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Extensive literature has been proposed for the analysis of correlated survival data. Subjects within a cluster share some common characteristics, e.g., genetic and environmental factors, so their time-to-event outcomes are correlated. The frailty model under proportional hazards assumption has been widely applied for the analysis of clustered survival outcomes. However, the prediction performance of this method can be less satisfactory when the risk factors have complicated effects, e.g., nonlinear and interactive. To deal with these issues, we propose a neural network frailty Cox model that replaces the linear risk function with the output of a feed-forward neural network. The estimation is based on quasi-likelihood using Laplace approximation. A simulation study suggests that the proposed method has the best performance compared with existing methods. The method is applied to the clustered time-to-failure prediction within the kidney transplantation facility using the national kidney transplant registry data from the U.S. Organ Procurement and Transplantation Network. All computer programs are available at https://github.com/rivenzhou/deep_learning_clustered.more » « less
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Holste, Gregory; Lin, Mingquan; Zhou, Ruiwen; Wang, Fei; Liu, Lei; Yan, Qi; Van_Tassel, Sarah H; Kovacs, Kyle; Chew, Emily Y; Lu, Zhiyong; et al (, npj Digital Medicine)Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classi cation approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA signi cantly outperformed a single-image baseline in 19/20 head-to- head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most in uential, prior imaging still provides additional prognostic value.more » « less
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