Randomization

How Does Randomization Prevent Bias

Research participants are randomized in clinical trials so that bias does not weaken the study results. Bias consists of human choices, beliefs, or any other factors besides those being studied that can affect a clinical trial's results. If physicians or participants themselves choose the group, assignments might be personally influenced and therefore unevenly slanted toward one side or the other.

For instance, if a study is not randomized physicians may unconsciously assign participants with a more hopeful prognosis to the experimental group, thus making the new therapy seem more effective than it really is. Conversely, participants with a less hopeful prognosis might pick the experimental treatment, making it look less effective than it really is. Randomization prevents such bias. In a randomized trial, investigators use a computer program or a table of random numbers to assign each study participant to a group. Randomization introduces a deliberate element of chance into the assignment of treatments to patients in a clinical trial. During subsequent analysis of the trial data, it provides a sound statistical basis for the quantitative evaluation of the evidence relating to treatment effects. It also tends to produce treatment groups in which the distributions of prognostic factors (known and unknown) are similar. In combination with blinding, randomization helps to avoid possible bias in the selection and allocation of patients arising from the predictability of treatment assignments. The randomization schedule of a clinical trial documents the random allocation of treatments to patients. In the simplest situation it is a sequential list of treatments (or treatment sequences in a cross-over study) or corresponding codes by patient number. The logistics of some studies, such as those with a screening phase, may make matters more complicated, but the unique preplanned assignment of treatment, or treatment sequence, to patient should be clear. Different designs of study require different procedures for generating randomization schedules. This procedure should be capable of being reproduced (if the need arises) through the use of the same random number table, or the same computer routine and seed for its random number generator. Although unrestricted randomization is an acceptable approach, some advantages can generally be gained by randomizing patients in blocks. This helps to increase the comparability of the treatment groups, particularly when patient characteristics may change over time, as a result, for example, of changes in recruitment policy. It also provides a better guarantee that the treatment groups will be of nearly equal size. In cross-over trials it provides the means of obtaining balanced designs with their greater efficiency and easier interpretation. Care must be taken to choose block lengths that are sufficiently short to limit possible imbalance but[Page 480] that are long enough to avoid predictability toward the end of the sequence in a block. Investigators should generally be blind to the block length. The use of two or more block lengths, randomly selected for each block, can achieve the same purpose, the prevention of bias. (Strictly, predictability does not matter in a double-blind trial, but the pharmacological effects of medicinal products often provide the opportunity for intelligent guesswork.)

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