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Group testing is a technique that can reduce the number of tests needed to identify infected members in a population, by pooling together multiple diagnostic samples. Despite the variety and importance of prior results, traditional work on group testing has typically assumed independent infections. However, contagious diseases among humans, like SARS-CoV-2, have an important characteristic: infections are governed by community spread, and are therefore correlated. In this paper, we explore this observation and we argue that taking into account the community structure when testing can lead to significant savings in terms of the number of tests required to guarantee a given identification accuracy. To show that, we start with a simplistic (yet practical) infection model, where the entire population is organized in (possibly overlapping) communities and the infection probability of an individual depends on the communities (s)he participates in. Given this model, we compute new lower bounds on the number of tests for zero-error identification and design community-aware group testing algorithms that can be optimal under assumptions. Finally, we demonstrate significant benefits over traditional, community-agnostic group testing via simulations using both noiseless and noisy tests
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Array testing for multiplex assays
Summary Group testing involves pooling individual specimens (e.g., blood, urine, swabs, etc.) and testing the pools for the presence of disease. When the proportion of diseased individuals is small, group testing can greatly reduce the number of tests needed to screen a population. Statistical research in group testing has traditionally focused on applications for a single disease. However, blood service organizations and large-scale disease surveillance programs are increasingly moving towards the use of multiplex assays, which measure multiple disease biomarkers at once. Tebbs and others (2013, Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project. Biometrics69, 1064–1073) and Hou and others (2017, Hierarchical group testing for multiple infections. Biometrics73, 656–665) were the first to examine hierarchical group testing case identification procedures for multiple diseases. In this article, we propose new non-hierarchical procedures which utilize two-dimensional arrays. We derive closed-form expressions for the expected number of tests per individual and classification accuracy probabilities and show that array testing can be more efficient than hierarchical procedures when screening individuals for multiple diseases at once. We illustrate the potential of using array testing in the detection of chlamydia and gonorrhea for a statewide screening program in Iowa. Finally, we describe an R/Shiny application that will help practitioners identify the best multiple-disease case identification algorithm.
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- Award ID(s):
- 1826715
- PAR ID:
- 10228696
- Date Published:
- Journal Name:
- Biostatistics
- Volume:
- 21
- Issue:
- 3
- ISSN:
- 1468-4357
- Page Range / eLocation ID:
- 417 to 431
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Summary In screening applications involving low-prevalence diseases, pooling specimens (e.g., urine, blood, swabs, etc.) through group testing can be far more cost effective than testing specimens individually. Estimation is a common goal in such applications and typically involves modeling the probability of disease as a function of available covariates. In recent years, several authors have developed regression methods to accommodate the complex structure of group testing data but often under the assumption that covariate effects are linear. Although linearity is a reasonable assumption in some applications, it can lead to model misspecification and biased inference in others. To offer a more flexible framework, we propose a Bayesian generalized additive regression approach to model the individual-level probability of disease with potentially misclassified group testing data. Our approach can be used to analyze data arising from any group testing protocol with the goal of estimating multiple unknown smooth functions of covariates, standard linear effects for other covariates, and assay classification accuracy probabilities. We illustrate the methods in this article using group testing data on chlamydia infection in Iowa.more » « less
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Abstract BackgroundPathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. ResultsTo address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. DynamicCtthreshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. ConclusionIn conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale.more » « less
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Problem definition: Infectious disease screening can be expensive and capacity constrained. We develop cost- and capacity-efficient testing designs for multidisease screening, considering (1) multiplexing (disease bundling), where one assay detects multiple diseases using the same specimen (e.g., nasal swabs, blood), and (2) pooling (specimen bundling), where one assay is used on specimens from multiple subjects bundled in a testing pool. A testing design specifies an assay portfolio (mix of single-disease/multiplex assays) and a testing method (pooling/individual testing per assay). Methodology/results: We develop novel models for the nonlinear, combinatorial multidisease testing design problem: a deterministic model and a distribution-free, robust variation, which both generate Pareto frontiers for cost- and capacity-efficient designs. We characterize structural properties of optimal designs, formulate the deterministic counterpart of the robust model, and conduct a case study of respiratory diseases (including coronavirus disease 2019) with overlapping clinical presentation. Managerial implications: Key drivers of optimal designs include the assay cost function, the tester’s preference toward cost versus capacity efficiency, prevalence/coinfection rates, and for the robust model, prevalence uncertainty. When an optimal design uses multiple assays, it does so in conjunction with pooling, and it uses individual testing for at most one assay. Although prevalence uncertainty can be a design hurdle, especially for emerging or seasonal diseases, the integration of multiplexing and pooling, and the ordered partition property of optimal designs (under certain coinfection structures) serve to make the design more structurally robust to uncertainty. The robust model further increases robustness, and it is also practical as it needs only an uncertainty set around each disease prevalence. Our Pareto designs demonstrate the cost versus capacity trade-off and show that multiplexing-only or pooling-only designs need not be on the Pareto frontier. Our case study illustrates the benefits of optimally integrated designs over current practices and indicates a low price of robustness. Funding: This work was supported by the National Science Foundation [Grant 1761842]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0296 .more » « less
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Pantea, Casian (Ed.)Limited testing capacity for COVID-19 has hampered the pandemic response. Pooling is a testing method wherein samples from specimens (e.g., swabs) from multiple subjects are combined into a pool and screened with a single test. If the pool tests positive, then new samples from the collected specimens are individually tested, while if the pool tests negative, the subjects are classified as negative for the disease. Pooling can substantially expand COVID-19 testing capacity and throughput, without requiring additional resources. We develop a mathematical model to determine the best pool size for different risk groups , based on each group’s estimated COVID-19 prevalence. Our approach takes into consideration the sensitivity and specificity of the test, and a dynamic and uncertain prevalence, and provides a robust pool size for each group. For practical relevance, we also develop a companion COVID-19 pooling design tool (through a spread sheet). To demonstrate the potential value of pooling, we study COVID-19 screening using testing data from Iceland for the period, February-28-2020 to June-14-2020, for subjects stratified into high- and low-risk groups. We implement the robust pooling strategy within a sequential framework, which updates pool sizes each week, for each risk group, based on prior week’s testing data. Robust pooling reduces the number of tests, over individual testing, by 88.5% to 90.2%, and 54.2% to 61.9%, respectively, for the low-risk and high-risk groups (based on test sensitivity values in the range [0.71, 0.98] as reported in the literature). This results in much shorter times, on average, to get the test results compared to individual testing (due to the higher testing throughput), and also allows for expanded screening to cover more individuals. Thus, robust pooling can potentially be a valuable strategy for COVID-19 screening.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1093/biostatistics/kxy058
