An Iterative, Frequentist Approach for Latent Class Analysis to Evaluate Conditionally Dependent Diagnostic Tests

Latent class analysis is a well-established method in human and veterinary medicine for evaluating the accuracy of diagnostic tests without a gold standard. An important assumption of this procedure is the conditional independence of the tests. If tests with the same biological principle are used, this assumption is no longer met. Therefore, the model has to be adapted so that the dependencies between the tests can be considered. Our approach extends the traditional latent class model with a term for the conditional dependency of the tests. This extension increases the number of parameters to be estimated and leads to negative degrees of freedom of the model, meaning that not enough information is contained in the existing data to obtain a unique estimate. As a result, there is no clear solution. Hence, an iterative algorithm was developed to keep the number of parameters to be estimated small. Given adequate starting values, our approach first estimates the conditional dependencies and then regards the resulting values as fixed to recalculate the test accuracies and the prevalence with the same method used for independent tests. Subsequently, the new values of the test accuracy and prevalence are used to recalculate the terms for the conditional dependencies. These two steps are repeated until the model converges. We simulated five application scenarios based on diagnostic tests used in veterinary medicine. The results suggest that our method and the Bayesian approach produce similar precise results. However, while the presented approach is able to calculate more accurate results than the Bayesian approach if the test accuracies are initially misjudged, the estimates of the Bayesian method are more precise when incorrect dependencies are assumed. This finding shows that our approach is a useful addition to the existing Bayesian methods, while it has the advantage of allowing simpler and more objective estimations.