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Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference.

ABSTRACT: Absence of a perfect reference test is an acknowledged source of bias in diagnostic studies. In the case of tuberculous pleuritis, standard reference tests such as smear microscopy, culture and biopsy have poor sensitivity. Yet meta-analyses of new tests for this disease have always assumed the reference standard is perfect, leading to biased estimates of the new test's accuracy. We describe a method for joint meta-analysis of sensitivity and specificity of the diagnostic test under evaluation, while considering the imperfect nature of the reference standard. We use a Bayesian hierarchical model that takes into account within- and between-study variability. We show how to obtain pooled estimates of sensitivity and specificity, and how to plot a hierarchical summary receiver operating characteristic curve. We describe extensions of the model to situations where multiple reference tests are used, and where index and reference tests are conditionally dependent. The performance of the model is evaluated using simulations and illustrated using data from a meta-analysis of nucleic acid amplification tests (NAATs) for tuberculous pleuritis. The estimate of NAAT specificity was higher and the sensitivity lower compared to a model that assumed that the reference test was perfect.

SUBMITTER: Dendukuri N

PROVIDER: S-EPMC3728030 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference.

Dendukuri Nandini N Schiller Ian I Joseph Lawrence L Pai Madhukar M

Biometrics 20120508 4

Absence of a perfect reference test is an acknowledged source of bias in diagnostic studies. In the case of tuberculous pleuritis, standard reference tests such as smear microscopy, culture and biopsy have poor sensitivity. Yet meta-analyses of new tests for this disease have always assumed the reference standard is perfect, leading to biased estimates of the new test's accuracy. We describe a method for joint meta-analysis of sensitivity and specificity of the diagnostic test under evaluation, ...[more]

PMID: 22568612

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Project description:BackgroundMany problems in bioinformatics involve classification based on features such as sequence, structure or morphology. Given multiple classifiers, two crucial questions arise: how does their performance compare, and how can they best be combined to produce a better classifier? A classifier can be evaluated in terms of sensitivity and specificity using benchmark, or gold standard, data, that is, data for which the true classification is known. However, a gold standard is not always available. Here we demonstrate that a Bayesian model for comparing medical diagnostics without a gold standard can be successfully applied in the bioinformatics domain, to genomic scale data sets. We present a new implementation, which unlike previous implementations is applicable to any number of classifiers. We apply this model, for the first time, to the problem of finding the globally optimal logical combination of classifiers.ResultsWe compared three classifiers of protein subcellular localisation, and evaluated our estimates of sensitivity and specificity against estimates obtained using a gold standard. The method overestimated sensitivity and specificity with only a small discrepancy, and correctly ranked the classifiers. Diagnostic tests for swine flu were then compared on a small data set. Lastly, classifiers for a genome-wide association study of macular degeneration with 541094 SNPs were analysed. In all cases, run times were feasible, and results precise. The optimal logical combination of classifiers was also determined for all three data sets. Code and data are available from http://bioinformatics.monash.edu.au/downloads/.ConclusionsThe examples demonstrate the methods are suitable for both small and large data sets, applicable to the wide range of bioinformatics classification problems, and robust to dependence between classifiers. In all three test cases, the globally optimal logical combination of the classifiers was found to be their union, according to three out of four ranking criteria. We propose as a general rule of thumb that the union of classifiers will be close to optimal.

