' The expert group, of which you are a member, said that. When the expert group made that comment about follow-up care, what patient or advocacy groups did you speak to? What patients who have had treatment outside the country did you speak to in order to make that comment? One would read that comment and say that all patients who have had the procedure are being seen once they return to Canada.
I have spoken to a large number of patients who have been treated outrageously in the system. Perhaps Dr. Juurlink, you can also comment on that because you made a comment about that.
Mr. Juurlink: I have spoken with many patients, and many are scared to tell their physicians.
The Chair: The question will go to Dr. Rubin first, and then I will invite you to come in on it.
Senator Cordy: What evidence did you gather from patients who had been treated outside the country in order to make that comment, which was very startling to people who had had the procedure done outside the country and who had been refused treatment. Where did you get your material to make that comment?
Dr. Rubin: Dr. Alain Beaudet responded to a similar question a couple of weeks ago from this panel. My response would be what I said during my remarks: It is absolutely unconscionable that any physician would decline to see any patient if they had a procedure done in Canada or outside Canada. Whether they agree with that procedure, they have a duty of care to that patient. The only circumstance where I would say that it would be acceptable to decline to treat a patient is if you felt that they would be better managed by someone else. My understanding of the regulations in Ontario, which is where I practise, are such that if you do not want to see a patient for any reason, your obligation is to inform that patient of different physicians with your same skill set who could take care of the patient, to ensure that they are in contact with them, and to provide their medical records to those other physicians. I cannot comment on where this information came from. I was a member of the panel, and I am here today as an individual. I was shocked when I heard that patients were being denied care.
Senator Cordy: I agree with everything you said, but the expert group said that it was not justified.
Mr. Juurlink: I have spoken with many patients who have had similar comments. Two members of the board of the CCSVI Society have also written briefs. Ms. Francine Deshaies was refused the ability to see someone with vascular expertise when she developed a clot in a stent that she had had placed.
The Chair: Do you have any comment?
Dr. Rubin: It strikes me that this is a regulatory issue for the individual colleges to address. If there are physicians who are not carrying out their duties, then that is the appropriate forum for that to be adjudicated.
Senator Cordy: I was surprised and disheartened to read that comment from the expert working group.
Dr. Rubin, you said that the veins are not strong enough to withstand venous angioplasty. Yet, we are using venous angioplasty for May-Thurner Syndrome, for example. Could each of you comment on the strength of the veins in terms of having venous angioplasty or having this procedure done?
Dr. Rubin: I do not believe I said that the veins are not strong enough. I believe I said that the veins have elastic properties and when you dilate a vein, it tends to recur. I alluded to the fact that we frequently dilate veins close to where the internal jugular is or sometimes the subclavian vein for patients with hemodialysis catheters and pacemaker wires. May-Thurner Syndrome is a condition whereby the left common iliac vein is crushed by the right common iliac artery. While you may be aware of some reports of people using balloon dilation in that setting, I never recommend it in that setting because even if you dilate the vein, the artery that overlies it will just re-crush the vein. Since this tends to happen in young people — most common in young women in their teens, you are looking at the possibility of inducing blood clots in that vein because of recurrent compression. As a referral centre, I see this not infrequently.
The worst possible outcome in my opinion is putting a stent in that vain because then you have a foreign body and the stent ends up getting crushed by the artery. I have seen that as well. While you have cited an example where some people use balloons to treat the left common iliac vein in May-Thurner Syndrome, it is certainly not my practice and not what I teach the residents in our program.
Mr. Juurlink: Because of atherosclerosis and hypertension, most of the research on vessels has been focused on arteries. We have made a lot of assumptions with veins. I used to think that veins had a surplus of drainage capacity. With the more recent MRI studies, perhaps that common assumption is wrong. The veins do have elasticity. With the balloon angioplasty, we have two fibrous components in the walls of the veins: collagen fibres, which withstand pulling forces; and the elastic fibres, which allow that distension and relapse.
With balloon angioplasty one tends to tear a little bit of the collagen fibres and, for a small period of time, the vein has a larger capacity than it had before. Then, inflammation and fibrosis set in and you have the re-stenosis of the vein. Angioplasty of the veins is not a permanent solution because most cases end up with re-stenosis.
