A recently published randomized, controlled, double-blind, study has reported efficacy of
zinc gluconate lozenge treatment of the
common cold. Because of a higher rate of side effects in the
zinc group and the lack of any confirmatory evidence of blinding efficacy, we are concerned about the possible contribution of bias to the study result. Unflavored
zinc gluconate tablets can be easily distinguished from the relatively tasteless, unflavored
calcium lactate tablets, which were used as placebo in the cited study, increasing our concern about bias. In order to be able to test
zinc lozenges in a second trial of
common cold therapy, we developed a matching placebo containing
denatonium benzoate (a bitter substance used to prevent thumb sucking in children) and then undertook a formal evaluation of blinding efficacy. This article reports the results of this evaluation, encompassing two randomized, controlled taste trials; the first trial of the placebo matching showed
zinc recipients to exhibit a higher rate of side effects and also a significantly higher proportion of subjects believing they were on "active" treatment. Alterations in dosage before the second taste trial yielded comparability of the placebo and
zinc lozenges. This study illustrates the pitfalls which may sometimes be encountered in performing and publishing studies in which
placebos are either not tested at all or tested in too small a subject population to detect a significant subjective difference between the placebo and the active medication.