Restricted randomization designs in clinical trials

Biometrics. 1979 Jun;35(2):503-12.


Though therapeutic clinical trials are often categorized as using either "randomization" or "historical controls" as a basis for treatment evaluation, pure random assignment of treatments is rarely employed. Instead various restricted randomization designs are used. The restrictions include the balancing of treatment assignments over time and the stratification of the assignment with regard to covariates that may affect response. Restricted randomization designs for clinical trials differ from those of other experimental areas because patients arrive sequentially and a balanced design cannot be ensured. The major restricted randomization designs and arguments concerning the proper role of stratification are reviewed here. The effect of randomization restrictions on the validity of significance tests is discussed.

MeSH terms

  • Clinical Trials as Topic*
  • Statistics as Topic*
  • Therapeutics / standards*