Measures of 'exposure needed for one additional patient to be harmed' in population-based case-control studies.

Abstract

The magnitude of risk for adverse drug reactions may be communicated by a measure of 'exposure needed for one additional patient to be harmed' (ENH). We present four ENH measures, based on four different counterfactual contrasts, as illustrated by the known effects of NSAID use on peptic ulcer bleeding. The four measures were basic ENH (estimating the excess risk when treating the entire source population versus treating no one), age-restricted ENH (the entire source population above, e.g. 50 years old treated versus no one above 50 years old treated), standardised ENH (a population of similar age and gender distribution as those actually treated versus same subjects not treated) and naturalistic ENH (those actually treated versus same subjects not treated). Data were derived from a case-control dataset on NSAIDs and severe peptic ulcer bleeding, collected in Funen County in 1995-2006. We incorporated prescription and census data to account for the source population's drug use. Estimates of basic, age-restricted, standardised and naturalistic ENH were 619 person-years (py) (95% confidence interval (CI): 558-684), 223 py (CI: 201-246), 131 py (CI: 118-144) and 162 py (CI: 151-173). The age-restricted ENH showed strong dependence on the chosen age limit. The differing counterfactual contrasts underlying the ENH result in widely different estimates. These differences reflect the clinical and epidemiological aspects of NSAID-related peptic ulcer bleeding. The ultimate choice of ENH measure will depend on epidemiological or clinical considerations and on availability of data.