Medication safety: opening up the black box.

To cite: Mintzes B. BMJ Qual Saf 2013;22:702–704. Medication-related adverse events are a major cause of disability and death, and one of the most common reasons that patients attend hospital emergency departments. Much of this harm is preventable, either because a less hazardous treatment is available, the medicine is not really needed, or it is inappropriate for this specific patient. Many initiatives exist to improve medicine use. Schiff et al call for a more judicious and precautionary approach to prescribing, with a focus on long-term as well as short-term health. To judge a medicine’s net benefit to a patient, prescribers need comprehensive, accurate information on potential harmful as well as beneficial effects. Given the importance of medicines in treatment, information on harm is surprisingly inconsistent and elusive. Approved product information describes adverse events experienced by patients in premarket studies as well as new safety signals once a drug is marketed. In their article, ‘Speaking the same language? International variations in the safety information accompanying top-selling prescription drugs’, Kesselheim et al describe differences in numbers and types of adverse events in product information for the same 20 top-selling medicines in the US, UK, Canada and Australia. There is no reason to suspect that Americans, Australians, Canadians or the English differ in vulnerability to harm from medicines. As well as numbers of events, individual adverse events—including life-threatening harm—were inconsistently listed. The size of patient safety populations on which assessments were based ranged widely, from a median of 3563 in Australia to 7819 in the UK. This was product information for the same medicines, produced by the same manufacturers, and obtained at the same time. Regulatory warnings of serious risks also differed: the US Food and Drug Administration (FDA) has issued boxed warnings for 15 (75%) of the 20 medicines examined; Canada for nine; Australia for none; the UK does not use boxed warnings as a regulatory tool. The contrast is remarkable, as is the high frequency of US boxed warnings among these 20 best-selling medicines, given that only 45 (8.2%) of 548 new medicines approved between 1975 and 1999 obtained black box warnings. US FDA black box warnings are reserved for problems linked to risks of death or serious injury. They can affect prescribing; antipsychotic drug use in elderly patients with dementia declined sharply following the black box warning of increased mortality. In one US analysis of 324 548 outpatients’ prescriptions, 10.4% of patients received drugs with black box warnings, but only 7% (0.7% of the sample), received prescriptions that violated the warnings. US research on black box warnings is not necessarily transferable to other countries as implementation differs. In Canada, boxed warnings are not as prominent, and there is no available list of all medications with such warnings. In the USA, drugs with black box warnings may not be advertised to the public in ‘reminder ads’, which state the name of the drug but provide no health or risk information. Canada imposes no similar limits. Although Canadian law prohibits directto-consumer advertising of prescription drugs, ‘reminder’ ads have been allowed through a shift in administrative policy since late 2000. In 2005–2006, four of eight drugs in Canadian TV ‘reminder ads’ had US black box warnings, and six had Canadian safety advisories. This raises questions about regulatory safeguards. Physicians are influenced by patient requests for advertised medicines, and the public may be poorly informed of a medication’s potential for harm. In Australia, new boxed warnings are listed in a national bulletin, Medicines Safety Update. As Kesselheim et al note, EDITORIAL