Semi-empirical likelihood inference for the ROC curve with missing data

The receiver operating characteristic (ROC) curve is one of the most commonly used methods to compare the diagnostic performance of two or more laboratory or diagnostic tests. In this paper, we propose semi-empirical likelihood based confidence intervals for ROC curves of two populations, where one population is parametric and the other one is non-parametric and both have missing data. After imputing missing values, we derive the semi-empirical likelihood ratio statistic and the corresponding likelihood equations. It is shown that the log-semi-empirical likelihood ratio statistic is asymptotically scaled chi-squared. The estimating equations are solved simultaneously to obtain the estimated lower and upper bounds of semi-empirical likelihood confidence intervals. We conduct extensive simulation studies to evaluate the finite sample performance of the proposed empirical likelihood confidence intervals with various sample sizes and different missing probabilities.     

Optimal designs for covariates’ models

A linear model with one treatment at V levels and first order regression on K continuous covariates with values on a K-cube is considered. The D-criterion is used to judge the ‘goodness’ of any design for estimating the parameters of this model. Since this criterion is based on the determinant of the information matrix M(d) of a design d, upper bounds for |M(d)| yield lower bounds for the D-efficiency of any design d in estimating the vector of parameters in the model. We consider here only classes of designs d for which the number N of observations to be taken is a multiple of V, that is, there exists R≥2 such that N=V×R.Under these conditions, we determine the maximum of |M(d)|, and conditions under which the maximum is attained. These conditions include R being even, each treatment level being observed the same number of times, that is, R times, and N being a multiple of four. For the other cases of congruence of N (modulo 4) we further determine upper bounds on |M (d)| for equireplicated designs, i.e. for designs with equal number of observations per treatment level. These upper bounds are shown to depend also on the congruence of V (modulo 4). For some triples (N,V,K), the upper bounds determined are shown to be attained.Construction methods yielding families of designs which attain the upper bounds of |M(d)| are presented, for each of the sixteen cases of congruence of N and V.We also determine the upper bound for D-optimal designs for estimating only the treatment parameters, when first order regression on one continuous covariate is present.     

Sample Size Calculation and Blinded Sample Size Recalculation in Clinical Trials Where the Treatment Effect is Measured by the Relative Risk

In clinical trials with binary endpoints, the required sample size does not depend only on the specified type I error rate, the desired power and the treatment effect but also on the overall event rate which, however, is usually uncertain. The internal pilot study design has been proposed to overcome this difficulty. Here, nuisance parameters required for sample size calculation are re-estimated during the ongoing trial and the sample size is recalculated accordingly. We performed extensive simulation studies to investigate the characteristics of the internal pilot study design for two-group superiority trials where the treatment effect is captured by the relative risk. As the performance of the sample size recalculation procedure crucially depends on the accuracy of the applied sample size formula, we firstly explored the precision of three approximate sample size formulae proposed in the literature for this situation. It turned out that the unequal variance asymptotic normal formula outperforms the other two, especially in case of unbalanced sample size allocation. Using this formula for sample size recalculation in the internal pilot study design assures that the desired power is achieved even if the overall rate is mis-specified in the planning phase. The maximum inflation of the type I error rate observed for the internal pilot study design is small and lies below the maximum excess that occurred for the fixed sample size design.     

THE EFFECTS OF CORRELATION AMONG OBSERVATIONS ON THE ACCURACY OF APPROXIMATING THE DISTRIBUTION OF SAMPLE MEAN BY ITS ASYMPTOTIC DISTRIBUTION1

In this paper, we investigate the effects of correlation among observations on the accuracy of approximating the distribution of sample mean by its asymptotic distribution. The accuracy is investigated by the Berry-Esseen bound (BEB), which gives an upper bound on the error of approximation of the distribution function of the sample mean from its asymptotic distribution for independent observations. For a given sample size (n₀) the BEB is obtained when the observations are independent. Let this be BEB. We then find the sample size (n_*) required to have BEB below BEB₀, when the observations are dependent. Comparison of n_* with n₀ reveals the effects of correlation among observations on the accuracy of the asymptotic distribution as an approximation. It is shown that the effects of correlation among observations are not appreciable if the correlation is moderate to small but it can be severe for extreme correlations.     

