A Unified Family of Covariate-Adjusted Response-Adaptive Designs Based on Efficiency and Ethics

Response-adaptive designs have recently attracted more and more attention in the literature because of its advantages in efficiency and medical ethics. To develop personalized medicine, covariate information plays an important role in both design and analysis of clinical trials. A challenge is how to incorporate covariate information in response-adaptive designs while considering issues of both efficiency and medical ethics. To address this problem, we propose a new and unified family of covariate-adjusted response-adaptive (CARA) designs based on two general measurements of efficiency and ethics. Important properties (including asymptotic properties) of the proposed procedures are studied under categorical covariates. This new family of designs not only introduces new desirable CARA designs, but also unifies several important designs in the literature. We demonstrate the proposed procedures through examples, simulations, and a discussion of related earlier work.

[1]  Feifang Hu,et al.  ST ] 1 7 O ct 2 00 6 ASYMPTOTIC PROPERTIES OF COVARIATE-ADJUSTED ADAPTIVE DESIGNS , 2006 .

[2]  Feifang Hu,et al.  Doubly adaptive biased coin designs with delayed responses , 2008 .

[3]  W. Rosenberger,et al.  Randomization in Clinical Trials: Theory and Practice , 2002 .

[4]  Charles A. Baylis,et al.  A Note on Probability. , 1951 .

[5]  Feifang Hu,et al.  Efficient randomized-adaptive designs , 2009, 0908.3435.

[6]  D G Altman,et al.  The hidden effect of time. , 1988, Statistics in medicine.

[7]  R. Kronmal,et al.  Lessons from the Stroke Prevention in Atrial Fibrillation Trials , 2003, Annals of Internal Medicine.

[8]  Diane D. Liu,et al.  Bayesian clinical trials at the University of Texas M. D. Anderson Cancer Center , 2009, Clinical trials.

[9]  L. J. Wei,et al.  Exact two-sample permutation tests based on the randomized play-the-winner rule , 1988 .

[10]  William F. Rosenberger,et al.  Utility of Covariate-Adjusted Response-Adaptive Randomization in Survival Trials , 2013 .

[11]  L. J. Wei,et al.  The Randomized Play-the-Winner Rule in Medical Trials , 1978 .

[12]  B. Efron.  Forcing a sequential experiment to be balanced , 1971 .

[13]  T. Mok,et al.  Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. , 2009, The New England journal of medicine.

[14]  W. Rosenberger,et al.  COVARIATE-ADJUSTED RESPONSE-ADAPTIVE DESIGNS FOR BINARY RESPONSE , 2001, Journal of biopharmaceutical statistics.

[15]  M Zelen,et al.  The randomization and stratification of patients to clinical trials. , 1974, Journal of chronic diseases.

[16]  Edward S. Kim,et al.  Bayesian adaptive design for targeted therapy development in lung cancer — a step toward personalized medicine , 2008, Clinical trials.

[17]  S. Pocock,et al.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. , 1975, Biometrics.

[18]  D. Berry.  Adaptive clinical trials: the promise and the caution. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  William F. Rosenberger,et al.  Response‐Adaptive Randomization , 2005 .

[20]  N Stallard,et al.  Optimal Adaptive Designs for Binary Response Trials , 2001, Biometrics.

[21]  Feifang Hu,et al.  Doubly adaptive biased coin designs with heterogeneous responses , 2009 .

[22]  Feifang Hu,et al.  Asymptotic properties of doubly adaptive biased coin designs for multitreatment clinical trials , 2003 .

[23]  Alessandra Giovagnoli,et al.  On the Large Sample Optimality of Sequential Designs for Comparing Two or More Treatments , 2005 .

[24]  William F. Rosenberger,et al.  Implementing Optimal Allocation in Sequential Binary Response Experiments , 2007 .

[25]  Uttam Bandyopadhyay,et al.  Adaptive designs for normal responses with prognostic factors , 2001 .

[26]  A. Atkinson.  Optimum biased coin designs for sequential clinical trials with prognostic factors , 1982 .

[27]  Alessandra Giovagnoli,et al.  Compound optimal allocation for individual and collective ethics in binary clinical trials , 2010 .

[28]  William F. Rosenberger,et al.  Asymptotically best response-adaptive randomization procedures , 2006 .

[29]  William F. Rosenberger,et al.  Asymptotic Properties of Adaptive designs for Clinical Trials with delayed Response , 2002 .

[30]  D. Berry,et al.  Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Diane M. Miller,et al.  Design of a multicenter randomized trial for the Stroke Prevention in Atrial Fibrillation Study. The Stroke Prevention in Atrial Fibrillation Investigators. , 1990, Stroke.

[32]  D. Taves,et al.  The use of minimization in clinical trials. , 2010, Contemporary clinical trials.

[33]  William F Rosenberger,et al.  Response‐Adaptive Randomization for Clinical Trials with Continuous Outcomes , 2006, Biometrics.

[34]  Feifang Hu.  Statistical issues in trial design and personalized medicine , 2012 .

[35]  Michael Woodroofe,et al.  Central Limit Theorems for Doubly Adaptive Biased Coin Designs , 1995 .

[36]  W F Rosenberger,et al.  Analysis of time trends in adaptive designs with application to a neurophysiology experiment. , 2000, Statistics in medicine.

[37]  P. McCullagh,et al.  Generalized Linear Models , 1984 .

[38]  H A Wendel,et al.  Randomization in clinical trials. , 1978, Science.

[39]  B. Freidlin,et al.  Outcome--adaptive randomization: is it useful? , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  J. H. Schuenemeyer,et al.  Generalized Linear Models (2nd ed.) , 1992 .

[41]  William F. Rosenberger,et al.  Handling Covariates in the Design of Clinical Trials. , 2008, 1102.3773.

[42]  Li-Xin Zhang,et al.  Asymptotic properties of covariate-adjusted response-adaptive designs , 2006 .

[43]  Douglas E. Faries,et al.  A Case Study of an Adaptive Clinical Trial in the Treatment of Out-Patients with Depressive Disorder , 1994 .