B.C.’s Drug Research Withdrawal

Can B.C. become a global centre for human drug trials? Until recently, the province was Canada’s leader in trial activity, but its share of the action has slipped significantly. A new network hopes to lure the lucrative business back to the province.

It’s a quiet afternoon at the clinical trial unit on the fourth floor of the Gordon and Leslie Diamond Health Care Centre at Vancouver General Hospital. While the building’s atrium hums with activity – couples laughing over smart phones and medical staff coming and going – the rooms that serve the needs of researchers are empty.

On one side of the short corridor are the modest south-facing offices where clinicians meet with patients and complete paperwork; on the other, the examination rooms common to any medical clinic where patients giving new drugs a test run are examined and the effects of the medications recorded.

There are no patient interviews or examinations scheduled today, but a block away, at the hospital’s Research Pavilion in the Willow Chest Centre, strategizing is taking place about how to keep the clinic’s rooms filled on a steady basis.

Canada is no lightweight on the global landscape as a site for clinical trials of new pharmaceuticals and medical devices, ranking fourth in the world. Until recently, B.C. was Canada’s leader in trial activity, claiming 54 per cent of a business estimated to be worth $1.5 billion annually. However, its share of the action has slipped significantly in recent years – three to four per cent a year, by some estimates – to the point where B.C. now claims a mere 28.5 per cent of the clinical trials conducted in Canada.

Simon Pimstone personifies the dilemma faced by drug researchers in B.C. The founder of Xenon Pharmaceuticals Inc., a Burnaby company focused on discovering drugs to address pain, anemia and metabolic and cardiovascular disease, Pimstone is a veteran of B.C.’s biotech scene, and heads one of the few homegrown biotechs to have progressed beyond the discovery stage to clinical trials. But, for reasons he insists have nothing to do with shortcomings in local capabilities, Xenon conducts most of its clinical trials elsewhere.

“It just depends on the indication we’re studying, and where it’s best to do that,” he says. “For the particular work we’re doing, B.C. just happens to be not well-suited.” Instead, Xenon is working with patients in Quebec – where attractive tax incentives for research exist – as well as in the U.S. and Europe, as part of the phase I and II clinical trials the company is conducting.

Drug trials work with relatively small groups of people – 20 to 80 for the first phase, and 100 to 300 for the second phase. Those two phases are a prelude to the third phase, which confirms a drug’s effectiveness and monitors side effects prior to the product’s approval.

The trials are performed according to protocols established by each country, but harmonized in accordance with the Switzerland-based International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, and with the consent of patients. Participants volunteer for the drug trials, sometimes in exchange for a nominal fee. They’re treated as any other patients would be, either on an outpatient basis or accommodated in hospital rooms with staff and monitoring equipment taking regular observations on reactions to the drugs on trial.

Pimstone estimates that taking a new drug through all three trial phases requires an investment of between $100 million and $200 million, but he quickly notes that only about one in 10 drugs under development ever makes it as far as clinical trials. Completing a single clinical trial takes an average of 780 days – more than two years – from initial protocol design to completion, and typically costs $2 million to $3 million. Much of that time is taken up with paperwork. Each trial requires a team of staff to oversee management of documents (from contracts to consent forms and ethics reports); recruit physicians and patients; and to collect, collate and analyze the wealth of data gathered from patients.

It sounds like a lot, and it is: clinical trials have become bigger and more complex in recent decades. A shift since the 1990s has also led researchers to work directly with real-world populations, field testing new drugs with patients who might benefit from them. Hospitals have become living laboratories for researchers, increasing the importance of strong networks and connections between institutions and trial sites. The complexity of the trials has also motivated companies to look for cheaper research locations, a search influenced by shifting exchange rates.

Back in 2004, when Canada’s dollar was cheap relative to the U.S. dollar, a clinical trial in Canada cost 22 per cent less than similar research in the U.S. Today, Canada is a cut above the U.S. in terms of cost, and much more expensive than the other leading industrialized nations. While Canada has held its own as the fourth-biggest site of clinical trials in the world, with 14 per cent of the market, it has been overtaken by South Africa, which claims 14.5 per cent of trials worldwide.

To cut costs, as many as 40 per cent of trials are managed by private firms that focus exclusively on clinical trials, such as B.C.-based Syreon Corp. and Aska Research. The privately managed trials cut the time spent by 30 per cent, according to industry estimates, and trial expenses by 10 or 20 per cent compared to those by corporate researchers or hospital and university labs.

The emergence of companies such as Syreon and Aska underscores the significant spinoff benefits clinical trials have for B.C. beyond the dollars spent directly on trials. Such companies create additional job opportunities and attract specialized research expertise to the province. “Clinical research will bring the top clinicians to B.C.,” notes Rob McMaster, executive director of the Vancouver Coastal Health Research Institute.

Xenon’s Pimstone estimates that two jobs are created for each research position the province attracts; these range from accounting staff to cleaners. And then there’s the money spent on research, he notes, which supports development of homegrown expertise: “There’s money that goes to associated clinical research personnel, principal investigators, that’s able to support graduate and post-graduate students in their clinical and research facilities.” Conversely, every research opportunity B.C. loses eliminates another handful of employment opportunities.

Most of the money for B.C. clinical trials comes from outside the province, for the simple reason that local biotech companies, like other tech startups, are primarily promising young firms with ideas and an appetite for capital. Growth depends on partnerships with larger companies – often, the big pharmaceutical firms.

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B.C.’s shrinking share

The good news is that B.C. is an attractive destination because of its world-class health-care system, teaching hospitals and universities producing skilled researchers. The province also boasts the largest network of clinical trial centres in western Canada, with more than five dozen research facilities, running the gamut from universities to hospitals and private labs. Other unique advantages include an ethnically diverse population, where most people have been treated with various drugs in the past, allowing for important information on interactions and contra-indications across a spectrum of ethnic and cultural backgrounds.