Senator Eggleton: If it is not a permanent solution, then does one have to go through these procedures again? Dr. Rubin, you mentioned that like a balloon, you blow it up, it comes back down, and you are back where you started. How long do people have the benefit of it, on average? What do you do when it does come down, if it is not permanent?
Mr. Juurlink: The experience, from what I have read, varies. From a few days to several years, the angioplasty procedure allows a greater venous drainage. The key is inflammation, which drives fibrosis. I think that there is no attention paid to this inflammatory-driven fibrosis. If we could reduce the inflammation, we probably could reduce the fibrosis and have a longer period of time when the veins remain inflated.
Dr. Rubin: This is much better studied in arteries. The way that balloons work in arteries is completely different from the way balloons work in veins. In arteries, you have an atherosclerotic plaque. When you put a balloon in, which can be inflated to very high pressures — 5, 10, or 15 atmospheres of pressures — you literally crack the plaque into thousands of pieces. After that, the artery remodels and tends to stay open. If we see that the artery is re-narrowed immediately, then we put a stent in that setting.
In veins there is no plaque; it is just scar tissue. When you do the dilation, as my colleague said, it can vary. You do not know how long it is going to last. It is less common to have to do this in veins because usually when a vein is narrowed, other veins can take over so you can maintain function. Some people have all of the main veins in their neck narrowed or blocked. You asked what you do in that case if you can no longer do balloons or if you have done it multiple times.
I have been a vascular surgeon for 18 years at Toronto General, and I have never done a vein bypass for someone with that type of narrowing. People just accommodate. They may have a swollen face. It is called superior vena cava syndrome. They can get swollen arms and a swollen face, but it does not tend to be life- or limb-threatening. You do the best you can, understanding that balloons were designed for arteries, not veins, and accepting that there will be an occurrence.
Senator Eggleton: I think Dr. Beaudet said a couple of weeks ago that CCSVI does not cause MS. There seems to be a general assertion that that is the case, but it does not say it is not related in some way or that the angioplasty procedure does not relieve MS. Is that a correct way of putting it?
Dr. Rubin: Senator, I think that is an excellent point. I am looking at this just from the objective evidence. If you have such low frequency of this condition in MS patients, healthy patients or patients with other diseases, it is hard to imagine how they could be related. However, that does not mean that if you put a balloon into a vein and you blow up that balloon, that somehow, in a way we have no understanding of, makes some people with MS better. It is that single fact combined with this post-mortem study and some studies that say there may be a relationship that persuades me personally that it is important to continue on with the Phase I/II trial.
I think there is an absence of scientific knowledge here, and it would be awful if we abandoned this and missed an opportunity to see if this works. At the same time, you need to proceed cautiously in medicine and science so that you do not repeat the mistakes that were made, for example, with the bone marrow transplantation in women that had metastatic breast cancer, where we ended up as a medical community causing more death than benefit.
Mr. Juurlink: The study Dr. Rubin referred to that was recently announced at the ECTRIMS meeting used ultrasonography to look at veins, which is a very tricky technology to look at structures, for example, in the chest.
There are alternative means to using MRI to look at blockages. In the last few days, Mark Haacke has published a paper looking at MRI studies involving a smaller population, with somewhere between 300 and 400 MS patients and maybe 30 non-MS patients. In those studies, using MRI, he could demonstrate blockages in 69 per cent of MS patients and 11 per cent of non-MS patients.
I think we have to be very careful of the technologies used to examine. I think it is still up in the air as to exactly what the proportion is.
Dr. Rubin: I agree that different imaging modalities can show different things. I think there was a study by an investigator in New York of 500 patients, which was reported in radiology, about an MR imaging study that failed to show any difference between MS patients and controls. It is somewhat dependent. The same way that ultrasound is a study, MR is an incredibly complicated modality, and there are many variables in how you do a study.
I actually think that the core of this argument should likely migrate from ``is there a relationship between CCSVI and multiple sclerosis'' to ``does putting a balloon into a vein improve patients with MS?'' We can argue for a long time about the relative merits of the different imaging studies. There are some for; there are some against. We will hear about all seven. I allude to the fact that two have been reported already. One was a pediatric study in Toronto, and one was a study done in Texas by MR. My understanding is both of those studies were negative, showing no difference between multiple sclerosis patients and otherwise healthy controls.
