title: Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies.
abstract: In pharmaco-epidemiology, the use of drugs is the determinant of interest when studying exposure-outcome associations. The increased availability of computerized information about drug use on an individual basis has greatly facilitated analyses of drug effects on a population-based scale. It seems likely that many negative findings in the early days of pharmaco-epidemiology can be explained by non-differential misclassification because of too simple (yes/no) exposure measures. In this paper, the authors discuss the importance of an adequate definition of drug exposure in pharmaco-epidemiological research and how this time-varying determinant can be analyzed in cohort studies. To reduce the risk of non-differential misclassification, a precise definition of exposure is mandatory and it is important to distinguish the complete follow-up period of a population into mutually exclusive episodes of non-use, past use and current use for each individual. By analyzing exposure to drugs as a time-dependent variable in a Cox regression model, cohort studies with complete coverage of all filled prescriptions can provide us with valid and precise risk estimates of drug-outcome associations. However, such estimates may be biased in the presence of time-dependent confounders which are themselves affected by prior exposure.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. b.stricker@erasmusmc.nl
authors.forename: B H Ch
authors.initials: BH
authors.lastname: Stricker
authors.forename: T
authors.initials: T
authors.lastname: Stijnen
mesh_terms: D015982:Bias; D001682:Biological Availability; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D015340:Epidemiologic Research Design; D006801:Humans; D017891:Pharmacoepidemiology / Q000379:methods*; D016016:Proportional Hazards Models; D013997:Time Factors