Double-Blinded Study

A randomized clinical trial is regarded as the most highly influential study design that provides the highest level of evidence in the assessment of therapeutic outcome in medical science because it increases the validity of the study by eliminating potential study-related biases. However, to address potential study-related biases, various criteria have been established to maintain such high level of evidence and are largely based on the quality of the trial. Thus, trial quality is an imperative component in any randomized clinical trial. If steps are taken to reduce potential bias, the appropriately size and direction of the intervention effect can be properly obtained. One method utilized to decrease the risk of potential bias that could mislead the intervention effect is double blinding.

Prior to the start of a randomized clinical trial, generation of the allocation sequence is imperative. In clinical trials, defining the manner as to how the allocation sequence is generated characterizes the type of study design as being randomized, quasi-random-ized, or a controlled clinical trial. If the generation of the allocation sequence was unpredictable, the two groups being compared are associated with less confounds between them and a true measure of the treatment effect can be obtained. Compromising the allocation sequence could contribute to selection bias.

According to the latest statement by the CONSORT group regarding improving quality trials in randomized clinical trial, allocation concealment represents the method utilized to employ the random allocation sequence. Such a method clarifies whether the allocation sequence was or was not properly concealed until interventions were assigned. Proper allocation concealment prevents the participants [Page 554]and the investigators from knowing in advance what treatment the subjects will receive. Therefore, both the participants and the investigators or the researcher responsible for the assessment of the intervention are both blinded (double blinding) to the treatment administered. Thus, adhering to allocation concealment by double blinding prevents influencing the subjects whether or not to enroll, adhere, or respond to a treatment regime; thereby, decreasing the risk of selection bias. In fact, a meta-analysis of various trials assessing if allocation concealment was inadequate/unclear or adequate indicated that trials with inadequate/unclear concealment yielded an overestimated treatment effect by 30 percent. The overestimated effect of lack of allocation concealment was twofold in comparison to the assessment of nonblinding versus blinding. Thus, allocation concealment is an imperative component to trial quality.

The lack of double blinding can further affect the true estimate of the treatment and contribute to performance bias by the patient and detection/measure-ment bias by the study investigators. Knowledge of the treatment by the study investigators and subjects could affect the outcome being expressed and measured; thus, affecting the true effect of the treatment. In addition, not accounting for study withdrawals or dropout rates, also referred to as attrition bias, may contribute to unbalanced sample groups; thus, the effects of the treatment could be inappropriately estimated. Methodological quality in randomized clinical trials is largely based upon the proper execution of the generation and concealment of the allocation sequence, and the assessment of withdrawals or dropouts. However, to properly perform such methods or avoid deleteriously affecting certain study events that may influence the treatment effect, double blinding is paramount.

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