It does not matter if you balloon dilate a person's vein and they get better with MS. Those observational studies will never tell you that.
Senator Eggleton: Professor Juurlink, you raised the question of doctors refusing treatment for people who have gone overseas for the procedure. Dr. Rubin, you have said it is unconscionable. You have made that very clear on a couple of occasions. I noted you said much the same thing in the Ontario MS Expert Advisory Group.
What is a person to do if they ran across this? What recourse is available? What would you suggest one do if they are refused medical treatment?
Dr. Rubin: I am obviously hesitant to answer that because I do not look after patients with multiple sclerosis, but I would say in general terms that any patient who is denied therapy has access to the Colleges of Physicians and Surgeons in their individual provinces.
More than that, I think it might be reasonable for doctors who have the same view as me to say, ``I will look after you if you have this procedure elsewhere.'' Perhaps that can become known in the medical community. I do not know how to police every individual physician in each province in our country, other than to provide clear messaging that says ``you have a duty as a physician to take care of patients.''
Mr. Juurlink: I think they should go before the Human Rights Commission. I think it is a matter of human rights. After a few decisions have been made, I think the problem would be resolved.
Senator Seidman: There is an ever-growing body of evidence since Zamboni first published his results in April of 2009. If you look at the peer-reviewed medical and radiography journals to date, there have been at least 20 reported studies looking at the relationship between CCSVI and MS and about six reported intervention studies.
Perhaps it is fortuitous, and indeed you mentioned that just last week there was the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. At these meetings were reported and published online the results of two fairly major, significant studies, one of which, Dr. Rubin, you put forward and, Mr. Juurlink, you also made reference to. I would like to just highlight these two studies that were reported only last week and then perhaps have your comments, if I may.
The COSMO study you referred to was a large, multi-centre, case-controlled study promoted by the Italian MS foundation to investigate the relationship between CCSVI and MS. The study significant was conducted in 35 Italian clinical centres with close to 2,000 patients. As you said, Dr. Rubin, the subjects they looked at were people with MS but also people with other neurological diseases. The prevalence they found was low enough in all cases — 3.2 per cent in MS and 2.8 per cent in other neurological diseases — to come to the conclusion that these results do not support the role of CCSVI as a potential causal factor in the development of MS. This was significant enough that the Italian Multiple Sclerosis Society declared the theory dead, which is interesting, since they were the ones who promoted the study to begin with.
If I look at the other study that was reported at that conference, this was a surgical intervention study. It was looking at the treatment and clinical outcome of an Italian cohort of 462 cases. Again, the Italian multiple sclerosis study group and the Italian society of neurology promoted this multi-centre study to collect this data. There were 31 MS centres that participated in this study.
They had 462 patients, and they followed them for 36 weeks. They used objective measures of the benefits of the intervention treatment, which was the usual endovascular treatment. What they found was no clear beneficial effect of endovascular treatment for CCSVI in MS, interestingly. However, they also found that 53 per cent of the patients reported some improvement.
The conclusions of that study said that all objective measures used following the treatment for these patients up to 36 weeks showed no positive clinical outcome. However, 53 per cent of the patients reported a positive effect.
Their conclusion was that the subjective positive effects reported by about 50 per cent of the patients could largely be due to the high expectation of patients for an intervention called ``liberation,'' a significant name for the treatment.
I am just asking you if you might comment, because it is fortuitous that only last week this significant congress in Europe reported on two major studies.
Dr. Rubin: It is with great hesitation that any scientist would comment on a study that he or she has not read in a peer-reviewed journal, so I do not know if this was a double-blind, randomized, placebo-controlled study, for example.
I think we commented on the observational study. In the intervention study, I should note that it was originally termed ``liberation'' by Dr. Zamboni not because people are liberated from MS but because the procedure liberates blood flow out of the brain.
Be that as it may, I think this is consistent with my earlier remark that we may not understand why putting a balloon in a vein causes people to be better. The only way you will really know if that is based on an expectation or placebo effect or is the real thing is if you do the type of double-blind, placebo-controlled, crossover study that was funded by the CIHR and the MS Society in Canada.
