HESA Committee Report

NDP Supplementary Report to the Standing Committee on Health’s study of the Post-Market Surveillance of Pharmaceuticals, June 2008
by Judy Wasylycia-Leis, MP

In our study of post-market surveillance, the Committee was presented with a rare consensus among the many witnesses that appeared before us: our current approach to drug safety is in trouble.  Canadians share this feeling and want and deserve a drug safety system that ensures, based on the best scientific evidence available, that the therapeutic drug products on the market are safe to use.  Why should Canadians expect any less?  Instead, we are confronted with a constant barrage of warnings and recalls – not about drugs that have been tampered with or that have been misused, but that through their approved use are causing harm to health and in some cases costing lives.   Properly prescribed drugs following government-approved manufacturer instructions are estimated to be the 4^th ranking cause of death in North America.  A recent study found that one of every nine visits to a Canadian emergency room is caused by medication problems – of which 39% are due to drug side-effects, including pain, bleeding, rashes, and hallucinations.

Hazardous drugs continue to gain market access. We were reminded of the more serious cases like COX-2 inhibitors with trade names like Celebrex and Vioxx with its hundreds of thousands of heart attacks and many thousands of deaths.   Prepulsid,  Evra patch, zelnorm, Heparin – the list goes on.  And then there are countless others that never make the headlines.  And that, in itself, is part of the problem.  Our existing post-market surveillance system picks up less than 10% of the adverse drug reactions that occur.  Statistics cannot begin to describe the pain and suffering caused to victims of serious reactions and their loved ones.  Simply including a long list of things we, as consumers, should look out for in miniscule print on the label or inside the package is not an acceptable answer.

Meanwhile, Canadians spent $27 billion on drugs last year and there is considerable pressure by pharmaceutical manufacturers to increase that spending and the profits it brings as quickly as possible.

How we got here

We find ourselves in this desperate state not as the result of some single cataclysmic mistake.  We have arrived here at the end of a 30-year journey where government after government has caved in and put public health protection at risk to further a corporate pharmaceutical agenda.  Along the way, it has reduced Health Canada’s capacity to independently ensure drug safety and created a departmental culture in which accommodating pharmaceutical ‘clients’ is the highest value – even overriding public safety. 

The de-professionalization of departmental scientific staff in the 1970s and 80s, fanned by ‘cut red tape’ rhetoric, escalated with the record Liberal financial cutbacks of the mid-90s and the conversion of the regulatory relationship into a ‘partnership’ with the pharmaceutical corporations.  This was followed quickly by the dismantling of the drug research labs in 1997 over NDP objections and the later introduction of strict new departmental deadlines for completing drug approvals to ensure speedy company access to markets. 

Paralleling the operational shift at Health Canada were repeated government efforts to “rationalize” the legal framework to remove liability and lessen departmental responsibility for Canadians’ safety: in the Health Protection Business Enterprise, in 1995-6; the Health Protection Branch Transition (Shared Responsibilities, Shared Vision), in 1998; Bill C-80, the Canada Food Safety and Inspection Act, in 1999; Health & Safety First – A Proposal to Renew Federal Health Protection Legislation (Safety First), in 2003; and in 2006, the Blueprint for Renewing Canada’s Health Products & Regulatory System (Blueprint for Renewal). 

Today, we find ourselves facing yet another round with Bill C-51, a bill that overlaps many of the issues examined in this study.  Central to this latest proposal is “progressive licencing”, a cause of concern to many witnesses who fear the government’s approach to life cycle monitoring will result in a relaxation of pre-market rigour and the increased use of conditional approvals.  In the words of the Department, “shifting the focus from pre-market review to one that continuously assesses a product's risks and benefits, both before and after it reaches the market, by putting conditions on the licence”.  Again, speedier approvals to pave the way for corporate profits. 

What’s the problem?

Our drug safety system is a continuum from pre-market trials through post-market use.  To assess post-market surveillance, therefore, we must also take into account the strengths and weaknesses of the pre-approval process.

Witnesses drew our attention to a number of serious weaknesses in our current pre-market system, including the lack of transparency in drug trials that is somehow excused by the government on commercial, proprietary grounds.  Despite greater openness elsewhere, in Canada commercial interests trump consumer and public interest.  Other weaknesses of concern to witnesses included:

• the manipulation or incomplete reporting of clinical trials by drug companies, as described in the Journal of the American Medical Association revelations concerning Vioxx in April; 
• that the use of rigid trial completion deadlines may result in premature and potentially harmful approval decisions evidenced through an increase in adverse reactions, as described in the March issue of the New England Journal of Medicine;
• efficacy questions from the lack of head-to-head comparisons and the estimation by the US Food and Drug Administration that 80% of “new drugs” entering the market are “me-too” drugs offering no improvement over drugs that are already available;
• the exclusion of non-therapeutic ingredients; and
• the lack of a registry to track all trials, once started.

