On 22 November 2011, the Senate adopted an Order of Reference authorizing the Senate Standing Committee on Social Affairs, Science and Technology to examine and report on prescription pharmaceuticals in Canada. The study includes four components, each to be studied separately, which are: the process to approve prescription pharmaceuticals with a particular focus on clinical trials; the post-approval monitoring of prescription pharmaceuticals; the off-label use of prescription pharmaceuticals; and the nature of unintended consequences in the use of prescription pharmaceuticals.
This report is on this first phase of the study, for which the committee heard from witnesses between 28 March and 30 May 2012. Over the course of 11 meetings, the committee heard testimony from Health Canada and Office of the Auditor General of Canada officials, representatives from the pharmaceutical and clinical trial industries, patient advocacy groups, medical, ethical and legal academics and finally, representatives of research ethics boards.
Issues of concern
The safety and efficacy of new drugs are thoroughly tested in human clinical trials, which are the final stage of drug development. This phase of development provides not only the data that is needed to assess safety and efficacy, but it can also provide, in some instances, early access to new medicines. Unfortunately, the proportion of global clinical trials being conducted in Canada has declined over the past decade. For companies seeking clinical trials the major factor, beyond the quality offered by clinical trial centres, is cost. Although financial factors such as currency, taxes and tax credits are elements of the cost consideration, they are largely beyond the committee's scope in this study. However, time is also an important element of cost, and while it is essential that trials be conducted thoroughly, the committee identified a factor that significantly impacts the time required to start up clinical trials in Canada - the absence of a standardized approach to research ethics review. This deficiency results in companies having to submit multiple research proposals to meet the requirements of research ethics boards at numerous trial sites. Thus, considerably more time and effort is needed to get clinical trials designed, approved and started in this country. As a result, the cost of testing drugs in clinical trials is high in Canada, making it less desirable to the industry as a destination for clinical trials.
Canada’s role in clinical trials of new drugs is critically important for attracting research dollars in the short term and improving access to new drugs in the longer term. The committee heard from witnesses about their concerns regarding clinical trial infrastructure and their suggestions for improvements. In response, this report makes recommendations that address issues such as: enhanced leadership of the federal government; transparency of the clinical trial process; standards and accreditation of research ethics review; barriers to patient recruitment; inclusion of vulnerable sub-groups of the population; drugs for rare diseases; and, the need to assess patent protection and tax incentives.
In the context of leadership, the committee is calling on the federal government to take initiatives that will position Canada more favourably on the global stage as a preferred jurisdiction for clinical trials. To that end, the committee recommends the creation of a National Framework for Coordinating Clinical Trials that will help to attract clinical trials to this country. Further, it envisions this Framework as one that will promote the importance of clinical trials and the benefits of participating in them. The Framework will also identify a point of contact between the pharmaceutical industry and the research community.
The committee heard considerable testimony regarding the lack of transparency and the need for increased public disclosure about ongoing clinical trials. It calls on the Minister of Health to authorize the necessary changes so that Health Canada has the authority to require the registration of a comprehensive set of clinical trial data on a publicly accessible database. This would include foreign trials that support submissions for drug approval in Canada. It is essential that the new requirements be strictly enforced.
The need for standardization of the research ethics review process and the accreditation of research ethics boards was raised frequently during the study. Ethics review is essential for all research involving humans. The committee heard from many witnesses that the ethics review of clinical trials lacks consistency since many trial sites can establish their own research ethics review board and can operate under their own guidelines. As such, the research ethics review process is in need of standardization. The committee acknowledges that there have been attempts in this regard but it suggests that success will only be achieved if all relevant stakeholders are involved in the process. Once research ethics review has been standardized, an accreditation program for research ethics boards must be developed. Additionally, the committee urges that adherence to such standards must be enforced with a requirement that ethics review of clinical trials must be obtained from an accredited research ethics board.
In terms of facilitating and increasing patient recruitment into clinical trials, witnesses spoke of the benefits associated with the creation of research networks. The committee recommends that the National Framework for Coordinating Clinical Trials promote the creation of research networks and provide guidance on centralizing ethics review and establishing internal databases to facilitate patient recruitment.
