The average area under correlated receiver operating characteristic curves: a nonparametric approach based on generalized two-sample Wilcoxon statistics

It is well known that, when sample observations are independent, the area under the receiver operating characteristic (ROC) curve corresponds to the Wilcoxon statistics if the area is calculated by the trapezoidal rule. Correlated ROC curves arise often in medical research and have been studied by various parametric methods. On the basis of the Mann–Whitney U-statistics for clustered data proposed by Rosner and Grove, we construct an average ROC curve and derive nonparametric methods to estimate the area under the average curve for correlated ROC curves obtained from multiple readers. For the more complicated case where, in addition to multiple readers examining results on the same set of individuals, two or more diagnostic tests are involved, we derive analytic methods to compare the areas under correlated average ROC curves for these diagnostic tests. We demonstrate our methods in an example and compare our results with those obtained by other methods. The nonparametric average ROC curve and the analytic methods that we propose are easy to explain and simple to implement.     

A test for crossing receiver operating characteristic (roc) curves

The receiver operating characteristic (ROC) curve gives a graphical representation of sensitivity and specificity of a prediction model when varying the decision treshold on a diagnostic criterion. A classical test for comparing the overall accuracies for two models -1 and 2- is based on the difference between ROC curves areas - related to its standard error. This test is designed for the situation where ROC curve 1 caps ROC curve 2. Often both curves cross :in this paper, a new test, based on the integrated difference between the curves, is proposed to deal with this situation. In a simulation experiment, the new test was less powerful than the old test for detecting an overall superiority, but much more powerfull against the crossing alternative.     

Applications of the Bootstrap in ROC Analysis

The problem of estimating standard errors for diagnostic accuracy measures might be challenging for many complicated models. We can address such a problem by using the Bootstrap methods to blunt its technical edge with resampled empirical distributions. We consider two cases where bootstrap methods can successfully improve our knowledge of the sampling variability of the diagnostic accuracy estimators. The first application is to make inference for the area under the ROC curve resulted from a functional logistic regression model which is a sophisticated modelling device to describe the relationship between a dichotomous response and multiple covariates. We consider using this regression method to model the predictive effects of multiple independent variables on the occurrence of a disease. The accuracy measures, such as the area under the ROC curve (AUC) are developed from the functional regression. Asymptotical results for the empirical estimators are provided to facilitate inferences. The second application is to test the difference of two weighted areas under the ROC curve (WAUC) from a paired two sample study. The correlation between the two WAUC complicates the asymptotic distribution of the test statistic. We then employ the bootstrap methods to gain satisfactory inference results. Simulations and examples are supplied in this article to confirm the merits of the bootstrap methods.     

Compare diagnostic tests using transformation-invariant smoothed ROC curves()

Receiver operating characteristic (ROC) curve, plotting true positive rates against false positive rates as threshold varies, is an important tool for evaluating biomarkers in diagnostic medicine studies. By definition, ROC curve is monotone increasing from 0 to 1 and is invariant to any monotone transformation of test results. And it is often a curve with certain level of smoothness when test results from the diseased and non-diseased subjects follow continuous distributions. Most existing ROC curve estimation methods do not guarantee all of these properties. One of the exceptions is Du and Tang (2009) which applies certain monotone spline regression procedure to empirical ROC estimates. However, their method does not consider the inherent correlations between empirical ROC estimates. This makes the derivation of the asymptotic properties very difficult. In this paper we propose a penalized weighted least square estimation method, which incorporates the covariance between empirical ROC estimates as a weight matrix. The resulting estimator satisfies all the aforementioned properties, and we show that it is also consistent. Then a resampling approach is used to extend our method for comparisons of two or more diagnostic tests. Our simulations show a significantly improved performance over the existing method, especially for steep ROC curves. We then apply the proposed method to a cancer diagnostic study that compares several newly developed diagnostic biomarkers to a traditional one.     

