Shuffle randomization

In a randomized clinical trial, study participants are assigned to various treatment arms through randomization. This random allocation of participants to treatment arms decreases bias and controls for numerous confounders (1). A common type of randomization is simple randomization, where each participant is randomly assigned to a treatment arm with a known (usually equal) probability, regardless of the treatment assignments of other study participants. For a two-arm trial, that would be achieved by tossing a fair coin. Although in the long run, on average this process will result in approximately equal numbers in each treatment arm, there is no guarantee of equally sized study groups, particularly for small samples. For example, if we want to randomize 10 participants to two treatment arms by flipping a fair coin, there is more than 6% chance of coming up with a severe imbalance as extreme as assigning eight participants to one arm and two to another arm or worse. Other randomization methods have been proposed to eliminate or at least reduce such extreme imbalance.