In this paper, we present three estimators of the ROC curve when missing observations arise among the biomarkers. Two of the procedures assume that we have covariates that allow to estimate the propensity and the estimators are obtained using an inverse probability weighting method or a smoothed version of it. The other one assumes that the covariates are related to the biomarkers through a regression model which enables us to construct convolution--based estimators of the distribution and quantile functions. Consistency results are obtained under mild conditions. Through a numerical study we evaluate the finite sample performance of the different proposals. A real data set is also analysed.
Accurate diagnosis of disease is of fundamental importance in clinical practice and medical research. Before a medical diagnostic test is routinely used in practice, its ability to distinguish between diseased and nondiseased states must be rigorously assessed through statistical analysis. The receiver operating characteristic (ROC) curve is the most popular used tool for evaluating the discriminatory ability of continuous-outcome diagnostic tests. It has been acknowledged that several factors (e.g., subject-specific characteristics, such as age and/or gender) can affect the test's accuracy be…
Continuous biomarkers are common for disease screening and diagnosis. To reach a dichotomous clinical decision, a threshold would be imposed to distinguish subjects with disease from non-diseased individuals. Among various performance metrics for a continuous biomarker, specificity at a controlled sensitivity level (or vice versa) is often desirable for clinical utility since it directly targets where the clinical test is intended to operate. Covariates, such as age, race, and sample collection, could impact the controlled sensitivity level in subpopulations and may also confound the associati…
The receiver operating characteristic (ROC) curve is a powerful statistical tool and has been widely applied in medical research. In the ROC curve estimation, a commonly used assumption is that larger the biomarker value, greater severity the disease. In this paper, we mathematically interpret ``greater severity of the disease" as ``larger probability of being diseased". This in turn is equivalent to assume the likelihood ratio ordering of the biomarker between the diseased and healthy individuals. With this assumption, we first propose a Bernstein polynomial method to model the distributions …
Identifying a biomarker or treatment-dose threshold that marks a specified level of risk is an important problem, especially in clinical trials. This risk, viewed as a function of thresholds and possibly adjusted for covariates, we call the threshold-response function. Extending the work of Donovan, Hudgens and Gilbert (2019), we propose a nonparametric efficient estimator for the covariate-adjusted threshold-response function, which utilizes machine learning and Targeted Minimum-Loss Estimation (TMLE). We additionally propose a more general estimator, based on sequential regression, that also…
When evaluating medical tests or biomarkers for disease classification, the area under the receiver-operating characteristic (ROC) curve is a widely used performance metric that does not require us to commit to a specific decision threshold. For the same type of evaluations, a different metric known as the average precision (AP) is used much more widely in the information retrieval literature. We study both metrics in some depths in order to elucidate their difference and relationship. More specifically, we explain mathematically why the AP may be more appropriate if the earlier part of the RO…
Sequential Testing for Assessing the Incremental Value of Biomarkers Under Biorepository Specimen Constraints with Robustness to Model Misspecification
Receiver operating characteristic (ROC) analysis is one of the most popular approaches for evaluating and comparing the accuracy of medical diagnostic tests. Although various methodologies have been developed for estimating ROC curves and its associated summary indices, there is no consensus on a single framework that can provide consistent statistical inference whilst handling the complexities associated with medical data. Such complexities might include covariates that influence the diagnostic potential of a test, ordinal test data, censored data due to instrument detection limits or correla…
The receiver operating characteristic (ROC) curve is the most popular tool used to evaluate the discriminatory capability of diagnostic tests/biomarkers measured on a continuous scale when distinguishing between two alternative disease states (e.g, diseased and nondiseased). In some circumstances, the test's performance and its discriminatory ability may vary according to subject-specific characteristics or different test settings. In such cases, information-specific accuracy measures, such as the covariate-specific and the covariate-adjusted ROC curve are needed, as ignoring covariate informa…
The Kendall plot ($\K$-plot) is a plot measuring dependence between the components of a bivariate random variable. The $\K$-plot graphs the Kendall distribution function against the distribution function of $VU$, where $V$ and $U$ are independent uniform $[0,1]$ random variables. We associate $\K$-plots with the receiver operating characteristic ($\ROC$) curve, a well-accepted graphical tool in biostatistics for evaluating the ability of a biomarker to discriminate between two populations. The most commonly used global index of diagnostic accuracy of biomarkers is the area under the $\ROC$ cur…
To assess the classification accuracy of a continuous diagnostic result, the receiver operating characteristic (ROC) curve is commonly used in applications. The partial area under the ROC curve (pAUC) is one of widely accepted summary measures due to its generality and ease of probability interpretation. In the field of life science, a direct extension of the pAUC into the time-to-event setting can be used to measure the usefulness of a biomarker for disease detection over time. Without using a trapezoidal rule, we propose nonparametric estimators, which are easily computed and have closed-for…
A new semiparametric model of the ROC curve based on the resilience family or proportional reversed hazard family is proposed which is an alternative to the existing models. The resulting ROC curve and its summary indices (such as area under the curve (AUC) and Youden index) have simple analytic forms. The partial likelihood method is applied to estimate the ROC curve. Moreover, the estimation methodologies of the resilience family of the ROC curve have been developed based on AUC estimators exploiting Mann-Whitney statistics and the Rojo approach. A simulation study has been carried out to as…
The accuracy of a diagnostic test is typically characterised using the receiver operating characteristic (ROC) curve. Summarising indexes such as the area under the ROC curve (AUC) are used to compare different tests as well as to measure the difference between two populations. Often additional information is available on some of the covariates which are known to influence the accuracy of such measures. We propose nonparametric methods for covariate adjustment of the AUC. Models with normal errors and non-normal errors are discussed and analysed separately. Nonparametric regression is used for…