Upper and lower bounds for the correlation ratio of order statistics from a sample without replacement

Using properties of the Hahn Polynomials, we give upper and lower bounds for the correlation ratio between order statistics of a sample without replacement from a finite population. The upper bound is attained when the population contains a lattice set. Except for particular cases, the lower bound is not sharp.     

On the probability of holes in truncated samples

For truncated data the existence of “holes” resp. inner risk sets may cause some problems when analyzing or applying the Lynden-Bell estimator. In this paper we derive sharp finite sample upper and lower bounds for the “probability of holes” and show that it goes to zero as sample size tends to infinity. In some selected cases also the rate of convergence is studied.     

Upper bounds for ruin probabilities under model uncertainty

Abstract

In this paper, we investigate some ruin problems for risk models that contain uncertainties on both claim frequency and claim size distribution. The problems naturally lead to the evaluation of ruin probabilities under the so-called G-expectation framework. We assume that the risk process is described as a class of G-compound Poisson process, a special case of the G-Lévy process. By using the exponential martingale approach, we obtain the upper bounds for the two-sided ruin probability as well as the ruin probability involving investment. Furthermore, we derive the optimal investment strategy under the criterion of minimizing this upper bound. Finally, we conclude that the upper bound in the case with investment is less than or equal to the case without investment.     

On Terrel's characterization of uniform distribution

Terrel (1983) (The Annals of Probability, Vol. 11, No. 3, 823–826) showed that the coefficient of correlation between the smaller and larger of a sample of size two is at most one-half, and this upper bound is attained only for continuous uniform distributions. His proof is of computational nature and is based on the properties of Legendre polynomials. We give an easier proof of Terrel's characterization and we show how our method can be used for obtaining sharper bounds within the class of discrete distributions onN points and also a characterization of the equidistant uniform distribution.     

Bounds for the variance of the graybill-deal estimator of the common mean of two normal distributions

In this note we derive sharp lower and upper bounds for the variance of the Graybill-Deal estimator of the common mean of two normal distributions with unknown variances when the sample sizes are not necessarily equal. We also derive similar bounds for the variance of the Brown-Cohen (1974) T _a(1) class of unbiased es-timators to which the Graybill-Deal estimator belongs. Further, we illustrate the sharpness of the bounds by numerical computations in the case of the Graybill-Deal estimator.     

On design and inference for two-stage adaptive clinical trials with dependent data

We consider two-stage adaptive designs for clinical trials where data from the two stages are dependent. This occurs when additional data are obtained from patients during their second stage follow-up. While the proposed flexible approach allows modifications of trial design, sample size, or statistical analysis using the first stage data, there is no need for a complete prespecification of the adaptation rule. Methods are provided for an adaptive closed testing procedure, for calculating overall adjusted p-values, and for obtaining unbiased estimators and confidence bounds for parameters that are invariant to modifications. A motivating example is used to illustrate these methods.     

A Note on Sample Size Determination for the Estimation of the Mean Vector of a Multivariate Population

In this article, we present a straightforward Bonferroni approach for determining sample size for estimating the mean vector of a multivariate population under two scenarios: (1) a pre-specified overall confidence level is desired; and (2) a pre-specified confidence level needs to be guaranteed for each individual variable. It is demonstrated that correlation between variables helps reduce the sample size. The formula to calculate the reduced sample size is derived. A binormal example is presented to illustrate the effect of correlation on sample size reduction for various values of the correlation coefficient.     

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.     

