New designs for the selection of treatments to be tested in randomized clinical trials

Authors

  • R. Simon,

    1. Biometric Research Branch, Division of Cancer Treatment, National Cancer Institute, 6130 Executive Blvd., Room 739, Rockville, MD 20852, U.S.A.
    Search for more papers by this author
  • P. F. Thall,

    1. Department of Biomathematics, Box 237, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, U.S.A.
    Search for more papers by this author
  • S. S. Ellenberg

    1. Division of Biostatistics and Epidemiology, Office of Establishment Licensing and Product Surveillance, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Room 400N, Rockville, MD 20852, U.S.A.
    Search for more papers by this author

Abstract

The most important aspect of phase III randomized clinical trials is the selection of the experimental treatments to be tested. Often this decision is based on uncontrolled phase II trials. Substantial statistical attention has been focused on the design of phase III trials and for simple phase II trials, which determine whether a new drug has any anti-disease activity. Much less statistical effort has been devoted to the design and analysis of phase II trials for screening active experimental treatments to determine whether they are sufficiently active, relative to standard treatments, to warrant the conduct of a large randomized phase III trial. This problem is particularly acute in the development of drug combinations where many regimens are possible. We review several designs for such screening trials which we have developed.

Ancillary