Clinical Trials in Canada

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BY J. ANDRÉ POTWOROWSKI, PhD

At the 25th anniversary meeting of the Canadian Society for Clinical Pharmacology (CSCP) last September, a group of distinguished panellists explored how to improve the clinical trials system in Canada. Abby Hoffman of Health Canada’s Pharmaceutical Management Strategies raised the basic policy question, “Do we want more clinical trials in Canada?” The group, composed largely of industrial and academic clinical researchers, responded unanimously, “Yes.” The reason was that clinical trials offer many benefits to Canada, all the way from advancing research in new therapies and finding new drugs for patients, to providing a valuable adjunct to standard health-care and economic spinoffs.

Although the question has never been explicitly debated in Canada’s public policy corridors, there has been a tacit assumption by many stakeholders that indeed Canada would stand to benefit by increasing the number of clinical trials and attracting more industry investment in clinical research. So what would be required to make this happen? What would we have to change to double or triple the capacity of Canada’s clinical trials system?

The panel offered many viewpoints and discussed the findings of a report entitled Accelerating Access for Patients to Best Medicines: The system and the challenge1, of which I was one of the principal authors. The research — financed by Industry Canada and Health Canada and carried out at the University of Ottawa’s (Ottawa, ON) Centre on Governance, and the Institute of Population Health — was a preliminary study of the stakeholders and components of the clinical trials system in Canada.

In addition to myself, the team was composed of Monique Bégin, former minister of health and author of the Canada Health Act, Judy Erola, also a former cabinet minister and former head of the pharmaceutical industry association Rx&D (Ottawa, ON), and Prof. George Wells, PhD, chairman of the department of Epidemiology and Community Medicine at the University of Ottawa’s faculty of Medicine. Research associate Scott Watson helped with the bibliographic review. The intention of the study — part of a major research project — was to describe the main parts of the system and to arrive at an initial understanding in order to focus attention on those parts of the system that could benefit from adoption of best practices.

Some 40 interviews with patients and opinion leaders, and a Web review of the literature, indicated that the clinical trials system in Canada represents a valuable asset to the innovation and delivery of health care. Clinical trials help generate new knowledge regarding novel medicines, while at the same time contributing significantly to health-care delivery, and to the health-care research and innovation capacity.

Traditionally, research regarding clinical trials has been sector-based. Projects would study clinical trials from the viewpoint of cost-effectiveness, the medicine chain, health-policy development or the regulatory dimension. The methodology itself might be the focus, or the organizational requirements.

In our study, we started from a systems analysis viewpoint, an integrated perspective. The exploratory research endeavoured to capture all the components that intersect with clinical trials in the drug-development process:
players/stakeholders, chains of activities, factors of influence, constraints.

Not surprisingly, patients were identified as being at the core of the process. Without patients, there would be no clinical trials — at least for the time being, with current science. As patients have a holistic sense of what they live and experience, it is not surprising that they offered opinions on a wide range of issues, covering almost all aspects of the clinical trials process. What they have to say is of no less value than an interview with a pharma executive, a regulator, or with an academic conducting a trial.

The clinical trials system turned out to be more complex than initially thought, and information on the system was far less easy to locate than expected. Instead of four nodes or groups of stakeholders, at least 13 were identified and described:

regulators: Health Canada and the Therapeutic Products Directorate (TBD)
research ethics boards
provincial formularies
research community:
allied health professionals: nurses, co-ordinators and associates
investigators
Canadian Institutes of Health Research (CIHR)
hospitals and universities
global pharma industry
biotech industry
clinical research organizations
private research clinics
site-management organizations
In terms of solid, verifiable data on the various components of the system, there is very little available. We estimated that the total dollars spent on clinical trials and related activities across all industries and academia is between $800 million and $1 billion per year, representing tens of thousands of jobs. The lion’s share is funded by large pharmaceutical companies. But it is not possible to tell how many trials are being carried out in Canada at any point in time, which trials are recruiting patients, for which therapies, and where they are located. Patients want to have access to that information in the form of a comprehensive inventory of clinical trials. The issue is what form that should take, and who should run it.

While Health Canada and its regulatory body have shown some improvement in the last few years, their mean time for approval of new medicines is beginning to creep up again to 1995 levels. Already there are public consultations being carried out by the Public Policy Forum (Ottawa, ON) to explore what might be the optimal model for TPD and the regulatory arm of Health Canada, to ensure they have the level of funding, resources and flexibility to meet the challenges of tomorrow’s technology.

Hospitals and universities appear to have a short-term revenue maximization perspective on industry-sponsored clinical trials, and run the risk of shutting themselves out of this growing activity. The slowness, unevenness and poor funding of research ethics boards is a contributing factor. We already see a growing number of private organizations, from private research clinics and private research ethics boards to site-management organizations and clinical research organizations, that are more than willing to take over the role traditionally held by academic health centres — but at significant profit.

Canadian biotech companies represent another set of complex players. They come in different stages of evolution, with different types of products, and each category of firm has different needs. These should be studied further to gain a proper understanding of the different categories in that industry, and its needs for specific assistance. In addition to the inevitable need for financing, there is also a shortage of resources and skills in the early phases of drug development, both in terms of outsourcing (formulation, manufacturing) and in finding appropriate senior executives with the required experience. This is particularly challenging when the new companies, generally founded by chemists or engineers, need to tackle the regulatory complexities of the health sector. Again, interaction with other stakeholders — e.g., university-based researchers in the health sector — could be better focused and improved. There is a need to explore more systematically the needs of biotechnology companies in various stages of development, not only in terms of capital financing, but also in terms of other skills and resources, e.g., formulation, manufacturing and early-phase drug development, including clinical trials.

CIHR, Canada’s star in the funding of health-care research, is spending less than five per cent of its budget on clinical trials. Even if it had additional funding, there is a perception that it would not have the needed expertise to review and manage these research projects. Yet it is through clinical trials that health-care discoveries and new medicines eventually reach the patient.

In brief, the clinical trials system in Canada is a tightly interwoven innovation system, crossing many lines and boundaries, a system about which we know very little. Because it is multidisciplinary and multijurisdictional, no single federal department can hope to understand it in its integrated state. This has to be done through an independent task force.

A number of research questions were identified at the end of the report, but if there is one challenge with which the authors would like to conclude, it is that the clinical trials system is a rich and beneficial innovation mechanism for Canada, which few, if any, have studied in an integrated systems manner.

What is worrisome is that other countries have already put in place aggressive and innovative policies to radically improve their national clinical trials systems, Australia being a prime example. Other countries include the biocapital of Singapore and the U.K., as well as the emerging economies of Eastern Europe or Latin America. Unless we do something about our clinical trials system very soon, these other countries will certainly take over this $1-billion industry and capture its benefits. And Canadian patients will be the first to suffer.

1) www.governance.uottawa.ca/research/clinical_trials-e.asp J. André Potworowski is associate director of R&D at the Centre for Research in Biopharmaceuticals and Biotechnology and adjunct professor at the School of Management, University of Ottawa. He also consults on health-care delivery systems and research and innovation strategies for corporations and governments. The report authors are preparing a Phase II of their initial study, which will consist of regional workshops aimed at identifying ways of increasing clinical trials capacity for those regions, and provide specialized Web-based training modules to promote best practices for increasing speed and quality of clinical research projects. J. André Potworowski can be reached at potworowski@management.uottawa.ca or by telephone at 613-580-2215.