Biomedical subjects

Benjamin Reiser

Publications and source records attributed to Benjamin Reiser.

8 recordsLinked to original sources

PubMed2006

ROC analysis for markers with mass at zero.

The receiver operating characteristic (ROC) curve and in particular the area under the curve (AUC) is commonly used to examine the discriminatory ability of diagnostic markers. Certain markers while basically continuous and non-negative have a positive probability mass (spike) at the value zero. We discuss a flexible modelling approach to such data and contrast it with the standard non-parametric approach. We show how the modelling approach can be extended to take account of the effect of explanatory variables. We motivate this problem and illustrate the modelling approach using data on the coronary calcium score, measured by electron beam tomography, which is a marker for atherosclerosis.

Adult↗

PubMed2006

Comparing the areas under two correlated ROC curves: parametric and non-parametric approaches.

In order to compare the discriminatory effectiveness of two diagnostic markers the equality of the areas under the respective Receiver Operating Characteristic Curves is commonly tested. A non-parametric test based on the Mann-Whitney statistic is generally used. Weiand et al. (1989) present a parametric test based on normal distributional assumptions. We extend this test using the Box-Cox power family of transformations to non-normal situations. These three test procedures are compared in terms of significance level and power by means of a large simulation study. Overall we find that transforming to normality is to be preferred. An example of two pancreatic cancer serum biomarkers is used to illustrate the methodology.

Area Under Curve↗

PubMed2006

Inference for the dependent competing risks model with masked causes of failure.

The competing risks model is useful in settings in which individuals/units may die/fail for different reasons. The cause specific hazard rates are taken to be piecewise constant functions. A complication arises when some of the failures are masked within a group of possible causes. Traditionally, statistical inference is performed under the assumption that the failure causes act independently on each item. In this paper we propose an EM-based approach which allows for dependent competing risks and produces estimators for the sub-distribution functions. We also discuss identifiability of parameters if none of the masked items have their cause of failure clarified in a second stage analysis (e.g. autopsy). The procedures proposed are illustrated with two datasets.

Algorithms↗

PubMed2005

Estimation of the Youden Index and its associated cutoff point.

The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.

Algorithms↗

PubMed2004

Adjusting the generalized ROC curve for covariates.

Receiver operating characteristic (ROC) curves and in particular the area under the curve (AUC), are widely used to examine the effectiveness of diagnostic markers. Diagnostic markers and their corresponding ROC curves can be strongly influenced by covariate variables. When several diagnostic markers are available, they can be combined by a best linear combination such that the area under the ROC curve of the combination is maximized among all possible linear combinations. In this paper we discuss covariate effects on this linear combination assuming that the multiple markers, possibly transformed, follow a multivariate normal distribution. The ROC curve of this linear combination when markers are adjusted for covariates is estimated and approximate confidence intervals for the corresponding AUC are derived. An example of two biomarkers of coronary heart disease for which covariate information on age and gender is available is used to illustrate this methodology.

Adult↗

PubMed2003

ROC curve analysis for biomarkers based on pooled assessments.

Interleukin-6 is a biomarker of inflammation which has been suggested as having potential discriminatory ability for myocardial infarction. Because of its high assaying cost it is very expensive to evaluate this marker. In order to reduce this cost we propose pooling the specimens. In this paper we examine the efficiency of ROC curve analysis, specifically the estimation of the area under the ROC curve, when dealing with pooled data. We study the effect of pooling when there are only a fixed number of individuals available for testing and pooling is carried out to save on the number of assays. Alternatively we examine how many pooled assays of size g are necessary to provide essentially the same information as N individual assays. We measure loss of information by means of the change in root mean square error of the estimate of the area under the ROC curve and study the extent of this loss via a simulation study.

Biomarkers↗

PubMed2002

Estimation of the area under the ROC curve.

The area under the receiver operating characteristic curve is frequently used as a measure for the effectiveness of diagnostic markers. In this paper we discuss and compare estimation procedures for this area. These are based on (i) the Mann-Whitney statistic; (ii) kernel smoothing; (iii) normal assumptions; (iv) empirical transformations to normality. These are compared in terms of bias and root mean square error in a large variety of situations by means of an extensive simulation study. Overall we find that transforming to normality usually is to be preferred except for bimodal cases where kernel methods can be effective.

Area Under Curve↗

PubMed2002

Parametric modeling for survival with competing risks and masked failure causes.

We consider a life testing situation in which systems are subject to failure from independent competing risks. Following a failure, immediate (stage-1) procedures are used in an attempt to reach a definitive diagnosis. If these procedures fail to result in a diagnosis, this phenomenon is called masking. Stage-2 procedures, such as failure analysis or autopsy, provide definitive diagnosis for a sample of the masked cases. We show how stage-1 and stage-2 information can be combined to provide statistical inference about (a) survival functions of the individual risks, (b) the proportions of failures associated with individual risks and (c) probability, for a specified masked case, that each of the masked competing risks is responsible for the failure. Our development is based on parametric distributional assumptions and the special case for which the failure times for the competing risks have a Weibull distribution is discussed in detail.

Carcinoma, Non-Small-Cell Lung↗