A two-stage design for choosing among several experimental treatments and a control in clinical trials

Biometrics. 1989 Jun;45(2):537-47.


In clinical trials where several experimental treatments are of interest, the goal may be viewed as identification of the best of these and comparison of that treatment to a standard control therapy. However, it is undesirable to commit patients to a large-scale comparative trial of a new regimen without evidence that its therapeutic success rate is acceptably high. We propose a two-stage design in which patients are first randomized among the experimental treatments, and the single treatment having the highest observed success rate is identified. If this highest rate falls below a fixed cutoff then the trial is terminated. Otherwise, the "best" new treatment is compared to the control at a second stage. Locally optimal values of the cutoff and the stage-1 and stage-2 sample sizes are derived by minimizing expected total sample size. The design has both high power and high probability of terminating early when no experimental treatment is superior to the control. Numerical results for implementing the design are presented, and comparison to Dunnett's (1984, in Design of Experiments: Ranking and Selection, T. J. Santner and A. C. Tamhane (eds), 47-66; New York: Marcel Dekker) optimal one-stage procedure is made.

MeSH terms

  • Biometry*
  • Clinical Trials as Topic / methods*
  • Humans
  • Models, Statistical
  • Random Allocation