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Perceived treatment, feedback, and placebo effects in double-blind RCTs: an experimental analysis

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Abstract

Introduction

In double-blind randomized placebo-controlled trials (RCT) of therapeutic interventions, the effects of the treatment may provide feedback that undermines blinding and consequently distorts measures of the effectiveness of the intervention.

Methods and Results

This possibility was confirmed in an experimental model using a dummy placebo procedure whereby participants were led to believe that they were taking part in testing a cognitive-enhancing drug. In two experiments, false feedback given about cognitive performance influenced participants’ beliefs about whether they had been allocated to the active treatment or placebo. These beliefs also appeared to influence actual cognitive performance in that participants who believed they had taken the active treatment had higher accuracy in Experiment 1 and faster reaction times in Experiment 2 than those who believed they had been given a placebo. The addition of no treatment control groups in Experiment 2 showed that these effects could not be accounted for by the feedback manipulation itself, thereby supporting expectancy as a causal factor.

Discussion

These results indicate the importance of assessing participants’ beliefs about their treatment allocation in real double-blind RCTs and considering if and how these may have affected the trial’s outcome.

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References

  • Bausell R, Lao L, Bergman S, Lee W-L, Berman BM (2005) Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants’ perceived assignments in two placebo-controlled trials. Eval Health Prof 28:9–26

    Article  PubMed  Google Scholar 

  • Benedetti F (2005) The importance of considering the effects of perceived group assignment in placebo-controlled trials. Eval Health Prof 28:5–6

    Article  PubMed  Google Scholar 

  • Benedetti F (2007) What do you expect from this treatment? Changing our mind about clinical trials. Pain 128:193–194

    Article  PubMed  Google Scholar 

  • Cohen J, Cohen P, West SG, Aiken LS (2003) Applied multiple regression/correlation analysis for the behavioral sciences, 3rd edn. Erlbaum, Mahwah

    Google Scholar 

  • Colagiuri B, Morley KC, Boakes RA, Haber PS (2009) Expectancy in double-blind placebo-controlled trials: an example from alcohol dependence. Psychother Psychosom 78:167–171

    Article  PubMed  Google Scholar 

  • Dar R, Stronguin F, Etter J-F (2005) Assigned versus perceived placebo effects in nicotine replacement therapy for smoking reduction in Swiss smokers. J Consult Clin Psychol 73:350–353

    Article  PubMed  Google Scholar 

  • Day SJ, Altman DG (2000) Statistics notes: blinding in clinical trials and other studies. Br Med J 321:504

    Article  CAS  Google Scholar 

  • Fergusson D, Glass KC, Waring D, Shapiro S (2004) Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials. Br Med J 328:432–436

    Article  Google Scholar 

  • Fredholm BB, Battig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    CAS  PubMed  Google Scholar 

  • Hróbjartsson A, Forfang E, Haahr MT, Als-Nielsen B, Brorson S (2007) Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding. Int J Epidemiol 36:654–663

    Article  PubMed  Google Scholar 

  • Hughes JR, Gulliver SB, Amori G, Mireault GC, Fenwick JF (1989) Effect of instructions and nicotine on smoking cessation, withdrawal symptoms and self-administration of nicotine gum. Psychopharmacology 99:486–491

    Article  CAS  PubMed  Google Scholar 

  • Karanicolas PJ, Bhandari M, Taromi B, Akl EA, Bassler D, Alonso-Coello P, Rigau D, Bryant D, Smith SE, Walter SD, Guyatt GH (2008) Blinding of outcomes in trials of orthopaedic trauma: an opportunity to enhance the validity of clinical trials. J Bone Jt Surg-Am Vol 90:1026–1033

    Article  Google Scholar 

  • Kirsch I, Rosadino M (1993) Do double-blind studies with informed consent yield externally valid results? Psychopharmacology 110:437–442

    Article  CAS  PubMed  Google Scholar 

  • Kirsch I, Weixel LJ (1988) Double-blind versus deceptive administration of a placebo. Behav Neurosci 102:319–323

