Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial

Biometrics. 1975 Mar;31(1):103-15.


In controlled clinical trials there are usually several prognostic factors known or thought to influence the patient's ability to respond to treatment. Therefore, the method of sequential treatment assignment needs to be designed so that treatment balance is simultaneously achieved across all such patients factor. Traditional methods of restricted randomization such as "permuted blocks within strata" prove inadequate once the number of strata, or combinations of factor levels, approaches the sample size. A new general procedure for treatment assignment is described which concentrates on minimizing imbalance in the distributions of treatment numbers within the levels of each individual prognostic factor. The improved treatment balance obtained by this approach is explored using simulation for a simple model of a clinical trial. Further discussion centers on the selection, predictability and practicability of such a procedure.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carmustine / therapeutic use
  • Clinical Trials as Topic
  • Cyclophosphamide / therapeutic use
  • Evaluation Studies as Topic
  • Humans
  • Lymphoma / drug therapy
  • Lymphoma / radiotherapy
  • Models, Theoretical
  • Prednisone / therapeutic use
  • Prognosis*
  • Statistics as Topic
  • Vincristine / therapeutic use


  • Vincristine
  • Cyclophosphamide
  • Carmustine
  • Prednisone