Dynamic Prediction using Time-Dependent Cox Survival Neural Network

The target of dynamic prediction is to provide individualized risk predictions over time which can be updated as new data become available. Motivated by establishing a dynamic prediction model for the progressive eye disease, age-related macular degeneration (AMD), we proposed a time-dependent Cox model-based survival neural network (tdCoxSNN) to predict its progression on a continuous time scale using longitudinal fundus images. tdCoxSNN extends the time-dependent Cox model by utilizing a neural network to model the non-linear effect of the time-dependent covariates on the survival outcome. Additionally, by incorporating the convolutional neural network (CNN), tdCoxSNN can take the longitudinal raw images as input. We evaluate and compare our proposed method with joint modeling and landmarking approaches through comprehensive simulations using two time-dependent accuracy metrics, the Brier Score and dynamic AUC. 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, in which multiple lab tests were longitudinally collected to predict the time-to-liver transplant. Our approach achieves satisfactory prediction performance in both simulation studies and the two real data analyses. tdCoxSNN was implemented in PyTorch, Tensorflow, and R-Tensorflow.

[1]  D. Zeng,et al.  Multivariate functional mixed model with MRI data: An application to Alzheimer's disease , 2023, Statistics in medicine.

[2]  S. Luo,et al.  Deep learning for the dynamic prediction of multivariate longitudinal and survival data , 2022, Statistics in medicine.

[3]  E. Chew,et al.  LONGL-Net: temporal correlation structure guided deep learning model to predict longitudinal age-related macular degeneration severity , 2022, PNAS nexus.

[4]  K. Suresh,et al.  Random survival forests for dynamic predictions of a time-to-event outcome using a longitudinal biomarker , 2021, BMC Medical Research Methodology.

[5]  Yifan Peng,et al.  Multi-task deep learning-based survival analysis on the prognosis of late AMD using the longitudinal data in AREDS , 2021, medRxiv.

[6]  Preston J. Putzel,et al.  Dynamic Survival Analysis for EHR Data with Personalized Parametric Distributions , 2021, MLHC.

[7]  Kevin S. Xu,et al.  Empirical Comparison of Continuous and Discrete-time Representations for Survival Prediction , 2021, SPACA.

[8]  Luo Xiao,et al.  Joint model for survival and multivariate sparse functional data with application to a study of Alzheimer's Disease , 2020, Biometrics.

[9]  Ruth H. Keogh,et al.  Dynamic survival prediction combining landmarking with a machine learning ensemble: Methodology and empirical comparison , 2020, Journal of the Royal Statistical Society: Series A (Statistics in Society).

[10]  Tao Sun,et al.  Genome‐wide association study‐based deep learning for survival prediction , 2020, Statistics in medicine.

[11]  Qingyu Chen,et al.  Predicting risk of late age-related macular degeneration using deep learning , 2020, npj Digital Medicine.

[12]  Jinsung Yoon,et al.  Dynamic Prediction in Clinical Survival Analysis Using Temporal Convolutional Networks , 2020, IEEE Journal of Biomedical and Health Informatics.

[13]  Changhee Lee,et al.  Dynamic-DeepHit: A Deep Learning Approach for Dynamic Survival Analysis With Competing Risks Based on Longitudinal Data , 2020, IEEE Transactions on Biomedical Engineering.

[14]  Natalia Gimelshein,et al.  PyTorch: An Imperative Style, High-Performance Deep Learning Library , 2019, NeurIPS.

[15]  Qi Yan,et al.  Deep-learning-based Prediction of Late Age-Related Macular Degeneration Progression , 2019, Nat. Mach. Intell..

[16]  Ida Scheel,et al.  Time-to-Event Prediction with Neural Networks and Cox Regression , 2019, J. Mach. Learn. Res..

[17]  Sheng Luo,et al.  Dynamic predictions in Bayesian functional joint models for longitudinal and time-to-event data: An application to Alzheimer’s disease , 2019, Statistical methods in medical research.

[18]  Glen P Martin,et al.  Dynamic models to predict health outcomes: current status and methodological challenges , 2018, Diagnostic and Prognostic Research.

[19]  Yifan Peng,et al.  DeepSeeNet: A deep learning model for automated classification of patient-based age-related macular degeneration severity from color fundus photographs , 2018, Ophthalmology.

