The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application

Abstract

Better understanding of biases related to selective prescribing of, and adherence to, preventive treatments has led to improvements in the design and analysis of pharmacoepidemiologic studies. One influential development has been the "active comparator, new user" study design, which seeks to emulate the design of a head-to-head randomized controlled trial. In this review, we first discuss biases that may affect pharmacoepidemiologic studies and describe their direction and magnitude in a variety of settings. We then present the historical foundations of the active comparator, new user study design and explain how this design conceptually mitigates biases leading to a paradigm shift in pharmacoepidemiology. We offer practical guidance on the implementation of the study design using administrative databases. Finally, we provide an empirical example in which the active comparator, new user study design addresses biases that have previously impeded pharmacoepidemiologic studies.

Keywords: confounding; pharmacoepidemiology; selection bias; study design.

Figure 1. Active comparator, new user (ACNU) study design schematics

The top panel illustrates how the ACNU study is designed to emulate a head-to-head randomized controlled trial. The bottom panel provides a detailed picture of how to identify periods of new use of drug A (the same process would apply to drug B) in a claims or other healthcare database. ^a One individual can have multiple new use periods. The individual can also be a new user of drug A and later a new user of drug B (or vice versa). Often, analyses will be restricted to the first period of new use. ^b The date of discontinuation (or switching or augmenting) may be used as a censoring date in as-treated analyses.