Executive Summary
INTRODUCTION
On November 22, 2011, the Senate adopted an Order of Reference authorizing the Standing Senate 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 the second phase of the study, for which the committee heard from witnesses between October 3 and November 21, 2012. Over the course of eight meetings, the committee heard testimony from Health Canada and Office of the Auditor General of Canada officials, representatives from the pharmaceutical industry, patient advocates, medical, ethical and legal academics and finally, representatives of national organizations concerned with pharmaceutical policy.
ISSUES OF CONCERN
The report Canada’s Clinical Trial Infrastructure: A Prescription for Improved Access to New Medicines (the Clinical Trials Report) from the first phase of this committee’s study on prescription pharmaceuticals discussed the issue of clinical testing of investigational drugs to assess their safety and efficacy. While the pre-approval assessment of safety and efficacy is critical and the clinical trials necessary for the assessment must be optimized, it is generally acknowledged that the safety and effectiveness profile of every new drug continues to evolve once it is used in the general population. Health Canada is responsible for monitoring this ‘real-world effectiveness’ of pharmaceuticals after they are granted market approval.
Traditionally, Health Canada has relied on reports of adverse drug reactions (ADRs) to identify safety signals and issue necessary advisories or warnings. ADR reporting, while mandatory for drug manufacturers when they are made aware of any, is voluntary for health professionals and the public. Although the number of ADR reports submitted to Health Canada has increased, this information still reflects only a small proportion of the actual ADRs experienced by the general population. Recently, the Drug Safety and Effectiveness Network (DSEN) was created within the Canadian Institutes of Health Research to carry out additional research on potential safety signals identified by Health Canada.
Health Canada has acknowledged the need to adopt a life-cycle approach to drug regulation and indicated to this committee that regulatory modernization is a departmental priority. The creation of DSEN helps to move post-approval monitoring from the traditional approach of relying on ADR reports to a more active surveillance model. However, the committee is concerned that Canada is neither keeping pace with international requirements nor following the legislative, regulatory and policy models in other jurisdictions in order to optimize the post-approval monitoring of prescription drugs in Canada.
In response, this report makes 19 recommendations that address issues such as: legislative and regulatory reform; the independence and effectiveness of DSEN; DSEN’s research model; data collection through electronic health records; ADR reporting; post-approval strategies for population sub-groups; communication strategies; and, implementing the necessary changes in response to the 2011 Auditor General report on regulating pharmaceuticals.
In terms of legislative and regulatory reform, the committee was told by almost all witnesses that Canada’s Food and Drugs Act is outdated and in need of modernization. Consistent with the committee’s observations in the Clinical Trials Report that modernization is essential to Canada’s management of pharmaceuticals, the committee recommends additional elements of pharmaceutical policy that must be implemented. In this regard the committee is calling on the Minister of Health to introduce drug legislation that provides additional authorities to the federal government. As well, regulatory reform must accompany a modernized legislative framework. The committee is encouraged by Health Canada’s repeated commitment to regulatory reform but notes that the department has indicated its intention for such an update for several years. Therefore the committee is calling on the Minister of Health to implement comprehensive regulatory reform which applies a life-cycle approach to drug management, including long-term studies of drug safety, beginning in 2013. The committee further specifies that the new approach to drug regulation must ensure that funding of post- approval activities is increased such that pre- and post-approval activities are equally funded by the department.
Although the committee heard considerable support for the recently created DSEN, it also heard concern from several witnesses about whether DSEN is sufficiently removed from the influence of the pharmaceutical industry, since CIHR promotes collaboration with the industry. The committee encourages DSEN in its work but would like measures taken to ensure its independence as well as its sustainability. These measures include: an assessment of its work and analysis of its ability to operate independently; a commitment by the federal government for sustained funding; budgetary independence from CIHR; and creation of a mechanism to review DSEN findings and, where relevant, monitor the actions taken by Health Canada in response to those findings.
Also in regard to DSEN, the committee notes the support among many witnesses for its organizational structure, but agrees with those who suggested that the research model currently used by DSEN could be further enhanced. As such, the committee suggests that DSEN could be used as a means to apply active reporting of ADRs. The committee urges the creation of clinical models that encourage active monitoring of ADRs with dedicated resources for filing reports with Health Canada. In this regard, it sees a further role for the research network capacity recommended in the Clinical Trials Report in active post-approval surveillance.
The electronic health record (EHR) was described by several witnesses as an effective means of improving the quality and quantity of ADR reports, which in turn improves the capacity for Health Canada and DSEN to assess potential safety issues. One aspect of a comprehensive EHR is data regarding dispensed prescriptions and the committee notes the success of British Columbia’s PharmaNet in this regard. The committee recommends that the Minister of Health discuss implementing similar systems with provincial and territorial counterparts. Further, the committee urges compatibility and linkability of dispensed prescription drug databases with patient electronic medical records (EMRs) and EHRs. Finally, the committee would like ADR reporting facilitated by linking the electronic ADR form through patient EMRs and EHRs.
With respect to specific sub-groups of the population such as children, pregnant and nursing women and the elderly, the committee emphasises that there should not be a lower threshold of drug safety and effectiveness. Similar to the concerns raised by this committee in the Clinical Trials Report, post-approval monitoring of prescription drugs must be strengthened in order to protect these sub-groups. Consistent with the committee’s recommendation at that time that more clinical trials include specific sub-groups, but acknowledging that additional information will need to be collected post-approval, the committee would like to see post-approval studies and systematic safety reviews in relevant sub-groups of the population. Finally, the committee notes that research conducted within DSEN in response to queries submitted by Health Canada or other stakeholders may result in identification of issues among these populations. It recommends that such secondary findings be considered for follow up studies.
Witnesses spoke of the need to improve and standardize the information being provided to those consuming the drugs. The committee agrees with concerns raised that the information provided to patients at the point of sale is not necessarily approved by Health Canada. The department should implement standardized Patient Information Leaflets (PILs) and prohibit the sale of any prescription drug unless accompanied by its PIL. The proposed PIL should also include information about the Health Canada website and phone number to which ADRs can be reported.
Witnesses also spoke of the need to improve communication about new drugs, and drugs with potential safety concerns, through labelling. In this regard the committee is recommending that Health Canada adopt the labelling requirements that have been implemented in the United States and the United Kingdom, which identify new products, a category of drug with a higher incidence of ADRs, as well as drugs that are linked to serious side effects. Implementation of this recommendation should help to encourage ADR reporting. Health Canada should also become more transparent in its identification of potential safety signals. The committee recommends that Health Canada provide information about the Risk Management Plans that have been submitted by drug manufacturers, the safety signals that have been identified, the status of subsequent assessments and the drugs for which manufacturers must conduct post-approval studies, including long-term follow-up.
Finally, the committee notes the Fall 2011 report of the Auditor General of Canada on the regulation of pharmaceuticals. The committee would like Health Canada to provide assurance that it has implemented all necessary changes in response to that report.
CONCLUSION
The committee acknowledges that Health Canada has improved its approach to post-approval monitoring of prescription pharmaceuticals in recent years. The department has implemented promising initiatives such as the Drug Safety and Effectiveness Network and has worked to improve efficiencies of post-approval monitoring activities within the Marketed Health Products Branch of Health Canada. However, there is still work to be done in its management of prescription pharmaceuticals. Health Canada and the Drug Safety and Effectiveness Network must continue their efforts in this regard. The committee would like to see this report’s recommendations implemented quickly to improve the safety of prescription drugs, to increase transparency in their management, and to foster trust among Canadians in our drug regulatory regime.