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Patrick Bossuyt

Publications and source records attributed to Patrick Bossuyt.

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Improving interpretation of latent class models for diagnostic tests by recognizing their measurands via directed acyclic graphs (DAGs)

Summary: In the absence of a perfect diagnostic test for a target condition, multiple imperfect tests may be used to arrive at a clinical diagnosis. Latent class analysis can be used to model such data with the objective of estimating test accuracy and target condition prevalence. Such models typically assume two latent classes - target condition positive and target condition negative. However, as we will illustrate in this manuscript, this would be an oversimplification if the different tests do not share the target condition as their measurand. We show how a Directed Acyclic Graph (DAG) can be used to illustrate the relationships between the relevant variables - the observed imperfect test results, their latent measurands, the latent target condition of interest and observed covariates - revealing any conditional dependence relations. The DAG helps determine the number of latent classes, underlying the observed data, and their labels. We show how the likelihood function changes due to incorporating the measurand of each test. We study the impact on identifiability of the model. Using simulation studies we show how ignoring the measurand of an imperfect test, when it is distinct from the target condition, can lead to biased estimates of test accuracy and prevalence. We illustrate the value of the proposed approach by re-analyzing two datasets used in previously published latent class analyses of tests for pediatric tuberculosis and leptospirosis.

stat.ME

Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis

Prognosis on the occurrence of relapses in individuals with Relapsing-Remitting Multiple Sclerosis (RRMS), the most common subtype of Multiple Sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients in future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings. We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real world data. We followed seven steps to develop and validate the prognostic model. Finally, we evaluated the potential clinical benefit of the developed prognostic model using decision curve analysis. We selected eight baseline prognostic factors: age, sex, prior MS treatment, months since last relapse, disease duration, number of prior relapses, expanded disability status scale (EDSS), and gadolinium enhanced lesions. We also developed a web application where the personalized probabilities to relapse within two years are calculated automatically. The optimism-corrected c-statistic is 0.65 and the optimism-corrected calibration slope was 0.92. The model appears to be clinically useful between the range 15% and 30% of the threshold probability to relapse. The prognostic model we developed offers several advantages in comparison to previously published prognostic models on RRMS. Importantly, we assessed the potential clinical benefit to better quantify the clinical impact of the model. Our web application, once externally validated in the future, could be used by patients and doctors to calculate the individualized probability to relapse within two years and to inform the management of their disease.

stat.AP