    Article  CAS  PubMed  Google Scholar 

  • Kluger AN, DeNisi A (1996) The effects of feedback interventions on performance: a historical review, a meta-analysis, and a preliminary feedback intervention theory. Psychol Bull 119:254–284

    Article  Google Scholar 

  • Lewis TL, Karlowski TR, Kapikian AZ, Lynch JM, Shaffer GW, George DA, Chalmers TC (1975) A controlled clinical trial of ascorbic acid for the common cold. Ann NY Acad Sci 258:505–512

    Article  CAS  PubMed  Google Scholar 

  • Margraf J, Ehlers A, Roth WT, Clark DB, Sheikh J, Agras WS, Taylor CB (1991) How “blind” are double-blind studies? J Consult Clin Psychol 59:184–187

    Article  CAS  PubMed  Google Scholar 

  • McNicol D (1972) A primer of signal detection. Allen & Unwin, London

    Google Scholar 

  • McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, Dillon S, Winfield H, Bjugstad KB, Freed CR (2004) Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 61:412–420

    Article  PubMed  Google Scholar 

  • Morin CM, Colecchi C, Brink D, Astruc M, Mercer J, Remsberg S (1995) How “blind” are double-blind placebo-controlled trials of benzodiazepine hypnotics? Sleep 18:240–245

    CAS  PubMed  Google Scholar 

  • Morley KC, Teesson M, Reid SC, Sannibale C, Thomson C, Phung N, Weltman M, Bell J, Richardson K, Haber PS (2006) Naltrexone versus acamprosate in the treatment of alcohol dependence: a multi-centre, randomized, double-blind, placebo-controlled trial. Addiction 101:1451–1462

    Article  PubMed  Google Scholar 

  • Nash JM, Holroyd KA, Rokicki LA, Kvaal S, Penzien DB (2002) The influence of placebo awareness on stimulant drug response in a double-blind trial. Psychopharmacology 161:213–221

    Article  CAS  PubMed  Google Scholar 

  • Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G, Benedetti F (2001) Response expectancies in placebo analgesia and their clinical relevance. Pain 93:77–84

    Article  CAS  PubMed  Google Scholar 

  • Price DD, Finniss DG, Benedetti F (2008) A comprehensive review of the placebo effect: recent advances and current thought. Ann Rev Psychol 59(2008):565–590

    Article  Google Scholar 

  • Shapiro AK, Shapiro E (1997) The powerful placebo: from ancient priest to modern physician. The John Hopkins University Press, Baltimore

    Google Scholar 

  • Sharpe L, Ryan B, Allard S, Sensky T (2003) Testing for the integrity of blinding in clinical trials: how valid are forced choice paradigms? Psychother Psychosom 72:128–131

    Article  PubMed  Google Scholar 

  • Thomas JL, Guo H, Lynam IM, Powell JN, Okuyemi KS, Bronars CA, Ahluwalia JS (2008) The impact of perceived treatment assignment on smoking cessation outcomes among African-American smokers. J Gen Intern Med 23:1361–1366

    Article  PubMed  Google Scholar 

  • Turner JA, Jensen MP, Warms CA, Cardenas DD (2002) Blinding effectiveness and association of pretreatment expectations with pain improvement in a double-blind randomized controlled trial. Pain 99:91–99

    Article  CAS  PubMed  Google Scholar 

  • Yeomans MR, Ripley T, Davies LH, Rusted JM, Rogers PJ (2002) Effects of caffeine on performance and mood depend on the level of caffeine abstinence. Psychopharmacology 164:241–249

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Psychology (A18), University of Sydney, Sydney, NSW, 2006, Australia

    Ben Colagiuri & Robert A. Boakes

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  1. Ben Colagiuri
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  2. Robert A. Boakes
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Correspondence to Ben Colagiuri.

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Colagiuri, B., Boakes, R.A. Perceived treatment, feedback, and placebo effects in double-blind RCTs: an experimental analysis. Psychopharmacology 208, 433–441 (2010). https://doi.org/10.1007/s00213-009-1743-9

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  • DOI: https://doi.org/10.1007/s00213-009-1743-9

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