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Discovering Cross-Reactivity in Urine Drug Screening Immunoassays through Large-Scale Analysis of Electronic Health Records.


ABSTRACT: BACKGROUND:Exposure to drugs of abuse is frequently assessed using urine drug screening (UDS) immunoassays. Although fast and relatively inexpensive, UDS assays often cross-react with unrelated compounds, which can lead to false-positive results and impair patient care. The current process of identifying cross-reactivity relies largely on case reports, making it sporadic and inefficient, and rendering knowledge of cross-reactivity incomplete. Here, we present a systematic approach to discover cross-reactive substances using data from electronic health records (EHRs). METHODS:Using our institution's EHR data, we assembled a data set of 698651 UDS results across 10 assays and linked each UDS result to the corresponding individual's previous medication exposures. We hypothesized that exposure to a cross-reactive ingredient would increase the odds of a false-positive screen. For 2201 assay-ingredient pairs, we quantified potential cross-reactivity as an odds ratio from logistic regression. We then evaluated cross-reactivity experimentally by spiking the ingredient or its metabolite into drug-free urine and testing the spiked samples on each assay. RESULTS:Our approach recovered multiple known cross-reactivities. After accounting for concurrent exposures to multiple ingredients, we selected 18 compounds (13 parent drugs and 5 metabolites) to evaluate experimentally. We validated 12 of 13 tested assay-ingredient pairs expected to show cross-reactivity by our analysis, discovering previously unknown cross-reactivities affecting assays for amphetamines, buprenorphine, cannabinoids, and methadone. CONCLUSIONS:Our findings can help laboratorians and providers interpret presumptive positive UDS results. Our data-driven approach can serve as a model for high-throughput discovery of substances that interfere with laboratory tests.

SUBMITTER: Hughey JJ 

PROVIDER: S-EPMC7055671 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Discovering Cross-Reactivity in Urine Drug Screening Immunoassays through Large-Scale Analysis of Electronic Health Records.

Hughey Jacob J JJ   Colby Jennifer M JM  

Clinical chemistry 20191002 12


<h4>Background</h4>Exposure to drugs of abuse is frequently assessed using urine drug screening (UDS) immunoassays. Although fast and relatively inexpensive, UDS assays often cross-react with unrelated compounds, which can lead to false-positive results and impair patient care. The current process of identifying cross-reactivity relies largely on case reports, making it sporadic and inefficient, and rendering knowledge of cross-reactivity incomplete. Here, we present a systematic approach to dis  ...[more]

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