Combined multiplex panel test results are a poor estimate of disease prevalence without adjustment for test error

Robert J Challen*, Anastasia Chatzilena, George Y Qian, Glenda Oben, Rachel Kwiatkowska, Catherine Hyams, Adam H R Finn, Krasimira Tsaneva-Atanasova, Leon Danon

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for.
Original languageEnglish
Article numbere1012062
Number of pages14
JournalPLoS Computational Biology
Volume20
Issue number4
DOIs
Publication statusPublished - 26 Apr 2024

Bibliographical note

Publisher Copyright:
Copyright: © 2024 Challen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fingerprint

Dive into the research topics of 'Combined multiplex panel test results are a poor estimate of disease prevalence without adjustment for test error'. Together they form a unique fingerprint.

Cite this