Adverse drug reactions (ADRs) in U.S. hospitals may be responsible for more than 100,000 deaths nationwide each year, making it one of the leading causes of death, according to an article in the April 14 issue of The Journal of American Medical Association (JAMA). Bruce H. Pomeranz and colleagues from the University of Toronto analyzed 39 studies of ADRs in the United States to estimate the incidence of serious and fatal adverse drug reactions in hospital patients. To obtain overall incidence rates of ADRs in hospitalized patients, researchers combined the incidence of ADRs in the hospital and the incidence of ADRs causing admission to the hospital. The authors estimated that 2,216,000 hospital patients experienced a serious ADR and 106,000 deaths were caused by ADRs in the United States. This could account for 4.6% of all causes of recorded death in 1994, making these reactions between the fourth and sixth leading cause of death.
As alarming as these data may be, they do not include deaths among non-hospitalized patients, or deaths caused directly by medical devices or surgery.
The World Health Organization defines ADRs as any noxious, unintended and undesired effect of a drug, which occurs at doses used in humans for prophylaxis [prevention], diagnosis or therapy. The authors define a serious ADR as one requiring hospitalization prolonging hospitalization, or one that is permanently disabling or results in death. The researchers found no significant correlation between ADR incidence and year the studies were conducted.
According to the JAMA authors, "This result seems surprising since great changes have occurred over the last four decades in U.S. hospitals that should have affected the incidence of ADRs. Perhaps, while length of hospital stay is decreasing, the number of drugs per day may be rising to compensate. Therefore, while the actual incidence of ADRs has not changed over the last 32 years, the pattern of their occurrence has, undoubtedly changed.
The authors determined that ADRs are one of the leading causes of death by using the highest and lowest possible estimates. Using the higher estimate placed ADRs as the fourth leading cause of death, behind heart disease (743,460 deaths), cancer (529,904 deaths) and stroke (150,108 deaths). Using the lower estimate placed ADRs as the sixth leading cause of death behind those previously mentioned, as well as pulmonary disease (101,077 deaths) and accidents (90,523 deaths). ADRs would then rank ahead of pneumonia and diabetes.
The article concludes: "While our results must be viewed with some circumspection because of the heterogeneity among the studies and small biases in the sample, these data suggest that ADRs represent an important clinical issue."
In an accompanying editorial in the April 15 JAMA, David W. Bates of Partners Healthcare Systems and Brigham and Women's Hospital, Boston, MA, cautions that there are several concerns about the way the study was done, although the authors adhered to the generally accepted criteria for meta-analyses. "First, an inherent limitation of meta-analysis is that combining the results of small, heterogeneous studies does not necessarily bring one closer to truth, particularly if the processes used to identify and to validate the presence of the events were heterogeneous. Second, the hospitals studied are probably not representative of hospitals at large. Such studies are more likely to be conducted in academic, tertiary care hospitals; these hospitals have sicker patients, and these patients have more ADRs. Another issue is whether the sites of care sampled within the institutions were representative of the institutions." Bates adds: "Nonetheless, these data are important, and even if the true incidence of ADRs is somewhat lower than that reported. . .it is still high, and much higher than generally recognized."
For more information: Bruce Pomeranz, Department of Zoology, Ramsay Wright Zoological, Labs, 25 Harbord Street, Toronto, Ontario, Canada M5S 1A1. Tel: 416-978-8646.
By Angelo DePalma