Highlights
- •Participants’ outcome expectations may contribute to clinical trial outcome variability.
- •Outcome expectations are influenced by a number of factors.
- •A brief, content-valid measure of outcome expectations is needed.
- •Adjusting for expectations in clinical trial analyses may improve assay sensitivity.
Abstract
Perspective
Key Words
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainReferences
- Development of the generic, multidimensional Treatment Expectation Questionnaire (TEX-Q) through systematic literature review, expert surveys and qualitative interviews.BMJ Open. 2020.; 10
- Expectancy in real and sham electroacupuncture: Does believing make it so?.J Natl Cancer Inst Monogr. 2014; 2014: 302-307
- Integrating acupuncture with exercise-based physical therapy for knee osteoarthritis: A randomized controlled trial.J Clin Rheumatol. 2013; 19: 308-316
- Treatment of pediatric migraine.N Engl J Med. 2017; 376: 1387-1388
- The placebo effect in pain therapies.Annu Rev Pharmacol Toxicol. 2019; 59: 191-211
- Placebo and nocebo effects.N Engl J Med. 2020; 382: 554-561
- Expectations.J Clin Psychol. 2011; 67: 184-192
- Simple pain rating scales hide complex idiosyncratic meanings.Pain. 2000; 85: 457-463
- Psychometric properties of the credibility/expectancy questionnaire.J Behav Ther Exp Psychiatry. 2000; 31: 73-86
- Cognitive interviewing: Verbal data in the design and pretesting of questionnaires.J Adv Nurs. 2003; 42: 57-63
- Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.Pain. 2012; 153: 1148-1158
- Assay sensitivity and study features in neuropathic pain trials: An ACTTION meta-analysis.Neurology. 2013; 81: 67-75
- Meta-analysis of assay sensitivity and study features in clinical trials of pharmacologic treatments for osteoarthritis pain.Arthritis Rheumatol. 2014; 66: 3327-3336
- Medicinal Products for Human Use: Guideline on Adjustment for Baseline Covariates in Clinical Trials. European Medicines Agency, Ed, London, UK2015
- Neuropathic pain clinical trials: Factors associated with decreases in estimated drug efficacy.Pain. 2018; 159: 2339-2346
- The relationship between patient and practitioner expectations and preferences and clinical outcomes in a trial of exercise and acupuncture for knee osteoarthritis.Eur J Pain. 2010; 14: 402-409
- Can patient expectations modulate the short-term effects of dry needling on sensitivity outcomes in patients with mechanical neck pain? A randomised clinical trial.Pain Med. 2021; 23: 965-976
- Do prognostic variables predict a set of outcomes for patients with chronic low back pain: A long-term follow-up secondary analysis of a randomized control trial.J Man Manip Ther. 2019; 27: 197-207
- The impact of treatment confidence on pain and related disability among patients with low-back pain: Results from the University of California, Los Angeles, low-back pain study.Spine J. 2002; 2 (discussion 399-401): 391-399
- Treatment success in neck pain: The added predictive value of psychosocial variables in addition to clinical variables.Scand J Pain. 2017; 14: 44-52
- Nonconscious activation of placebo and nocebo pain responses.Proc Natl Acad Sci U S A. 2012; 109: 15959-15964
- Lessons from a trial of acupuncture and massage for low back pain: Patient expectations and treatment effects.Spine (Phila Pa 1976). 2001; 26: 1418-1424
- Altered placebo and drug labeling changes the outcome of episodic migraine attacks.Sci Transl Med. 2014; 6: 218ra215
- Expectancy-induced placebo analgesia in children and the role of magical thinking.J Pain. 2014; 15: 1282-1293
- Initial content validation and roadmap for a new patient-reported outcome measure of pain intensity.J Pain. 2022; 23: 1945-1957
- Treatment assignment guesses by study participants in a double-blind dose escalation clinical trial of saw palmetto.J Altern Complement Med. 2014; 20: 48-52
- The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain.Pain. 2007; 128: 264-271
- Content validity of the credibility and expectancy questionnaire in a pain rehabilitation setting.Pain Pract. 2017; 17: 902-913
