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Predictive modeling for diagnostic tests with high specificity, but low sensitivity: a study of the glycerol test in patients with suspected Meniere's disease.

ABSTRACT: A high specificity does not ensure that the expected benefit of a diagnostic test outweighs its cost. Problems arise, in particular, when the investigation is expensive, the prevalence of a positive test result is relatively small for the candidate patients, and the sensitivity of the test is low so that the information provided by a negative result is virtually negligible. The consequence may be that a potentially useful test does not gain broader acceptance. Here we show how predictive modeling can help to identify patients for whom the ratio of expected benefit and cost reaches an acceptable level so that testing these patients is reasonable even though testing all patients might be considered wasteful. Our application example is based on a retrospective study of the glycerol test, which is used to corroborate a suspected diagnosis of Menière's disease. Using the pretest hearing thresholds at up to 10 frequencies, predictions were made by K-nearest neighbor classification or logistic regression. Both methods estimate, based on results from previous patients, the posterior probability that performing the considered test in a new patient will have a positive outcome. The quality of the prediction was evaluated using leave-one-out cross-validation, making various assumptions about the costs and benefits of testing. With reference to all 356 cases, the probability of a positive test result was almost 0.4. For subpopulations selected by K-nearest neighbor classification, which was clearly superior to logistic regression, this probability could be increased up to about 0.6. Thus, the odds of a positive test result were more than doubled.

SUBMITTER: Lutkenhoner B

PROVIDER: S-EPMC3832512 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Predictive modeling for diagnostic tests with high specificity, but low sensitivity: a study of the glycerol test in patients with suspected Menière's disease.

Lütkenhöner Bernd B Basel Türker T

PloS one 20131118 11

A high specificity does not ensure that the expected benefit of a diagnostic test outweighs its cost. Problems arise, in particular, when the investigation is expensive, the prevalence of a positive test result is relatively small for the candidate patients, and the sensitivity of the test is low so that the information provided by a negative result is virtually negligible. The consequence may be that a potentially useful test does not gain broader acceptance. Here we show how predictive modelin ...[more]

PMID: 24260193

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Project description:BackgroundRecent advances in magnetic resonance imaging make it possible to visualize the presumed pathophysiologic correlate of Menière's disease: endolymphatic hydrops. As traditional diagnostic tests can provide only indirect evidence, they are hardly competitive in this respect and need to be rethought. This is done here for the glycerol test.MethodsThe data of a previous retrospective analysis of the glycerol test in patients with suspected Menière's disease are reinterpreted using a simple model. The mean threshold reduction (MTR) in the frequency range from 125 to 1500 Hz (calculated from audiograms obtained immediately before and four hours after the glycerol intake) is used as the test statistic. The proposed model explains the frequency distribution of the observed MTR by the convolution of a Gaussian probability density function (representing measurement errors) with a template representing the frequency distribution of the true MTR. The latter is defined in terms of two adjustable parameters. After fitting the model to the data, the performance of the test is evaluated using receiver operating characteristic (ROC) analysis.ResultsThe cumulative frequency distribution of the observed MTR can be explained almost perfectly by the model. According to the ROC analysis performed, the capability of the currently used audiometric procedure to detect a glycerol-induced threshold reduction corresponds to a diagnostic test of rather high accuracy (area under the ROC curve greater than 0.9). Simulations show that methodological improvements could further enhance the performance.ConclusionsOwing to their ability to reveal functional aspects without an obvious morphological correlate, traditional test for Menière's disease could be decisive for defining the stage of the disease. A distinctive feature of the glycerol test is that it is capable of determining, with high accuracy, whether the pathophysiologic condition of the inner ear is partially reversible. Prospectively, this could help to estimate the chances of specific therapies.

Project description:BackgroundLassa fever virus has been enlisted as a priority pathogen of epidemic potential by the World Health organization Research and Development (WHO R & D) Blueprint. Diagnostics play a crucial role in epidemic preparedness. This systematic review was conducted to determine the sensitivity and specificity of Lassa fever diagnostic tests for humans.MethodsWe searched OVID Medline, OVID Embase, Scopus and Web of Science for laboratory based and field studies that reported the performance of diagnostic tests for Lassa fever in humans from 1 January 1990 to 25 January 2019. Two reviewers independently screened all the studies and included only studies that involved the evaluation of a Lassa fever diagnostic test and provided data on the sensitivity and specificity. The quality of the studies was assessed using the QUADAS-2 criteria. Data on the study location, study design, type of sample, index test, reference tests and diagnostic performance were extracted from the studies.ResultsOut of a total of 1947 records identified, 1245 non-duplicate citations were obtained. Twenty-six (26) full-text articles examined which identified 08 studies meeting pre-defined criteria. Only one study was a field evaluation study. The sensitivity and specificity of the point of care (RDT) against the Nikisins qPCR were 91.2%(95% CI:75.2-97.7) and 86%(95% CI: 71.4-94.2) at temperatures 18-30 °C, while the sensitivity and specificity of the single IgM ELISA assay against standard RT-PCR were 31.1%(95%CI: 25.6-37) and 95.7%(95%CI:92.8-97.7). The sensitivity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 88%(95%CI:77-95), 25.9%(95%CI:20.8-31.6), and 90.7%(95%CI:84.13-97.27) respectively. The specificity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 90%(95%CI:88-91), 100%(95%CI:98.2-100), and 96.3%(95%CI:92.2-100) respectively.ConclusionLassa fever has assays for antigenaemia, IgM, IgG and PCR detection. The RDT reportedly performed well but more data are needed from other countries and at temperatures above 30 °C. Most combined immunoassays perform better than the single IgM. Multiplex and pan-Lassa assays are needed. More well conducted field studies are needed.Trial registrationProspero registration number: CRD42018091585 .

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Dataset Information

Predictive modeling for diagnostic tests with high specificity, but low sensitivity: a study of the glycerol test in patients with suspected Meniere's disease.

Publications

Predictive modeling for diagnostic tests with high specificity, but low sensitivity: a study of the glycerol test in patients with suspected Menière's disease.

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