Mr. Juurlink: As I mentioned earlier, I do not know whether angioplasty will improve symptoms. All I know is that so many dozens and dozens of people with MS have reported to me that they have been able to get out of wheelchairs and walk, for example. I think we need a properly controlled clinical study to determine.
We do have thousands of Canadians going abroad. If this is a futile activity, which puts some in danger of their lives, then we need a proper controlled study showing this is futile. However, if they do go abroad, and whether physicians think they are engaging in dangerous activities or not, they should be treated, if need be, when they come back to this country.
Senator Seidman: If I understand both of you correctly, that is very much the point, that there is enough confusion around this, that clinical trials, to settle this in a scientific objective fashion, are really what is needed.
Mr. Juurlink: Yes.
Dr. Rubin: Yes.
Senator Munson: I would like to get your opinions on why we are here as well. This is Bill S-204, and it has to do with a national strategy for a chronic cerebrospinal venous insufficiency act. This is what we are discussing. At one point, we will have to come to a point of saying ``yes'' or ``no'' to this particular bill. I would like to know if you support this bill or not.
Mr. Juurlink: There should not be a necessity for this bill, but because of so many people with MS having problems, yes, I would support the bill.
Dr. Rubin: I think that my role here is as an expert witness to try to give panel members the understanding necessary to decide if the elements of the bill warrant it going forward or not.
I certainly agree that there should be collection of data for all MS patients. I think there may have been a missed opportunity. However, in reference to what Senator Cordy said earlier, the problem with collecting that data, in my experience and that of others, is that people who go overseas frequently come back with an incomplete record of exactly what transpired. We do not get a CD that has the actual images of what was done and we do not have baseline data. If we had those things, certainly that could contribute to our knowledge.
I would also say that, as I recall from the bill, if this proposes doing a prospective randomized trial, we are doing that. In that respect, it seems reasonable to proceed. However, I want to be clear on my role as a witness, not giving an opinion as to whether or not the bill should be passed.
Senator Munson: Thank you for that. Would it help our deliberations and give us better insight if we had patients who have gone through this as witnesses at the committee?
Mr. Juurlink: Yes, I think.
Senator Munson: Why?
Mr. Juurlink: They are the individuals who are often refused treatment when they come back to Canada. I think it would be good to hear a few firsthand stories.
Dr. Rubin: In my remarks, I said that I was sympathetic to the pain that these people experience, but the truth is that there is no way that I can accurately represent what it is like to have MS or what it is like to be told there is a therapy that might cure me. Therefore, as this is a transparent process, I think that you should absolutely hear from patients that have MS, patients who have benefited from their procedure and patients who had the procedure and had no benefit or indeed had complications. I think that would give you the opportunity to understand the full spectrum of what is going on and will help in making an informed decision.
Senator Merchant: I come from Saskatchewan. Mr. Juurlink, you know we have a very high incidence of MS in Saskatchewan. I am sure Dr. Rubin is aware of that as well. Do you feel it is important for patients who would choose to come before us to appear in person, or do you think it is just as good for them to submit a written submission? Is it better for us to see them here, if they are able to appear, and hear from both sides, those who have had success and those who have not, or is it just as good to ask them to write something about it to us?
Mr. Juurlink: I think human-to-human contact has greater impact than paper-to-human contact.
Dr. Rubin: I think there is nothing like looking someone in the eye when you are talking to them.
Senator Merchant: I thank you for that.
With our study in Saskatchewan, professor, the province decided to go ahead and carry on these trials in New York. Did they consult with you or the MS Society at all? Did you have any participation in the decision making?
Mr. Juurlink: No.
Senator Merchant: You do not know why they decided to go ahead with the study?
Mr. Juurlink: Oh, I have some suspicions why, but my fear is that the study is not complete enough. Personally, I think they should be looking at blood flow through vein tissue, white matter and grey matter before and after and to see if that correlates with functional outcomes. No, they did not consult.
Dr. Rubin: I had no role in that decision making.
[Translation]
Senator Verner: I will speak to you in French, if I may. Is the interpretation working for you? Okay. I will make sure to speak slowly so that it is easier.
First, I would like to make a comment about what you said here about patients who go abroad, and who return to Canada and do not get follow-up care after the procedure they underwent while they were out of the country. I would simply like to say that this seems unacceptable to me, and I hope that we will find a way to correct the situation. We are not in a country where this type of horror story should be allowed.