- Patient expectations as predictors of outcome in patients with acute low back pain.J Gen Intern Med. 2008; 23: 148-153
- Expectations of recovery: A prognostic factor in patients with neck pain undergoing manual therapy treatment.Eur J Pain. 2016; 20: 1384-1391
- Estimation of treatment allocation in a randomised, double-blinded, placebo-controlled trial.Swiss Med Wkly. 2019; 149: w20114
- Should placebo be used routinely for chronic pain in older people?.Maturitas. 2014; 79: 389-400
- Treatment expectations and preferences as predictors of outcome of acupuncture for chronic back pain.Spine (Phila Pa 1976). 2010; 35: 1471-1477
- Pain and placebo in pediatrics: A comprehensive review of laboratory and clinical findings.Pain. 2014; 155: 2229-2235
- Loeser award lecture: Size does matter, but it isn't everything: The challenge of modest treatment effects in chronic pain clinical trials.Pain. 2020; 161: S3-s13
- Trial forge guidance 1: What is a Study Within A Trial (SWAT)?.Trials. 2018; 19: 139
- Blinding effectiveness and association of pretreatment expectations with pain improvement in a double-blind randomized controlled trial.Pain. 2002; 99: 91-99
U.S. Food and Drug Administration: Patient-focused drug development: Colecting comprehensive and representative input. Guidance for Industry, FDA Staff, and Other Stakeholders.(Research, C.f.D.E.a.R.C.f.B.E.a., Ed.), U.S. Food and Drug Administration, Silver Spring, MD, 2020.
U.S. Food and Drug Administration: Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products: Guidance for Industry.(Research, C.f.D.E.a., Ed.), Silver Spring, MD, 2021.
- The impact of placebo, psychopathology, and expectations on the response to acupuncture needling in patients with chronic low back pain.J Pain. 2010; 11: 555-563
- Cognitive Interviewing: A tool for Improving Questionnaire Design.SAGE Publications, Inc, Thousand Oaks, CA2004
- Analysis of the Cognitive Interview in Questionnaire Design.Oxford University Press, New York, NY2015
- Randomized trial of the effect of drug presentation on asthma outcomes: the American Lung Association Asthma Clinical Research Centers.J Allergy Clin Immunol. 2009; 124: 436-444
- Predicting prognostic factors in a randomized controlled trial of acupuncture versus topiramate treatment in patients with chronic migraine.Clin J Pain. 2013; 29: 982-987
- Development of the Stanford Expectations of Treatment Scale (SETS): A tool for measuring patient outcome expectancy in clinical trials.Clin Trials. 2012; 9: 767-776
Article info
Publication history
Publication stage
In Press Journal Pre-ProofFootnotes
Financial support for this article was provided by a NIH K award (K24NS126861; JSG) and the ACTTION public-private partnership with the FDA (U01FD007474; RHD), which has received research contracts, grants, or other revenue from the FDA, multiple pharmaceutical and device companies, philanthropy, and other sources. No official endorsement by the FDA or the pharmaceutical and device companies that have provided unrestricted grants to support the activities of ACTTION should be inferred. JTF reports over the past 3 years funding from NIH-NCATS – UL1 Grant (Co-I), NIH-NIDDK - U01 Grant (CoI), from NIH-NINDS - U24 Grant (PI), and two FDA-BAA Contracts; and compensation for serving on two NIH DSMBs and advisory boards or consulting on clinical trial methods from Vertex and Lilly. During than the past 3 years, DCT has received research grants and contracts from the US Food and Drug Administration and US National Institutes of Health and has received compensation for consulting on clinical trial and patient preferences from Eli Lilly & Company, Flexion, Novartis/GlaxoSmithKline, and Pfizer. RHD has received in the past 5 years research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health, and compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, Glenmark, Gloriana, Grace, Hope, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG. The remaining authors report no conflicts of interest related to this work.
