Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial

Anthony Lembo, John M Kelley, Judy Nee, Sarah Ballou, Johanna Iturrino, Vivian Cheng, Vikram Rangan, Jesse Katon, William Hirsch, Irving Kirsch, Kathryn Hall, Roger B Davis, Ted J Kaptchuk, Anthony Lembo, John M Kelley, Judy Nee, Sarah Ballou, Johanna Iturrino, Vivian Cheng, Vikram Rangan, Jesse Katon, William Hirsch, Irving Kirsch, Kathryn Hall, Roger B Davis, Ted J Kaptchuk

Abstract

It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (ie, open-label placebos [OLPs]) have recently been shown to be effective in some conditions. This study had 2 objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS) and, second, to compare the efficacy of OLP against double-blind placebo (DBP). In a 6-week, 3-arm, randomized clinical trial, participants were randomized in equal proportions to 3 arms: OLP, DBP, or NPC. Two hundred sixty-two adults (72.9% women), with a mean age of 42.0 (SD = 18.1) years, participated in the primary study. The mean improvement on the IBS Severity Scoring System from baseline to the 6-week end point was significantly greater in OLP compared with that in NPC (90.6 vs 52.3, P = 0.038). Open-label placebo and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485). Standardized effect sizes were moderate for OLP vs NPC (d = 0.43) and small for OLP vs DBP (d = 0.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than those on NPC. Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective and that OLP could play a role in the management of patients with refractory IBS.

Trial registration: ClinicalTrials.gov NCT02802241.

Copyright © 2021 International Association for the Study of Pain.

Figures

Figure 1:
Figure 1:
Patient Flow Diagram.
Figure 2:
Figure 2:
Outcomes at 6-week Endpoint. (A) Primary Outcome: Improvement on the IBS Severity Scoring System (IBS-SSS). (B) Secondary Outcome: Global Improvement in IBS Symptoms (IBS-GIS). (C) Secondary Outcome: Percent of Participants Reporting Adequate Relief of Symptoms (IBS-AR).

References

    1. Ballou S, Kaptchuk TJ, Hirsch W, Nee J, Iturrino J, Hall KT, Kelley JM, Cheng V, Kirsch I, Jacobson E, Conboy L, Lembo A, Davis RB. Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial. Trials 2017;18:234.
    1. Beecher HK. The powerful placebo. J Am Med Assoc 1955;159:1602–1606.
    1. Bishop FL, Aizlewood L, Adams AEM. When and why placebo-prescribing is acceptable and unacceptable: a focus group study of patients’ views. PLoS ONE 2014;9:e101822.
    1. Blease C, Colloca L, Kaptchuk TJ. Are open-Label Placebos Ethical? Informed Consent and Ethical Equivocations. Bioethics 2016;30:407–414.
    1. Burke MJ. “It’s All in Your Head”-Medicine’s Silent Epidemic. JAMA Neurol 2019.
    1. Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain 2016.
    1. Cohen J A power primer. Psychol Bull 1992;112:155–159.
    1. Enderlein G Pocock SJ: Clinical Trials — a practical approach. John Wiley & Sons, Chichester — New York — Brisbane — Toronto — Singapore 1983, 265 S., £ 16.95. Biometrical Journal 1985;27:634–634.
    1. Fässler M, Meissner K, Schneider A, Linde K. Frequency and circumstances of placebo use in clinical practice--a systematic review of empirical studies. BMC Med 2010;8:15.
    1. Ford AC, Talley NJ, Spiegel BMR, Foxx-Orenstein AE, Schiller L, Quigley EMM, Moayyedi P. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 2008;337:a2313.
    1. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997;11:395–402.
    1. Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci 2003;48:1317–1323.
    1. Hayter AJ. The Maximum Familywise Error Rate of Fisher’s Least Significant Difference Test. Journal of the American Statistical Association 1986;81:1000–1004.
    1. Hoenemeyer TW, Kaptchuk TJ, Mehta TS, Fontaine KR. Open-Label Placebo Treatment for Cancer-Related Fatigue: A Randomized-Controlled Clinical Trial. Sci Rep 2018;8:2784.
    1. Hull SC, Colloca L, Avins A, Gordon NP, Somkin CP, Kaptchuk TJ, Miller FG. Patients’ attitudes about the use of placebo treatments: telephone survey. BMJ 2013;347:f3757.
    1. Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 2014;6:218ra5.
    1. Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, Lembo AJ. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS ONE 2010;5:e15591.
    1. Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. BMJ (Clinical research ed) 2020;370:m1668.
    1. Kaptchuk TJ, Miller FG. Open label placebo: can honestly prescribed placebos evoke meaningful therapeutic benefits? BMJ 2018;363:k3889.
    1. 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.
    1. Kermen R, Hickner J, Brody H, Hasham I. Family physicians believe the placebo effect is therapeutic but often use real drugs as placebos. Fam Med 2010;42:636–642.
    1. Kleine-Borgmann J, Schmidt K, Hellmann A, Bingel U. Effects of open-label placebo on pain, functional disability, and spine mobility in patients with chronic back pain: a randomized controlled trial. Pain 2019;160:2891–2897.
    1. Meissner K, Höfner L, Fässler M, Linde K. Widespread use of pure and impure placebo interventions by GPs in Germany. Fam Pract 2012;29:79–85.
    1. Olliges E, Stroppe S, Haile A, Malhis M, Funke S, Meissner K. Open-label placebo for elderly patients with chronic knee pain: effects of pain, functionality and quality of life. Abstract #P201 2nd Official SIPS Conference2019.
    1. Passos MCF, Lembo AJ, Conboy LA, Kaptchuk TJ, Kelly JM, Quilty MT, Kerr CE, Jacobson EE, Hu R, Friedlander E, Drossman DA. Adequate relief in a treatment trial with IBS patients: a prospective assessment. Am J Gastroenterol 2009;104:912–919.
    1. Sandler AD, Bodfish JW. Open-label use of placebos in the treatment of ADHD: a pilot study. Child Care Health Dev 2008;34:104–110.
    1. Schaefer M, Harke R, Denke C. Open-Label Placebos Improve Symptoms in Allergic Rhinitis: A Randomized Controlled Trial. Psychother Psychosom 2016;85:373–374.
    1. Tilburt JC, Emanuel EJ, Kaptchuk TJ, Curlin FA, Miller FG. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938.
    1. Tyson J, Kennedy K. Guide to clinical trials. Bert Spilker, Raven Press. New York, 1991. No. of pages: xxv + 1156. Price: $162.50. ISBN: 0-88167-767-1. Statistics in Medicine 1993;12:1648–1648.
    1. Use of Placebo in Clinical Practice. American Medical Association; n.d. Available: . Accessed 27 Mar 2020.
    1. Wells RE. To Tell the Truth, the Whole Truth, May Do Patients Harm: The Problem of the Nocebo Effect for Informed Consent. Am J Bioeth 2012;12:22–29.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다