Lang Zeng

Lang Zeng, Jipeng Zhang, Wei Chen et al.

The aim of dynamic prediction is to provide individualized risk predictions over time, which are updated as new data become available. In pursuit of constructing a dynamic prediction model for a progressive eye disorder, age-related macular degeneration (AMD), we propose a time-dependent Cox survival neural network (tdCoxSNN) to predict its progression using longitudinal fundus images. tdCoxSNN builds upon the time-dependent Cox model by utilizing a neural network to capture the non-linear effect of time-dependent covariates on the survival outcome. Moreover, by concurrently integrating a convolutional neural network (CNN) with the survival network, tdCoxSNN can directly take longitudinal images as input. We evaluate and compare our proposed method with joint modeling and landmarking approaches through extensive simulations. We applied the proposed approach to two real datasets. One is a large AMD study, the Age-Related Eye Disease Study (AREDS), in which more than 50,000 fundus images were captured over a period of 12 years for more than 4,000 participants. Another is a public dataset of the primary biliary cirrhosis (PBC) disease, where multiple lab tests were longitudinally collected to predict the time-to-liver transplant. Our approach demonstrates commendable predictive performance in both simulation studies and the analysis of the two real datasets.

Lang Zeng, Weijing Tang, Zhao Ren et al.

The stochastic gradient descent (SGD) algorithm has been widely used to optimize deep Cox neural network (Cox-NN) by updating model parameters using mini-batches of data. We show that SGD aims to optimize the average of mini-batch partial-likelihood, which is different from the standard partial-likelihood. This distinction requires developing new statistical properties for the global optimizer, namely, the mini-batch maximum partial-likelihood estimator (mb-MPLE). We establish that mb-MPLE for Cox-NN is consistent and achieves the optimal minimax convergence rate up to a polylogarithmic factor. For Cox regression with linear covariate effects, we further show that mb-MPLE is $\sqrt{n}$-consistent and asymptotically normal with asymptotic variance approaching the information lower bound as batch size increases, which is confirmed by simulation studies. Additionally, we offer practical guidance on using SGD, supported by theoretical analysis and numerical evidence. For Cox-NN, we demonstrate that the ratio of the learning rate to the batch size is critical in SGD dynamics, offering insight into hyperparameter tuning. For Cox regression, we characterize the iterative convergence of SGD, ensuring that the global optimizer, mb-MPLE, can be approximated with sufficiently many iterations. Finally, we demonstrate the effectiveness of mb-MPLE in a large-scale real-world application where the standard MPLE is intractable.

Haoling Wang, Lang Zeng, Tao Sun et al.

Predicting time-to-event outcomes when event times are interval censored is challenging because the exact event time is unobserved. Many existing survival analysis approaches for interval-censored data rely on strong model assumptions or cannot handle high-dimensional predictors. We develop ICODEN, an ordinary differential equation-based neural network for interval-censored data that models the hazard function through deep neural networks and obtains the cumulative hazard by solving an ordinary differential equation. ICODEN does not require the proportional hazards assumption or a prespecified parametric form for the hazard function, thereby permitting flexible survival modeling. Across simulation settings with proportional or non-proportional hazards and both linear and nonlinear covariate effects, ICODEN consistently achieves satisfactory predictive accuracy and remains stable as the number of predictors increases. Applications to data from multiple phases of the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to two Age-Related Eye Disease Studies (AREDS and AREDS2) for age-related macular degeneration (AMD) demonstrate ICODEN's robust prediction performance. In both applications, predicting time-to-AD or time-to-late AMD, ICODEN effectively uses hundreds to more than 1,000 SNPs and supports data-driven subgroup identification with differential progression risk profiles. These results establish ICODEN as a practical assumption-lean tool for prediction with interval-censored survival data in high-dimensional biomedical settings.