I would like to come back to the bill before us. I would like to hear your comments about what seems to me to be a contradiction, or at least something that creates confusion. In the whereas clauses of the bill, it states that multiple clinical trials have demonstrated the safety of using balloon angioplasty in treating CCSVI. At the same time, on the on the information site of the Multiple Sclerosis Society of Canada, in reference to this intervention, the society states that ``We cannot advocate for a procedure that is not yet backed by scientific evidence. We believe this would be fundamentally irresponsible for us as an organization with people affected by MS as our first priority.'' It seems to me there is a contradiction between the statement made in the bill—first, we do not know where the certainties are coming from and, at the same time, the Multiple Sclerosis Society of Canada is not giving an opinion on it or encouraging patients to have the intervention, even though it respects their choice. Could you please comment on that?
[English]
Mr. Juurlink: There is a risk in any intervention, but I think it is a relatively modest risk with angioplasty, even though some patients have died.
I would like to point out that one of the clinically approved drugs is Tysabri, and more than 50 people have already died from taking Tysabri.
I think the risk is small, and if there is appropriate follow-up care, it becomes even smaller.
The Chair: Could I ask you to put that in perspective? Do you know how many MS patients have taken that drug?
Mr. Juurlink: Tysabri?
The Chair: Yes.
Mr. Juurlink: Offhand, I do not recall. No, I do not recall.
Dr. Rubin: You have alluded to the safety data that has been reported in publications in comparison to the safety data that has appeared in publications of trials. There is an unexplained difference there because while hundreds or thousands of patients appear in these trials of safety data, there is no mention or no recording of death — which I understand has happened four times — brain stem stroke; clots in veins that are relatively more prevalent just based on what I have seen in my own clinical practice; injuries to cranial nerves that happened when stents were placed that were too large for the vein that was there, to the nerves that run alongside them resulted in issues with swallowing, for example; and parasitic infection.
You may ask, ``How does someone get a parasite from this?'' The reality is that people have travelled to some countries where there are endemic parasites. They do not get those types of infections in Canada and have returned with those infections, and at least one published case required prolonged hospitalization. That is a consequence of medical tourism, not a consequence of the procedure per se.
It is hard to reconcile those, and the reason why we published an article outlining one death and one stroke was to call attention to the fact that this had happened. I know it was that article that contributed to the FDA warning on multiple sclerosis and CCSVI.
[Translation]
Senator Verner: Consequently, it seems a little risky to me to affirm the safety of the treatment. Do you not think so as well? I understand what you have explained, Mr. Juurlink, about the positive effects, meaning that there is always a risk with any treatment. I am with you on that. But it was the fact of stating the safety of the intervention. That was my main issue.
[English]
Dr. Rubin: Yes. This is a very important point. The problem here is that when you talk about four deaths and people who have had nerve injuries or clots, that is the numerator in the equation. The denominator, or the number of people who had the procedure, is not entirely known. If you say out of 10,000 there were four deaths, four out of 10,000 for a potentially life-saving procedure would actually be considered a relatively low death rate if you were talking about other diseases. It must be put in context. It is wrong, misleading and inappropriate to simply talk about the complications out of context.
As I said in my remarks, if the initial heart surgeons would have been scared away from developing heart bypass because a couple of patients died, we would not have heart bypass today. Any time you do a new procedure, unfortunately, people are going to die or have complications. As I said in my remarks, the issue is balancing that risk against the potential benefits of the treatment.
If it turns out that balloon dilation for multiple sclerosis helps 50 per cent of people, just to pull out a number, and 1 per cent suffer devastating complications or death, it will be up to the medical community and patients with MS to decide whether that is an appropriate risk-benefit ratio. That is the process of informed consent.
When I operate on someone and say ``I will fix the aneurysm in your abdomen,'' I tell them, ``There is a 1 per cent chance that you could die from this in the next 30 days.'' They have to know that before they can agree or not agree to proceed.
The problem here is that you cannot accurately assess the risk of vein dilation therapy for multiple sclerosis because the appropriately controlled, blinded studies, in my opinion, have not been reported, and that is required to really further this discussion.
