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.     

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.     

Testing the difference between two Kolmogorov–Smirnov values in the context of receiver operating characteristic curves

The maximum vertical distance between a receiver operating characteristic (ROC) curve and its chance diagonal is a common measure of effectiveness of the classifier that gives rise to this curve. This measure is known to be equivalent to a two-sample Kolmogorov–Smirnov statistic; so the absolute difference D between two such statistics is often used informally as a measure of difference between the corresponding classifiers. A significance test of D is of great practical interest, but the available Kolmogorov–Smirnov distribution theory precludes easy analytical construction of such a significance test. We, therefore, propose a Monte Carlo procedure for conducting the test, using the binormal model for the underlying ROC curves. We provide Splus/R routines for the computation, tabulate the results for a number of illustrative cases, apply the methods to some practical examples and discuss some implications.     

Generalized Confidence Interval Estimation for the Difference in Paired Areas Under the ROC Curves in the Absence of a Gold Standard

Receiver operating characteristic (ROC) curves can be used to assess the accuracy of tests measured on ordinal or continuous scales. The most commonly used measure for the overall diagnostic accuracy of diagnostic tests is the area under the ROC curve (AUC). A gold standard (GS) test on the true disease status is required to estimate the AUC. However, a GS test may be too expensive or infeasible. In many medical researches, the true disease status of the subjects may remain unknown. Under the normality assumption on test results from each disease group of subjects, we propose a heuristic method of estimating confidence intervals for the difference in paired AUCs of two diagnostic tests in the absence of a GS reference. This heuristic method is a three-stage method by combining the expectation-maximization (EM) algorithm, bootstrap method, and an estimation based on asymptotic generalized pivotal quantities (GPQs) to construct generalized confidence intervals for the difference in paired AUCs in the absence of a GS. Simulation results show that the proposed interval estimation procedure yields satisfactory coverage probabilities and expected interval lengths. The numerical example using a published dataset illustrates the proposed method.     

A non-inferiority test for diagnostic accuracy in the absence of the golden standard test based on the paired partial areas under receiver operating characteristic curves

Non-inferiority tests are often measured for the diagnostic accuracy in medical research. The area under the receiver operating characteristic (ROC) curve is a familiar diagnostic measure for the overall diagnostic accuracy. Nevertheless, since it may not differentiate the diverse shapes of the ROC curves with different diagnostic significance, the partial area under the ROC (PAUROC) curve, another summary measure emerges for such diagnostic processes that require the false-positive rate to be in the clinically interested range. Traditionally, to estimate the PAUROC, the golden standard (GS) test on the true disease status is required. Nevertheless, the GS test may sometimes be infeasible. Besides, in a lot of research fields such as the epidemiology field, the true disease status of the patients may not be known or available. Under the normality assumption on diagnostic test results, based on the expectation-maximization algorithm in combination with the bootstrap method, we propose the heuristic method to construct a non-inferiority test for the difference in the paired PAUROCs without the GS test. Through the simulation study, although the proposed method might provide a liberal test, as a whole, the empirical size of the proposed method sufficiently controls the size at the significance level, and the empirical power of the proposed method in the absence of the GS is as good as that of the non-inferiority in the presence of the GS. The proposed method is illustrated with the published data.     

Nonparametric estimation of the ROC curve based on smoothed empirical distribution functions

The receiver operating characteristic (ROC) curve is a graphical representation of the relationship between false positive and true positive rates. It is a widely used statistical tool for describing the accuracy of a diagnostic test. In this paper we propose a new nonparametric ROC curve estimator based on the smoothed empirical distribution functions. We prove its strong consistency and perform a simulation study to compare it with some other popular nonparametric estimators of the ROC curve. We also apply the proposed method to a real data set.     

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.     

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.     

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.     

Optimal Threshold from ROC and CAP Curves

Receiver Operating Characteristic (ROC) and Cumulative Accuracy Profile (CAP) curves are used to assess the discriminatory power of different credit-rating approaches. The thresholds of optimal classification accuracy on an ROC curve and of maximal profit on a CAP curve can be found by using iso-performance tangent lines, which are based on the standard notion of accuracy. In this article, we propose another accuracy measure called the true rate. Using this rate, one can obtain alternative optimal thresholds on both ROC and CAP curves. For most real populations of borrowers, the number of the defaults is much less than that of the non defaults, and in such cases using the true rate may be more efficient than using the accuracy rate in terms of cost functions. Moreover, it is shown that both alternative optimal thresholds by using the true rate are the identical, and this single threshold coincides with the score corresponding to Kolmogorov–Smirnov statistic used to test the homogeneous distribution functions of the defaults and non defaults, whereas the optimal threshold by using the accuracy does not the same as the score corresponding to Kolmogorov–Smirnov statistic. These facts are explored with some simulation and illustrative examples.     

