Penalized Variable Selection for Multi-center Competing Risks Data

We consider variable selection in competing risks regression for multi-center data. Our research is motivated by deceased donor kidney transplants, from which recipients would experience graft failure, death with functioning graft (DWFG), or graft survival. The occurrence of DWFG precludes graft failure from happening and therefore is a competing risk. Data within a transplant center may be correlated due to a latent center effect, such as varying patient populations, surgical techniques, and patient management. The proportional subdistribution hazard (PSH) model has been frequently used in the regression analysis of competing risks data. Two of its extensions, the stratified and the marginal PSH models, can be applied to multi-center data to account for the center effect. In this paper, we propose penalization strategies for the two models, primarily to select important variables and estimate their effects whereas correlations within centers serve as a nuisance. Simulations demonstrate good performance and computational efficiency for the proposed methods. It is further assessed using an analysis of data from the United Network of Organ Sharing.

[1]  Runze Li,et al.  Tuning parameter selectors for the smoothly clipped absolute deviation method. , 2007, Biometrika.

[2]  Lee-Jen Wei,et al.  Cox-Type Regression Analysis for Large Numbers of Small Groups of Correlated Failure Time Observations , 1992 .

[3]  Myriam Labopin,et al.  Competing risks regression for clustered data. , 2012, Biostatistics.

[4]  Douglas E Schaubel,et al.  A Comprehensive Risk Quantification Score for Deceased Donor Kidneys: The Kidney Donor Risk Index , 2009, Transplantation.

[5]  John A. Nelder,et al.  Conditional and Marginal Models: Another View , 2004 .

[6]  Trevor Hastie,et al.  Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent. , 2011, Journal of statistical software.

[7]  Douglas E Schaubel,et al.  Centre-specific variation in renal transplant outcomes in Canada. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[9]  Ewout W. Steyerberg,et al.  Prognostic Models With Competing Risks: Methods and Application to Coronary Risk Prediction , 2009, Epidemiology.

[10]  Youngjo Lee,et al.  Variable selection in subdistribution hazard frailty models with competing risks data , 2014, Statistics in medicine.

[11]  David V Glidden,et al.  Modelling clustered survival data from multicentre clinical trials , 2004, Statistics in medicine.

[12]  M. Durão,et al.  Kidney transplantation from donors without a heartbeat. , 2002, The New England journal of medicine.

[13]  D. Manninen,et al.  The center effect in kidney transplantation. , 1991, Transplantation proceedings.

[14]  Jason Fine,et al.  Competing Risks Regression for Stratified Data , 2011, Biometrics.

[15]  P. Grambsch,et al.  Modeling Survival Data: Extending the Cox Model , 2000 .

[16]  Ravi Varadhan,et al.  Model selection in competing risks regression , 2013, Statistics in medicine.

[17]  Jianqing Fan,et al.  Variable Selection via Nonconcave Penalized Likelihood and its Oracle Properties , 2001 .

[18]  John O'Quigley,et al.  Proportional hazards models with frailties and random effects , 2002, Statistics in medicine.

[19]  H. Zou The Adaptive Lasso and Its Oracle Properties , 2006 .

[20]  J. Briggs,et al.  RENAL TRANSPLANTATION IN THE UNITED KINGDOM AND IRELAND—THE CENTRE EFFECT , 1985, The Lancet.

[21]  Jianwen Cai,et al.  Marginal and Conditional Models for the Analysis of Multivariate Failure Time Data , 1992 .

[22]  Mei-Jie Zhang,et al.  Marginal Models for Clustered Time‐to‐Event Data with Competing Risks Using Pseudovalues , 2011, Biometrics.

[23]  R. Tibshirani,et al.  Generalized Additive Models , 1991 .

[24]  Youngjo Lee,et al.  Analysis of clustered competing risks data using subdistribution hazard models with multivariate frailties , 2016, Statistical methods in medical research.

[25]  W. Weimar,et al.  Ischemia times and donor serum creatinine in relation to renal graft failure , 2003, Transplantation.

[26]  D. Hunter,et al.  Variable Selection using MM Algorithms. , 2005, Annals of statistics.

[27]  D. Goldfarb,et al.  Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. , 2003, The Journal of urology.

[28]  M. Christiaans,et al.  Kidney Transplantation From Donors After Cardiac Death: A 25-Year Experience , 2010, Transplantation.

[29]  Zhixuan Fu,et al.  Penalized variable selection in competing risks regression , 2017, Lifetime data analysis.

[30]  Robert M. Merion,et al.  Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors1 , 2002, Transplantation.

[31]  Jianqing Fan,et al.  Variable Selection for Cox's proportional Hazards Model and Frailty Model , 2002 .

[32]  Jianqing Fan,et al.  A Selective Overview of Variable Selection in High Dimensional Feature Space. , 2009, Statistica Sinica.

[33]  Patrick Royston,et al.  A new measure of prognostic separation in survival data , 2004, Statistics in medicine.

[34]  Harald Binder,et al.  Quantifying the predictive accuracy of time‐to‐event models in the presence of competing risks , 2011, Biometrical journal. Biometrische Zeitschrift.

[35]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

[36]  J M Morales,et al.  Long‐Term Experience With Kidney Transplantation From Hepatitis C‐Positive Donors Into Hepatitis C‐Positive Recipients , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[37]  Hao Helen Zhang,et al.  Adaptive Lasso for Cox's proportional hazards model , 2007 .

[38]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[39]  R. Tibshirani The lasso method for variable selection in the Cox model. , 1997, Statistics in medicine.

[40]  Alicja R. Rudnicka,et al.  Measures to assess the prognostic ability of the stratified Cox proportional hazards model , 2009, Statistics in medicine.

[41]  Sylvie Chevret,et al.  Analysing multicentre competing risks data with a mixed proportional hazards model for the subdistribution , 2006, Statistics in medicine.

[42]  L. J. Wei,et al.  Regression analysis of multivariate incomplete failure time data by modeling marginal distributions , 1989 .

[43]  J. Robins,et al.  Recovery of Information and Adjustment for Dependent Censoring Using Surrogate Markers , 1992 .

[44]  Cun-Hui Zhang Nearly unbiased variable selection under minimax concave penalty , 2010, 1002.4734.

[45]  Nicholas J Christian,et al.  Hierarchical likelihood inference on clustered competing risks data , 2016, Statistics in medicine.