Generalized additive regression for group testing data.

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.

A Robust Regression Methodology via M-estimation.

A robust regression methodology is proposed via M-estimation. The approach adapts to the tail behavior and skewness of the distribution of the random error terms, providing for a reliable analysis under a broad class of distributions. This is accomplished by allowing the objective function, used to determine the regression parameter estimates, to be selected in a data driven manner. The asymptotic properties of the proposed estimator are established and a numerical algorithm is provided to implement the methodology. The finite sample performance of the proposed approach is exhibited through simulation and the approach was used to analyze two motivating datasets.

Estimating covariate-adjusted measures of diagnostic accuracy based on pooled biomarker assessments.

There is a need for epidemiological and medical researchers to identify new biomarkers (biological markers) that are useful in determining exposure levels and/or for the purposes of disease detection. Often this process is stunted by high testing costs associated with evaluating new biomarkers. Traditionally, biomarker assessments are individually tested within a target population. Pooling has been proposed to help alleviate the testing costs, where pools are formed by combining several individual specimens. Methods for using pooled biomarker assessments to estimate discriminatory ability have been developed. However, all these procedures have failed to acknowledge confounding factors. In this paper, we propose a regression methodology based on pooled biomarker measurements that allow the assessment of the discriminatory ability of a biomarker of interest. In particular, we develop covariate-adjusted estimators of the receiver-operating characteristic curve, the area under the curve, and Youden's index. We establish the asymptotic properties of these estimators and develop inferential techniques that allow one to assess whether a biomarker is a good discriminator between cases and controls, while controlling for confounders. The finite sample performance of the proposed methodology is illustrated through simulation. We apply our methods to analyze myocardial infarction (MI) data, with the goal of determining whether the pro-inflammatory cytokine interleukin-6 is a good predictor of MI after controlling for the subjects' cholesterol levels.

A general regression framework for group testing data, which incorporates pool dilution effects.

Group testing, through the use of pooling, has been widely implemented as a more efficient means to screen individuals for infectious diseases. Typically, in these settings, practitioners are tasked with the complimentary goals of both case identification and estimation. For these purposes, many group testing strategies have been proposed, which address issues such as preserving anonymity in estimation studies, quality control, and classification. In general, these strategies require that a significant number of the individuals be retested, either in pools or individually. In order to provide practitioners with a general methodology that can be used to accurately and precisely analyze data of this form, herein, we propose a binary regression framework that can incorporate data arising from any group testing strategy. Further, we relax previously made assumptions regarding testing error rates by relating the diagnostic testing results to the latent biological marker levels of the individuals being tested. We investigate the finite sample performance of our proposed methodology through simulation and by applying our techniques to hepatitis B data collected as part of a study involving Irish prisoners.