Dataset Information

Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds.

ABSTRACT:

Background

Bivariate random effects meta-analysis of diagnostic tests is becoming a well established approach when studies present one two-by-two table or one pair of sensitivity and specificity. When studies present multiple thresholds for test positivity, usually meta-analysts reduce the data to a two-by-two table or take one threshold value at a time and apply the well developed meta-analytic approaches. However, this approach does not fully exploit the data.

Methods

In this paper we generalize the bivariate random effects approach to the situation where test results are presented with k thresholds for test positivity, resulting in a 2 by (k+1) table per study. The model can be fitted with standard likelihood procedures in statistical packages such as SAS (Proc NLMIXED). We follow a multivariate random effects approach; i.e., we assume that each study estimates a study specific ROC curve that can be viewed as randomly sampled from the population of all ROC curves of such studies. In contrast to the bivariate case, where nothing can be said about the shape of study specific ROC curves without additional untestable assumptions, the multivariate model can be used to describe study specific ROC curves. The models are easily extended with study level covariates.

Results

The method is illustrated using published meta-analysis data. The SAS NLMIXED syntax is given in the appendix.

Conclusion

We conclude that the multivariate random effects meta-analysis approach is an appropriate and convenient framework to meta-analyse studies with multiple threshold without losing any information by dichotomizing the test results.

SUBMITTER: Hamza TH

PROVIDER: S-EPMC2787531 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Publications

Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds.

Hamza Taye H TH Arends Lidia R LR van Houwelingen Hans C HC Stijnen Theo T

BMC medical research methodology 20091110

<h4>Background</h4>Bivariate random effects meta-analysis of diagnostic tests is becoming a well established approach when studies present one two-by-two table or one pair of sensitivity and specificity. When studies present multiple thresholds for test positivity, usually meta-analysts reduce the data to a two-by-two table or take one threshold value at a time and apply the well developed meta-analytic approaches. However, this approach does not fully exploit the data.<h4>Methods</h4>In this pa ...[more]

PMID: 19903336

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Project description:BackgroundMachine learning (ML) can be an effective tool to extract information from attribute-rich molecular datasets for the generation of molecular diagnostic tests. However, the way in which the resulting scores or classifications are produced from the input data may not be transparent. Algorithmic explainability or interpretability has become a focus of ML research. Shapley values, first introduced in game theory, can provide explanations of the result generated from a specific set of input data by a complex ML algorithm.MethodsFor a multivariate molecular diagnostic test in clinical use (the VeriStrat® test), we calculate and discuss the interpretation of exact Shapley values. We also employ some standard approximation techniques for Shapley value computation (local interpretable model-agnostic explanation (LIME) and Shapley Additive Explanations (SHAP) based methods) and compare the results with exact Shapley values.ResultsExact Shapley values calculated for data collected from a cohort of 256 patients showed that the relative importance of attributes for test classification varied by sample. While all eight features used in the VeriStrat® test contributed equally to classification for some samples, other samples showed more complex patterns of attribute importance for classification generation. Exact Shapley values and Shapley-based interaction metrics were able to provide interpretable classification explanations at the sample or patient level, while patient subgroups could be defined by comparing Shapley value profiles between patients. LIME and SHAP approximation approaches, even those seeking to include correlations between attributes, produced results that were quantitatively and, in some cases qualitatively, different from the exact Shapley values.ConclusionsShapley values can be used to determine the relative importance of input attributes to the result generated by a multivariate molecular diagnostic test for an individual sample or patient. Patient subgroups defined by Shapley value profiles may motivate translational research. However, correlations inherent in molecular data and the typically small ML training sets available for molecular diagnostic test development may cause some approximation methods to produce approximate Shapley values that differ both qualitatively and quantitatively from exact Shapley values. Hence, caution is advised when using approximate methods to evaluate Shapley explanations of the results of molecular diagnostic tests.

Project description:BackgroundNetwork meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models.MethodsWe extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that did not report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were fitted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS.ResultsAll models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates.ConclusionsMultivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making.

Dataset Information

Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds.

Background

Methods

Results

Conclusion

Publications

Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds.

Similar Datasets

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