Background: Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. Method: Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. Results: Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). Conclusions: Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports.

Schulz KF, Chalmers I, Hayes RJ, Altmann DG: Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408-412.
Jüni P, Altman DG, Egger M: Assessing the quality of controlled clinical trials. BMJ 2001;323:42-46.
Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA: Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 2008;336:601-605.
Perlis RH, Ostacher M, Fava M, Nierenberg AA, Sachs GS, Rosenbaum JF: Assuring that double-blind is blind. Am J Psychiatry 2010;167:250-252.
Kelley JM, Kaptchuk TJ, Cusin C, Lipkin S, Fava M: Open-label placebo for major depressive disorder: a pilot randomized controlled trial. Psychother Psychosom 2012;81:312-314.
Merlo-Pich E, Alexander RC, Fava M, Gomeni R: A new population-enrichment strategy to improve efficiency of placebo-controlled clinical trials of antidepressant drugs. Clin Pharmacol Ther 2010;88:634-642.
Papakostas GI, Fava M: Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol 2009;19:34-40.
Başoğlu M, Marks I, Livnou M, Swinson R: Double-blindness procedures, rater blindness, and ratings of outcome: observations from a controlled trial. Arch Gen Psychiatry 1997;54:744-748.
Boutron I, Estellat C, Ravaud P: Review of blinding in randomized controlled trials found results inconsistent and questionable. J Clin Epidemiol 2005;58:1220-1226.
Hróbjartsson A, Forfang E, Haahr MT, Als-Nielsen B, Brorson S: Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding. Int J Epidemiol 2007;36:654-663.
Rickels K, Lipman RS, Fisher S, Park LC, Uhlenhuth EH: Is a double-blind clinical trial really double-blind? Report of doctors' medication guesses. Psychopharmacologia 1970;16:329-336.
Kleber HD, Weissman MM, Rounsaville BJ, Wilber CH, Prusoff BA, Riordan CE: Imipramine as treatment for depression in addicts. Arch Gen Psychiatry 1983;40:649-653.
Ney PG, Collins C, Spensor C: Double blind: double talk, or are there ways to do better research? Med Hypotheses 1986;21:119-126.
Oxtoby A, Jones A, Robinson M: Is your ‘double-blind' design truly double-blind? Br J Psychiatry 1989;155:700-701.
Fisher S, Greenberg RP: How sound is the double-blind design for evaluating psychotropic drugs? J Nerv Ment Dis 1993;181:345-350.
Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, Greenberg RM, Crowe RR, Cooper TB, Prudic J: Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: randomized controlled trial. JAMA 2001;285:1299-1307.
Fergusson D, Cranley Glass K, Waring D, Shapiro S: Turning a blind eye: the success of blinding reported in a random sample of randomized, placebo controlled trials. BMJ 2004;328:432.
Ghaemi SN: Clinician's Guide to Statistics and Mental Health. Cambridge, Cambridge University Press, 2009, pp 19-20.
Fitzgerald PB, Benitez J, de Castella A, Daskalakis ZJ, Brown TL, Kulkarni J: A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression. Am J Psychiatry 2006;163:88-94.
James EK, Bloch DA, Lee KK, Kraemer HC, Fuller RK: An index for assessing blindness in a multi-center clinical trial of disulfiram for alcohol cessation: a VA cooperative study. Stat Med 1996;15:1421-1434.
Bang H, Ni L, Davis CE: Assessment of blinding in clinical trials. Control Clin Trials 2003;25:143-156.
Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsche PC, Lang T, CONSORT GROUP (Consolidated Standards of Reporting Trials): The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 2001;134:663-694.
Colagiuri B, Boakes RA: Perceived treatment, feedback, and placebo effects in double-blind RCTs: an experimental analysis. Psychopharmacology 2010;208:433-441.
Rief W, Bingel U, Schedlowski M, Enck P: Mechanisms involved in placebo and nocebo responses and implications for drug trials. Clin Pharmacol Ther 2011;90:722-726.
Sackett DL: Measuring the success of blinding RCTs: don't, must, can't, or needn't? Int J Epidemiol 2007;36:664-665.
Schulz KF, Altmann DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010;152:726-732.
Crumley ET, Wiebe N, Cramer K, Klassen TP, Hartling L: Which resources should be used to identify RCT/CCTs for systematic reviews: systematic review. BMC Med Res Methodol 2005;5:24.
Galandi D, Schwarzer G, Antes G: Demise of the randomized controlled trial: bibliometric study of the German-language healthcare literature, 1948 to 2004. BMC Med Res Methodol 2006;6:30.
Baethge C: The languages of medicine. Dtsch Arztebl Int 2008;105:37-40.
Heidenreich U, Baethge C: German language psychiatry journals in Germany: a quantitative analysis. Psychiatr Prax 2012;39:26-33.
Kolahi J, Bang H, Park J: Towards a proposal for assessment of blinding success in clinical trials. Commun Dent Oral Epidemiol 2009;37:477-484.
Hróbjartsson A, Boutron I: Blinding in randomized clinical trials: imposed impartiality. Clin Pharmacol Ther 2011;90:732-736.
Sharpe L, Ryan B, Allard S, Sansky T: Testing for the integrity of blinding in clinical trials: how valid are forced choice paradigms? Psychother Psychosom 2003;72:128-131.
Hopton AK, MacPherson H: Assessing blinding in randomised controlled trials of acupuncture: challenges and recommendations. Chin J Integr Med 2011;17:173-176.
Bang H, Flaherty SP, Kolahi J, Park J: Blinding assessment in clinical trials: a review of statistical methods and a proposal of blinding assessment protocol. Clin Res Regul Aff 2010;27:42-51.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.