Project description:ObjectiveThe Bayesian model plays an important role in diagnostic test evaluation in the absence of the gold standard, which used the external prior distribution of a parameter combined with sample data to yield the posterior distribution of the test characteristics. However, the correlation between diagnostic tests has always been a problem that cannot be ignored in the Bayesian model evaluation. This study will discuss how different Bayesian model, correlation scenarios, and prior distribution affect the outcome.MethodsThe data analyzed in this study was gathered during studies of patients presenting to the Nanjing Chest Hospital with suspected tuberculosis. The diagnostic character of T-SPOT.Tb and KD38 tuberculosis antibody test were evaluated in different Bayesian model, and discharge diagnosis as a gold standard was used to verify the model results in the end.ResultThe comparison of four models under the conditional independence situation found that Bayesian probabilistic constraint model was consistent with the Conditional Covariance Bayesian model. The results were mainly affected by prior information. The sensitivity and specificity of the two tests in Conditional Covariance Bayesian model in prior constraint situation were considerably higher than the Bayesian probabilistic constraint model in prior constraint situation. The results of the four models under the conditional dependence situation were similar to the conditional independence situation; pD was also negative with no prior constraint situation in both model Bayesian probabilistic constraint model and Conditional Covariance Bayesian model. The Deviance Information Criterion of Bayesian probabilistic constraint model was close to model Conditional Covariance Bayesian model, but pD of Conditional Covariance Bayesian model in Prior constraint situation (pD=2.40) was higher than the Bayesian probabilistic constraint model in Prior constraint situation (pD=1.66).ConclusionThe result of Conditional Covariance Bayesian model in prior constraint with conditional independence situation was closest to the result of gold standard evaluation in our data. Both of the two Bayesian methods are the feasible way for the evaluation of diagnostic test in the absence of the gold standard diagnostic. Prior source, priority number, and conditional dependencies should be considered in the method selection, the accuracy of posterior estimation mainly depending on the prior distribution.

Project description:BackgroundSpatial modeling is increasingly utilized to elucidate relationships between demographic, environmental, and socioeconomic factors, and infectious disease prevalence data. However, there is a paucity of studies focusing on spatio-temporal modeling that take into account the uncertainty of diagnostic techniques.Methodology/principal findingsWe obtained Schistosoma japonicum prevalence data, based on a standardized indirect hemagglutination assay (IHA), from annual reports from 114 schistosome-endemic villages in Dangtu County, southeastern part of the People's Republic of China, for the period 1995 to 2004. Environmental data were extracted from satellite images. Socioeconomic data were available from village registries. We used Bayesian spatio-temporal models, accounting for the sensitivity and specificity of the IHA test via an equation derived from the law of total probability, to relate the observed with the 'true' prevalence. The risk of S. japonicum was positively associated with the mean land surface temperature, and negatively correlated with the mean normalized difference vegetation index and distance to the nearest water body. There was no significant association between S. japonicum and socioeconomic status of the villages surveyed. The spatial correlation structures of the observed S. japonicum seroprevalence and the estimated infection prevalence differed from one year to another. Variance estimates based on a model adjusted for the diagnostic error were larger than unadjusted models. The generated prediction map for 2005 showed that most of the former and current infections occur in close proximity to the Yangtze River.Conclusion/significanceBayesian spatial-temporal modeling incorporating diagnostic uncertainty is a suitable approach for risk mapping S. japonicum prevalence data. The Yangtze River and its tributaries govern schistosomiasis transmission in Dangtu County, but spatial correlation needs to be taken into consideration when making risk prediction at small scales.

Project description:ObjectiveTo systematically review methods developed and employed to evaluate the diagnostic accuracy of medical test when there is a missing or no gold standard.Study design and settingsArticles that proposed or applied any methods to evaluate the diagnostic accuracy of medical test(s) in the absence of gold standard were reviewed. The protocol for this review was registered in PROSPERO (CRD42018089349).ResultsIdentified methods were classified into four main groups: methods employed when there is a missing gold standard; correction methods (which make adjustment for an imperfect reference standard with known diagnostic accuracy measures); methods employed to evaluate a medical test using multiple imperfect reference standards; and other methods, like agreement studies, and a mixed group of alternative study designs. Fifty-one statistical methods were identified from the review that were developed to evaluate medical test(s) when the true disease status of some participants is unverified with the gold standard. Seven correction methods were identified and four methods were identified to evaluate medical test(s) using multiple imperfect reference standards. Flow-diagrams were developed to guide the selection of appropriate methods.ConclusionVarious methods have been proposed to evaluate medical test(s) in the absence of a gold standard for some or all participants in a diagnostic accuracy study. These methods depend on the availability of the gold standard, its' application to the participants in the study and the availability of alternative reference standard(s). The clinical application of some of these methods, especially methods developed when there is missing gold standard is however limited. This may be due to the complexity of these methods and/or a disconnection between the fields of expertise of those who develop (e.g. mathematicians) and those who employ the methods (e.g. clinical researchers). This review aims to help close this gap with our classification and guidance tools.

Dataset Information

Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference.

Publications

Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference.

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