M S Pepe

..It is hoped that the presentation in this paper will both encourage the use of regression analysis for evaluating diagnostic tests and help guide the choice of the most appropriate regression analysis approach in applications...

..The impact of error in the gold standard reference test on the design and evaluation of comparative screening test studies is also discussed...

..Finally, we note the relationship between regression models for the mean placement value and recently proposed models for the area under the ROC curve which is the classic summary index of discrimination...

..A single approach for statistical evaluation and comparison of markers is not yet established...

..The author argues for reporting components of the Net Reclassification Index because they are more clinically relevant than is the single numerical summary measure...

..Instead we demonstrate that an approach that maximizes an alternative objective function characterizing classification accuracy performs better...

..Model fitting by maximizing the AUC rather than the likelihood should be considered when the goal is to derive a marker combination score for classification or prediction...

..Such justification must be based in part on a clear clinical definition of disease and biological knowledge about mechanisms giving rise to test results...

..The methods are demonstrated with data on prostate-specific antigen and risk factors from the Prostate Cancer Prevention Trial, 1993-2003...

..Applications to two datasets are presented...

..Common biases that pervade the biomarker research literature would be eliminated if these rigorous standards were followed...

..The conditional-UMVUE appears to be a very good choice...

..However, results to date have been disappointing. In addition, statistical methods to quantify the predictive information in markers have not been standardized...

..In addition, the serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated...

..Asymptotic distribution theory is developed to facilitate inference and to provide insight into factors influencing variability of estimated model parameters...

..The method holds promise as a robust and technically easy way of evaluating information about future prognosis that may be gleaned from a patient's current and past clinical status...

..Our approach leads naturally to a procedure for sample-size calculations, appropriate for exploratory studies that seek to identify differentially expressed genes...

..We apply the methods to prostate-specific antigen (PSA), a marker for predicting risk of prostate cancer...

..Our approach naturally extends use of the Mann-Whitney statistic in a fashion that is analogous to how linear models extend the t-test. We illustrate the methodology with data from clinical trials of a therapy for Cystic Fibrosis...

..CF physicians should be aware of the impact of choice of reference equation in both clinical care and research...

..We report on the results of a simulation study designed to examine the properties of this test under a variety of conditions. The method is illustrated with data from a study of methods for diagnosis of coronary artery disease...

..We illustrate the method on simulated ordinal data representing radiologists' ratings of mammography images and on rating data from a national image reading study of mammography screening...

..They draw analogies and contrasts throughout with studies of association...

..Advantages of the CRS relative to other approaches include that the CRS is explicitly defined, does not depend on the results of the new test under investigation, and is easy to interpret...

..However, we also show that matching greatly complicates estimation of the incremental value of the marker. We recommend that matching be carefully considered in the context of these findings...

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..We conclude that the depth of postprandial ghrelin suppression is proportional to ingested caloric load but that recovery of plasma ghrelin is not a critical determinant of intermeal interval...

..Although statistical methodology is well developed for comparing diagnostic tests in terms of their sensitivities and specificities, comparative inference about predictive values is not...

..We use the regression framework to compare two prostate-specific antigen biomarkers and to evaluate the dependence of biomarker accuracy on the time prior to clinical diagnosis of prostate cancer...

..The methods presented in this paper have the potential to be useful in a number of areas including the design of clinical trials and health policy analysis...

..Using a marginal regression framework, we describe how to estimate differences in predictive accuracy and how to test whether the observed difference is statistically significant...

..72% for PET) and considerably lower expense means it may be preferred to PET early in staging to identify inoperable patients...

..Relative to our previous submission, Aims 1 and 5 have been eliminated while aims 2, 3 and 4 have been elaborated upon and expanded. ..

..Programs written in Stata will be made available through the Stata archive, the EDRN and through a 'Diagnostics and Biomarkers Statistical Center' web site. ..

..Relative to our previous submission, Aims 1 and 5 have been eliminated while aims 2, 3 and 4 have been elaborated upon and expanded. ..

..Relative to our previous submission, Aims 1 and 5 have been eliminated while aims 2, 3 and 4 have been elaborated upon and expanded. ..

..abstract_text> ..

..Software to implement analyses will use standard statistical packages when possible and will be fully documented so that it can be shared with colleagues. ..

..Programs written in Stata will be made available through the Stata archive, the EDRN and through a 'Diagnostics and Biomarkers Statistical Center'web site. ..