Mr. Juurlink: I agree with Dr. Rubin, but if the trials are done in this country with proper follow-up care, that risk is lessened than if patients go abroad and come back.
Senator Buth: I have a process question. In your experience in terms of dealing with new treatments, what would be a standard process for looking at a new treatment for a new disease, for a specific disease?
Dr. Rubin: If you are talking about a procedure that involves a device, you either must have approval from Health Canada formally in terms of them saying ``this is safe, go ahead'' — I am paraphrasing, of course — or you must have an exemption specifically for the use of such devices. There are multiple devices I currently use where I have to write to Health Canada for each patient and say, ``I am going to do this; is this okay?'' Again, I am paraphrasing.
After a certain amount of data has been collected, Health Canada meets and reviews the data. The way that it works in Canada is different than the FDA. In Canada, a panel of experts presents the data to Health Canada, and then Health Canada decides whether it is safe or not safe for use. In the U.S. it is the physicians who make that decision in conjunction with the administration. I only know this because I am a member of the Health Canada panel. That is my shortest possible answer to this question.
Senator Buth: Would it be a normal procedure to legislate a process to go through in terms of determining how to use a specific treatment? This bill is a bit unusual in that it is specifically legislating a specific treatment for a specific disease. Do you have any experience with other bills that might have done that?
Dr. Rubin: I am sorry, and I am not trying to be evasive, but this is my first experience with this process. I have not read other bills and I do not know what the usual process is.
Mr. Juurlink: With respect to your question, I do not know, but I would like to just consider Tysabri. I am not sure how Tysabri got approval for clinical trials. Tysabri is an antibody that blocks one of the cell adhesion molecules with which immune cells must interact to get into a tissue.
The thinking behind the use of Tysabri is to prevent activated immune cells from entering the brain and spinal cord, but of course this will prevent activated immune cells from entering tissues elsewhere, so you are basically crippling immune responses to an infection. The deaths from Tysabri are due to a brain viral infection. The rationale behind the use of Tysabri baffles me, because you are crippling immune responses to infection in general and not just specifically to MS, so I have no idea.
Senator Buth: I think we are more familiar with how drugs are regulated, rather than a process, a device or something like that, so I was just curious in terms of how the regulation process would normally work and whether or not this bill was atypical or typical.
Senator Seth: Dr. Rubin, I see you have extensive experience in cardiovascular surgery, cardiology surgery. My question is very simple. I want to summarize. If a patient walks into your office — and you were practising, seeing a multiple sclerosis patient — and the patient asks for CCSVI surgery, what would be your answer? This summarizes everything. What should I be answering?
Dr. Rubin: This is actually not difficult for me to answer because I have provided the same answer every time when patients have seen me. I say that there is controversy about whether there is actually a relationship between vein narrowing and multiple sclerosis. I say there is controversy about the outcome of the balloon dilation treatment, and that if they wanted to pursue this, I think it should only be done in the context of a research ethics board approved clinical trial. I do not accept the notion, as published in, I believe, the Journal of Vascular and Interventional Radiology, that individual physicians with individual patients can decide to just go ahead and do this because there has been anecdotal evidence of benefit. That is certainly physicians' rights and patients' rights, but that is not what I would advise patients to do.
Senator Seth: Patients say that other countries are doing this, so why can it not be done in Canada? This is the next question.
Dr. Rubin: I think there is an accepted process for the evaluation of new technologies. It is important to proceed cautiously. I am sympathetic; although, as I said before, I do not really understand what it is like to have multiple sclerosis. When we rush to treatments, errors get made in terms of judgment and patients can suffer. You are trying to balance appropriate therapy in the safest way possible, and practising the ``do no harm'' principle of medicine, recognizing that some patients will be harmed if they go forward with this treatment.
Senator Cordy: It has been a good dialogue about MS and the challenges that are faced by people who have MS and who wish to have the treatment done.
Dr. Rubin, you said you have to look at the balance, risk/benefits, and patients should be looking after their own health care in terms of making those choices. From the testimony we heard yesterday from witnesses, we certainly should be asking the same things about drugs like Tysabri, which was fast-tracked by Health Canada. We know that more than 50 people have died and hundreds of people have brain infection from Tysabri. It would be good if doctors also gave that kind of information to their patients in terms of drugs. I thank you both very much for this.
