Methodologic issues in studies of mortality following epilepsy: Measures, types of studies, sources of cases, cohort effects, and competing risks

This paper addresses methodologic issues in studies of mortality, and the impact of these issues in studies of mortality in epilepsy. One important issue is to identify the question: Is it whether epilepsy increases the risk of dying? Or is it whether the underlying condition that led to epilepsy, itself associated with an increased risk for death, is the cause of increased mortality observed in epilepsy? Each measure for estimating mortality requires specific study designs. The mortality rate, case fatality, standardized mortality ratio (SMR) are calculated in prospective or retrospective cohort studies of death in epilepsy. Because the SMR is obtained by indirect standardization, it uses the age- and gender-distribution of the study group with epilepsy, which differs across studies. Thus, the SMR is impossible to compare across studies. The proportionate mortality ratio considers only the proportion of deaths that are due to epilepsy and is useful when denominators are unavailable, often the case in the developing world. Mortality studies in prevalent cohorts of people with epilepsy are compared to those in incident cohorts of epilepsy. The impact of different sources of cases on mortality in epilepsy is discussed. Finally, cohort effects and competing risks are examined. We conclude that the gold standard for studies on mortality should be a population-based cohort of incident cases. Only this type of cohort permits a complete collection of data and the observation of the clinical phase of the disease from the diagnosis of epilepsy to the outcome of the study, death.