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Placebo Response in Patients with Oral Therapy for Overactive Bladder: A Systematic Review and Meta-analysis

  • Hadi Mostafaei
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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  • Florian Janisch
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Department of Urology, Medical University of Hamburg, Hamburg, Germany
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  • Keiichiro Mori
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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  • Fahad Quhal
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
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  • Benjamin Pradere
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Department of Urology, CHRU Tours, Francois Rabelais University, Tours, France
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  • Sakineh Hajebrahimi
    Affiliations
    Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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  • Claus G. Roehrborn
    Affiliations
    Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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  • Shahrokh F. Shariat
    Correspondence
    Corresponding author at: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Tel. +43 664 800 165 1010.
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

    Department of Urology, University of Jordan, Amman, Jordan

    European Association of Urology Research Foundation, Arnhem, The Netherlands
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Published:March 02, 2021DOI:https://doi.org/10.1016/j.euf.2021.02.005

      Abstract

      Context

      The role of a placebo response in the management of overactive bladder (OAB) remains unclear.

      Objective

      The aim of this review is to methodically study the placebo response extracted from the control arms of randomized clinical trials assessing therapy in patients with OAB.

      Evidence acquisition

      Medline (PubMed), The Cochrane Library, EMBASE, and Scopus were searched to identify randomized controlled trials (RCTs) published until September 2019. Randomized placebo-controlled trials investigating oral drug therapy for OAB were included. The articles were critically appraised by two reviewers. The primary outcomes were the placebo response in the main patient-reported urinary outcomes together with assessing the impact of patient demographic factors on the placebo response.

      Evidence synthesis

      The initial search resulted in 1982 records after reviewing the titles and abstracts, and reference lists of other systematic reviews; 57 studies with an overall estimated 12 901 patients were included in the meta-analysis. The included studies were of overall high/acceptable quality. The standardized mean difference was −0.45 (95% confidence interval [CI] −0.51 to −0.40; p < 0.001) for daily micturition episodes, −0.33 (95% CI −0.42 to −0.24; p < 0.001) for daily nocturia episodes, −0.46 (95% CI −0.55 to −0.37; p < 0.001) for urgency urinary incontinence episodes, −0.50 (95% CI −0.61 to −0.39; p < 0.001) for daily urgency episodes, −0.51 (95% CI −0.60 to −0.43; p < 0.001) for daily incontinence episodes, and 0.25 (95% CI 0.211–0.290; p < 0.001) for volume voided per micturition. The meta-regression of age-related impact of the placebo response on nocturia showed a slope of −0.02 (p < 0.001).

      Conclusions

      Placebo has a statistically significant effect on improving symptoms and signs associated with OAB; this effect is age dependent. However, there is no consensus on what change of OAB symptoms and signs is clinically meaningful for the affected patient. Taken together, the placebo response seems to be non-negligible in OAB, supporting the need for placebo control in RCTs.

      Patient summary

      Placebo is an inert treatment method often used in clinical research for comparison with active treatment. However, studies show that placebo has an effect of its own. A placebo response means the total improvement resulting from receiving a placebo. In our study, placebo had a significant role in improving the symptoms of overactive bladder.

      Keywords

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