Optimal Response‐Adaptive Designs for Continuous Responses in Phase III Trials

Optimal response-adaptive designs in phase III clinical trial set up are gaining more interest. Most of the available designs are not based on any optimal consideration. An optimal design for binary responses is given by Rosenberger et al. (2001) and one for continuous responses is provided by Biswas and Mandal (2004). Recently, Zhang and Rosenberger (2006) proposed another design for normal responses. This paper illustrates that the Zhang and Rosenberger (2006) design is not suitable for normally distributed responses, in general. The approach cannot be extended for other continuous response cases, such as exponential or gamma. In this paper, we first describe when the optimal design of Zhang and Rosenberger (2006) fails. We then suggest the appropriate adjustments for designs in different continuous distributions. A unified framework to find optimal response-adaptive designs for two competing treatments is proposed. The proposed methods are illustrated using some real data.

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

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

[3]  R. Poole,et al.  Pregabalin for the treatment of postherpetic neuralgia , 2003, Neurology.

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

[5]  N. L. Johnson,et al.  Continuous Univariate Distributions. , 1995 .

[6]  John A. Nelder,et al.  Generalized linear models. 2nd ed. , 1993 .

[7]  Anastasia Ivanova,et al.  A play-the-winner-type urn design with reduced variability , 2003 .

[8]  James K. Lindsey,et al.  Applying Generalized Linear Models , 2000 .

[9]  Atanu Biswas,et al.  Bayesian Adaptive Biased‐Coin Designs for Clinical Trials with Normal Responses , 2005, Biometrics.

[10]  C. Rout,et al.  A Reevaluation of the Role of Crystalloid Preload in the Prevention of Hypotension Associated with Spinal Anesthesia for Elective Cesarean Section , 1993, Anesthesiology.

[11]  A. Biswas,et al.  Inference for a RPW‐Type Clinical Trial with Repeated Monitoring for the Treatment of Rheumatoid Arthritis , 2004 .

[12]  L. Hayre.  Two-population sequential tests with three hypotheses , 1979 .

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

[14]  William F. Rosenberger,et al.  Asymptotic Inference with Response-Adaptive Treatment Allocation Designs , 1993 .

[15]  L. J. Wei,et al.  The Generalized Polya's Urn Design for Sequential Medical Trials , 1979 .

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

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

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

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

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

[21]  A. Biswas,et al.  An adaptive allocation for continuous response using Wilcoxon–Mann–Whitney score , 2004 .