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Special Report
19 April 2016

What clinicians should know about differential placebo effects

Authors: Mikala C Osani and Raveendhara R Bannuru [email protected]Author Info & Affiliations
Publication: J. Comp. Eff. Res.
Volume 5, Number 3
https://doi.org/10.2217/cer-2015-0005
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Abstract

Research is inconclusive as to whether placebo interventions can result in clinical improvement. A number of methodological concepts must be taken into consideration when estimating differential effects of placebo interventions. Using network meta-analysis, researchers can move beyond the lack of direct comparisons available between different placebo interventions by making multiple pairwise comparisons. This design allows us to account for several components of the placebo effect. The additive effects of placebos may be beneficial in clinical practice if physicians can utilize them in a non-deceptive manner to optimize patient care. Researchers and clinicians should be aware of the existence of differential placebo responses when considering selecting appropriate placebo controls in the design of future clinical trials and when formulating treatment regimens.

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References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Zhang W, Robertson J, Jones AC et al. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann. Rheum. Dis. 67(12), 1716–1723 (2008).
PubMed
Google Scholar
2.
Wampold BE, Minami T, Tierney SC et al. The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials. J. Clin. Psychol. 61(7), 835–854 (2005).
PubMed
Google Scholar
• A re-analysis of a meta-analysis by Hróbjartsson et al. which demonstrated a robust placebo effect and highlighted that placebo effects can be hidden or even diminished based on meta-analysis design and based on heterogeneous disease characteristics.
3.
Hróbjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst. Rev. (1), CD003974 (2010).
PubMed
Google Scholar
• Systematic review and meta-analysis examining the effects of placebo treatments in 156 trials encompassing 46 different clinical conditions. Authors found that placebo treatments had a weak, if nonexistent effect.
4.
Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet 375(9715), 686–695 (2010).
PubMed
Google Scholar
•• A review that details the biological and clinical background of the placebo effect and expands upon the ethical considerations involved with applying placebo treatment to real-world clinical practice.
5.
Price DD, Finniss DG, Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annu. Rev. Psychol. 59, 565–590 (2008).
PubMed
Google Scholar
6.
Holden JD. Hawthorne effects and research into professional practice. J. Eval. Clin. Pract. 7(1), 65–70 (2001).
PubMed
Google Scholar
7.
Vase L, Riley JL 3rd, Price DD. A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain 99(3), 443–452 (2002).
PubMed
Google Scholar
8.
Delgado-Rodriguez M, Llorca J. Bias. J. Epidemiol. Community Health 58(8), 635–641 (2004).
PubMed
Google Scholar
9.
Whitney CW, Von Korff M. Regression to the mean in treated versus untreated chronic pain. Pain 50(3), 281–285 (1992).
PubMed
Google Scholar
10.
Ernst E, Resch KL. Concept of true and perceived placebo effects. BMJ 311(7004), 551–553 (1995).
PubMed
Google Scholar
11.
Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res. Synth. Methods 3(2), 80–97 (2012).
PubMed
Google Scholar
12.
Jansen JP et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health 14(4), 417–428 (2011).
PubMed
Google Scholar
13.
Bannuru RR et al. Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials. Ann. Intern. Med. 163(5), 365–372 (2015).
PubMed
Google Scholar
•• A systematic review and network meta-analysis exploring the differential placebo effects and their implications on the effects of active treatments in randomized controlled trials (RCTs) involving osteoarthritis patients.
14.
Walach H. The efficacy paradox in randomized controlled trials of CAM and elsewhere: beware of the placebo trap. J. Altern. Complement. Med. 7(3), 213–218 (2001).
PubMed
Google Scholar
15.
Traut EF, Passarelli EW. Placebos in the treatment of rheumatoid arthritis and other rheumatic conditions. Ann. Rheum. Dis. 16(1), 18–22 (1957).
PubMed
Google Scholar
16.
Grenfell RF, Briggs AH, Holland WC. A double-blind study of the treatment of hypertension. JAMA 176, 124–128 (1961).
PubMed
Google Scholar
17.
Morison RA, Woodmansey A, Young AJ. Placebo responses in an arthritis trial. Ann. Rheum. Dis. 20, 179–185 (1961).
PubMed
Google Scholar
18.
Kaptchuk TJ et al. Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ 332(7538), 391–397 (2006).
PubMed
Google Scholar
•• Single-blind RCT comparing the placebo counterparts for two different active interventions for persistent arm pain. Sham accupuncture was directly compared to an oral placebo. Authors concluded that the sham device had greater effects than oral placebo on self-reported outcomes over the longer course of treatment, but not during the 2-week run-in period.
19.
Conaghan PG et al. A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology (Oxford) 52(7), 1303–1312 (2013).
PubMed
Google Scholar
20.
Kaptchuk TJ et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 336(7651), 999–1003 (2008).
PubMed
Google Scholar
•• Single-blind RCT directly comparing two different placebo treatments with a group receiving no treatment in patients with irritable bowel syndrome, which found that nonspecific effects of certain treatments can reach statistical and clinical significance.
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