THE EVOLUTION OF CLINICAL-PRACTICE AND TIME TRENDS IN DRUG EFFECTS

Evidence from contemporary studies suggests that the quantification of adverse drug effects through state-of-the-art non-experimental method s may be confounded by some aspects of clinical practice. Support for this hypothesis is manifest in the finding that drug effects sometimes show within-study time trends when clinical practice with regard to d rug use is evolving. Three studies which show simultaneous trends in p rescription frequency and drug effects are discussed as examples. Thes e include a study of benzodiazepines in the etiology of hip fracture, postmenopausal estrogens as a preventive for major coronary disease an d human insulin as a risk factor for severe hypoglycemia. For instance , during a period when clinical perceptions regarding the safety of be nzodiazepine use in the elderly underwent gradual change, the relative risk for hip fracture among long half-life benzodiazepine users decli ned progressively from 2.0 (95% CI, 1.6-2.5) in 1977-79 to 1.3 (95% CI , 0.9-1.8) in 1984-85. The implications of these observations are set against the scientific objectives which guide etiologic research.