In the absence of a centralized procedure, EMEA currently relies on authorities in the 25 member states to collect and collate drug safety data. But in the wake of the recent withdrawal of Merck's Vioxx (rofecoxib), director general Thomas Lönngren has called for a better method, telling the Financial Times that there is an urgent need to build up independent networks of intensive drug monitoring.
EMEA's authority and power are not as wide as FDA's. Most medicines now have to go through the agency for union-wide approval, but in many areas EMEA functions mostly as a coordinator of the activities of member state agencies, such as the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.That is about to change. Starting in November, EMEA will be able to approve drugs conditionally, requiring further safety studies to be carried out before the product is given a full license. In a similar vein, the United Kingdom's Department of Health is investigating the possibility of introducing a further tier of trials before full registration is permitted. A drug would be given a limited license to be used in a wider population of patients, under close monitoring.
Step Change In an attempt to improve pharmacovigilance, the United Kingdom has already announced changes to its "yellow card" scheme. Set up in 1964 in the aftermath of the thalidomide tragedy, the system requires doctors to fill out cards when patients experience adverse reactions to medicines. The cards are torn out of the back of the prescribers' "bible," the British National Formulary (BNF), then sent to the government's Committee for the Safety of Medicines. Newly approved drugs are flagged in the BNF with black triangles, prompting doctors to keep a close eye on them.
A recent amendment to the scheme allows doctors to post details of suspected reactions online and encourages patients to report adverse events themselves. MHRA will publish anonymous data on suspected ADRs on its website, which will be available to the public.
Although all medicines have safety issues, risks have to be balanced against potential benefits. The serious side effects of some cancer drugs, for example, would not be tolerated in a product to treat, say, depression.
In the current climate, there is a danger that the careful balance between risk and benefit may be upset. Serious side effects with very low incidence, such as those seen with Vioxx, are unlikely to show up until the drug enters widespread use. Although close monitoring is essential, an over-cautious approach would lead to the delay of medicines that offer huge benefits to patients.
Industry View The pharma industry, although it has generally welcomed the more careful monitoring of side effects, is concerned with the idea of having approvals and safety monitoring carried out by separate entities. "I think to focus on safety is important. But the outcry that we should have separate safety and efficacy evaluation units is not a good trend," says Tachi Yamada, GlaxoSmithKline's chairman of R&D.
Pharma companies in Europe believe it already takes too long for new medicines to reach patients. When a drug has been given EU approval, it will not be available to patients in the different member states until local health authorities make final decisions about issues such as reimbursement. Separate bodies for efficacy and safety will likely lead to further delays by adding another layer of bureaucracy.
The European Federation of Pharmaceutical Industries and Associations, which represents the pharma companies, has said it will issue its own proposals this year for post-marketing surveillance of pharma products. But there remains a huge amount of public concern about whether the medicines doctors prescribe are safe. There has to be a happy medium between risk and benefit, but working out where that line is, particularly in light of knee-jerk reactions to high-profile withdrawals, will not be easy. And a separation of efficacy evaluation from safety monitoring would only make that harder.
Sarah Houlton, PhD,
is Pharmaceutical Executive's global
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