Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 69

Randomization Schedule

Olga M. Kuznetsova

69.1 Introduction

The randomization schedule is used in a clinical trial to assign subjects randomly to one of the treatment regimens studied in the trial. Randomization helps to make the treatment groups comparable in baseline characteristics (both measured and not measured) and thus lessen the potential for bias in the evaluation of the treatments. It also allows causal inference with respect to intervention effects. The schedule is generated prior to the trial start and provides the list of treatment assignments by subject number (allocation number). In a stratified trial, a range of allocation numbers is designated for each stratum, and a separate randomization schedule is provided for each stratum. Subjects randomized into the trial are assigned allocation numbers in order of entry in their respective randomization stratum and receive the corresponding treatment. Typically, the randomization schedule is also used to prepackage the study drug and label the drug kits with the allocation number (and the study visits to be given to the patient). The schedule is concealed until the trial is closed and the database is locked to ensure the proper blinding (masking) of the trial.

The choice of the randomization procedure for a trial should be evaluated carefully. The first section outlines relevant considerations and describes the most commonly used allocation procedure—permuted block randomization. Two approaches to generation ...