Evaluating diagnostic tests in veterinary medicine

Abstract

Diagnostic tests are of vital importance in a number of veterinary fields and are essential for decision-making by veterinary practioners, researchers and the veterinary authorities. The development and evaluation of laboratory diagnostic tests as well as the interpretation of test results engage a number of different veterinary disciplines including virologists, parasitologists, bacteriologists, laboratory experts, clinicians as well as epidemiologists and biostatisticians. This thesis was devised shortly after the section of epidemiology came into existence at the Vetsuisse Faculty end of 2009. The aim is to interrelate veterinary epidemiology - being closely linked to virology, parasitology, bacteriology and clinical medicine - with biostatistics. Thus allowing innovative concepts and recent software developments to provide solutions and answers in our veterinary field. After a brief introduction into diagnostic tests, the thesis is structured into three main parts. First, from a laboratory perspective, aspects of analytical sensitivity and specificity are illustrated by three peer-reviewed papers presenting practical applications of veterinary diagnostic tests for feline calicivirus and porcine parvovirus. Second, in the context of assessing agreement and method comparison studies, categorical test results are compared by Cohen’s k and continuous measurements by linear mixed effects models extending the classical use of Bland-Altman plots with limits of agreement. The former is illustrated in a publication on the diagnostic test Interferon-Gamma to classify bovines being infected with Mycobacterium bovis when analysing samples from the same animals in five different laboratories and from different anatomical locations. Two peer-reviewed papers aim to assess the agreement of serumspecific lipase, as a diagnostic test for feline pancreatitis with a commercial test kit and ultrasonographic findings. In the context of comparing continuous measurements, i.e. cardiac output and blood pressure measured directly and indirectly, two peer-reviewed paper illustrate the application of linear mixed effects models to simultaneously assess bias, precision and covariate information. Typical pitfalls arising in method comparison studies are summarised in a review paper. Building upon the previous parts, the third part adds to the existing knowledge by presenting novel and innovative approaches when assessing the performance of diagnostic tests in the absence of a perfect gold standard. So-called no gold standard models (NGS) are applied to assess the diagnostic test accuracies in the context of zoonotic diseases such as bovine tuberculosis, porcine toxoplasmosis as well as canine and vulpine echinococcosis. Additionally, these models are applied to assess diagnostic test accuracies to diagnose Brachyspira hyodysenteriae, an economically important disease in pigs. Furthermore, they are also utilised to assess diagnostic accuracies of diagnostic tools for subclinical mastitis in dairy cattle. In this part, Bayesian approaches are presented, together with technical aspects including conditional dependencies, Markov Chain Monte Carlo simulations and aspects of model selection. The innovative aspects and main novelty of the work presented in this thesis pertain to the incorporation of covariate information and random effects. Whereas covariate information in the form of risk factors has been included in statistical analyses since decades, considering random effects to account for clustering of animals at herd level just became possible with increased computational power. Nowadays dealing appropriately with the hierarchical structure of animal data is considered as good statistical practice and warranted in epidemiological studies to avoid biased results. However, diagnostic test studies including covariate information and random effects are scarce. The aim of this thesis is to fill this gap by showcasing a number of Bayesian latent class analyses for various infectious diseases in animals.