Avaliação de testes diagnósticos na ausência de padrão ouro considerando relaxamento da suposição de independência condicional, covariáveis e estratificação da população: uma abordagem Bayesiana
Pereira, Gilberto de Araujo
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The application of a gold standard reference test in all or part of the sample under investigation is often not feasible for the majority of diseases affecting humans, either by a lack of consensus on which testing may be considered a gold standard, the high level of invasion of the gold standard technique, the high cost of financially large-scale application, or by ethical questions, so to know the performance of existing tests is essential for the process of diagnosis of these diseases. In statistical modeling aimed to obtain robust estimates of the prevalence of the disease (x ) and the performance parameters of diagnostic tests (sensitivity (Se) and specificity (Sp)), various strategies have been considered such as the stratification of the population, the relaxation of the assumption of conditional independence, the inclusion of covariates, the verification type (partial or total) and the techniques to replace the gold standard. In this thesis we propose a new structure of stratification of the population considering both the prevalence rates and the parameters of test performance among the different strata (EHW). A Bayesian latent class modeling to estimate these parameters was developed for the general case of K diagnostic tests under investigation, relaxation of the assumption of conditional independence according to the formulations of the fixed effect (FECD) and random (RECD) with dependent order (h _ k) and M covariates. The application of models to two data sets about the performance evaluation of diagnostic tests used in screening for Chagas disease in blood donors showed results consistent with the sensitivity studies. Overall, we observed for the structure of stratification proposal (EHW) superior performance and estimates closer to the nominal values when compared to the structure of stratification when only the prevalence rates are different between the strata (HW), even when we consider data set with rates of Se, Sp and x close among the strata. Generally, the structure of latent class, when we have low or high prevalence of the disease, estimates of sensitivity and specificity rates have higher standard errors. However, in these cases, when there is high concordance of positive or negative results of the tests, the error pattern of these estimates are reduced. Regardless of the structure of stratification (EHW, HW), sample size and the different scenarios used to model the prior information, the model of conditional dependency from the FECD and RECD had, from the information criteria (AIC, BIC and DIC), superior performance to the structure of conditional independence (CI) and to FECD with improved performance and estimates closer to the nominal values. Besides the connection logit, derived from the logistic distribution with symmetrical shape, find in the link GEV, derived from the generalized extreme value distribution which accommodates symmetric and asymmetric shapes, a interesting alternative to construct the conditional dependence structure from the RECD. As an alternative to the problem of identifiability, present in this type of model, the criteria adopted to elicit the informative priors by combining descriptive analysis of data, adjustment models from simpler structures, were able to produce estimates with low standard error and very close to the nominal values.