The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal anti-inflammatory drugs on upper gastrointestinal tract disease.

BACKGROUND: Considerable differences in the estimates of the risk of upper gastrointestinal tract disease associated with treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) have been observed. We conducted a meta-analysis of epidemiologic studies of upper gastrointestinal tract disease related to NSAIDs to answer the following research questions: Are study characteristics (study design and quality) associated with different estimates of risk, for both aspirin and nonaspirin NSAIDs? Does the risk increase for particular groups of patients, such as women and the elderly?
METHODS: Thirty-four studies addressing severe upper gastrointestinal tract disease associated with NSAIDs (including aspirin and nonaspirin NSAIDs) were examined and scored according to a quality checklist that we designed for this review.
RESULTS: Only 44% of the studies controlled for major confounding variables (age and sex). While exposure was defined as current in 40% and 78% of the studies for nonaspirin NSAIDs and aspirin, respectively, few investigations checked for history of ulcer disease and concurrent diseases or other comedications known to be risk factors for upper gastrointestinal tract bleeding. The overall risk ratio, by means of a random-effects regression model, was 3.0 (95% confidence interval, 1.9 to 4.7). The individual estimates for aspirin and nonaspirin NSAIDs were similar. Both with and without control for quality, cohort studies provided a lower risk ratio estimate than did case-control studies.
CONCLUSIONS: The design and quality of the studies appear to be strong independent predictors of the risk estimate; cohort studies were associated with lower risk estimates than case-control studies, and satisfactory studies were associated with lower risk estimates than unsatisfactory studies.