However, a number of factors have contributed to B.C.’s shrinking slice of the clinical-trial pie. Jurisdictions such as Quebec offer clinical trial teams tax incentives above and beyond the federal program of Scientific Research and Experimental Development credits, which remain the key government incentives that companies in B.C. can expect.

While tax incentives are out of the hands of local researchers, an equally important problem the local research community has been addressing is the fact that B.C.’s research facilities are a patchwork of institutions and policies, with no single operating standard among the various institutions. This has meant that multi-site trials have long required researchers to submit to multiple ethics agreements and protocol documents, increasing the paperwork required to do trials as well as the time and expense.

To address the issue, a number of institutions including the province’s six health authorities, Genome B.C., LifeSciences B.C., the Michael Smith Foundation for Health Research and UBC’s medical school, banded together in April 2010 to create the B.C. Clinical Research Infrastructure Network (BCCRIN).

The idea of a network was spearheaded by Pierre Meulien, the former chief scientific officer for Genome B.C., who was instrumental in establishing the Irish Clinical Research Infrastructure Network. (Ireland’s organization is a member of the European Clinical Research Infrastructure Network, which helps co-ordinate clinical trial activity throughout Europe.) A model similar to what BCCRIN has adopted was pioneered locally by the B.C. Cancer Agency and Vancouver Prostate Centre.

A single co-ordinating organization can allow for improvements such as reciprocity between trial units on matters such as ethics and contract standards. Six facilities recently agreed to harmonize contract procedures, eliminating the need for different contracts when trials occur at different locations. “That saves a lot of time and effort and frees up resources to conduct research instead of doing a lot of bureaucratic activities that don’t really necessarily add a lot of value,” says Heather Harris-Harper, operations director for BBCRIN.

One of the first orders of business for BCCRIN was developing an asset map enumerating the institutions and trials in the province, published in 2010. The document summarizes resources available to researchers and clinical trial activity in B.C. for the past five years. This year, BCCRIN is launching an economic impact study that aims to put dollar figures to the activity.

With the province touting technology development in the B.C. Jobs Plan as “helping to develop the commercial opportunities of tomorrow,” and in turn future job opportunities, the numbers have become politically important. “The provincial government is very interested in these kinds of figures, and especially in jobs,” says Harris. “We need to be able to go back to the government to say the sector employs this many jobs.”

BCCRIN has also drafted a business plan identifying areas for further action, which seeks to reverse the flow of business by streamlining the processes that govern clinical trials in B.C., including research contracts, ethics policies and data collection systems. Streamlining of processes is also being advocated at the national level, sponsored by Rx&D, the pharmaceutical industry’s national research advocacy group, the Association of Canadian Academic Healthcare Organizations and Canadian Institutes of Health Research.

But as McMaster remarks, the B.C. initiative will develop a common framework for research organizations that facilitates research across a number of sites, and help small research groups operate to international standards.

“It wasn’t necessarily to address deficiencies; it was to actually know what level we wanted to be working at,” McMaster explains. “It’s a real benefit to smaller groups that don’t have the expertise. They can use the guidelines in the manual to implement [trials] at international levels.”

An accreditation program debuting this fall will also allow researchers to achieve an internationally recognized level of certification. BCCRIN will host the qualifying exam, and cover 80 per cent of participation costs.

The efforts to improve research standards and the calibre of research personnel is occurring parallel to efforts to improve participation in clinical trials. The business plan targets patient recruitment and retention as a key focus. A study this summer of participation in clinical trials will survey the opinions of 1,000 people who have participated or declined to participate in a clinical trial.

“We want to look at the reasons why they made that decision so we can better understand what’s driving participation rates, and this will feed into our greater strategy around recruitment and awareness to drive protocols and recruitment campaigns going forward,” Harris says.

The province’s enhancement as a site for clinical trials will ensure it not only becomes a destination of choice for such research, but also boost the local biotech sector. “By making the improvements that BCCRIN is proposing to the clinical research landscape we would expect to be able to stem the flow on those jobs, and perhaps bring more investment into the province and increase those jobs,” Harris says. “They’re living-wage jobs; they’re decent paying jobs within the clinical research sector. They’re not McD jobs,” she adds.

Those high-paying jobs are something the province wants to attract as part of its jobs plan, and are an argument for ongoing funding for research programs and staffing requirements at participating institutions. “It’s an economic advantage to the institution – not in dollars, in expertise and retention,” McMaster says. “It makes it a career path for many. It keeps that level of expertise local as opposed to going offshore.”

It’s hoped the expertise will not only spawn new companies, but attract the big-name (and, ideally, well-capitalized) partners that local biotech startups need to pursue later-stage trials and take ideas to market. “We contribute significantly on the preclinical research side into the province’s economy because that’s where most of our companies in B.C. are,” Pimstone says. “In terms of the large clinical trials, that’s generally money that comes from large multinational companies outside B.C.”

BioPartnering North America is an event in Vancouver each spring that showcases local biotech companies to global players such as GlaxoSmithKline, Merck and Roche. Vancouver-based Sirius Genomics Inc., for example, works with drug manufacturers to identify patients who, by virtue of genetic factors, respond favourably to the manufacturers’ products. During a recent BioPartnering North America conference Sirius was introduced to Roche, which has opened doors for it to grow its own business and engage in trials and testing opportunities.

“It’s very beneficial to the community, and the fundamental reason is that partnerships are what grow life sciences,” says Chris Wagner, president and CEO of Sirius. “Partnerships allow us to tap into other companies’ abilities and work together to not only fund these things but to do the best research we can.”