Unreported formal assessment of unblinding occurred in 4 of 10 randomized clinical trials, unreported loss of blinding in 1 of 10 trials

Objectives Randomized clinical trials often involve blinding as a methodological procedure to avoid bias. Unfortunately, blinding procedures may be unsuccessful, but the risk of unblinding is rarely reported in trial publications. Our primary aim was to assess the occurrence of unreported assessment of the risk of unblinding in randomized clinical trials and to describe the assessment procedures involved. Our secondary aim was to assess the occurrence of unreported suspected or overt unblinding and the mechanisms of unblinding. Study Design and Setting A Web-based questionnaire survey of authors to trial publications which did not report risk of unblinding. Respondents were corresponding authors to a random sample of PubMed indexed articles on blinded randomized clinical trials published in 2010. We initially sampled 300 publications of which 24 reported on risk of unblinding. Results Of the 276 contacted trial authors, 129 (47%) responded. Assessment of the risk of unblinding was conducted in 56 trials (43%), often based on a pretrial evaluation involving a group of healthy assessors trying to identify differences between experimental and control interventions. When we included informal assessments of the risk of unblinding, the number of trials assessing the risk of unblinding increased to 75 (58%). Suspected or overt unblinding occurred in 14 trials (11%), mostly based on perceptible differences between experimental and control interventions. Conclusion Approximately 4 of 10 trials assessed risk of unblinding without reporting such assessments in the trial publication, and approximately 1 in 10 trials identified cases of overt or suspected unblinding, also without reporting them. Unblinding is not an exceptional event in randomized clinical trials; it occurs regularly but is rarely reported.