A theoretical analysis showed that blinding cannot eliminate potential for bias associated with beliefs about allocation in randomized clinical trials.
OBJECTIVE
To explore the theoretical justification for blinding in randomized trials and make recommendations concerning the implementation and interpretation of blinded randomized trials.


METHODS
A theoretical analysis was conducted of the potential for bias in randomized trials with successful blinding (ie, trials in which beliefs about allocation to treatment or control groups are independent of actual allocation). The analysis identified conditions that must be satisfied to ensure that blinding eliminates the potential for bias associated with beliefs about allocation.


RESULTS
Even when beliefs about allocation are independent of actual allocation, they can still cause bias. The potential for bias is eliminated when the belief is uniformly one of complete ambivalence about allocation.


CONCLUSIONS
Even when blinding succeeds in making beliefs about allocation independent of actual allocation, beliefs about allocation may still cause bias. It is difficult to determine the extent of bias in any particular trial. Bias could be eliminated by establishing a state of complete ambivalence about the allocation of every trial participant, but universal ambivalence may be difficult to achieve and may reduce the generalizability of the trial's findings.
School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
Erin
E
Mathieu
Neuroscience Research Australia, Barker St, Randwick, City Road, Camperdown, NSW 2031, Australia. Electronic address: r.herbert@neura.edu.au.
Robert D
RD
Herbert
Sydney School of Public Health, University of Sydney, City Road, Camperdown, NSW 2006, Australia.
Kevin
K
McGeechan
Faculty of Science, University of Sydney, City Road, Camperdown, NSW 2006, Australia; Faculty of Engineering and Information Technologies, University of Sydney, City Road, Camperdown, NSW 2006, Australia.
Jemma J
JJ
Herbert
Sydney School of Public Health, University of Sydney, City Road, Camperdown, NSW 2006, Australia.
Alexandra L
AL
Barratt
D015982:Bias; D004311:Double-Blind Method; D006801:Humans; D008962:Models, Theoretical; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards
Bias; Blinding; Clinical trials; Masking; RCTs; Randomized controlled trials