--- title: "Randomize placebo trial-determine the placebo effect size. | Sutter Health" description: "True placebo effect sizes can be analyzed through a proper inverse placebo RCT design." url: "https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404" --- 1. [Home](https://www.sutterhealth.org/) / 2. [Research](https://www.sutterhealth.org/research) / 3. [Research publications](https://www.sutterhealth.org/research/publications) / 4. Randomize placebo trial-determine the placebo effect size. # Randomized placebo-controlled placebo trial to determine the placebo effect size. Gerdesmeyer L, Klueter T, Rahlfs VW, Muderis MA, Saxena A, Gollwitzer H, Harrasser N, Stukenberg M, & Prehn-Kristensen A. _Pain Physician. 20(5):387-396._ 2017-07-01 ## Abstract BACKGROUND: It is the gold standard to use a placebo treatment as the control group in prospective randomized controlled trials (RCTs). Although placebo-controlled trials can reveal an effect of an active treatment, the pure effect of a placebo treatment alone has never been presented or evaluated. No evidence-based, placebo-therapeutic options are currently available, and no placebo-controlled trials have been performed to elucidate the pure placebo effect. OBJECTIVES: To analyze the pure placebo effect on clinical, chronic pain through a blinded RCT. STUDY DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Medical University centers. METHODS: One-hundred eighty-two patients suffering from chronic plantar heel pain for over 6 months,who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. As an exploratory outcome, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the Mann-Whitney-U tests for group comparisons; treatment efficiency was calculated by the effect size coefficient and benchmarks for the Mann-Whitney estimator according to the t-test of 2 independent samples for quantitative data, as well as the Fisher's exact test for binary data. RESULTS: Patients from both groups did not differ with respect to heel pain ratings at baseline, for both the VAS (P = .476) and RMS (P = .810) scores. After 6 weeks, patients receiving the blinded placebo treatment reported less heel pain on both scales (VAS: P = .031; RMS: P = .004). Change scores of pain ratings were significantly higher in the blinded placebo group than in the un-blinded placebo group (VAS: P = .002; RMS: P = .002). LIMITATIONS: As the study represents the first to use an inverse placebo RCT (IPRCT), further conceptual and methodological issues need to be addressed to describe detailed, underlying mechanisms. Specific contextual, intrapersonal, and interpersonal factors modulating the placebo effects should be addressed in future IPRCTs. CONCLUSIONS: The present study indicated that true placebo effect sizes can be analyzed through a proper IPRCT design. Instead of treating high numbers of patients with placebos in a RCT, which increases the risk for subjects not receiving the active treatment, the IPRCT technique seems to be much more appropriate to analyze the effect sizes of any active treatment, in accordance with the Good Clinical Practice guidelines and Declarations of Helsinki. [PubMed abstract](https://www.ncbi.nlm.nih.gov/pubmed/28727701) ## Research topics - [Biostatistics](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Biostatistics%5C%22%22) - [Musculoskeletal Disorders](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Musculoskeletal+Disorders%5C%22%22) - [Pain](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Pain%5C%22%22) ## Related publications [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) - Publication ### [Methods for assessing fracture risk prediction models: experience with FRAX in a large integrated health care delivery system.](https://www.sutterhealth.org/research/publications/using-frax-in-large-healthcare-delivery-system-1055312749) Pressman AR, Lo JC, Chandra M, Ettinger B. J Clin Densitom. 14(4):407-15. doi: 10.1016/j.jocd.2011.06.006. Epub 2011 Oct 1. 2011 Oct 01 - Publication ### [Use of electronic health records for early detection of high-cost, low back pain patients.](https://www.sutterhealth.org/research/publications/use-ehrs-to-detect-high-cost-low-back-pain-pts-1055312584) Maeng DD, Stewart WF, Yan X, Boscarino JA, Mardekian J, Harnett J, Von Korff MR. Pain Res Manag. 20(5):234-40. Epub 2015 Aug 20. 2015 Sep 01 - Publication ### [Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial.](https://www.sutterhealth.org/research/publications/tramadol-vs-codeine-and-acetaminophen-chronic-pain-1055312321) Mullican WS, Lacy JR; TRAMAP-ANAG-006 Study Group. Clin Ther. 23(9):1429-45. 2001 Sep 01 - Publication ### [Patterns of health care utilization for low back pain.](https://www.sutterhealth.org/research/publications/health-care-utilization-in-low-back-pain-1055312713) Stewart WF, Yan X, Boscarino JA, Maeng DD, Mardekian J, Sanchez RJ, Von Korff MR. J Pain Res. 8:523-35. doi: 10.2147/JPR.S83599. eCollection 2015. 