Implementing optimal allocation for sequential continuous responses with multiple treatments

Abstract In practice, it is important to find optimal allocation strategies for continuous response with multiple treatments under some optimization criteria. In this article, we focus on exponential responses. For a multivariate test of homogeneity, we obtain the optimal allocation strategies to maximize power while (1) fixing sample size and (2) fixing expected total responses. Then the doubly adaptive biased coin design [Hu, F., Zhang, L.-X., 2004. Asymptotic properties of doubly adaptive biased coin designs for multi-treatment clinical trials. The Annals of Statistics 21, 268–301] is used to implement the optimal allocation strategies. Simulation results show that the proposed procedures have advantages over complete randomization with respect to both inferential (power) and ethical standpoints on average. It is important to note that one can usually implement optimal allocation strategies numerically for other continuous responses, though it is usually not easy to get the closed form of the optimal allocation theoretically.

[1]  Steven N. Goodman A birthday, an anniversary, and an agenda for Clinical Trials , 2004 .

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

[3]  M Zelen,et al.  Estimation of exponential survival probabilities with concomitant information. , 1965, Biometrics.

[4]  T. Louis,et al.  Sequential allocation in clinical trials comparing two exponential survival curves. , 1977, Biometrics.

[5]  P. De Wals,et al.  Methods for estimating the duration of bacterial carriage. , 1985, International journal of epidemiology.

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

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

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

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

[10]  John M. Lachin,et al.  Biostatistical Methods: The Assessment of Relative Risks , 2000 .

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

[12]  Feifang Hu,et al.  Maximizing power and minimizing treatment failures in clinical trials , 2004, Clinical trials.

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

[14]  M. Zelen,et al.  Application of Exponential Models to Problems in Cancer Research , 1966 .

[15]  Mordecai Avriel,et al.  Nonlinear programming , 1976 .

[16]  D. Shulz,et al.  A novel method for quantifying passive-avoidance behavior based on the exponential distribution of step-through latencies , 1986, Pharmacology Biochemistry and Behavior.

[17]  Jeffrey R. Eisele The doubly adaptive biased coin design for sequential clinical trials , 1994 .

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