Deep neural networks for predicting restricted mean survival times

AVAILABILITY AND IMPLEMENTATION Restricted mean survival time (RMST) is a useful summary measurement of the time-to-event data, and it has attracted great attention for its straightforward clinical interpretation. In this article, I propose a deep neural network model that directly relates the RMST to its baseline covariates for simultaneous prediction of RSMT at multiple times. Each subject's survival time is transformed into a series of jackknife pseudo observations and then used as quantitative response variables in a deep neural network model. By using the pseudo values, a complex survival analysis is reduced to a standard regression problem, which greatly simplifies the neural network construction. By jointly modelling RMST at multiple times, the neural network model gains prediction accuracy by information sharing across times. The proposed network model was evaluated by extensive simulation studies and was further illustrated on three real datasets. In real data analyses, I also used methods to open the blackbox by identifying subject-specific predictors and their importance in contributing to the risk prediction. SUPPLEMENTARY INFORMATION The source code is freely available at http://github.com/lilizhaoUM/DnnRMST.

[1]  Douglas E Schaubel,et al.  Estimating Differences in Restricted Mean Lifetime Using Observational Data Subject to Dependent Censoring , 2011, Biometrics.

[2]  Maja Pohar Perme,et al.  Pseudo-observations in survival analysis , 2010, Statistical methods in medical research.

[3]  Ying Ding,et al.  Estimating Mean Survival Time: When is it Possible? , 2013, Scandinavian journal of statistics, theory and applications.

[4]  Lihui Zhao,et al.  On the restricted mean survival time curve in survival analysis , 2016, Biometrics.

[5]  John P Klein,et al.  Regression Modeling of Competing Risks Data Based on Pseudovalues of the Cumulative Incidence Function , 2005, Biometrics.

[6]  Yoshiaki Uyama,et al.  Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Pseudo-observations under covariate-dependent censoring , 2019, Journal of Statistical Planning and Inference.

[8]  D. Schaubel,et al.  Double Inverse‐Weighted Estimation of Cumulative Treatment Effects Under Nonproportional Hazards and Dependent Censoring , 2011, Biometrics.

[9]  L. Fried,et al.  Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. , 1993, Annals of epidemiology.

[10]  Xun Zhu,et al.  Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data , 2018, PLoS Comput. Biol..

[11]  P. Royston,et al.  The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt , 2011, Statistics in medicine.

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

[13]  Susan Murray,et al.  Incorporating longitudinal biomarkers for dynamic risk prediction in the era of big data: A pseudo‐observation approach , 2020, Statistics in medicine.

[14]  Dai Feng,et al.  Deep Neural Networks for Survival Analysis Using Pseudo Values , 2019, IEEE Journal of Biomedical and Health Informatics.

[15]  P. Heagerty,et al.  Survival Model Predictive Accuracy and ROC Curves , 2005, Biometrics.

[16]  Jon Arni Steingrimsson,et al.  Deep learning for survival outcomes , 2019, Statistics in medicine.

[17]  Thomas A Gerds,et al.  Pseudo-observations for competing risks with covariate dependent censoring , 2014, Lifetime data analysis.

[18]  John P. Klein,et al.  SAS and R functions to compute pseudo-values for censored data regression , 2008, Comput. Methods Programs Biomed..

[19]  A A Tsiatis,et al.  Sequential Methods for Comparing Years of Life Saved in the Two‐Sample Censored Data Problem , 1999, Biometrics.

[20]  John P. Klein,et al.  Regression Analysis of Restricted Mean Survival Time Based on Pseudo-Observations , 2004, Lifetime data analysis.

[21]  Susan Murray,et al.  Restricted mean models for transplant benefit and urgency , 2012, Statistics in medicine.

[22]  David M. Zucker,et al.  Restricted Mean Life with Covariates: Modification and Extension of a Useful Survival Analysis Method , 1998 .

[23]  Lihui Zhao,et al.  Predicting the restricted mean event time with the subject's baseline covariates in survival analysis. , 2014, Biostatistics.

[24]  Hemant Ishwaran,et al.  Random Survival Forests , 2008, Wiley StatsRef: Statistics Reference Online.

[25]  Chrysta Lienczewski,et al.  Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multi-disciplinary approach , 2012, Kidney international.

[26]  M. Overgaard,et al.  Asymptotic theory of generalized estimating equations based on jack-knife pseudo-observations , 2017 .

[27]  Carlos Guestrin,et al.  "Why Should I Trust You?": Explaining the Predictions of Any Classifier , 2016, ArXiv.

[28]  Valarie B Ashby,et al.  Evaluating center‐specific long‐term outcomes through differences in mean survival time: Analysis of national kidney transplant data , 2019, Statistics in medicine.

[29]  Yoshua Bengio,et al.  Random Search for Hyper-Parameter Optimization , 2012, J. Mach. Learn. Res..

[30]  J. Klein,et al.  Generalised linear models for correlated pseudo‐observations, with applications to multi‐state models , 2003 .

[31]  A A Tsiatis,et al.  Efficient Estimation of the Distribution of Quality‐Adjusted Survival Time , 1999, Biometrics.

[32]  Susan Murray,et al.  Statistical consequences of a successful lung allocation system – recovering information and reducing bias in models for urgency , 2017, Statistics in medicine.

[33]  Theodore Karrison,et al.  Restricted Mean Life with Adjustment for Covariates , 1987 .

[34]  D. Schaubel,et al.  Modeling restricted mean survival time under general censoring mechanisms , 2018, Lifetime data analysis.

[35]  A A Tsiatis,et al.  Causal Inference on the Difference of the Restricted Mean Lifetime Between Two Groups , 2001, Biometrics.