Randomization in Clinical Trials

Abstract

The most compelling way to establish that an intervention definitively causes a clinical outcome is to randomly allocate patients into treatment groups. Randomization helps to ensure that a certain proportion of patients receive each treatment and that the treatment groups being compared are similar in both measured and unmeasured patient characteristics. 1,2 Simple or unrestricted, equal randomization of patients between 2 treatment groups is equivalent to tossing a fair coin for each patient assignment. 2,3 As the sample size increases, the 2 groups will become more perfectly balanced. However, this balance is not guaranteed when there are relatively few patients enrolled in a trial. In the coin toss scenario, obtaining several consecutive heads, for example, is more likely than typically perceived. 1,4 If a long series of assignments to 1 group occurred when randomizing patients in a clinical trial, imbalances between the groups would occur.Imbalances between groups can be minimized in small sample-size studies by restricting the randomization procedure. Restricted randomization means that simple randomization is applied within defined groups of patients. Two recent articles in JAMA used restrictions on the randomization procedure: Bilecen et al 5 used permuted block randomization, a restricted randomization method used to help ensure the balance of the number of patients assigned to each treatment group. 3 Kim et al 6 used a stratified randomization scheme together with permuted block randomization. Stratified randomization is a restricted randomization method used to balance one or a few prespecified prognostic characteristics between treatment groups. 1 Explanation of the ConceptWhat Are Permuted Blocks and Stratified Randomization?

Reporting Quality of Randomized Controlled Trials for the Treatment of Eczema with Chinese Patent Medicine Based on the CONSORT‐CHM Formulas 2017

“…Randomization is the major hallmark of a RCT. Its ultimate objectives are to create balanced treatment groups and to minimize the risk of biased results [ 22 ]. Inadequate randomization methods may exaggerate the estimate of the intervention effect [ 23 ].…”

Application of Freire’s adult education model in modifying the psychological constructs of health belief model in self-medication behaviors of older adults: a randomized controlled trial

“…After informed consent was obtained by a healthcare worker who was not involved in the recruitment of participants, the older adults were randomized into control and intervention groups by permuted block randomization and a table of random numbers [ 26 ]. The older adults who met the criteria of self-medication behavior filled out the pre-test questionnaires.…”

HABIT efficacy and sustainability trial, a multi-center randomized controlled trial to improve hydroxyurea adherence in youth with sickle cell disease: a study protocol

“…A 1:1 randomization plan was performed before the start of the trial using a computer-generated assignment sequence in permuted blocks of eight [77] stratified by study site. The randomization plan will be maintained centrally at the Columbia site.…”