Misclassification is present in nearly every epidemiologic study, yet is rarely quantified in analysis in favor of a focus on random error. In this review, we discuss past and present wisdom on misclassification and what measures should be taken to quantify this influential bias, with a focus on bias in pharmacoepidemiologic studies. To date, pharmacoepidemiology primarily utilizes data obtained from administrative claims, a rich source of prescription data but susceptible to bias from unobservable factors including medication sample use, medications filled but not taken, health conditions that are not reported in the administrative billing data, and inadequate capture of confounders. Due to the increasing focus on comparative effectiveness research, we provide a discussion of misclassification in the context of an active comparator, including a demonstration of treatment effects biased away from the null in the presence of nondifferential misclassification. Finally, we highlight recently developed methods to quantify bias and offer these methods as potential options for strengthening the validity and quantifying uncertainty of results obtained from pharmacoepidemiologic research.
Keywords: Bayesian bias analysis; administrative claims; comparative effectiveness; measurement error; misclassification; modified maximum likelihood; multiple imputation for measurement error; new user design; pharmacoepidemiology; probabilistic bias analysis; propensity score calibration; regression calibration.