Further, witnesses described how research networks can be helpful in promoting inclusion of vulnerable sub-groups of the population in clinical trials. It is essential that this information be available to Health Canada when it assesses new drugs for safety and efficacy. The committee calls for changes to the drug regulatory regime such that there is a requirement for clinical trial design to reflect the population that can reasonably be expected to consume the drug once it is on the market. Further, market approval must only be granted by Health Canada if clinical trial data is available about all relevant population sub-groups.
The issue of rare diseases and the need for specific policy measures aimed at encouraging drug development and improved drug access for patients with rare diseases (an Orphan Drug Policy), were also examined by this committee. The committee notes that the issue of an Orphan Drug Policy has been raised previously at this committee, most recently during its study on the 2004 Health Accord, and that Health Canada has recently taken action. On 3 October 2012, the Minister of Health announced the creation of an Orphan Drug Framework to encourage research and development as well as facilitate authorization of new drugs. This report calls on the Minister of Health to ensure that this new framework addresses additional concerns such as clinical trial design and reducing or eliminating user fees. In addition, the National Framework for Coordinating Clinical Trials must promote Canada as a preferred site for conducting clinical trials for orphan drugs and facilitate the work of stakeholders to develop strategies for maximizing patient recruitment into such trials.
Representatives of the pharmaceutical industry voiced frustration over patent protection for prescription pharmaceuticals and emphasized that Canada has fallen behind other countries in terms of patent life. They suggested that the shorter patent life granted in Canada compared to other jurisdictions is a disincentive to pursue innovation in this country. In terms of tax incentives, these witnesses suggested that recent changes to the Scientific Research and Economic Development Tax Incentive Program, which reduced the general tax credit available to industry from 20% to 15%, will similarly discourage clinical trial activity in Canada. As potential deterrents to clinical trial investment, the committee would like these concerns addressed comprehensively by an expert advisory committee.
Officials from the Office of the Auditor General, which reported on Health Canada’s performance regarding the regulation of pharmaceuticals in November 2011, discussed their concerns about Health Canada’s role in clinical trial regulation. In its report, the Auditor General highlighted issues with: Health Canada’s inspections of clinical trial sites; the department’s handling of adverse event reports from clinical trials; and, the transparency of authorized clinical trials. The committee wants the recommendations of the Auditor General addressed immediately. It is also recommending that Health Canada increase its inspection activity in order to meet its target of conducting inspections of 2% of clinical trial sites and accelerate the implementation of electronic reporting of adverse drug reactions so that manual data entry can be eliminated. The Auditor General’s report had raised these concerns, but had not issued recommendations related to them.
Several witnesses mentioned that the Food and Drugs Act requires updating and that this has been attempted in the past. The committee heard, for example, that the penalties provided in the Act are not sufficient to deter non-compliance and that they should be increased. It also heard that additional authorities should be granted to the Minister of Health in order to increase the level of transparency in terms of the information that the department can make available to the public. The committee recommends that the necessary statutory changes be pursued in order to modernize drug regulation in Canada.
Finally, the committee would like Health Canada to regularly monitor and publicly report on the impact that implementing these recommendations has on clinical trial activity in Canada.
Canada can no longer rely on an international reputation for conducting good quality research to attract clinical trials to this country. Declining clinical trial activity means lost opportunities for Canada to be a global leader in drug innovation. It must act now to improve clinical trial infrastructure so that efficiencies can be realized and this critical phase of research can proceed swiftly. While the committee acknowledges that attracting research dollars by improving the clinical trial infrastructure is important, it emphasizes that patient safety cannot be compromised.
This committee is calling upon the federal government to bring Canada’s clinical trial requirements and obligations in line with other countries and to engage all stakeholders so that the needed infrastructure improvements can be accomplished. Implementation of the recommendations in this report will result in an increase in Canada’s global competiveness in the clinical trial sector and ultimately to improved access to innovative medicine for Canadians.