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.     

Powerful nonparametric statistics to compare k independent ROC curves

The authors deal with the problem of comparing receiver operating characteristic (ROC) curves from independent samples. From a nonparametric approach, they propose and study three different statistics. Their asymptotic distributions are obtained and a resample plan is considered. In order to study the statistical power of the introduced statistics, a simulation study is carried out. The (observed) results suggest that, for the considered models, the new statistics are more powerful than the usually employed ones (the Venkatraman test and the usual area under the ROC curve criterion) in non-uniform dominance situations and quite good otherwise.     

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.     

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.     

A new method for the comparison of survival distributions

The assessment of overall homogeneity of time‐to‐event curves is a key element in survival analysis in biomedical research. The currently commonly used testing methods, e.g. log‐rank test, Wilcoxon test, and Kolmogorov–Smirnov test, may have a significant loss of statistical testing power under certain circumstances. In this paper we propose a new testing method that is robust for the comparison of the overall homogeneity of survival curves based on the absolute difference of the area under the survival curves using normal approximation by Greenwood's formula. Monte Carlo simulations are conducted to investigate the performance of the new testing method compared against the log‐rank, Wilcoxon, and Kolmogorov–Smirnov tests under a variety of circumstances. The proposed new method has robust performance with greater power to detect the overall differences than the log‐rank, Wilcoxon, and Kolmogorov–Smirnov tests in many scenarios in the simulations. Furthermore, the applicability of the new testing approach is illustrated in a real data example from a kidney dialysis trial. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

ROC curve and covariates: extending induced methodology to the non-parametric framework

Continuous diagnostic tests are often used to discriminate between diseased and healthy populations. The receiver operating characteristic (ROC) curve is a widely used tool that provides a graphical visualisation of the effectiveness of such tests. The potential performance of the tests in terms of distinguishing diseased from healthy people may be strongly influenced by covariates, and a variety of regression methods for adjusting ROC curves has been developed. Until now, these methodologies have assumed that covariate effects have parametric forms, but in this paper we extend the induced methodology by allowing for arbitrary non-parametric effects of a continuous covariate. To this end, local polynomial kernel smoothers are used in the estimation procedure. Our method allows for covariate effect not only on the mean, but also on the variance of the diagnostic test. We also present a bootstrap-based method for testing for a significant covariate effect on the ROC curve. To illustrate the method, endocrine data were analysed with the aim of assessing the performance of anthropometry for predicting clusters of cardiovascular risk factors in an adult population in Galicia (NW Spain), duly adjusted for age. The proposed methodology has proved useful for providing age-specific thresholds for anthropometric measures in the Galician community.     

Prediction of disease status: A regressive model approach for repeated measures

In this paper, regressive models are proposed for modeling a sequence of transitions in longitudinal data. These models are employed to predict the future status of the outcome variable of the individuals on the basis of their underlying background characteristics or risk factors. The estimation of parameters and also estimates of conditional and unconditional probabilities are shown for repeated measures. The goodness of fit tests are extended in this paper on the basis of the deviance and the Hosmer–Lemeshow procedures and generalized to repeated measures. In addition, to measure the suitability of the proposed models for predicting the disease status, we have extended the ROC curve approach to repeated measures. The procedure is shown for the conditional models for any order as well as for the unconditional model, to predict the outcome at the end of the study. The test procedures are also suggested. For testing the differences between areas under the ROC curves in subsequent follow-ups, two different test procedures are employed, one of which is based on permutation test. In this paper, an unconditional model is proposed on the basis of conditional models for the disease progression of depression among the elderly population in the USA on the basis of the Health and Retirement Survey data collected longitudinally. The illustration shows that the disease progression observed conditionally can be employed to predict the outcome and the role of selected variables and the previous outcomes can be utilized for predictive purposes. The results show that the percentage of correct predictions of a disease is quite high and the measures of sensitivity and specificity are also reasonably impressive. The extended measures of area under the ROC curve show that the models provide a reasonably good fit in terms of predicting the disease status during a long period of time. This procedure will have extensive applications in the field of longitudinal data analysis where the objective is to obtain estimates of unconditional probabilities on the basis of series of conditional transitional models.