Clinical Development in Canada - the pros and cons

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By Tonya Costoff and Shawn Lawrence

Deciding where to conduct a company’s clinical development is a massive decision that companies don’t take lightly. Companies need to consider such important factors as the cost involved, what the regulations are in that particular country, if there are enough people that would take part in the study and how hard/easy it would be to set up the logistics. With so many companies choosing to do these trials in such hot spots as Eastern Europe and India, it’s also important to look at what Canada has to offer in terms of clinical development opportunities.

Biotechnology Focus spoke to industry representatives to ask what their thoughts are on the pros and cons of doing clinical development in Canada. Here’s what they had to say.

Regulatory Representative
Michelle DelaCroix, head of CanReg’s CTA Unit. DelaCroix’s team of six people work exclusively on clinical trial applications (CTAs), and are responsible for approximately 10% of all CTAs sent to Health Canada. DelaCroix commented on clinical development in Canada, having this to say:

“We in Canada, pride ourselves on conducting efficient, high quality clinical trials. With several large cities of over one million people, varied ethnic groups and lifestyle we have at our availability a vast subject population for many new drugs under development. Subjects and investigators are open to clinical research. Many Canadian hospital and universities have developed Clinical Research Groups in order to conduct studies in compliance with GCP and the Food and Drug Regulations. Canada’s subject population is acceptable for FDA submissions for New Drug Applications, which can be viewed as a must in the financial survival of pharmaceutical and biotech companies.

The change in the Canadian Food and Drug Regulations in September 2001, brought a mechanism for Clinical Trial Application submission and a regulated review period of 30 days for therapeutic and biologic products. An even more appealing aspect of doing clinical trials in Canada is the seven day administrative review of Phase I studies in healthy volunteers. This makes Canada very attractive for the conduct of bioequivalence/bioavailability studies.

While the seven day review is a target, many reasons such as safety concerns, work load of the directorate, etc., may result in a Clinical Trial Application (CTA) defaulting to the 30 day review. In January 2004, the Natural Health Products Directorate (NHPD) opened its doors and started accepting CTAs. The NHPD currently offers no regulated review period for CTAs, and by definition, many products previously considered therapeutics would be classified under their jurisdiction for clinical development. The Health Canada Inspectorate began inspections of clinical trial sites in 2002, providing feedback to researchers, ethic boards and sponsors regarding the conduct of the clinical trials and adherence to GCP and the regulations.

Currently there are no agency fees for CTAs. Many Clinical Research Organizations (CROs) are based within Southwestern Ontario and Quebec, where the vast amount of the Canadian population is located. While the newly strong Canadian dollar has made conducting clinical trials within Canada less economically attractive than five years ago, it still remains a high quality, cost-effective solution for study sponsors.

Overall, suffice it to say that Health Canada, investigators and Canada’s population is committed to seeing research of new products continue and remain in Canada.”

Canadian Biotech Company Representative

Wendy Cuthbert, vice president, Clinical Development at Viventia Biotech Inc. had this to say:

What are the benefits and risks?

Canada’s regulatory environment would have to be at the top of the list for benefits – specifically the default 30 day approval time and Health Canada’s willingness to work collaboratively on issues. Though approval times could be as short as two months in some Eastern European countries, others took up to six months (India over 12 months). No mechanism exists to inquire or estimate when approval will be granted, so planning study start-up activities is challenging.

Patient costs in Canada are on par with the US and Eastern Europe and much less expensive than Europe as a whole. India still has significantly lower costs (approx 50% less per patient). Consider though that Eastern Europe was also close to India’s cost levels about five years ago and one starts to wonder where India is headed in the next five years.

India and Eastern Europe have more issues around patient retention, compliance and data quality. These can be overcome, but require additional oversight and management. Supply procurement and import/export of drug and human tissue samples add additional procedures to deal with in these countries as well. It’s important to understand the standard of care in the therapeutic area under development in each of these countries (and often the differences from site to site) to ensure that the study protocol can be executed.

How does Canada compare to these countries in speed, quality and efficiency?

Speed for start-up activities including site contracts is comparable in all of the countries, especially when compared to some of the larger academic institutions in the US. All seem to be comparable for efficiency in study execution as well. Eastern Europe has more language challenges and their knowledge of GCP is not as wide spread; protocol adherence and patient compliance also require more scrutiny. India is comparable to Canada for quality, though retention of patients in longer term studies can be difficult, particularly in the public facilities that draw on rural patients (over 70% of the population of India is considered rural).

Are there cost advantages to doing development in Canada?

Yes – for a Canadian Biotech company, it is much less expensive to do clinical trials in Canada. Though patient costs in India may be less, significant costs for travel, courier, translations, site supplies, phone and data lines and increased auditing and co-monitoring increase this considerably.

In your experience, does it come down to cost in the end? Is that the driving factor?

I would not say that cost is a driving factor, though it is one of several factors that combine with others when deciding where to run clinical trials. The main driver for us and many companies is access to patients in order to be able to complete a study in as short a time as possible. Disease prevalence and competing trials influence this number significantly.

What pros/cons are there for project management in doing research in Canada?

Primarily it would be that trials in Canada require less oversight from a project management perspective. Logistics are simpler and there is less to have to deal with overall so that translates into a more straightforward and traditional project management approach.

Final thoughts?

Canada has a lot to offer with respect to clinical development for Canadian and non-Canadian companies. As an industry, I think we should take more initiative in educating both patients and physicians on clinical trials in order to increase the number of patients and sites available to participate and leverage patient advocacy groups and investigator consortiums to assist in this.

Wendy Hill of Gap Strategies had this to say:

What are the benefits/risks to doing clinical development in Canada?

For Canadian biotech it is helpful to go to Health Canada for your first-in-man clinical study. In this way you get a regulatory perspective on your chemistry and manufacturing, your analytical and your non-clinical data for your product. Then you can go to the FDA for your first IND with some safety data in human, which is a more complete package. As a clinical trial community, Canada is still quite small, and you get a good co-operation for a multi-centered clinical trial. This aids in patient recruitment, protocol design and overall efficiency. In general, clinical sites in Canada are very good recruiters for patients in clinical trials. Also, the clinical trial sites have invested in the education of their clinical trial personal in GCP, therefore the data coming out of the clinical trial sites is of good quality and accepted by the FDA.

One risk might be if you don’t consult the FDA early and they have a different opinion on your clinical development, then you might have to backtrack and do some more work for filing of your IND.

How does Canada compare to such countries as Eastern Europe, India and China in speed, quality and efficiency?

These countries have the population to draw from for clinical studies but there still are questions about the quality of the data from these regions. While the costs are lower in these countries, it becomes more costly to manage these trials remotely from Canada. Because these countries are located so far away, you cannot monitor the quality of the data easily, putting at risk your drug filing.

Are there cost advantages to doing development in Canada?

There used to be a cost advantage to doing it here. Now that the dollar is on par and the academic overheads are equivalent to the US, the disadvantage no longer exists.

In your experience, does it come down to cost in the end? Is that the driving factor?

No, because of the cost parity right now. The driving factors influencing your decision are where you can access the patient population for your clinical trial or if you would like to work with an investigator who is a world expert in the therapeutic area, you may go to their native country. If the auxiliary services do not exist to support the clinical trial, you may need to go elsewhere.

What pros/cons are there for project management in doing research in Canada?

The main benefit of conducting clinical trials in Canada is that it is easier to manage and coordinate the clinical trial and the logistic costs may be cheaper. You’re also better able to monitor the quality of the data because you are closer to where the clinical trial is being conducted.