Hurry up and wait for a CCSVI strategy

MS drugs get fast-tracked all the time. Why can't a clinical trial get the same treatment?

Update 2: The second reading of Bill C-280 is now scheduled for Thursday, December 8 at 6:30.

Update: The second reading and debate for Bill C-280 was pushed off the House of Commons schedule on Nov. 30 due to other business. It hasn’t been rescheduled. Stay tuned.

CPAC is not always recommended viewing but tonight’s programming is must-see-TV. At 5:30 pm EST (and later in endless loop) Liberal MP Kirsty Duncan’s private member’s Bill C-280 calling for a national CCSVI strategy is set for second reading and debate. (If the House of Commons vote scheduled to begin at 6:15 pm goes past 7:01 pm, private member’s business will be cancelled and rescheduled for another time at the discretion of the Speaker.)

Duncan, a Ph.D. and adjunct professor at the University of Toronto, was the Liberals’ public health critic when she initiated the 2010 sub-committee on neurological diseases, which called upon Italian vascular specialist Paolo’s Zamboni to answer questions about his hypothesis that venous malfunctions in the neck and chest are linked to multiple sclerosis—and that venous angioplasty can relieve MS symptoms dramatically. The member for Etobicoke North is calling for CCSVI clinical treatment trials as well as a national tracking program for the estimated thousands of Canadians who’ve traveled offshore for treatment—and have been denied after-care upon return.

Canadians might think they’re watching a re-run. It’s not, though the Conservatives have been all over CCSVI in the past week. Leon Benoit, MP for Vegreville-Wainwright, proposed a private member’s motion calling for a national tracking system and to increase patient awareness of CCSVI treatment. And on Friday, Health Minister Leona Aglukkaq announced that the Canadian Institute of Health Research (CIHR) was calling for proposals for a “small scale” phase I and phase II clinical trials into CCSVI.

Duncan’s bill is expected to create schisms within party caucuses as CCSVI supporters take on the skeptics. It already has support among CCSVI advocates, the same groups that expressed frustration and anger with the minister’s CIHR announcement. Response to that was fast—and for the most part furious—particularly to the news actual trials wouldn’t commence for another year, which would mean CCSVI screening and treatment for MS patients would be in lock-down for a decade. That’s a typical timeline for clinical trials—but devastatingly slow-moving to those with MS, a degenerative disease for which a year can make the difference between walking and being bedridden. Some 55,000 to 75,000 Canadians are estimated to be afflicted with the condition—though those are old numbers in need of updating says the MS Society of Canada, which estimates multiple sclerosis costs the Canadian economy more than $1 billion a year.

In a press release, the advocacy group CCSVI Ontario blasted “the waste of time and money on unnecessary safety [phase I] and efficacy [phase II] trials” into venous angioplasty, which is accepted practice and already used in neck veins to improve blood flow in kidney dialysis patients. CCSVI Alberta was even more impassioned: “To allow people to suffer and die while a potential life-saving treatment is at hand is unethical, bordering on criminal.” Like other groups, it advocates a large scale phase II/III [treatment] trial in multiple centres immediately.

Michael Shannon, a medical doctor with extensive experience designing and running large clinical trials, says that a phase I safety trial, which could take at least 18 months, is “a 100 per cent total waste of time and money.” CCSVI clinical trials are already well underway in the U.S.,” he notes. “The fact the FDA has approved three double-blinded clinical trials at phase II level should convey to anyone who understands the regulatory process that the FDA is satisfied with the general safety of this procedure which is routinely used throughout North America for all kinds of medical conditions requiring arterial or venous intervention.”

Dr Shannon, who has held several high-level federal government positions, including Director General of The Laboratory Centres for Disease Control, heads the Scientific Advisory Board of the CCSVI Coalition. He estimates that a phase I clinical trial would take at least 18 months to complete, cost more than $1 million and contribute absolutely nothing in the way of new information to the large body of safety information already available for this procedure. His group is advocating for an “adaptive phase II, phase III” trial, which can expedite the regulatory process without compromising its scientific rigor and which could save an additional half year of time.

“Disease-modifying” MS drugs to alleviate symptoms, a market estimated to hit $15 billion by 2015, are “fast-tracked” to market all the time. In Oct 2008 Health Canada fast-tracked Biogen Idec’s Tysabri, despite concerns it can cause a rare fatal brain infection called progressive multifocal leukoencephalopathy (PML). (The total worldwide total reported cases of Tysabri-linked PML stands at 181; the death count at 38.) This month, the FDA fast-tracked Tovaxin, a drug developed to treat secondary progressive MS on the grounds that no other therapies were available for this group. On its website, the MS Society of Canada expresses urgency that the newly approved oral drug, Gilenya, be covered by provincial health plans: “The MS Society of Canada is working closely with the provincial and territorial governments, urging them to make quick and positive decisions to include Gilenya in their list of drugs for reimbursement under their public drug plans.”

MS patient and CCSVI activist Christoper Alkenbrack of Wolfville, Nova Scotia expresses cynicism about the pace the process has played out. In August 2010, the CIHR, Canada’s scientific funding body, conducted a closed-door meeting that resulted in a decision that Canada adopt a wait-and-see attitude toward clinical trials. Ten months later, on June 28, 2011, it did an about-face after being presented with a meta-analysis of CCSVI research. Five months after that, the minister of health announced clinical trials, less than a week before Bill C-280 was to be debated. Alkenbrack, a former high school principal who says he has benefited markedly from CCSVI treatment, questions whether those with experience dealing with CCSVI experts will be involved in the trials: “I suppose that I could reconsider my position if they actually put the real experts in charge of the studies, but up to this point, it has not been the case,” he wrote on CCSVI Facebook page.

Sandra Birrell, president of the National CCSVI Society in Victoria, BC, is buoyed that steps are being taken: “At least the Canadian government is doing something,” she says. “It might be appallingly slow for those of us who are waiting but we actually have movement.” Birrell says she has faith in the system, though notes “there are aspects that obviously are not nimble enough to respond to something like this. It’s a model built to test new drugs.”

She expresses frustration, however, that a vascular condition has been sucked into the neurological/auto-immune MS research paradigm. A dangerous precedent is being set, she says: “Have they studied breast implants in relation to MS? Or interventions covered by the health system like laparoscopy? What this means is that every time something comes along that could affect a chronic illness, those with that chronic illness will be withheld that new treatment until the full effects of that treatment on their chronic illness are well understood.”

Meanwhile, as the politicians debate, Canadians already are participating in CCSVI clinical trials—only not in Canada. Many (their exact numbers are unknown due to the fact these are blinded studies) have been treated at one of the three FDA-, IRB-approved trials currently in phase II trials in the U.S. and a phase III trial underway in Poland. And more are scheduled. The Saskatchewan provincial government is spending $2 million for 80 to 90 MS patients to travel to Albany, N.Y., for CCSVI treatment after efforts to get an in-province treatment trial running by year-end failed. Provided that doesn’t hit a roadblock, we’ll have some science about CCSVI treatment far sooner. Until then, if you’re interested in a glimpse of how politics, medicine and business collide, tune into CPAC tonight.

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