Generalized Likelihood Ratio Statistics and Uncertainty Adjustments in   Efficient Adaptive Design of Clinical Trials
  A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to implement, maintain the prescribed Type I error probability, and are asymptotically efficient. Practical issues involved in clinical trials allowing mid-course adaptation and the large literature on this subject are discussed, and comparisons between the proposed and existing designs are presented in extensive simulation studies of their finite-sample performance, measured in terms of the expected sample size and power functions. 
Jay Bartroff and Tze Leung Lai
math.ST stat.ME stat.TH