Utility of Covariate-Adjusted Response-Adaptive Randomization in Survival Trials

作者：Sverdlov Oleksandr^*; Rosenberger William F; Ryeznik Yevgen

来源：Statistics in Biopharmaceutical Research, 2013, 5(1): 38-53.

DOI：10.1080/19466315.2012.754376

• Adaptive design
• Censoring
• Efficiency
• Ethical concern
• Power
• Unequal allocation

Covariate-adjusted response-adaptive (CARA) randomization is used in clinical trials to balance the competing goals of assigning a greater number of study subjects to the better treatment and achieving high statistical efficiency in estimating treatment effects in the presence of covariates, while maintaining randomness in treatment assignments. In this article, we propose CARA randomization procedures for survival intervention trials with two treatment arms when the primary outcomes follow an exponential regression model. We demonstrate, through extensive simulation, that our CARA procedures can achieve some reduction in the number of events in the study without compromising power and Type I error, compared with balanced randomization designs, including in situations when the exponential model is misspecified. We conclude that the proposed CARA procedures can be suitable alternatives to the traditional balanced randomization designs in survival trials, provided response data are available during the recruitment phase to enable adaptations in the design. We illustrate the proposed methodology by redesigning two survival trials from the literature.

• 出版日期2013-2