One of the parts of the bill involves clinical trials. The bill was brought in last year, in June of 2011. Since that time, the government has announced that clinical trials will start. In fact, recently, the last week of September, the government announced that people will be brought forward and the process will actually be in place starting November 1. That is a positive thing. That aspect of the bill can be removed.
However, remaining in the bill will be the fact that we should have a national strategy for MS. As it currently stands, we have different treatments available to people, depending on what province you are in. I would like your comments on the need for a national strategy.
You both talked about the collection of data. That is part of the bill, that we collect data from those who have had the procedure done. You both talked about follow-up care and the fact that Canadians who are returning from another country are not getting follow-up care, and that that is unacceptable in a country like Canada.
You both gave suggestions for patients who are not getting follow-up care. One suggestion was that you contact the College of Physicians and Surgeons, and another was that you contact the Human Rights Commission.
Some patients I have spoken to are a bit worried about contacting the College of Physicians and Surgeons, and say, ``If I contact the college, who will then treat me?'' They are nervous that perhaps the person about whom they have made the complaint, who obviously has not treated them, would not treat them. Perhaps some of their colleagues might say, ``No, I do not want to treat someone who is going to the College of Physicians and Surgeons.''
This is a major concern, and you both said that in your comments. Can we legislate follow-up care? Dr. Beaudet, when he was here last week, said that he had been in touch with the physicians and surgeons in Canada, and they all said this is not a concern. However, the hundreds of people I have spoken to have said it is a concern. They have been told to go back to Poland if they like the medical system so well in Poland. They have been told that even though they do not want to take drugs anymore because they are feeling better after the procedure, if they do not continue with the drugs, they will have their driver's licence taken away from them.
You both spoke passionately about the need for follow-up care. If you have a heart attack in Florida and you come back to Canada, you are treated, so there appears to be discrimination for those who have had the procedure for MS done outside the country.
What do we do? It is frustrating for them, and it is frustrating for me to hear their stories. What would you suggest? Some of the provinces have excellent rules to follow in terms of follow-up care: my province of Nova Scotia, when you read it; and the one in Ontario you were involved in, Dr. Rubin. What they have done for follow-up care is a model; it is excellent, but people are not getting it.
Dr. Rubin: Senator, I am not sure what more I can say other than to say that this is an issue for the colleges. This is a professional practice issue. I understand the sensitivities that you outlined. I do not really have any solutions, other than what I said already.
Mr. Juurlink: I am afraid it is probably a situation similar to that of a few years ago when ulcers were considered to be either a psychiatric or pharmacological problem. It turned out that 90 per cent or greater of ulcers could be gotten rid of through antibiotics. It took some time to change the mindset. We need clinical trials that unequivocally show yes or no, that angioplasty has some effect. We have a mindset out there that is convinced that MS is primarily an immune disorder rather than a consideration that, with MS, immune involvement may be secondary to something else. I do not know how you change that perspective, except through clinical trials.
Senator Cordy: I am also wondering about the need for collecting data about those who have had the procedure outside the country. Would it not be helpful to have data on Canadians who have travelled outside the country to have the procedure done? Do you have to have the procedure done more than once? We talked about the elasticity of the veins. I have spoken to people who have had the procedure done twice. They have gone back outside the country. It is unfortunate that it is medical tourism. Should we not be collecting the data with made-in-Canada information about Canadians?
Dr. Rubin: I again go back to my experience when I have asked people who I have seen in my clinic if they have detailed reports of what was done. Do they have the actual images to show me what was done? Do they have baseline assessments and then subsequent assessments after the procedure? I have not seen anyone who has been able to give me that information.
The problem here is that it is impossible to legislate what happens in another country or to mandate that those people come back with the appropriate information. I think that that is unconscionable in the same way that I am aware that there are some clinics that are offering to coat a stent with your own stem cells and that that will somehow be an even better treatment for you. We have very little understanding so far of how stem cells work in the most rigorously controlled environments, so I think that is an equally unconscionable practice. If there were a way to obtain that information, I would certainly be interested in understanding it.
I can specifically reference one patient who was treated in Mexico, came back and had a swollen left arm, and when we further evaluated her because she was a little short of breath, we found that the clot had broken off and travelled to her lungs. She had a deep vein thrombosis, pulmonary embolus from a stent placed in a vein that I would just never do for that indication. She had no idea that this was life-threatening, which it is, and she had no idea that she would be left with a long-term lung disability because of this clot.