An application of lomax distributions in receiver operating characteristic(roc)curve analysis

Receiver operating characteristic(ROC)curves are useful for studying the performance of diagnostic tests. ROC curves occur in many fields of applications including psychophysics, quality control and medical diagnostics. In practical situations, often the responses to a diagnostic test are classified into a number of ordered categories. Such data are referred to as ratings data. It is typically assumed that the underlying model is based on a continuous probability distribution. The ROC curve is then constructed from such data using this probability model. Properties of the ROC curve are inherited from the model. Therefore, understanding the role of different probability distributions in ROC modeling is an interesting and important area of research. In this paper the Lomax distribution is considered as a model for ratings data and the corresponding ROC curve is derived. The maximum likelihood estimation procedure for the related parameters is discussed. This procedure is then illustrated in the analysis of a neurological data example.     

COMBINING MULTIPLE MARKERS FOR MULTI‐CATEGORY CLASSIFICATION: AN ROC SURFACE APPROACH

The Receiver Operating Characteristic (ROC) curve and the Area Under the ROC Curve (AUC) are effective statistical tools for evaluating the accuracy of diagnostic tests for binary‐class medical data. However, many real‐world biomedical problems involve more than two categories. The Volume Under the ROC Surface (VUS) and Hypervolume Under the ROC Manifold (HUM) measures are extensions for the AUC under three‐class and multiple‐class models. Inference methods for such measures have been proposed recently. We develop a method of constructing a linear combination of markers for which the VUS or HUM of the combined markers is maximized. Asymptotic validity of the estimator is justified by extending the results for maximum rank correlation estimation that are well known in econometrics. A bootstrap resampling method is then applied to estimate the sampling variability. Simulations and examples are provided to demonstrate our methods.     

Two transformation models for estimating an ROC curve derived from continuous data

A receiver operating characteristic (ROC) curve is a plot of two survival functions, derived separately from the diseased and healthy samples. A special feature is that the ROC curve is invariant to any monotone transformation of the measurement scale. We propose and analyse semiparametric and parametric transformation models for this two-sample problem. Following an unspecified or specified monotone transformation, we assume that the healthy and diseased measurements have two normal distributions with different means and variances. Maximum likelihood algorithms for estimating ROC curve parameters are developed. The proposed methods are illustrated on the marker CA125 in the diagnosis of gastric cancer.     

A Flexible Method for Estimating the ROC Curve

In this paper we propose a flexible method for estimating a receiver operating characteristic (ROC) curve that is based on a continuous-scale test. The approach is easily understood and efficiently computed, and robust to the smooth parameter selection, which needs intensive computation when using local polynomial and smoothing spline techniques. The results from our simulation experiment indicate that the moderate-sample numerical performance of our estimator is better than the empirical ROC curve estimator and comparable to the local linear estimator. The availability of easy implementation is also illustrated by our simulation. We apply the proposed method to two real data sets.     

Adjusting ROC curves for covariates in the presence of verification bias

The ROC (receiver operating characteristic) curve is frequently used for describing effectiveness of a diagnostic marker or test. Classical estimation of the ROC curve uses independent identically distributed samples taken randomly from the healthy and diseased populations. Frequently not all subjects undergo a definitive gold standard assessment of disease status (verification). Estimation of the ROC curve based on data only from subjects with verified disease status may be badly biased (verification bias). In this work we investigate the properties of the doubly robust (DR) method for estimating the ROC curve adjusted for covariates (ROC regression) under verification bias. We develop the estimator's asymptotic distribution and examine its finite sample size properties via a simulation study. We apply this procedure to fingerstick postprandial blood glucose measurement data adjusting for age.     

An alternative method for global and partial comparison of two diagnostic systems based on ROC curves

In this paper, an alternative method for the comparison of two diagnostic systems based on receiver operating characteristic (ROC) curves is presented. ROC curve analysis is often used as a statistical tool for the evaluation of diagnostic systems. However, in general, the comparison of ROC curves is not straightforward, in particular, when they cross each other. A similar difficulty is also observed in the multi-objective optimization field where sets of solutions defining fronts must be compared with a multi-dimensional space. Thus, the proposed methodology is based on a procedure used to compare the performance of distinct multi-objective optimization algorithms. In general, methods based on the area under the ROC curves are not sensitive to the existence of crossing points between the curves. The new approach can deal with this situation and also allows the comparison of partial portions of ROC curves according to particular values of sensitivity and specificity of practical interest. Simulations results are presented. For illustration purposes, considering real data from newborns with very low birthweight, the new method was applied in order to discriminate the better index for evaluating the risk of death.     

