An Evaluation of Longitudinal Measures of Anticholinergic Exposure for Application in Retrospective Administrative Data Analyses

Abstract

IntroductionAs continuous exposure to anticholinergics has been associated with adverse outcomes, accurately measuring exposure is important. However, no gold standard measure is available, and the performance of existing measures has not been compared. Our objective was to compare the properties of the Cumulative Anticholinergic Burden (CAB) measure against two existing measures of anticholinergic exposure and to assess their compatibility for use in observational studies based on claims data.MethodsThe average daily dose, cumulative dose and CAB measures were evaluated on: the applicability for use with anticholinergic burden scales, the ability to consider duration and/or accumulation of exposure, and consideration of anticholinergic dose, potency, and residual effect. To calculate each measure empirically, Truven MarketScan claims data from 2012 to 2015 were analyzed. Cumulative anticholinergic exposure over 1-year post-enrollment was calculated for each measure using Anticholinergic Cognitive Burden scale scores. Median [interquartile range (IQR)] and ranges of measure scores, and Spearman’s correlation coefficients between measures, were estimated. Due to the differing methods of calculation, the absolute values of each score cannot be compared.ResultsThe properties of the different measures varied, with only the CAB considering both dose and theoretical potency. The cohort included 99,742 individuals (mean age = 73.1 years; 54.9% female). Among individuals prescribed anticholinergics (n = 55,969), 1-year median (IQR) scores based on average daily dose, cumulative dose and CAB measures were 0.9 (0.3–1.5), 16.9 (7.3–33.9) and 203 (68–500), respectively. Measures were highly inter-correlated (r2 = 0.74-0.83).ConclusionsConsidering both potency and dose, the CAB may prove a more comprehensive measure of anticholinergic burden; however, additional research is necessary to demonstrate whether it has any association with relevant health-related outcomes.FundingAstellas Pharma Global Development, Inc.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01035-z) contains supplementary material, which is available to authorized users.

Fall/Fracture-Related Healthcare Costs and Their Association with Cumulative Anticholinergic Burden in People with Overactive Bladder

“…Cumulative anticholinergic exposure was examined using the cumulative anticholinergic burden measure [17], which calculates anticholinergic burden as a unitless score. Unlike other measures, the cumulative anticholinergic burden measure takes into account dose and potency, both of which have been identified as contributors to anticholinergic burden [24]. Specifically, it considers (1) intensity of anticholinergic exposure (by a medication's defined daily dose) [25,26]; (2) strength of anticholinergic activity [calculated using Anticholinergic Cognitive Burden (ACB) scale scores; the ACB comprises a published list of around 100 anticholinergic drugs (Appendix 1 in ESM)] [27]; and (3) period of exposure (set over the 12 months prior); reflecting an individual's cumulative standardized daily dose of all anticholinergic medications over time [28].…”

Analysis of anticholinergic adverse effects using two large databases: The US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database

“…Typical anticholinergics were not listed in the major suspected drugs of CNS; instead, cholinesterase inhibitors were ranked in FAERS, and antiviral drugs were ranked in JADER. However, the accumulation of anticholinergic effects might be one of the factors inducing central AEs, since several drugs with anticholinergic effects are included in the major suspected drugs [ 48 ]. The patient’s background factors may also need to be considered, as we adopted “cognitive impairment” and “confusional state” as CNS in this analysis.…”

Anticholinergic Burden and Associated Healthcare Resource Utilization in Older Adults with Overactive Bladder

“…Risk was only increased with > 1096 total standardized daily doses (TSDDs), which is equivalent to 3 years of daily dosing with a single strong anticholinergic [ 21 ]. In another publication, which evaluated longitudinal measures of anticholinergic burden, an exposure period of 1 year was chosen; however, the authors state that this was arbitrary and that the exposure period should be determined on a case-by-case basis [ 22 ]. It was therefore decided to use a 2-year post-index period in the current study, rather than just 1 year, to allow sufficient time to collect resource use data.…”