Changes in beliefs identify unblinding in randomized controlled trials: a method to meet CONSORT guidelines
Section snippets
Introduction and background
The randomized, placebo-controlled trial is often described as the gold standard for research involving human participants. An important aim of the study design is to allow comparisons between groups of participants whose characteristics are, on average, as similar as possible with the exception of the intervention being studied. This is achieved primarily through randomization, which aims to prevent selection bias and balance the distribution of measured and unmeasured confounding variables
Methods
We previously investigated participant blinding in a community-based pilot study in northern California to investigate the effect on gastrointestinal infectious illness of water treatment units installed at the kitchen sink [25], [26]. To promote successful blinding, the active and placebo units were designed to be externally identical and to produce water with similar characteristics such as temperature, taste and odor. The active unit consisted of a filter and ultraviolet light system in
Results
Water treatment units were installed in 80 households, 3 of which were subsequently excluded from the study [25]; the remaining 77 households comprised 236 individuals. Participants aged ≥12 years (N=179) were asked to report their beliefs on 8 occasions and did so on average 6.6 times (median 8, interquartile range 6–8). Valid responses were provided at week 2 by 172 (96%) respondents, at week 16 by 145 (81%) and on all 8 occasions by 123 (69%); 132 (74%) reported their beliefs on at least 6
Discussion
In most evaluations of blinding, participants are only asked to try to identify their intervention group at the end of the trial. For a simple comparison of beliefs at the end of the trial to identify significant intergroup differences caused by unblinding depends on the assumption that participants are undecided at baseline with respect to beliefs. By actually measuring beliefs at baseline in the sequential analysis, we increased our sensitivity to identify changes in belief indicative of
Conclusion
In summary, assessment of blinding effectiveness via changes in beliefs identified group-related differences in participants' beliefs that were not identified by cross-sectional analyses of beliefs at the end of the trial. The longitudinal evidence for unblinding was statistically significant and was supported by evidence that beliefs were associated with—and hence might bias—the primary study outcome, suggesting that the intervention effect should be reported within belief strata.
Our
Acknowledgement
Funding for this work was provided through Cooperative Agreement U50/CCU915546-02-1 from the Centers for Disease Control and Prevention. For their contributions to this work, we thank Anne Benker, Sue Binder, Cliff Bowen, Susan Burns, Rebecca Calderon, Joshua Ergas, Kim Fox, Allen Hightower, Ron Hoffer, Alan Hubbard, Dennis Juranek, Asheena Khalakdina, Catherine Ma, Daniel Mills, Gretchen Rothrock, Art Reingold, Sona Saha, Rick Sakaji, Suhminder Sandhu, Susan Shaw, Kate Steiner, Duc Vugia.
References (33)
- et al.
Placebos, active control groups, and the unpredictability paradox
Biol. Psychiatry
(2000) In randomized controlled trials, should subjects in both placebo and drug groups be expected to guess that they are taking drug 50% of the time?
Med. Hypotheses
(2002)- et al.
Double blind: double talk or are there ways to do better research
Med. Hypotheses
(1986) - et al.
Assessment of blinding in clinical trials
Control. Clin. Trials
(2004) - et al.
Improving the quality of reporting of randomized controlled trials. The CONSORT statement
JAMA
(1996) - et al.
The revised CONSORT statement for reporting randomized trials: explanation and elaboration
Ann. Intern. Med.
(2001) - et al.
Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials
BMJ
(2004) - et al.
The landscape and lexicon of blinding in randomized trials
Ann. Intern. Med.
(2002) A critique of the double-blind clinical trial. Part 1
Altern. Ther. Health Med.
(1996)A critique of the double-blind clinical trial. Part 2
Altern. Ther. Health Med.
(1996)
Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials
Cephalalgia
Adherence to treatment and health outcomes
Arch. Int. Med.
Are randomized controlled trials controlled? Patient preferences and unblind trials
J. R. Soc. Med.
Assessment of double-blindness at the conclusion of the beta-blocker heart attack trial
JAMA
How blind was the patient blind in AMIS?
Clin. Pharmacol. Ther.
Ascorbic acid for the common cold. A prophylactic and therapeutic trial
JAMA
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