Local linear smoothing of receiver operating characteristic (ROC) curves

For measuring the accuracy of a continuous diagnostic test, the receiver operating characteristic (ROC) curve is often used. The empirical ROC curve is the most commonly used non-parametric estimator for the ROC curve. Recently, Lloyd (J. Amer. Statist. Assoc. 93(1998) 1356) proposed a kernel smoothing estimator for the ROC curve and showed his estimator has better mean square error than the empirical ROC curve estimator. However, Lloyd's estimator involves two bandwidths and has a boundary problem. In addition, his choice of bandwidths is ad hoc. In this paper we propose another kernel smoothing estimator which involves only one bandwidth and does not have the boundary problem. Furthermore, our choice of the bandwidth is asymptotically optimal.     

Nonparametric estimation of the ROC curve for length-biased and right-censored data

Abstract

ROC curve is a fundamental evaluation tool in medical researches and survival analysis. The estimation of ROC curve has been studied extensively with complete data and right-censored survival data. However, these methods are not suitable to analyze the length-biased and right-censored data. Since this kind of data includes the auxiliary information that truncation time and residual time share the same distribution, the two new estimators for the ROC curve are proposed by taking into account this auxiliary information to improve estimation efficiency. Numerical simulation studies with different assumed cases and real data analysis are conducted.     

ROC curve estimation based on local smoothing

ROC curve is a graphical representation of the relationship between sensitivity and specificity of a diagnostic test. It is a popular tool for evaluating and comparing different diagnostic tests in medical sciences. In the literature,the ROC curve is often estimated empirically based on an empirical distribution function estimator and an empirical quantile function estimator. In this paper an alternative nonparametric procedure to estimate the ROC Curve is suggested which is based on local smoothing techniques. Several numerical examples are presented to evaluate the performance of this procedure.     

Comparing Performance of Multiclass Classification Systems with ROC Manifolds: When Volume and Correct Classification Fails

Higher dimensional surfaces are used to examine the diagnostic performance of multiclass classification systems. These surfaces are extensions of the ROC curve and are known as ROC surfaces or manifolds. Manifolds may be constructed from either the correct classifications or from the misclassifications of the diagnostic system. Comparisons of the usefulness of each of these ROC manifolds with respect to the performance of the diagnostic system are made with emphasis on inferences from volume under the surface and optimal operating points (thresholds) of the system. Recommendations for when to use each type of ROC manifold and performance measure are discussed.     

Semi-parametric estimation of ROC curves based on binomial regression modelling

This paper presents a method of estimating a receiver operating characteristic (ROC) curve when the underlying diagnostic variable X is continuous and fully observed. The new method is based on modelling the probability of response given X , rather than the distribution of X given response. The method offers advantages in modelling flexibility and computational simplicity. The resulting ROC curve estimates are semi-parametric and can, in principle, take an infinite variety of shapes. Moreover, model selection can be based on standard methods within the binomial regression framework. Statistical accuracy of the curve estimate is provided by a simply implemented bootstrap approach.     

Confidence intervals and bands for the binormal ROC curve revisited

Two types of confidence intervals (CIs) and confidence bands (CBs) for the receiver operating characteristic (ROC) curve are studied: pointwise CIs and simultaneous CBs. An optimized version of the pointwise CI with the shortest width is developed. A new ellipse-envelope simultaneous CB for the ROC curve is suggested as an adaptation of the Working-Hotelling-type CB implemented in a paper by Ma and Hall (1993). Statistical simulations show that our ellipse-envelope CB covers the true ROC curve with a probability close to nominal while the coverage probability of the Ma and Hall CB is significantly smaller. Simulations also show that our CI for the area under the ROC curve is close to nominal while the coverage probability of the CI suggested by Hanley and McNail (1982) uniformly overestimates the nominal value. Two examples illustrate our simultaneous ROC bands: radiation dose estimation from time to vomiting and discrimination of breast cancer from benign abnormalities using electrical impedance measurements.     

