Neural Network for Correlated Survival Outcomes Using Frailty Model
Pub. online: 26 March 2025
Type: Statistical Data Science
Open Access
Received
5 September 2024
5 September 2024
Accepted
1 March 2025
1 March 2025
Published
26 March 2025
26 March 2025
Abstract
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.
References
Aalen OO (1989). A linear regression model for the analysis of life times. Statistics in Medicine, 8(8): 907–925. https://doi.org/10.1002/sim.4780080803
Balan TA, Putter H (2020). A tutorial on frailty models. Statistical Methods in Medical Research, 29(11): 3424–3454. https://doi.org/10.1177/0962280220921889
Ching T, Zhu X, Garmire LX (2018). Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data. PLoS Computational Biology, 14(4): e1006076. https://doi.org/10.1371/journal.pcbi.1006076
Faraggi D, Simon R (1995). A neural network model for survival data. Statistics in Medicine, 14(1): 73–82. https://doi.org/10.1002/sim.4780140108
Fine JP, Ying Z, Wei L (1998). On the linear transformation model for censored data. Biometrika, 85(4): 980–986. https://doi.org/10.1093/biomet/85.4.980
Gerds TA, Schumacher M (2006). Consistent estimation of the expected Brier score in general survival models with right-censored event times. Biometrical Journal, 48(6): 1029–1040. https://doi.org/10.1002/bimj.200610301
Glidden DV, Vittinghoff E (2004). Modelling clustered survival data from multicentre clinical trials. Statistics in Medicine, 23(3): 369–388. https://doi.org/10.1002/sim.1599
Hao J, Kim Y, Mallavarapu T, Oh JH, Kang M (2018). Cox-pasnet: Pathway-based sparse deep neural network for survival analysis. In: 2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) (H. Zheng, X. Hu, Z. Callejas, H. Schmidt, D. Griol, J. Baumbach, J. Dickerson, and L. Zhang, editors), 381–386. IEEE.
Harrell Jr FE, Lee KL, Califf RM, Pryor DB, Rosati RA (1984). Regression modelling strategies for improved prognostic prediction. Statistics in Medicine, 3(2): 143–152. https://doi.org/10.1002/sim.4780030207
He K, Kalbfleisch JD, Li Y, Li Y (2013). Evaluating hospital readmission rates in dialysis facilities; adjusting for hospital effects. Lifetime Data Analysis, 19: 490–512. https://doi.org/10.1007/s10985-013-9264-6
Hens N, Wienke A, Aerts M, Molenberghs G (2009). The correlated and shared gamma frailty model for bivariate current status data: An illustration for cross-sectional serological data. Statistics in Medicine, 28(22): 2785–2800. https://doi.org/10.1002/sim.3660
Katzman JL, Shaham U, Cloninger A, Bates J, Jiang T, Kluger Y (2018). Deepsurv: Personalized treatment recommender system using a Cox proportional hazards deep neural network. BMC Medical Research Methodology, 18(1): 1–12. https://doi.org/10.1186/s12874-017-0458-6
Lee H, Ha I, Lee Y (2023). Deep neural networks for semiparametric frailty models via h-likelihood. arXiv preprint: https://arxiv.org/2307.06581/.
Lin J, Luo S (2022). Deep learning for the dynamic prediction of multivariate longitudinal and survival data. Statistics in Medicine, 41(15): 2894–2907. https://doi.org/10.1002/sim.9392
Lin X, Taylor JM, Ye W (2008). A penalized likelihood approach to joint modeling of longitudinal measurements and time-to-event data. Statistics and its Interface, 1(1): 33–45. https://doi.org/10.4310/SII.2008.v1.n1.a4
Mandel F, Ghosh RP, Barnett I (2023). Neural networks for clustered and longitudinal data using mixed effects models. Biometrics, 79(2): 711–721. https://doi.org/10.1111/biom.13615
Martinsson E (2017). Wtte-rnn: Weibull time to event recurrent neural network a model for sequential prediction of time-to-event in the case of discrete or continuous censored data, recurrent events or time-varying covariates. Doctoral dissertation, Chalmers University of Technology and University of Gothenburg.
Paik MC, Tsai WY, Ottman R (1994). Multivariate survival analysis using piecewise gamma frailty. Biometrics, 50(4), 975–988. https://doi.org/10.2307/2533437
Ripatti S, Palmgren J (2000). Estimation of multivariate frailty models using penalized partial likelihood. Biometrics, 56(4): 1016–1022. https://doi.org/10.1111/j.0006-341X.2000.01016.x
Rizopoulos D, Molenberghs G, Lesaffre EM (2017). Dynamic predictions with time-dependent covariates in survival analysis using joint modeling and landmarking. Biometrical Journal, 59(6): 1261–1276. https://doi.org/10.1002/bimj.201600238
Shih JH, Louis TA (1995). Assessing gamma frailty models for clustered failure time data. Lifetime Data Analysis, 1: 205–220. https://doi.org/10.1007/BF00985771
Sun T, Wei Y, Chen W, Ding Y (2020). Genome-wide association study-based deep learning for survival prediction. Statistics in Medicine, 39(30): 4605–4620. https://doi.org/10.1002/sim.8743
Tanner KT, Sharples LD, Daniel RM, Keogh RH (2021). Dynamic survival prediction combining landmarking with a machine learning ensemble: Methodology and empirical comparison. Journal of the Royal Statistical Society. Series A. Statistics in Society, 184(1): 3–30. https://doi.org/10.1111/rssa.12611
Wiegrebe S, Kopper P, Sonabend R, Bender A (2023). Deep learning for survival analysis: A review. arXiv preprint: https://arxiv.org/2305.14961.
Wu R, Qiao J, Wu M, Yu W, Zheng M, Liu T, et al. (2024). Neural frailty machine: Beyond proportional hazard assumption in neural survival regressions. In: Advances in Neural Information Processing Systems (A. Globerson, L. Mackey, D. Belgrave, A. Fan, U. Paquet, J. Tomczak, and C. Zhang, editors), 36.
Yu Z, Liu L (2011). A joint model of recurrent events and a terminal event with a nonparametric covariate function. Statistics in Medicine, 30(22): 2683–2695. https://doi.org/10.1002/sim.4297
Yu Z, Liu L, Bravata DM, Williams LS (2014). Joint model of recurrent events and a terminal event with time-varying coefficients. Biometrical Journal, 56(2): 183–197. https://doi.org/10.1002/bimj.201200160
Yu Z, Liu L, Bravata DM, Williams LS, Tepper RS (2013). A semiparametric recurrent events model with time-varying coefficients. Statistics in Medicine, 32(6): 1016–1026. https://doi.org/10.1002/sim.5575