Authors' objectives

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

Searching

The following electronic databases were searched: MEDLINE (1966-1996), Excerpta Medica (1980-1996), International Pharmaceutical Abstracts (1970-1996), Science Citation Index (1989-1996). 'adverse drug' or 'adverse reaction' or 'drug-related' or 'drug-induced' and 'hospital' were used as keywords along with the following MeSH terms where appropriate 'hospitalisation', 'drugs' and 'drug therapy/adverse effects'. The reference sections of all retrieved articles were manually searched and letters were sent to researchers in the field to request unpublished data, in order to try and reduce the possibility of publication bias occurring. Studies were only included if English translations were available.

Study selection

Assessment of study quality

The authors do not report a method for assessing validity.A formal assessment of validity was not carried out but the authors tried to increase the overall quality of the database of selected studies by excluding the lowest quality studies (ie retrospective studies) and excluding ADRs that were classified as 'possible' (ie an ADR which follows a reasonable temporal sequence and for which the ADR is a known response for the drug, but which may also be explained by the patient's clinical state)

Data extraction

A random selection of studies were checked for agreement by two authors independently. The intraclass correlation coefficients ranged from 0.89 to 0.92 for the data extracted including the incidences of serious, fatal and all severity ADRs. The following information was extracted: year of study, ward and hospital type, mean age, average length of time in hospital, average number of drug exposures, information on non-serious, serious and fatal ADRs.

Methods of synthesis

Results of the review

There were 39 prospective studies: 18 in-patient studies including 34,463 participants, and 21 admission studies including 28,017 participants.

Linear regression showed that for ADRIn, the number of drug exposures and the length of hospital stay jointly accounted for 43% of the variance (r=0.65, P=0.009, n=18). If age was included for ARDAd, in addition to the aforementioned factors, the variance was reduced to 27% (r=0.52, P=0.04, n=14). The combined sample used in the meta-analysis differed significantly from the US hospital population as a whole with respect to length of stay and gender. There was no significant correlation between the year of publication and the incidences of ADRIn (r=0.27, P=0.14, n=18) and ARDAd (r=0.23, P=0.34, n=21). Medical wards were over represented in the included studies, and unfortunately there was insufficient power to determine the possible effects that ward-type distribution may have on the results. Teaching hospitals were also over represented, however there were no significant differences with regard to teaching and non-teaching hospitals in terms of ARD incidences.

In-patient ADRs (ADRIn): Incidence of ADRs - Serious ADRs (n=12 studies; 22,502 participants) 2.1% (95% CI: 1.9, 2.3); Fatal ADRs (n=10 studies; 28,872 participants) 0.19% (95% CI: 1.13, 0.26); All severity (ie non-serious, serious and fatal) ADRs (n=18 studies; 34,463 participants) 10.9% (95% CI: 7.9, 13.9). Estimated number of hospital patients in 1994 with ADRs in thousands - Serious 702 (95% CI: 635, 770); Fatal 63 (95% CI: 41, 81); All severity 3607 (95% CI: 2618, 4596).

Admission ADRs (ADRAd):

Incidence of ADRs - Serious ADRs (n=21 studies; 28017 participants) 4.7% (95% CI: 3.1-6.2); Fatal ADRs (n=6 studies; 17,753 participants) 0.13% (95% CI: 0.04, 0.21); All severity ADRs (not reported as by definition all ADRs are serious otherwise the patient would not have been admitted to hospital). Estimated number of hospital patients in 1994 with ADRs in thousands - Serious 1547 (95% CI: 1033, 2060); Fatal 43 (95% CI: 15, 71); All severity 1547 (95% CI: 1033, 2060). 8/21 ADRAd studies included the proportion of type A (dose-dependent ADRs) and type B (idiosyncratic and/or allergic ADRs). For All severity 76.2% (95% CI: 71.0, 81.4) were type A reactions and 23.8% (95% CI: 18.6, 29.0%) were type B reactions.

In-patient ADRS (ADRIn) and Admission ADRs (ADRAd) combined:

Incidence of ADRs - Serious ADRs (n=33 studies; 50,519 participants) 6.7% (95% CI: 5.2, 8.2); Fatal ADRs (n=16 studies; 46,625 participants) 0.32% (95% CI: 0.23, 0.41); All severity ADRs (n=39 studies; 62,480 participants) 15.1% (95% CI: 12.0, 18.1). Estimated number of hospital patients in 1994 with ADRs in thousands - Serious ADRs 2216 (95% CI: 1721, 2711); Fatal ADRs 106 (95% CI: 76, 137; All severity ADRs 4986 (95% CI: 3976, 5995).

Authors' 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.

CRD commentary

This is a clearly described study that uses an extensive literature search with defined search terms and well-defined inclusion criteria. Some relevant information may have been excluded however, as only studies with English language translations were assessed. The methods used to extract data from the included studies are described, but the authors fail to state how decisions were made about the relevance of the studies and their quality. Additional information in the results tables regarding the age of study participants, the study setting and length of the study period, would have been useful. Heterogeneity is inevitable in this meta-analysis due to the all-inclusive inclusion criteria with regards to the type of participants and drug treatments studied. The authors describe the steps taken to reduce the heterogeneity including using a random-effects model and 95% CI intervals to highlight the issue. In view of these limitations and the results presented, the authors' cautious conclusions would appear to be valid.

Implications of the review for practice and research

The authors did not state any implications for practice or further research.

Funding

National Science Engineering Research Council.

Bibliographic details

Lazarou J, Pomeranz B H, Corey P N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279(15): 1200-1205. [PubMed: 9555760]

Original Paper URL

http://jama.ama-assn.org/

Indexing Status

Subject indexing assigned by NLM

MeSH

Data Collection; Drug-Related Side Effects and Adverse Reactions; Health Care Surveys; Hospitals /statistics & numerical data; Humans; Iatrogenic Disease /epidemiology; Incidence; Inpatients /statistics & numerical data; Linear Models; Prospective Studies; United States /epidemiology

AccessionNumber

11998008466

Database entry date

31/01/2000

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.