ABSTRACT

Objective.—To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients.

Data Sources.—Four electronic databases were searched from 1966 to 1996.

Study Selection.—Of 153, we selected 39 prospective studies from US hospitals.

Data Extraction.—Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death.

Data Synthesis.—The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2,216,000 (1,721,000-2,711,000) hospitalized patients had serious ADRs and 106,000 (76,000-137,000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.

Conclusions.—The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.

ADVERSE DRUG REACTIONS MAY CAUSE OVER 100,000 DEATHS AMONG HOSPITALIZED PATIENTS EACH YEAR

Study suggests adverse drug reactions are among the top causes of death in U.S.

CHICAGO—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, M.D., Ph.D., 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, the 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 percent of all causes of recorded death in 1994, making these reactions between the fourth and sixth leading cause of death.

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. They write: "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 write.

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 authors conclude: "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."