2015 Aug 12 - Publication ### [Racial and ethnic disparities in opioid prescribing for long bone fractures at discharge from the emergency department: a cross-sectional analysis of 22 centers from a health care delivery system in Northern California.](https://www.sutterhealth.org/research/publications/racial-disparities-opiod-prescribing-for-fractures-in-ed-1055312717) Romanelli RJ, Shen Z, Szwerinski N, Scott A, Lockhart S, Pressman AR. Ann Emerg Med. pii: S0196-0644(19)30417-2. doi: 10.1016/j.annemergmed.2019.05.018. \[Epub ahead of print\] 2019 Jul 01 [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) ```json {"@context":"https://schema.org","@type":"MedicalOrganization","name":"Sutter Health","@id":"https://www.sutterhealth.org/#medicalorganization","url":"https://www.sutterhealth.org","logo":"https://www.sutterhealth.org/static/images/sutter-health-logo.svg","address":{"@type":"PostalAddress","streetAddress":"2200 River Plaza Drive","addressLocality":"Sacramento","addressRegion":"CA","postalCode":"95833","addressCountry":"US"},"areaServed":{"@type":"AdministrativeArea","name":"California"},"sameAs":["https://www.facebook.com/SutterHealth","https://www.instagram.com/sutterhealth/","https://x.com/SutterHealth","https://www.youtube.com/sutterhealth","https://www.linkedin.com/company/sutter-health","https://en.wikipedia.org/wiki/Sutter_Health"]} ``` ```json {"@context":"https://schema.org","@type":"BreadcrumbList","@id":"https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404#breadcrumblist","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://www.sutterhealth.org/"},{"@type":"ListItem","position":2,"name":"Research","item":"https://www.sutterhealth.org/research"},{"@type":"ListItem","position":3,"name":"Research publications","item":"https://www.sutterhealth.org/research/publications"},{"@type":"ListItem","position":4,"name":"Randomize placebo trial-determine the placebo effect size."}]} ``` ```json {"@context":"https://schema.org","@type":"MedicalScholarlyArticle","@id":"https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404#medicalscholarlyarticle","name":"Randomized placebo-controlled placebo trial to determine the placebo effect size.","headline":"Randomize placebo trial-determine the placebo effect size.","abstract":"BACKGROUND: It is the gold standard to use a placebo treatment as the control group in prospective randomized controlled trials (RCTs). Although placebo-controlled trials can reveal an effect of an active treatment, the pure effect of a placebo treatment alone has never been presented or evaluated. No evidence-based, placebo-therapeutic options are currently available, and no placebo-controlled trials have been performed to elucidate the pure placebo effect. OBJECTIVES: To analyze the pure placebo effect on clinical, chronic pain through a blinded RCT. STUDY DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Medical University centers. METHODS: One-hundred eighty-two patients suffering from chronic plantar heel pain for over 6 months,who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. As an exploratory outcome, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the Mann-Whitney-U tests for group comparisons; treatment efficiency was calculated by the effect size coefficient and benchmarks for the Mann-Whitney estimator according to the t-test of 2 independent samples for quantitative data, as well as the Fisher's exact test for binary data. RESULTS: Patients from both groups did not differ with respect to heel pain ratings at baseline, for both the VAS (P = .476) and RMS (P = .810) scores. After 6 weeks, patients receiving the blinded placebo treatment reported less heel pain on both scales (VAS: P = .031; RMS: P = .004). Change scores of pain ratings were significantly higher in the blinded placebo group than in the un-blinded placebo group (VAS: P = .002; RMS: P = .002). LIMITATIONS: As the study represents the first to use an inverse placebo RCT (IPRCT), further conceptual and methodological issues need to be addressed to describe detailed, underlying mechanisms. Specific contextual, intrapersonal, and interpersonal factors modulating the placebo effects should be addressed in future IPRCTs. CONCLUSIONS: The present study indicated that true placebo effect sizes can be analyzed through a proper IPRCT design. Instead of treating high numbers of patients with placebos in a RCT, which increases the risk for subjects not receiving the active treatment, the IPRCT technique seems to be much more appropriate to analyze the effect sizes of any active treatment, in accordance with the Good Clinical Practice guidelines and Declarations of Helsinki.","description":"True placebo effect sizes can be analyzed through a proper inverse placebo RCT design.","keywords":["Biostatistics","Musculoskeletal Disorders","Pain"],"datePublished":"2017-07-01","url":"https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404","inLanguage":"en-US","identifier":[{"@type":"PropertyValue","propertyID":"PMID","value":"28727701"}],"sameAs":["https://pubmed.ncbi.nlm.nih.gov/28727701/"],"isPartOf":{"@type":"Periodical","name":"Pain Physician"},"author":[{"@type":"Person","name":"Gerdesmeyer L"},{"@type":"Person","name":"Klueter T"},{"@type":"Person","name":"Rahlfs VW"},{"@type":"Person","name":"Muderis MA"},{"@type":"Person","name":"Saxena A"},{"@type":"Person","name":"Gollwitzer H"},{"@type":"Person","name":"Harrasser N"},{"@type":"Person","name":"Stukenberg M"},{"@type":"Person","name":"Prehn-Kristensen A"}],"sourceOrganization":{"@type":"MedicalOrganization","name":"Palo Alto Medical Foundation Research Institute"},"about":[{"@type":"DefinedTerm","name":"Biostatistics","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Biostatistics%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Musculoskeletal Disorders","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Musculoskeletal+Disorders%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Pain","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Pain%22%5D%7D%5D&verticalKey=research_publication"}],"mainEntityOfPage":{"@type":"WebPage","@id":"https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404","breadcrumb":{"@id":"https://www.sutterhealth.org/research/publications/randomize-placebo-trial-determine-the-placebo-effect-size-1055312404#breadcrumblist"}}} ```