To quantify placebo effects and responses in randomized controlled trials (RCTs) on neck pain and explore how they would influence the treatment of neck pain.
We searched MEDLINE (PubMed), EMBASE (Ovid), CINAHL (EBSCO), Physiotherapy Evidence Database (PEDro), and World Health Organization International Clinical Trials Registry Platform from the inception of August 15, 2021, to identify relevant RCTs.
Study Selection and Data Extraction
The abstracts and full texts of potential studies were independently screened, and data extraction was also independently performed by 2 researchers. Scales of the score measuring neck pain and the scores both at baseline and the endpoint were extracted.
A total of 60 RCTs were included. The mean improvement in the pain score after placebo treatment was 15.65 (mean difference [MD]=-15.65, 95% confidence interval; CI [-19.19, -12.12]; P<.05), which we defined as the placebo response. In the active groups, it was 25.91 (MD=-25.91, 95% CI [-29.15, -22.68]; P<.05), and in the no-treatment groups, it was 5.80 (MD=-5.80, 95% CI [13.28, 1.69]; P=.13). Using the 3 MDs from the 3 groups, the placebo effect was calculated to account for 38.0% of the pain score improvement in the active group.
The pain scores of patients with neck pain were reduced after treatment with placebos, but the magnitude of pain score reduction was not clinically significant enough. The 38.0% amount of pain score reduction in patients treated with active interventions was caused by placebo. Interventions with considerable clinically significance for neck pain were still required.
List of abbreviations:CI (confidence interval), MD (mean difference), RCT (randomized controlled trial)
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- Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment.New Engl J Med. 2001; 344: 1594-1602
- Placebo response and remission rates in randomised trials of induction and maintenance therapy for ulcerative colitis.Cochrane Database Syst Rev. 2017; 9Cd011572
- Cutoff criteria for the placebo response: a cluster and machine learning analysis of placebo analgesia.Sci Rep. 2021; 11: 19205
- Effectiveness of placebo interventions for patients with nonspecific low back pain: a systematic review and meta-analysis.Pain. 2021; 162: 2792-2804
- Pain, placebo, and test of treatment efficacy: a narrative review.Br J Anaesth. 2019; 123: e254-e262
- Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice.BMJ. 2020; 370: m1668
- Less pain, more gain: should placebo be a clinical therapeutic?.Arthritis Rheumatol. 2020; 72: 511-514
- Placebo analgesia: friend or foe?.Curr Rheumatol Rep. 2006; 8: 418-424
- Placebo analgesia: psychological and neurobiological mechanisms.Pain. 2013; 154: 511-514
- An examination of the observed placebo effect associated with the treatment of low back pain—a systematic review.Pain Res Manage. 2011; 16: 45-52
- Appropriateness of sham or placebo acupuncture for randomized controlled trials of acupuncture for nonspecific low back pain: a systematic review and meta-analysis.J Pain Res. 2018; 11: 83-94
- An investigation of factors contributing to higher levels of placebo response in clinical trials in neuropathic pain: a systematic review and meta-analysis.Clin Drug Investig. 2015; 35: 67-81
- Meta-analysis of placebo responses in central neuropathic pain: impact of subject, study, and pain characteristics.Pain. 2016; 157: 530-540
- The placebo response in pediatric abdominal pain-related functional gastrointestinal disorders: a systematic review and meta-analysis.J Pediatr. 2017; 182 (e7): 155-163
- The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis.Lancet Gastroenterol Hepatol. 2021; 6: 459-473
- Epidemiology, diagnosis, and treatment of neck pain.Mayo Clin Proc. 2015; 90: 284-299
- Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2012; 380: 2163-2196
- Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396: 1204-1222
- Technical supplement to chapter 4: searching for and selecting studies.Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). 2022; (editors) (Available at:)
- Transcutaneous electrical nerve stimulation (TENS) for chronic neck pain.Cochrane Database Syst Rev. 2019; 12Cd011927
- Electrotherapy for neck pain.Cochrane Database Syst Rev. 2013; CD004251
- RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019; 366: l4898
- The smallest worthwhile effect of primary care physiotherapy did not differ across musculoskeletal pain sites.J Clin Epidemiol. 2018; 101: 44-52
- The placebo response in double-blind randomised trials evaluating regenerative therapies for Parkinson's disease: a systematic review and meta-analysis.J Parkinsons Dis. 2022; 12: 759-771
- The long-lasting effects of “Placebo Injections” in knee osteoarthritis: a meta-analysis.Cartilage. 2021; 13: 185s-196s
- Statistical methods in handling placebo effect.Int Rev Neurobiol. 2020; 153: 103-120
- Assessment of placebo response in objective and subjective outcome measures in rheumatoid arthritis clinical trials.JAMA Netw Open. 2020; 3e2013196
Published online: November 20, 2022
Accepted: October 26, 2022
Received in revised form: October 25, 2022
Received: October 3, 2022
Publication stageIn Press Journal Pre-Proof
Supported by the National Natural Science Foundation of China (No. 81873197 and No. 72074161) and the Key Program of Sichuan Provincial Science and Technology Department, China (No. 2019YFSO194).
© 2022 by the American Congress of Rehabilitation Medicine.