Fitting Roc Curves Using Non-linear Binomial Regression

The performance of a diagnostic test is summarized by its receiver operating characteristic (ROC) curve. Empirical data on a test's performance often come in the form of observed true positive and false positive relative frequencies, under varying conditions. This paper describes a family of models for analysing such data. The underlying ROC curves are specified by a shift parameter, a shape parameter and a link function. Both the position along the ROC curve and the shift parameter are modelled linearly. The shape parameter enters the model non-linearly but in a very simple manner. One simple application is to the meta-analysis of independent studies of the same diagnostic test, illustrated on some data of Moses, Shapiro & Littenberg (1993). A second application to so-called vigilance data is given, where ROC curves differ across subjects, and modelling of the position along the ROC curve is of primary interest.     

Tests for serial correlation in mean and variance of a sequence of time series objects

In this era of Big Data, large-scale data storage provides the motivation for statisticians to analyse new types of data. The proposed work concerns testing serial correlation in a sequence of sets of time series, here referred to as time series objects. An example is serial correlation of monthly stock returns when daily stock returns are observed. One could consider a representative or summarized value of each object to measure the serial correlation, but this approach would ignore information about the variation in the observed data. We develop Kolmogorov–Smirnov-type tests with the standard bootstrap and wild bootstrap Ljung–Box test statistics for serial correlation in mean and variance of time series objects, which take the variation within a time series object into account. We study the asymptotic property of the proposed tests and present their finite sample performance using simulated and real examples.     

Between a ROC and a hard place: Teaching prevalence plots to understand real world biomarker performance in the clinic

The Receiver Operating Characteristic (ROC) curve and the Area Under the Curve (AUC) of the ROC curve are widely used in discovery to compare the performance of diagnostic and prognostic assays. The ROC curve has the advantage that it is independent of disease prevalence. However, in this note, we remind scientists and clinicians that the performance of an assay upon translation to the clinic is critically dependent upon that very same prevalence. Without an understanding of prevalence in the test population, even robust bioassays with excellent ROC characteristics may perform poorly in the clinic. While the exact prevalence in the target population is not always known, simple plots of candidate assay performance as a function of prevalence rate give a better understanding of the likely real‐world performance and a greater understanding of the likely impact of variation in that prevalence on translation to the clinic.     

Detection and Localization in Test Accuracy: A Bayesian Perspective

In assessing the area under the ROC curve for the accuracy of a diagnostic test, it is imperative to detect and locate multiple abnormalities per image. This approach takes that into account by adopting a statistical model that allows for correlation between the reader scores of several regions of interest (ROI).

The ROI method of partitioning the image is taken. The readers give a score to each ROI in the image and the statistical model takes into account the correlation between the scores of the ROI's of an image in estimating test accuracy. The test accuracy is given by Pr[Y > Z] + (1/2)Pr[Y = Z], where Y is an ordinal diagnostic measurement of an affected ROI, and Z is the diagnostic measurement of an unaffected ROI. This way of measuring test accuracy is equivalent to the area under the ROC curve. The parameters are the parameters of a multinomial distribution, then based on the multinomial distribution, a Bayesian method of inference is adopted for estimating the test accuracy.

Using a multinomial model for the test results, a Bayesian method based on the predictive distribution of future diagnostic scores is employed to find the test accuracy. By resampling from the posterior distribution of the model parameters, samples from the posterior distribution of test accuracy are also generated. Using these samples, the posterior mean, standard deviation, and credible intervals are calculated in order to estimate the area under the ROC curve. This approach is illustrated by estimating the area under the ROC curve for a study of the diagnostic accuracy of magnetic resonance angiography for diagnosis of arterial atherosclerotic stenosis. A generalization to multiple readers and/or modalities is proposed.

A Bayesian way to estimate test accuracy is easy to perform with standard software packages and has the advantage of employing the efficient inclusion of information from prior related imaging studies.