Changing the mindset about unblinding in clinical trials
Fergusson et al have usefully highlighted the problem of unblinding in clinical trials.1 They propose that item 11b of the CONSORT statement2 should be revised to make assessment of blinding a requirement.
Their data suggest that more often than not blinding in clinical trials is compromised. In the circumstances, merely reporting whether a trial is blinded may be insufficient. In fact, there is bias in the wording of item 11b of the CONSORT statement. The item in the checklist is "If done, how the success of blinding was evaluated". In other words, it seems to imply that assessment of blinding will confirm its validity. We need to change our mindset to whether it matters if and when the blind is broken.
Reporting of the assessment of blinding is uncommon. Correlation of outcome measures with degree of unblinding is even less common and was only done in a few of the 15 trials reported by Fergusson et al. For example, Sackheim et al found a robust association with relapse status and patients’ guesses.3 As pointed out by Fergusson et al, the direction of the causality of this association may be difficult to ascertain. After all, if treatment is obviously effective it is not possible technically to perform a trial double-blind. This may be the explanation of the association found by Sackheim et al. On the other hand, it could be a reflection of bias introduced through unblinding. How we evaluate the efficacy of active treatment is unclear. Breaking of the double-blinding has been interpreted as the explanation for a positive trial result.4 Why should this not be the case in more trials which conclude that active treatment is effective?
Fergusson et al’s suggested minimum set of information for the assessment of blinding includes counts of the correctness of patients’ guesses. As they note, this is particularly beneficial in trials with subjective outcomesor outcomes reported by patients. However, raters’ guesses may be more important in trials where the outcome measures are dependent on such scores. It is possible for patients to remain blind, but for raters still to be unblinded leading to significant correlation with outcome measures.5
- Fergusson D, Glass KC, Waring D, Shapiro S. Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials. BMJ, doi:10.1136/bmj.37952.631667.EE (published 22 January 2004) [Full text]
- CONSORT statement website http://www.consort-statement.org/
- Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001; 285: 1299-1307. [Full Text]
- Karlowski TR, Chalmers TC, Frenkel LD et al Ascorbic acid for the common cold. Journal of the American Medical Association 1975; 231: 1038-42.
- Double DB. Unblinding in trials of the withdrawal of anticholinergic agents in patients maintained on neuroleptics. Journal of Nervous and Mental Disease 1995; 183: 599-602 [Medline]
Competing interests: No competing interests