Subverting randomization in controlled trials.

Abstract

Recent empirical evidence supports the importance of adequate randomization in controlled trials. Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment. While that provides empirical evidence of bias being interjected into trials, trial investigators rarely document the sensitive details of subverting the intended purpose of randomization. This article relates anonymous accounts run the gamut from simple to intricate operations, from transillumination of envelopes to searching for code in the office files of the principal investigator. They indicate that deciphering is something more frequent than a rate occurrence. These accounts prompt some methodological recommendations to help prevent deciphering. Randomized controlled trials appear to annoy human nature--if properly conducted, indeed they should.