On optimal treatment regimes selection for mean survival time

In clinical studies with time-to-event as a primary endpoint, one main interest is to find the best treatment strategy to maximize patients' mean survival time. Due to patient's heterogeneity in response to treatments, great efforts have been devoted to developing optimal treatment regimes by integrating individuals' clinical and genetic information. A main challenge arises in the selection of important variables that can help to build reliable and interpretable optimal treatment regimes as the dimension of predictors may be high. In this paper, we propose a robust loss-based estimation framework that can be easily coupled with shrinkage penalties for both estimation of optimal treatment regimes and variable selection. The asymptotic properties of the proposed estimators are studied. Moreover, a model-free estimator of restricted mean survival time under the derived optimal treatment regime is developed, and its asymptotic property is studied. Simulations are conducted to assess the empirical performance of the proposed method for parameter estimation, variable selection, and optimal treatment decision. An application to an AIDS clinical trial data set is given to illustrate the method.

[1]  Anastasios A. Tsiatis,et al.  A consistent estimator for the distribution of quality adjusted survival time , 1997 .

[2]  S. Hammer,et al.  A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. , 1996, The New England journal of medicine.

[3]  Min Zhang,et al.  Estimating optimal treatment regimes from a classification perspective , 2012, Stat.

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

[5]  Marie Davidian,et al.  Improving Efficiency of Inferences in Randomized Clinical Trials Using Auxiliary Covariates , 2008, Biometrics.

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

[7]  Jianqing Fan,et al.  Censored Regression - Local Linear-approximations and Their Applications , 1994 .

[8]  Eric B. Laber,et al.  A Robust Method for Estimating Optimal Treatment Regimes , 2012, Biometrics.

[9]  S. Murphy,et al.  Optimal dynamic treatment regimes , 2003 .

[10]  Peter Dayan,et al.  Q-learning , 1992, Machine Learning.

[11]  Susan A. Murphy,et al.  A-Learning for approximate planning , 2004 .

[12]  Zhiliang Ying,et al.  On the linear transformation model for censored data , 1998 .

[13]  Cun-Hui Zhang,et al.  A group bridge approach for variable selection , 2009, Biometrika.

[14]  S. Murphy,et al.  Variable Selection for Qualitative Interactions. , 2011, Statistical methodology.

[15]  Ji Zhu,et al.  A ug 2 01 0 Group Variable Selection via a Hierarchical Lasso and Its Oracle Property Nengfeng Zhou Consumer Credit Risk Solutions Bank of America Charlotte , NC 28255 , 2010 .

[16]  Zhiliang Ying,et al.  Predicting Survival Probabilities with Semiparametric Transformation Models , 1997 .

[17]  Wenbin Lu,et al.  Variable selection for optimal treatment decision , 2013, Statistical methods in medical research.

[18]  D. Rubin Estimating causal effects of treatments in randomized and nonrandomized studies. , 1974 .

[19]  James M. Robins,et al.  Optimal Structural Nested Models for Optimal Sequential Decisions , 2004 .

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

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

[22]  S. Murphy,et al.  PERFORMANCE GUARANTEES FOR INDIVIDUALIZED TREATMENT RULES. , 2011, Annals of statistics.

[23]  Peter Dayan,et al.  Technical Note: Q-Learning , 2004, Machine Learning.

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

[25]  Z. Ying,et al.  Analysis of transformation models with censored data , 1995 .

[26]  C. Watkins Learning from delayed rewards , 1989 .

[27]  J. V. Ryzin,et al.  Regression Analysis with Randomly Right-Censored Data , 1981 .

[28]  M. Davidian,et al.  Covariate adjustment for two‐sample treatment comparisons in randomized clinical trials: A principled yet flexible approach , 2008, Statistics in medicine.

[29]  Donglin Zeng,et al.  Estimating Individualized Treatment Rules Using Outcome Weighted Learning , 2012, Journal of the American Statistical Association.

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

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