[20]  Dimitris Rizopoulos,et al.  Joint models with multiple longitudinal outcomes and a time-to-event outcome: a corrected two-stage approach , 2018, Stat. Comput..

[21]  Changhee Lee,et al.  DeepHit: A Deep Learning Approach to Survival Analysis With Competing Risks , 2018, AAAI.

[22]  Uri Shaham,et al.  DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network , 2016, BMC Medical Research Methodology.

[23]  Cécile Proust-Lima,et al.  Individual dynamic predictions using landmarking and joint modelling: Validation of estimators and robustness assessment , 2017, Statistical methods in medical research.

[24]  Jeremy M G Taylor,et al.  Comparison of joint modeling and landmarking for dynamic prediction under an illness‐death model , 2017, Biometrical journal. Biometrische Zeitschrift.

[25]  R. Kolamunnage-Dona,et al.  Time-dependent ROC curve analysis in medical research: current methods and applications , 2017, BMC Medical Research Methodology.

[26]  Hein Putter,et al.  Understanding Landmarking and Its Relation with Time-Dependent Cox Regression , 2016, Statistics in Biosciences.

[27]  Yuan Yu,et al.  TensorFlow: A system for large-scale machine learning , 2016, OSDI.

[28]  Franck Dernoncourt,et al.  Sequential Short-Text Classification with Recurrent and Convolutional Neural Networks , 2016, NAACL.

[29]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[30]  Sergey Ioffe,et al.  Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift , 2015, ICML.

[31]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[32]  Laine Thomas,et al.  Tutorial: Survival Estimation for Cox Regression Models with Time-Varying Coe?cients Using SAS and R , 2014 .

[33]  Dimitris Rizopoulos,et al.  The R Package JMbayes for Fitting Joint Models for Longitudinal and Time-to-Event Data using MCMC , 2014, 1404.7625.

[34]  Jean-François Dartigues,et al.  Estimating and comparing time‐dependent areas under receiver operating characteristic curves for censored event times with competing risks , 2013, Statistics in medicine.

[35]  Geert Molenberghs,et al.  Dynamic predictions with time‐dependent covariates in survival analysis using joint modeling and landmarking , 2013, Biometrical journal. Biometrische Zeitschrift.

[36]  Hemant Ishwaran,et al.  Evaluating Random Forests for Survival Analysis using Prediction Error Curves. , 2012, Journal of statistical software.

[37]  Dimitris Rizopoulos,et al.  Dynamic Predictions and Prospective Accuracy in Joint Models for Longitudinal and Time‐to‐Event Data , 2011, Biometrics.

[38]  Simon G Thompson,et al.  Joint modelling of longitudinal and time-to-event data with application to predicting abdominal aortic aneurysm growth and rupture , 2011, Biometrical journal. Biometrische Zeitschrift.

[39]  D. Lin,et al.  On the Breslow estimator , 2007, Lifetime data analysis.

[40]  H. V. Houwelingen Dynamic Prediction by Landmarking in Event History Analysis , 2007 .

[41]  M. Schumacher,et al.  Consistent Estimation of the Expected Brier Score in General Survival Models with Right‐Censored Event Times , 2006, Biometrical journal. Biometrische Zeitschrift.

[42]  George A. Williams,et al.  The Age-Related Eye Disease Study (AREDS): design implications. AREDS report no. 1. , 1999, Controlled clinical trials.

[43]  B. Efron The Efficiency of Cox's Likelihood Function for Censored Data , 1977 .

[44]  A. Dubrawski,et al.  Deep Parametric Time-to-Event Regression with Time-Varying Covariates , 2021, SPACA.

[45]  Ing,et al.  Deep learning for the partially linear Cox model , 2022, The Annals of Statistics.

[46]  Katharina Burger,et al.  Counting Processes And Survival Analysis , 2016 .

[47]  Nitish Srivastava,et al.  Dropout: a simple way to prevent neural networks from overfitting , 2014, J. Mach. Learn. Res..

[48]  J. Kalbfleisch The Efficiency of Cox's Likelihood Function for Censored Data , 2008 .

[49]  Yann LeCun,et al.  The mnist database of handwritten digits , 2005 .

[50]  M. Davidian,et al.  Joint modelling of longitudinal and time-to-event data: an overview , 2004 .

[51]  L. Fisher,et al.  Time-dependent covariates in the Cox proportional-hazards regression model. , 1999, Annual review of public health.