Classification under uncertainty: data analysis for diagnostic antibody testing

DOI10.1093/IMAMMB/DQAB007zbMATH Open1472.92124arXiv2012.10021OpenAlexW3190855910WikidataQ113819098 ScholiaQ113819098MaRDI QIDQ5157583FDOQ5157583

Authors: Paul N. Patrone, Anthony José Kearsley 

Publication date: 19 October 2021

Published in: Mathematical Medicine and Biology: A Journal of the IMA (Search for Journal in Brave)

Abstract: Formulating accurate and robust classification strategies is a key challenge of developing diagnostic and antibody tests. Methods that do not explicitly account for disease prevalence and uncertainty therein can lead to significant classification errors. We present a novel method that leverages optimal decision theory to address this problem. As a preliminary step, we develop an analysis that uses an assumed prevalence and conditional probability models of diagnostic measurement outcomes to define optimal (in the sense of minimizing rates of false positives and false negatives) classification domains. Critically, we demonstrate how this strategy can be generalized to a setting in which the prevalence is unknown by either: (i) defining a third class of hold-out samples that require further testing; or (ii) using an adaptive algorithm to estimate prevalence prior to defining classification domains. We also provide examples for a recently published SARS-CoV-2 serology test and discuss how measurement uncertainty (e.g. associated with instrumentation) can be incorporated into the analysis. We find that our new strategy decreases classification error by up to a decade relative to more traditional methods based on confidence intervals. Moreover, it establishes a theoretical foundation for generalizing techniques such as receiver operating characteristics (ROC) by connecting them to the broader field of optimization.

Full work available at URL: https://arxiv.org/abs/2012.10021

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zbMATH Keywords

classificationoptimal decision theoryantibodySARS-CoV-2serology

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical applications (general) (92C50)

Cited In (5)

• Prevalence estimation and optimal classification methods to account for time dependence in antibody levels
• Optimal classification and generalized prevalence estimates for diagnostic settings with more than two classes
• Minimizing uncertainty in prevalence estimates
• Prevalence estimation methods for time-dependent antibody kinetics of infected and vaccinated individuals: a Markov chain approach
• Optimal decision theory for diagnostic testing: minimizing indeterminate classes with applications to saliva-based SARS-CoV-2 antibody assays

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