Clinical Trials

❘❙❚■ Chapter 8 | BlindingThis approach might benefit treatments that have fewer side-effects. However,side-effects may be less because the treatment is less clinically effective. Safetystudies often have a single-blind design that allows investigators to detectside-effects more readily.Double-blinded studiesIn double-blinded studies, neither the patient nor the investigator knows theidentity of the assigned intervention [2–4]. A number of biases are thus reduced,such as investigators’ preconceptions of the treatments used in the study. Thisreduces the ability of the investigators to monitor the safety of treatments, so aDMSC must regularly review the rate of adverse events in each arm of the trial.Operating these committees is difficult, as they must meet regularly enough to beable to detect differences promptly, avoiding needless further harm to patients,while avoiding early termination of a trial due to a chance difference.What specific problems do double-blinded studies have?Double-blinded studies are complex and their validity depends on the investigatorsand participants remaining blinded. A study of a drug is easily unblinded if themedications are not identical in appearance. Although most patients only receiveone drug – unless they are involved in a crossover study, where each participanttakes both the new and standard treatments – they often meet and could comparepills and tablets. Medical staff also have the opportunity to compare themedications of both groups, and can unblind the study. It is therefore important touse carefully matched medications, especially in crossover studies.To prevent imperfect matching, a panel unconnected with the study should carryout a pre-test by comparing samples of the drugs. Perfect matches are rare, andimperfect matches are tolerated so long as they do not reveal the identity of theagent. Dyes such as vanilla can mask a distinctive odor, and quassin will givepreparations a bitter taste that masks flavor and discourages the patient frombiting the tablets in half, but it is usually best to avoid such extreme measures.The ideal method of blinding is to use agents that appear identical by formulatingthem appropriately or by enclosing them in identical capsules.Triple-blinded studiesIn triple-blinded studies, as well as the investigators and participants, all membersof the sponsor’s project team (eg, the project clinician, statistician, and datamanager), and even the DMSC, are blinded [2]. This lessens the chance that theDMSC will stop the trial early in favor of either treatment, and makes evaluationsof the results more objective. However, this hampers the DMSC’s ability tomonitor safety and efficacy endpoints, and some investigators might feeluncomfortable when participating because there is no one to oversee the results78