Statistical Evaluation of Continuous-Scale Diagnostic Tests with Missing Data

The receiver operating characteristic (ROC) curve methodology is the statistical methodology for assessment of the accuracy of diagnostics tests or bio-markers. Currently most widely used statistical methods for the inferences of ROC curves are complete-data based parametric, semi-parametric or nonparametric methods. However, these methods cannot be used in diagnostic applications with missing data. In practical situations, missing diagnostic data occur more commonly due to various reasons such as medical tests being too expensive, too time consuming or too invasive. This dissertation aims to develop new nonparametric statistical methods for evaluating the accuracy of diagnostic tests or biomarkers in the presence of missing data. Specifically, novel nonparametric statistical methods will be developed with different types of missing data for (i) the inference of the area under the ROC curve (AUC, which is a summary index for the diagnostic accuracy of the test) and (ii) the joint inference of the sensitivity and the specificity of a continuous-scale diagnostic test. In this dissertation, we will provide a general framework that combines the empirical likelihood and general estimation equations with nuisance parameters for the joint inferences of sensitivity and specificity with missing diagnostic data. The proposed methods will have sound theoretical properties. The theoretical development is challenging because the proposed profile log-empirical likelihood ratio statistics are not the standard sum of independent random variables. The new methods have the power of likelihood based approaches and jackknife method in ROC studies. Therefore, they are expected to be more robust, more accurate and less computationally intensive than existing methods in the evaluation of competing diagnostic tests. INDEXWORDS: AUC, Bootstrap, Diagnostic tests, Empirical likelihood, Estimating equations, Imputation, Jackknife, Missing data, ROC curve, Sensitivity, Specificity, Verification bias STATISTICAL EVALUATION OF CONTINUOUS-SCALE DIAGNOSTIC TESTS WITH MISSING DATA