A Meta-analysis of Prospective Studies

Jason Lazarou, MSc; Bruce H. Pomeranz, MD, PhD; Paul N. Corey, PhD

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 effect 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 [Cl], 5.2 %-8.2%) and of fatal ADRs was 0.32% (95% Cl, 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

Perhaps, our most surprising result was the large number of fatal ADRs. We estimated that in 1994 in the United States 106 000 (95% CI, 76 000-137 000) hospital patients died from an ADR. Thus, we deduced that ADRs may rank from the fourth to sixth leading cause of death. Even if the lower confidence limit of 76 000 fatalities was used to be conservative, we estimated that ADRs could still constitute the sixth leading cause of death in the United States, after heart disease (743 460), cancer (529 904), stroke (150 108), pulmonary disease (101 077), and accidents (90 523); this would rank ADRs ahead of pneumonia (75 719) and diabetes (53 894). Moreover, when we used the mean value of 106 000 fatalities, we estimated that ADRs could rank fourth, after heart disease, cancer, and stroke as a leading cause of death. 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.

aus JAMA, April 15, 1998-Vol 279, No. 15:1200-1205