Regression models for group testing data with pool dilution effects.
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ABSTRACT:
SUBMITTER: McMahan CS
PROVIDER: S-EPMC3590921 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Group testing, where specimens are tested initially in pools, is widely used to screen individuals for sexually transmitted diseases. However, a common problem encountered in practice is that group testing can increase the number of false negative test results. This occurs primarily when positive individual specimens within a pool are diluted by negative ones, resulting in positive pools testing negatively. If the goal is to estimate a population-level regression model relating individual disease status to observed covariates, severe bias can result if an adjustment for dilution is not made. Recognizing this as a critical issue, recent binary regression approaches in group testing have utilized continuous biomarker information to acknowledge the effect of dilution. In this paper, we have the same overall goal but take a different approach. We augment existing group testing regression models (that assume no dilution) with a parametric dilution submodel for pool-level sensitivity and estimate all parameters using maximum likelihood. An advantage of our approach is that it does not rely on external biomarker test data, which may not be available in surveillance studies. Furthermore, unlike previous approaches, our framework allows one to formally test whether dilution is present based on the observed group testing data. We use simulation to illustrate the performance of our estimation and inference methods, and we apply these methods to 2 infectious disease data sets.
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Project description:Group (pooled) testing is becoming a popular strategy for screening large populations for infectious diseases. This popularity is owed to the cost savings that can be realized through implementing group testing methods. These methods involve physically combining biomaterial (eg, saliva, blood, urine) collected on individuals into pooled specimens which are tested for an infection of interest. Through testing these pooled specimens, group testing methods reduce the cost of diagnosing all individuals under study by reducing the number of tests performed. Even though group testing offers substantial cost reductions, some practitioners are hesitant to adopt group testing methods due to the so-called dilution effect. The dilution effect describes the phenomenon in which biomaterial from negative individuals dilute the contributions from positive individuals to such a degree that a pool is incorrectly classified. Ignoring the dilution effect can reduce classification accuracy and lead to bias in parameter estimates and inaccurate inference. To circumvent these issues, we propose a Bayesian regression methodology which directly acknowledges the dilution effect while accommodating data that arises from any group testing protocol. As a part of our estimation strategy, we are able to identify pool specific optimal classification thresholds which are aimed at maximizing the classification accuracy of the group testing protocol being implemented. These two features working in concert effectively alleviate the primary concerns raised by practitioners regarding group testing. The performance of our methodology is illustrated via an extensive simulation study and by being applied to Hepatitis B data collected on Irish prisoners.
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Project description:Group testing, where subjects are tested in pools rather than individually, has a long history of successful application in infectious disease screening. In this article, we develop group testing regression models to include covariate effects that are best regarded as random. We present approaches to fit mixed effects models using maximum likelihood, investigate likelihood ratio and score tests for variance components, and evaluate small sample performance using simulation. We illustrate our methods using chlamydia and gonorrhea data collected by the state of Nebraska as part of the Infertility Prevention Project.
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Project description:A Bayesian framework for group testing under dilution effects has been developed, using lattice-based models. This work has particular relevance given the pressing public health need to enhance testing capacity for coronavirus disease 2019 and future pandemics, and the need for wide-scale and repeated testing for surveillance under constantly varying conditions. The proposed Bayesian approach allows for dilution effects in group testing and for general test response distributions beyond just binary outcomes. It is shown that even under strong dilution effects, an intuitive group testing selection rule that relies on the model order structure, referred to as the Bayesian halving algorithm, has attractive optimal convergence properties. Analogous look-ahead rules that can reduce the number of stages in classification by selecting several pooled tests at a time are proposed and evaluated as well. Group testing is demonstrated to provide great savings over individual testing in the number of tests needed, even for moderately high prevalence levels. However, there is a trade-off with higher number of testing stages, and increased variability. A web-based calculator is introduced to assist in weighing these factors and to guide decisions on when and how to pool under various conditions. High-performance distributed computing methods have also been implemented for considering larger pool sizes, when savings from group testing can be even more dramatic.
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Project description:Group testing involves pooling individual specimens (e.g., blood, urine, swabs, etc.) and testing the pools for the presence of a disease. When individual covariate information is available (e.g., age, gender, number of sexual partners, etc.), a common goal is to relate an individual's true disease status to the covariates in a regression model. Estimating this relationship is a nonstandard problem in group testing because true individual statuses are not observed and all testing responses (on pools and on individuals) are subject to misclassification arising from assay error. Previous regression methods for group testing data can be inefficient because they are restricted to using only initial pool responses and/or they make potentially unrealistic assumptions regarding the assay accuracy probabilities. To overcome these limitations, we propose a general Bayesian regression framework for modeling group testing data. The novelty of our approach is that it can be easily implemented with data from any group testing protocol. Furthermore, our approach will simultaneously estimate assay accuracy probabilities (along with the covariate effects) and can even be applied in screening situations where multiple assays are used. We apply our methods to group testing data collected in Iowa as part of statewide screening efforts for chlamydia, and we make user-friendly R code available to practitioners.
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Project description: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.
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Project description:Group testing, where individual specimens are composited into groups to test for the presence of a disease (or other binary characteristic), is a procedure commonly used to reduce the costs of screening a large number of individuals. Group testing data are unique in that only group responses may be available, but inferences are needed at the individual level. A further methodological challenge arises when individuals are tested in groups for multiple diseases simultaneously, because unobserved individual disease statuses are likely correlated. In this paper, we propose new regression techniques for multiple-disease group testing data. We develop an expectation-solution based algorithm that provides consistent parameter estimates and natural large-sample inference procedures. We apply our proposed methodology to chlamydia and gonorrhea screening data collected in Nebraska as part of the Infertility Prevention Project and to prenatal infectious disease screening data from Kenya.
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Project description:Due to reductions in both time and cost, group testing is a popular alternative to individual-level testing for disease screening. These reductions are obtained by testing pooled biospecimens (eg, blood, urine, swabs, etc.) for the presence of an infectious agent. However, these reductions come at the expense of data complexity, making the task of conducting disease surveillance more tenuous when compared to using individual-level data. This is because an individual's disease status may be obscured by a group testing protocol and the effect of imperfect testing. Furthermore, unlike individual-level testing, a given participant could be involved in multiple testing outcomes and/or may never be tested individually. To circumvent these complexities and to incorporate all available information, we propose a Bayesian generalized linear mixed model that accommodates data arising from any group testing protocol, estimates unknown assay accuracy probabilities and accounts for potential heterogeneity in the covariate effects across population subgroups (eg, clinic sites, etc.); this latter feature is of key interest to practitioners tasked with conducting disease surveillance. To achieve model selection, our proposal uses spike and slab priors for both fixed and random effects. The methodology is illustrated through numerical studies and is applied to chlamydia surveillance data collected in Iowa.
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Project description:Group testing, as a cost-effective strategy, has been widely used to perform large-scale screening for rare infections. Recently, the use of multiplex assays has transformed the goal of group testing from detecting a single disease to diagnosing multiple infections simultaneously. Existing research on multiple-infection group testing data either exclude individual covariate information or ignore possible retests on suspicious individuals. To incorporate both, we propose a new regression model. This new model allows us to perform a regression analysis for each infection using multiple-infection group testing data. Furthermore, we introduce an efficient variable selection method to reveal truly relevant risk factors for each disease. Our methodology also allows for the estimation of the assay sensitivity and specificity when they are unknown. We examine the finite sample performance of our method through extensive simulation studies and apply it to a chlamydia and gonorrhea screening data set to illustrate its practical usefulness.
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