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Custom Programmed Randomization Routines

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A variety of randomization methods have been used to determine treatment/intervention assignments of study subjects in controlled clinical trials. The purpose of using randomization methods is to remove bias in the allocation of treatment assignments and ensure study treatment arms comparable with respect to known and unknown risk factors. A randomization scheme is desired to be unpredictable in the allocation of treatments and in the end of recruitment to produce balanced allocations that achieve approximately the preset treatment allocation ratios.

Simple randomization method assigns a treatment or placebo to a study subject by chance based on pre-set probabilities. This method often yields imbalanced allocations in which the distribution of study subjects in each arm deviates substantially from the desired allocation ratios, resulting in loss of power and logistical problems. This problem is of particular concern when sample size is small. A more commonly used method is permuted block randomization instead. Study subjects are divided into a large number of blocks, typically a small block of 2, 4, or 6, and simple randomization is done in each block. This method can ensure the approximate balance at end of recruitment, minimize chance of imbalance due to unexpected shortfall in enrollment and facilitate planning and implementation of the treatment administration process. A drawback of this method is that once the first few assignments in a block are revealed future assignments will become known or predictable. A variation of the permuted-block randomization that randomly mixes blocks of different sizes has been widely used to overcome this problem.

MRC creates custom randomization programs specific to the needs of the research study.