Weaknesses at the post-market end of the continuum were also pointed out. One of the oft-heard criticisms was that our system is passive and does not provide pro-active surveillance, waiting for trouble to emerge.  One obvious aspect of that passivity is Health Canada’s over-reliance on the American FDA to initiate warnings and recalls.  Heparin provides a recent example.  Other weaknesses include:

• the need for more human resources within Health Canada for both pre- and post-market surveillance – a situation made worse by the internal competition for those inadequate resources between pre- and post-market monitors — not to mention other departmental areas; 
• the lack of a mechanism to address the dangers of off-label prescribing (Health Canada’s inability to pursue additional approvals for new applications of drugs — a power reserved for the original marketing firm;
• the lack of post-market standards;
• in relation to adverse reaction reporting:
• the low reporting rate of only about 10% of serious, unexpected incidents;
• no uniform quality standard;
• inadequate analytical capacity;
• no timeframe for action or even the requirement of feedback;
• the lack of public and professional awareness and training in submitting reports;
• poor communication — the presentation of information, such as it is, is not easily understood;
• the need for greater integration with the Common Drug Review and national formulary process; and
• the slow progress on electronic records and the urgent need for the integration of systems across jurisdictions and the integration of drug registries, health outcomes and patient records.

Conclusion and Recommendations
The post-market surveillance of drugs is an important responsibility of the government.  Finding solutions to the many weaknesses that have developed in our drug safety program is as complex as the problems themselves.  The following recommendations provide direction to improving drug safety for all Canadians based on testimony before the Committee.  It should be noted, however, that the success of these recommendations, or others, depends on a change in the culture within Health Canada that reasserts the dominance of the precautionary principle and public safety together with the government’s provision of additional financial and human resources to fully implement a pro-active drug safety strategy.  We therefore recommend that the government:

• Reassert the predominance of the precautionary principle as the philosophical cornerstone and practical guide in the regulation of drug safety;

• Increase transparency throughout the drug safety regime ensuring that the public, health professionals and regulators have access to information that will impact on their health.  For example, by:
• setting up a web site with postings of all pre-approval clinical trials and a summary & rationale of each decision,
• requiring all protocols and results of clinical trials – including those not completed – to be provided to the government regulator,
• requiring all suspected adverse reaction reports and the protocol and results of post-market safety evaluations to be made public;

• End its ‘partnership’ relationship with the pharmaceutical industry and return to its mission of health protection.  For example, it should dispense with its system of deadlines for pre-market approvals in all but clearly specified circumstances such as breakthrough drugs and the treatment of terminal conditions;

• Provide budgetary and human resources adequate to fully conduct its health protection responsibilities for drugs, including the pro-active post-market surveillance of approved drugs (Post-market surveillance is a public responsibility and its design and administration can not be left to manufacturers’ risk management planning with its inherent conflict of interest.);

• Establish an independent oversight regulatory safety board, separate from the regulator, to investigate problems arising after approvals;

• Actively support the accelerated development of the National Pharmaceutical Strategy’s Drug Effectiveness and Safety Network as an independent tool for the post-market regulation of drugs;

• Increase support for the Canada Infoway and the integration of electronic health records into the post-market surveillance of drugs and adverse reactions in a national tracking system modeled on the British Columbia’s PharmaNet data system;

• Vigorously maintain support for the Common Drug Review, and CADTH;

• Tighten and enforce restrictions against direct-to-consumer advertising of drugs, as recommended by the Committee in Opening the Medicine Cabinet;

• Require that gender analysis be included in all pre- and post-market safety assessments of drugs;

• Improve adverse drug reaction reporting and response through, for example:
• enforcing the existing mandatory requirement for the pharmaceutical industry to report serious adverse drug reactions, and that this reporting encompass all suspected adverse effects they become aware of, including within clinical trials and events reported outside of Canada
• making public periodic safety update reports
• providing financial support for the specialized training of additional ADR analysts
• increasing the education of both the public & health professionals about ADR reporting
• introducing the use of a Black Triangle or other easily-recognizable symbol indicting the need for attention to adverse reaction potential
• including the reporting of the impact of adverse drug reactions in population health statistics, for example from hospital and coroner data
• evaluating the effectiveness of warnings
• designating deadlines for responses to ADR reports 
• providing timely feedback to the originators of ADR reports.

In addition, the government needs the authority to require post-marketing studies and to initiate testing for additional uses of approved drugs.