Improving the biomarker diagnostic capacity via functional transformations

The use of the area under the receiver-operating characteristic, ROC, curve (AUC) as an index of diagnostic accuracy is overwhelming in fields such as biomedical science and machine learning. It seems that a larger AUC value has become synonymous with a better performance. The functional transformation of the marker values has been proposed in the specialized literature as a procedure for increasing the AUC and therefore the diagnostic accuracy. However, the classification process is based on some regions (classification subsets) which support the decision made; one subject is classified as positive if its marker is within this region and classified as negative otherwise. In this paper we study the capacity of improving the classification performance of univariate biomarkers via functional transformations and the impact of this transformation on the final classification regions based on a real-world dataset. Particularly, we consider the problem of determining the gender of a subject based on the Mode frequency of his/her voice. The shape of the cumulative distribution function of this characteristic in both the male and the female groups makes the resulting classification problem useful for illustrating the differences between having useful diagnostic rules and obtaining an optimal AUC value. Our point is that improving the AUC by means of a functional transformation can produce classification regions with no practical interpretability. We propose to improve the classification accuracy by making the selection of the classification subsets more flexible while preserving their interpretability. Besides, we provide different graphical approximations which allow us a better understanding of the classification problem.     

A Note on the Upper Bound to Variance of the Sample Extreme from a Finite Population

We construct a new upper bound for the variance of the sample minimum and maximum in the case of a simple random sample drawn without replacement. The bound is optimal in the form provided. Similar bounds are shown for the other order statistics.     

Detecting change in a hazard regression model with right-censoring

The hazard function plays an important role in survival analysis and reliability, since it quantifies the instantaneous failure rate of an individual at a given time point t, given that this individual has not failed before t. In some applications, abrupt changes in the hazard function are observed, and it is of interest to detect the location of such a change. In this paper, we consider testing of existence of a change in the parameters of an exponential regression model, based on a sample of right-censored survival times and the corresponding covariates. Likelihood ratio type tests are proposed and non-asymptotic bounds for the type II error probability are obtained. When the tests lead to acceptance of a change, estimators for the location of the change are proposed. Non-asymptotic upper bounds of the underestimation and overestimation probabilities are obtained. A short simulation study illustrates these results.     

Sharp bounds for L-statistics from dependent samples of random length

Several distribution-free bounds on expected values of L-statistics based on the sample of possibly dependent and nonidentically distributed random variables are given in the case when the sample size is a random variable, possibly dependent on the observations, with values in the set {1,2,…}. Some bounds extend the results of Papadatos (2001a) to the case of random sample size. The others provide new evaluations even if the sample size is nonrandom. Some applications of the presented bounds are also indicated.     

Closed-Form Approximation for the AOQL of Attributes Acceptance Sample Plans

We derive upper and lower bounds at the point at which the average outgoing quality limit (AOQL) of an attributes acceptance sampling plan is achieved. Using a simple average of these bounds to approximate the ordinate of the AOQL, we develop an accurate, closed-form approximation to the AOQL. The bounds and approximation show how the parameters of a sampling plan affect the AOQL and can be used to study the behavior of the AOQL and other measures of the plan's performance.     

Improved variance bounds for unbiased estimation in inverse sampling

Sathe (1977) derived sharper variance bounds for inverse sample unbiased estimator of the negative binomial parameter p. In the present writing improved upper/lower variance bounds are achieved and the relative improvement is numerically illustrated.     

Optimal bounds on the bias of quasimidranges

We derive sharp upper and lower bounds on expectations of sample quasimidranges, that is, arithmetic means of two fixed order statistics of the sample, expressed in various scale units. They can be considered as the bounds on the bias of estimating unknown mean of the parent distribution by the above statistics. While determining the appropriate projection, we consider two new auxiliary functions whose usage provides analytical conditions determining the form of corresponding greatest convex minorant. The results are illustrated with numerical examples.     

Sensitivity,specificity and ROC-curves in multiple reader diagnostic trials—A unified,nonparametric approach

In diagnostic trials, the performance of a product is most frequently measured in terms such as sensitivity, specificity and the area under the ROC-curve (AUC). In multiple-reader trials, correlated data appear in a natural way since the same patient is observed under different conditions by several readers. The repeated measures may have quite an involved correlation structure. Even though sensitivity, specificity and the AUC are all assessments of diagnostic ability, a unified approach to analyze all such measurements allowing for an arbitrary correlation structure does not exist. Thus, a unified approach for these three effect measures of diagnostic ability will be presented in this paper. The fact that sensitivity and specificity are particular AUCs will serve as a basis for our method of analysis. As the presented theory can also be used in set-ups with correlated binomial random-variables, it may have a more extensive application than only in diagnostic trials.