In the same way that you are passionate about saying that people should come back with this information, I am equally passionate about saying that for these people who go overseas, at great personal expense in many cases I have heard about, I am not getting the sense that the informed consent procedure that would apply in Canada is applying there and that they are being told all of the different things that can happen. Just because this procedure is usually safe, by law, in Canada, you have to tell patients about complications that are common and not so dangerous, and complications that are rare but potentially devastating. I do not get the sense that the informed consent process is uniformly carried out for people who go overseas.
Senator Cordy: It is important that we hear the not-so-good stories of people who have gone outside the country. I am not saying that we only collect the data from those who have successes. I think it is important that we have the collection of data period. Perhaps if people knew that the data was being collected when they returned, they would then be a little bit more careful about ensuring that they have the proper things with them when they come back to Canada.
Dr. Rubin: I agree with you completely.
The Chair: I would like to get clarification of something that both of you touched on and get it on the record in a little more detail.
Professor Juurlink, you referenced the number of deaths with regard to a particular drug. Dr. Rubin, you have articulately made the point that the issue is the case of the number of deaths reported through the medical procedure. It is important to put that in the perspective of the total number of people who underwent the procedure in order to help determine the risk benefit in these cases. The same would be true with regard to numbers of adverse events with regard to a drug. It should be compared against the number of persons taking it. Would that be a reasonable assumption?
Second, we have heard about the idea of the fast-tracking of the medical procedure or drug for very serious diseases. Professor Juurlink, you mentioned in this specific case fast-tracking with regard to — if I am incorrectly referring to your testimony, forgive me, but you will clarify it.
Mr. Juurlink: I did not mention that. One of the senators mentioned that.
The Chair: It was directed to you. I apologize.
The point is that there is the additional factor of fast-tracking through much more limited study of a procedure or drug when dealing with a disease or symptom that is considered to be perhaps life-threatening and for which there may not be good alternate treatments. In that case, the risk benefit evaluation is sometimes a little bit different. Could you just comment on my question about the fact that the number of adverse outcomes from a drug should be taken into consideration against the number of people taking it, and secondly, if in fact that risk benefit ratio is somehow affected in the initial evaluation of the outcomes by the severity of the indication that is being treated?
Dr. Rubin: I will preface my comments by again reminding the committee that I am not an expert in multiple sclerosis. However, as a practising physician, there is no doubt in my mind that you have to know what the denominator is in a drug trial the same way as in a device trial. I think there is a perception that because it is a device, you can see it and feel it and it is real in three dimensions, that somehow that gets treated differently in the evaluation process than a drug, but the potential for them to be dangerous you could say it is equal. I do not know why there would be a different standard for one versus the other.
Mr. Juurlink: I agree. You need the context, the numbers.
The Chair: Thank you. My colleagues have already referred to this, but on behalf of all my colleagues, I want to say to you that your testimony has been remarkably clear and articulate with regard to potentially complex issues here, but also you have been able to direct your answers in a manner that, from my perspective, is completely understandable to our committee and I am sure will be extremely helpful to us in evaluating this particular issue before us.
I also want to thank my colleagues for the clarity today of their questions. I think that has helped elicit the answers I have just referred to.
Dr. Rubin: I would like to point out that I think it is important to not confuse the desire for a clear understanding of science with any perception that any physician would not like this procedure to go forward and be successful. I do not have a vested interest one way or the other. I just want to ensure that there is a process that leads to therapies for multiple sclerosis that are safe and effective and that there is a clear path that science and medicine have developed to ensure that that is what happens. When you migrate away from that, there are challenges, and the question here relates to the pressure to migrate away from that path. Please do not confuse what is skepticism about results with a desire to not improve the lives of patients with multiple sclerosis.
The Chair: I say this to all witnesses: If, after leaving here, something occurs to you, as it often does in life, ``I wish I would have thought of that at that particular point,'' or if there is any other issue that occurs to you with regard to the issues you have discussed here today, we have your written submissions, and we will certainly welcome follow-up input from you should that occur to you. With that, thank you again.
(The committee adjourned.)