Allocation concealment and blinding: when ignorance is bliss

In reply: Allocation concealment refers to ignorance of future treatment assignment before randomisation whereas masking or blinding is most commonly used to refer to the concealment of treatment assignment after randomisation.1

There are two criteria for successful concealment of allocation: (i) physical concealment of the process of random assignment to treatment, and (ii) concealment of any pattern of consecutive assignments. Successful concealment of the process must prevent unauthorised access to randomisation lists, envelopes or algorithms; the best way is to use a centralised or remote service for randomisation, whereby an independent party other than the clinician or investigator accesses a secure sequence list or a secure computer system to generate the next allocation.2,3 Successful concealment of the pattern of random assignments prevents investigators from predicting a future treatment assignment on the basis of pattern recognition of allocations to date. Identifying a pattern of previous allocations can occur in open-label trials, in which all parties are aware of allocated treatments after randomisation, or if the blinding of patients and investigators has been compromised. The likely success of concealing the allocation process can reasonably be judged by its description in most trial reports (usually found in the Methods section). However, it is usually more difficult to assess the likelihood that investigators could have predicted future allocations.

Unsuccessful concealment of treatment assignment after randomisation (masking or blinding) should be detailed in the trial report. In circumstances where the blinding has been substantially compromised, exploring the results of treatment separately among participants who were unblinded and those who remained blinded, should be considered, although these are no longer randomised comparisons. In the study by Karlowski et al,4 the placebo did not match the active treatment in taste, which alerted the investigators to the likely occurrence of significant unblinding within the study. To their credit, the investigators sought to quantify the extent of unblinding by means of a questionnaire at study close-out, and reported their findings by results of these responses. The particular grouping of responses, however, has been the subject of some discussion,5,6 and while the interpretation of a possible placebo effect has been challenged, it has not necessarily been disproven. (The absence of a placebo effect could be proven only if information concerning perceived benefits of vitamin C related more to cold frequency than cold symptoms. Biologically, it is far more plausible for a placebo effect to result in fewer cold symptoms reported than fewer colds reported.) This trial highlights the impact of compromised blinding in the reporting of trial results, emphasising the importance of maintaining adequate blinding for reliable and unbiased trial results.

Good quality reporting of trials, in accordance with the CONSORT statement,7 includes describing the processes in enough detail to assure readers that any pattern of randomisation is not predictable. Authors should report issues relating to allocation concealment, blinding (where appropriate) and randomisation sufficiently to convey the message that these essential trial principles were successfully achieved.8