According to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions [29], a lack of blinding of participants and personnel in randomized trials increases the risk of bias. The areas most affected are performance (i.e., there may be differences in the care that is provided in each arm) and detection bias (i.e., there may be differences between the groups in how outcome is determined). For many reasons discussed previously, while double-blinding is the standard method for medication trials in general, it is unsuitable for disulfiram trials. One might infer that this meta-analysis is biased by using predominantly open-label trials. In disulfiram research, we propose that one revisit the meaning of quality RCTs. A meta-analysis of disulfiram would be of no practical use if it consisted of only double-blind trials. The use of an open-label design in efficacy trials with this atypical medication could be viewed as indispensable rather than as evidence of poor study quality.
