Efficient randomized-adaptive designs

Response-adaptive randomization has recently attracted a lot of attention in the literature. In this paper, we propose a new and simple family of response-adaptive randomization procedures that attain the Cramer-Rao lower bounds on the allocation variances for any allocation proportions, including optimal allocation proportions. The allocation probability functions of proposed procedures are discontinuous. The existing large sample theory for adaptive designs relies on Taylor expansions of the allocation probability functions, which do not apply to nondifferentiable cases. In the present paper, we study stopping times of stochastic processes to establish the asymptotic efficiency results. Furthermore, we demonstrate our proposal through examples, simulations and a discussion on the relationship with earlier works, including Efron's biased coin design.

[1]  Jianhua Hu,et al.  Optimal biased coins for two-arm clinical trials , 2008 .

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

[3]  William F. Rosenberger,et al.  Optimality, Variability, Power , 2003 .

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

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

[6]  Duncan Macrae,et al.  UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation , 1996, The Lancet.

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

[8]  L. J. Wei,et al.  The Adaptive Biased Coin Design for Sequential Experiments , 1978 .

[9]  William F Rosenberger,et al.  Response-adaptive randomization for clinical trials with continuous outcomes. , 2006, Biometrics.

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

[11]  Richard L. Smith Properties of Biased Coin Designs in Sequential Clinical Trials , 1984 .

[12]  C. Assaid,et al.  The Theory of Response-Adaptive Randomization in Clinical Trials , 2007 .

[13]  J. Matthews,et al.  Randomization in Clinical Trials: Theory and Practice; , 2003 .

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

[15]  Feifang Hu,et al.  Asymptotics in randomized urn models , 2005 .

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

[17]  J. Ware Investigating Therapies of Potentially Great Benefit: ECMO , 1989 .

[18]  P. Hall,et al.  Martingale Limit Theory and Its Application , 1980 .

[19]  M. Zelen,et al.  Play the Winner Rule and the Controlled Clinical Trial , 1969 .

[20]  R. G. Cornell,et al.  Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. , 1985, Pediatrics.

[21]  B. Turnbull,et al.  Group Sequential Methods with Applications to Clinical Trials , 1999 .

[22]  Thomas A. Louis,et al.  Sequential treatment allocation in clinical trials , 1971 .

[23]  W. Rosenberger,et al.  The theory of response-adaptive randomization in clinical trials , 2006 .

[24]  Feifang Hu,et al.  Asymptotic theorems of sequential estimation-adjusted urn models , 2006 .

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

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

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