Nutrasource Blog

Clinical research in Canada has been declining year over year since 2010.  Fluctuations are sometimes seen due to the changing strength of the Canadian versus American dollar as the costs are typically quite similar between countries.  Another factor in the recent downturn has been partially credited to Sponsors and contract research organizations (CROs) placing studies in foreign countries or being misinformed that data must be produced in the country they are marketing in.  These factors have led to CROs and sites to move to, or open operations in, other countries to adapt.

Despite the decline in Canadian-based clinical trials over the past five years, there are several advantages to carrying out clinical research in Canada.  Read on to learn about the key differences between clinical trials run in Canada and the United States, and how your company can benefit from bringing your research north of the border.

In the natural health product/dietary supplement industry there are clear differences between countries in how clinical trials are regulated.  In Canada, the regulations governing natural health products—the Natural Health Product Regulations—came into effect in 2004.  We cannot ignore that our industry faced challenges over the past 10 years with these new regulations; however, Health Canada has worked toward streamlining operations to provide quicker market access as well as committing to faster turnaround times on clinical trial application reviews.

Currently, a well-compiled clinical trial application will usually be reviewed by Health Canada in approximately three to 6 weeks from time of filing.  This review is not always required, for example, if a product has a valid licence in Canada (known as a Natural Product Number, or NPN) and is being compared in a bioavailability study to another product that has a valid NPN.  In these cases, a Health Canada application may not be necessary as this may be considered a post-marketing study.  Similarly, food trials which study the effects of foods that are available in Canada do not require approval from Health Canada, and only require review by an ethics board.

While the additional step of a clinical trial application is not required in the United States, the review of the study by Health Canada provides regulatory insight, review of scientific design and overall merit of the study.  To minimize impact on timelines for a Canadian study, several initiatives can be taken.  For example, obtaining ethics approval may be done once initial feedback is received from Health Canada so that both Health Canada authorization and ethics approval are received at the same time.  Identifying potential candidates through electronic medical record review can also be performed prior to ethics approval to speed time of recruitment.

Health Canada reviews and comments on aspects of study design such as sample size determination and study design, including duration, endpoints, appropriateness of the population and safety of the subjects.  The purpose of this review and commentary is to ensure proper tests and inclusion/exclusion criteria are being used.  As part of the clinical trial application, quality information regarding the study product is submitted, which can be cross-referenced for future product licence applications or clinical trial applications, expediting those processes.  When submitting study documents to an ethics board, the ethics board is only assessing ethical aspects of the study design rather than scientific merit or robustness.  Sponsors therefore gain a competitive advantage by conducting studies in Canada as they are exposed to a level of regulatory scrutiny they otherwise would not have received.

Conducting natural health product clinical trials in Canada allows the Sponsor to investigate populations and endpoints which, in the U.S., could trigger the need to file an Investigational New Drug (IND) Application.  In the U.S., the filing of an IND can trigger a cascade of events depending on the product’s current position in the marketplace.  This could a) result in adulteration warning letters from the Food and Drug Administration (FDA); b) require changes to manufacturing under drug Good Manufacturing Processes (GMPs) instead of dietary supplement/food GMPs; and c) require (if an IND applies) that the Sponsor list the trial publicly on a registry such as clinicaltrials.gov.  While it may be advantageous to list on clinicaltrials.gov for publication purposes, it also provides a public forum to see what the competition is researching.

Through Health Canada’s process there is no public listing of natural health product studies.  In some cases companies may want to research a natural product to see if it has potential to be a pharmaceutical without investing the substantial amount required to change manufacturing and file an IND in the U.S. to study this proof of concept.  Canada is an ideal country to conduct drug development research for natural health products/supplements as it can be conducted under the natural health product regulations and GMPs while still having regulatory oversight.  Upon success, and acquiring proper drug development knowledge from your research partner, the information can be used in the IND application process to transition the dietary supplement to a drug in the U.S. without affecting any current marketing of the product as a dietary supplement.  Moreover, positive research conducted in Canada on at risk populations with treatment efficacy endpoints which may otherwise trigger an IND in the U.S., can be used to support claims in both countries, thereby preventing FTC action.

Another key difference between Canada and the U.S. with regards to clinical trials is that Canada has a medicare system.  Participants that volunteer for clinical trials in Canada are doing so because they are interested in being part of research and future health care options, rather than as free medical advice and/or treatments.  Canada has high standards with respect human rights and ethical treatment of clinical trial participants.  Canada has additional ethics requirements that are not common between Canada and the U.S.  For this reason, all research ethics boards in Canada can oversee research conducted in Canada as well as in the U.S., but not all U.S. research ethics boards can oversee research conducted in Canada.

Once you have chosen to conduct your clinical research in Canada, the next step is to seek out an experienced CRO with a strong track record and wide range of expertise in the natural health product, supplement and pharmaceutical space.  As a solution provider, Nutrasource regularly conducts and manages all aspects of clinical development program in-house including:

• Natural health product and pharmaceutical product development strategy plans and their management;
• Filing clinical and market access regulatory applications for approval;
• Protocol writing and design compliant with industry and regulatory standards;
• Site selection and management;
• Recruiting and seeing study participants;
• Clinical data management in a 21 CFR Part 11 environment;
• Statistical analysis and report writing.

Our unique combination of experience and expertise in marketed health products, including both natural health products and pharmaceuticals, provides Sponsors with an unparalleled advantage in designing and conducting cost-effective clinical studies to withstand the rigorous scrutiny of Health Canada, the FDA and Federal Trade Commission (FTC), and the European Food Safety Authority (EFSA) for claims substantiation, product development and unique market positioning.