ABSTRACT
Randomized controlled trials (RCTs) are performed for both methodological and ethical reasons. Methodologically, the use of randomization is meant to prevent bias. Ethically, the use of randomization (and blinding) is meant to ensure fairness—that each study participant has an equal chance of being assigned to a particular arm of the trial. This paper will survey how bias and randomization have been dealt with historically. In the first half of the twentieth century, alternative allocation was characterized as “random,” even though researchers could predict the group into which the next participant would be assigned. In the mid-twentieth century, researchers tried to eliminate bias by using random sampling numbers to assign study participants. Later, to achieve similar objectives, the permuted block design was applied. As a historical “lesson learned,” this paper will argue that just as alternative allocation had to be replaced with an early form of randomization, so likewise must permuted block strategy be critically reassessed now to ensure continued methodological rigor in the execution of clinical trials in the future.
