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Adverse drug reactions (ADRs) are a leading cause of death in the USA, say Canadian researchers. Bruce Pomeranz and colleagues at the University of Toronto estimate that ADRs could account for more than 100 000 deaths in the USA each year, making them the fourth commonest cause of death after heart disease (nearly 750 000 deaths), cancer (530 000), and stroke (150 000) (JAMA 1998; 279: 1200-05).
A meta-analysis of 39 prospective studies, covering a period of 32 years, revealed a 6.7% incidence of serious and fatal ADRs, and a 0.32% death rate, among patients admitted to hospital because of an ADR and those having an ADR while in hospital. The analysis examined only ADRs attributed to drugs that were "properly prescribed and administered". Drug-administration errors, non-compliance, overdose, drug abuse, therapeutic failures, and "possible" ADRs were excluded. Even at the most conservative estimate, say the authors, ADRs would still be the sixth commonest cause of death. "The figures are much higher than expected and suggest that ADRs are considerably under-reported", says Pomeranz.
*Figure 1. Adverse reactions too common* - not shown
76% of ADRs were dose-dependent (rather than idiosyncratic or allergic), suggesting, say the authors, that many adverse reactions result from the use of drugs with unavoidably high toxicity. Some ADRs may be due to inadequate monitoring of therapies and doses, and the authors cite evidence that careful drug monitoring in hospital-eg, of warfarin treatment-reduces the incidence of ADRs. Direct costs of ADRs could amount to US$4 billion a year, they add.
"The buzz word is 'awareness' ", says Pomeranz. "The hope is that this will lead to a decreasing incidence of ADRs." Surprisingly, continues Pomeranz, "the incidence of ADRs is the same now as it was over 30 years ago". This suggests that a tendency towards multiple drug therapies could be maintaining the risk despite a reduction in hospital stays.
Pomeranz's research suggests that ADR incidence is much the same worldwide, "but there are too few published studies to give an accurate picture". Charles Medawar (Social Audit, London, UK) has found that accurate statistics for ADRs in the UK are hard to come by, despite his repeated requests to official sources, including to the Secretary of State for Health, Frank Dobson. "However, there seems to be agreement that adverse drug reactions account for 3-5% of hospital admissions, and that is an awful lot of cases", he adds. "In addition, about 15% of inpatients have their hospital stay prolonged by adverse drug reactions, of which probably half could be avoided. We cannot expect to reduce this burden until drug-induced illness is actually defined as a problem, concludes Medawar.
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