Dataset Information

Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease.

ABSTRACT: Many medical diagnostic studies involve three ordinal diagnostic populations in which the diagnostic accuracy can be summarized by the volume or partial volume under the receiver operating characteristic surface for a diagnostic marker. When the diagnostic populations are clustered, e.g. by families, we propose to model the diagnostic marker by a general linear mixed model that takes into account of the correlation on the diagnostic marker from members of the same clusters. This model then facilitates the maximum likelihood estimation and statistical inferences of the diagnostic accuracy for the diagnostic marker. This approach naturally allows the incorporation of covariates as well as missing data when some clusters do not have subjects on all diagnostic groups in the estimation of, and the subsequent inferences on the diagnostic accuracy. We further study the performance of the proposed methods in a large simulation study with clustered data. Finally, we apply the proposed methodology to the data of several biomarkers collected by the Dominantly Inherited Alzheimer Network, an international family-clustered registry to study autosomal dominant Alzheimer disease which is a rare form of Alzheimer disease caused by mutations in any of the three genes including the amyloid precursor protein, presenilin 1 and presenilin 2. We estimate the accuracy of several cerebrospinal fluid and neuroimaging biomarkers in differentiating three diagnostic and genetic populations: normal non-mutation carriers, asymptomatic mutation carriers, and symptomatic mutation carriers.

SUBMITTER: Xiong C

PROVIDER: S-EPMC5841923 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease.

Xiong Chengjie C Luo Jingqin J Chen Ling L Gao Feng F Liu Jingxia J Wang Guoqiao G Bateman Randall R Morris John C JC

Statistical methods in medical research 20171128 3

Many medical diagnostic studies involve three ordinal diagnostic populations in which the diagnostic accuracy can be summarized by the volume or partial volume under the receiver operating characteristic surface for a diagnostic marker. When the diagnostic populations are clustered, e.g. by families, we propose to model the diagnostic marker by a general linear mixed model that takes into account of the correlation on the diagnostic marker from members of the same clusters. This model then facil ...[more]

PMID: 29182052

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Project description:In disease diagnosis, individuals are usually assumed to be one of the two basic types, healthy or diseased, as typically based on an established gold standard. Candidate markers for diagnosing a disease often are much cheaper and less invasive than the gold standard but must be evaluated against the gold standard for their sensitivity and specificity to accurately diagnose the disease. When candidate diagnostic markers are fully measured, receiver operating characteristic curves have been the standard approaches for assessing diagnostic accuracy. However, full measurements of diagnostic markers may not be available above or below certain limits due to various practical and technical limitations. For example, in the diagnosis of Alzheimer disease using cerebrospinal fluid biomarkers, the Roche Elecsys® immunoassays have a measuring range for multiple cerebrospinal fluid molecular concentrations. Many cognitive tests used in diagnosing dementia due to Alzheimer disease are also subject to detection limits, often referred to as the floor and ceiling effects in the neuropsychological literature. We propose a new statistical methodology for estimating the diagnostic accuracy when a diagnostic marker is subject to detection limits by dividing the entire study sample into two sub-samples by a threshold of the diagnostic marker. We then propose a family of estimators to the area under the receiver operating characteristic curve by combining a conditional nonparametric estimator and another conditional semi-parametric estimator derived from Cox's proportional hazards model. We derive the variance to the proposed estimators, and further, assess the performance of the proposed estimators as a function of possible thresholds through an extensive simulation study, and recommend the optimum thresholds. Finally, we apply the proposed methodology to assess the ability of several cerebrospinal fluid biomarkers and cognitive tests in diagnosing early stage Alzheimer disease dementia.

Dataset Information

Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease.

Publications

Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease.

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