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• W4315705557 abstract "Abstract Background The natural history of many chronic diseases is characterized by periods of increased disease activity, commonly referred to as flare-ups or exacerbations. Accurate characterization of the burden of these exacerbations is an important research objective. Methods The purpose of this work was to develop a statistical framework for nuanced characterization of the three main features of exacerbations: their rate, duration, and severity, with interrelationships among these features being a particular focus. We jointly specified a zero-inflated accelerated failure time regression model for the rate, an accelerated failure time regression model for the duration, and a logistic regression model for the severity of exacerbations. Random effects were incorporated into each component to capture heterogeneity beyond the variability attributable to observed characteristics, and to describe the interrelationships among these components. Results We used pooled data from two clinical trials in asthma as an exemplary application to illustrate the utility of the joint modeling approach. The model fit clearly indicated the presence of heterogeneity in all three components. A novel finding was that the new therapy reduced not just the rate but also the duration of exacerbations, but did not have a significant impact on their severity. After controlling for covariates, exacerbations among more frequent exacerbators tended to be shorter and less likely to be severe. Conclusions We conclude that a joint modeling framework, programmable in available software, can provide novel insights about how the rate, duration, and severity of episodic events interrelate, and enables consistent inference on the effect of treatments on different disease outcomes. Trial registration Ethics approval was obtained from the University of British Columbia Human Ethics Board (H17-00938)." @default.
• W4315705557 created "2023-01-12" @default.
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• W4315705557 date "2023-01-12" @default.
• W4315705557 modified "2023-10-14" @default.
• W4315705557 title "A parametric model to jointly characterize rate, duration, and severity of exacerbations in episodic diseases" @default.
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• W4315705557 doi "https://doi.org/10.1186/s12911-022-02080-5" @default.
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