Step-forward Randomization in Multicenter Emergency Treatment Clinical Trials


  • Presented at the 29th annual meeting of Society for Clinical Trials, St. Louis, MO, May 2008.

  • This work was supported by the National Institute of Neurological Diseases and Stroke (NINDS) grants U01 NS054630, U01 NS040406, and U01 NS052220. The manuscript was reviewed by Dr. Myron D. Ginsberg (PI, ALIAS Trial), Dr. Michael D. Hill (co-PI, ALIAS Trial), Dr. Joseph P. Broderick (PI, IMS III Trial), and Dr. Thomas Tomsick (co-PI, IMS III Trial), as well as by the NINDS Project Officers of the two trials (Drs. Claudia Moy and Scott Janis).

Address for correspondenceand reprints: Wenle Zhao, PhD; e-mail:


The authors present a new centralized randomization method for multicenter emergency treatment clinical trials. With this step-forward method, treatment randomization for the next subject is performed immediately after the enrollment of the current subject. This design ensures the readiness of the treatment assignment for each subject at the point of study enrollment, and it simultaneously provides effective control on treatment assignments balance and distributions of covariates. The authors also discuss procedures of the step-forward randomization method along with its implementation for two National Institute of Neurological Disorders and Stroke–funded multicenter acute stroke trials, one double-blinded and one open-labeled. Advantages and limitations are presented based on experience gained in these two trials.

ACADEMIC EMERGENCY MEDICINE 2010; 17:659–665 © 2010 by the Society for Academic Emergency Medicine