Health Canada needs broader powers to assess the safety of new prescription drugs, including the power to require post-market trials, says the former director general of the department's Therapeutics Products Directorate.
“Drug safety has been brought into the spotlight once again . . . and we have to bring more structure” to this area, says Dr. Robert Peterson, a pediatrician who left Health Canada last year and is now director of the British Columbia Child and Youth Health Research Network.
International regulations adequately address drug safety about 75% of the time, Peterson told the University of British Columbia Centre for Health Services and Research Policy conference in February.
But important safety information does not surface for about 20% of drugs until after they are marketed and patients have begun taking them, he said. About 3% of the time, new drugs have unexpected and catastrophic adverse effects on patients.
“Three percent is not acceptable,” says Peterson.
All drugs have side effects and these side effects can't all be predicted on the basis of clinical trials, he said. “A large clinical trial would be 5000 [people], and a 1 in 10 000 adverse reaction would be obscured,” he said.
The current regulatory framework has a “narrow focus on pre-market requirement,” he told the Vancouver conference. Peterson wants to see requirements for post-market trials and provisional licensing of drugs, for the control of off-label use, and for more complete information for prescribers and patients.
Health Canada currently has no regulatory authority to control off-label use of drugs, Peterson said, which must be looked at “through the lens of drug safety.”
According to Health Canada, “some of the issues raised by Dr. Peterson are ones that Health Canada is looking at, primarily through a discussion on the modernization of our regulatory framework and through legislative renewal.”
Similarly, there are now no regulations governing Phase 4 (post-market approval) trials, which are in fact specifically exempt under Food and Drug Act regulations, he told the conference.
But Phase 4 trials are frequently required to validate actual efficacy, especially when surrogate measures — instead of clinical outcomes — are used in Phase 3 trials, he noted.
The current voluntary system does not work. Despite promises made by pharmaceutical companies, “often these trials are not completed or even started . . . commitments are not being followed through.”
Health Canada has no authority to compel changes to product labels after approval — with the exception of the “blunt instrument” of revoking market approval. And it does not require the provision to prescribers of strictly educational material about new drugs, he said. It is “absolutely absurd” to assume that product monographs can provide prescribers with a “distinctive competency” to prescribe, since monographs don't present information in an educational format. A monograph for a drug may state that regular tracking of liver function is important, but it won't explain why this might be highly important, he said.
Where there are substantial safety risks with a drug — for example, the antipsychotic clozapine — some useful educational material has been created, and Australia in particular has produced several model documents, he said. Prescribers and patients need more information about “what is known, and not known, about a drug.”
Health Canada has only limited options for conditional release of a drug, whereas in Europe provisional authorization of a drug subject to yearly renewals is now possible, he said. This type of arrangement allows for clear limits on prescribing, regulated outcome reporting, and even a requirement for trials comparing a new drug to one already on the market.
Peterson also wants increased use of linked databases to track the use and impact of drugs on patients. “Governments have walked away from drug development and left this to the commercial sector,” he said. But by promoting data linkage and drug safety, governments can re-engage.
The former regulator acknowledged that changes to regulations take time, often several years. In the interim, he suggested that insurance companies or employers could make decisions about the conditions under which they would cover drug costs, addressing for example the off-label use of a drug.
Peterson worked for the changes he now advocates during his 5-year tenure at Health Canada. It was not frustration with the pace of change that led to his departure, he said. “But I also knew there were issues with a minority government and another election coming that might delay some of these changes.” His decision to leave was also prompted by consideration of what he wanted to do with the remainder of his career.
Peterson continues his involvement with regulatory matters as chair of the regulatory advisory board of the UK-based Centre for Medicines Research International, he said. He is also a member of the Canadian Expert Drug Advisory Committee, which provides advice to the Common Drug Review.