Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2005

Open Access 01-12-2005 | Research article

The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

Authors: Harald Walach, Catarina Sadaghiani, Cornelia Dehm, Dick Bierman

Published in: BMC Medical Research Methodology | Issue 1/2005

Login to get access

Abstract

Background and purpose

Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability.

Methods

We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out.

Results

We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%.

Conclusion

Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.
Appendix
Available only for authorised users
Literature
1.
2.
Kienle GS, Kiene H: The powerful placebo effect: Fact or fiction?. J Clin Epidemiol. 1997, 50: 1311-1318.CrossRefPubMed
3.
McDonald CJ, McCabe GP: How much of the placebo effect is really statistical regression? (letter). Stat Med. 1989, 8: 1301-1302.CrossRefPubMed
4.
McDonald CJ, Mazzuca SA, McCabe GP: How much of the placebo 'effect' is really statistical regression?. Stat Med. 1983, 2: 417-427.CrossRefPubMed
5.
Kirsch I: Specifying nonspecifics: Psychological mechanisms of placebo effects. The Placebo Effect: Interdisciplinary Explorations. Edited by: Harrington A. 1997, Cambridge MA: Harvard University Press, 166-186.
6.
7.
8.
Moerman DE, Jonas WB: Deconstructing the placebo effect and finding the meaning response. Ann Int Med. 2002, 136: 471-476.CrossRefPubMed
9.
Hróbjartsson A: What are the main methodological problems in the estimation of placebo effects?. J Clin Epidemiol. 2002, 55: 430-435.CrossRefPubMed
10.
Hróbjartsson A, Gotzsche PC: Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl Med. 2001, 344: 1594-1602.CrossRef
11.
Walach H, Sadaghiani C: Plazebo und Plazebo-Effekte: Eine Bestandsaufnahme. Psychother Psychosom med Psychol. 2002, 52: 332-342.CrossRefPubMed
12.
Vase L, Riley JL, Price DD: A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain. 2002, 99: 443-452.CrossRefPubMed
13.
Amanzio M, Pollo A, Maggi G, Benedetti F: Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain. 2001, 90: 205-215.CrossRefPubMed
14.
Vase L, Robinson ME, Verne GN, Price DD: The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients: An empirical investigation. Pain. 2003, 105: 17-25.CrossRefPubMed
15.
Walach H, Maidhof C: Is the placebo effect dependent on time?. Expectancy, Experience, and Behavior. Edited by: Kirsch I. 1999, Washington, DC: American Psychological Association, 321-332.CrossRef
16.
17.
18.
Walsh TB, Seidman SN, Sysko R, Gould M: Placebo response in studies of major depression: variable, substantial, and growing. J Am Med Assoc. 2002, 287: 1840-1847.CrossRef
19.
Jüni P, Witschi A, Bloch R, Egger M: The hazards of scoring the quality of clinical trials for meta-analysis. J Am Med Assoc. 1999, 282: 1054-1060.CrossRef
20.
Moher D, Jadad AR, Tugwell P: Assessing the quality of randomized controlled trials. Current issues and future directions. International Journal of Technology Assessment in Health Care. 1996, 12: 195-208.CrossRefPubMed
21.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al: Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996, 17: 1-12.CrossRefPubMed
22.
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet. 1998, 352: 609-613.CrossRefPubMed
23.
Clark HD, Wells GA, Huet C, McAlister FA, Salmi LR, Fergusson D, et al: Assessing the quality of randomized trials: reliability of the Jadad scale. Control Clin Trials. 1999, 20: 448-452.CrossRefPubMed
24.
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA: Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992, 45: 255-265.CrossRefPubMed
25.
The Cochrane Library (database on disk and CDROM): The Cochrane Collaboration. Edited by: Mulrow CD, Oxman AD. 1997, Oxford, Update Software. Cochrane Collaboration Handbook, updated September 1997
26.
Orwin RG: Evaluating coding decisions. The Handbook of Research Synthesis. Edited by: Cooper H, Hedges LV. 1994, New York: Russell Sage Foundation, 139-162.
27.
Fleiss JL: Statistical Methods for Rates and Proportions. 1981, New York: Wiley, 2
28.
Hedges LV, Olkin I: Statistical Methods for Meta-Analysis. 1985, Orlando: Academic Press
29.
Kirsch I, Sapirstein G: Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medications. Expectancy, Experience, and Behavior. Edited by: Kirsch I. 1999, Washington, DC: American Psychological Association, 303-320.CrossRef
30.
Evans FJ: The placebo response in pain reduction. International Symposium on Pain. Edited by: Bonica JJ. 1974, New York: Raven Press, 289-296.
31.
McQuay H, Carroll D, Moore A: Variation in the placebo effect in randomised controlled trials of analgesics: all is blind as it seems. Pain. 1996, 64: 331-335.CrossRefPubMed
32.
Walach H, Jonas WB: Placebo research: The evidence b ase for harnessing self-healing capacities. J Altern Complement Med. 2004, 10: S103-S112.CrossRefPubMed
33.
Frank JD: Non-specific aspects of treatment: the view of a psychotherapist. Non-Specific Aspects of Treatment. Edited by: Shepherd M, Sartorius N. 1989, Bern: Huber, 95-114.
34.
Moerman DE: Meaning, Medicine, and the "Placebo Effect". 2002, Cambridge: Cambridge University PressCrossRef
35.
de la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ: Expectation and dopamine release: Mechanism of the placebo effect in parkinson's disease. Science. 2001, 293: 1164-1166.CrossRefPubMed
36.
Leuchter AF, Cook IA, Witte EA, Morgan M, Abrams M: Changes in brain function of depresses subjects during treatment with placebo. Am J Psychiatry. 2002, 159: 122-129.CrossRefPubMed
37.
Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, et al: The functional neuroanatomy of the placebo effect. Am J Psychiatry. 2002, 159: 728-737.CrossRefPubMed
38.
Pariente J, White P, Frackowiak RS, Lewith G: Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage. 2005, 25: 1161-1167.CrossRefPubMed
39.
Petrovic P, Kalso E, Petersson KM, Ingvar M: Placebo and opioid analgesia – imaging a shared neuronal network. Science. 2002, 295: 1737-1740.CrossRefPubMed
40.
Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, et al: Placebo-induced changes in fMRI in the anticipation and experience of pain. Science. 2004, 303: 1162-1167.CrossRefPubMed
41.
Atmanspacher H, Römer H, Walach H: Weak quantum theory: Complementarity and entanglement in physics and beyond. Foundations of Physics. 2002, 32: 379-406.CrossRef
42.
Wackermann J, Seiter C, Keibel H, Walach H: Correlations between brain electrical activities of two spatially separated human subjects. Neurosci Lett. 2003, 336: 60-64.CrossRefPubMed
Metadata
Title
The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis
Authors
Harald Walach
Catarina Sadaghiani
Cornelia Dehm
Dick Bierman
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2005
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/1471-2288-5-26

Other articles of this Issue 1/2005

BMC Medical Research Methodology 1/2005 Go to the issue

Research article

Which resources should be used to identify RCT/CCTs for systematic reviews: a systematic review

Research article

The strengths and limitations of meta-analyses based on aggregate data

Research article

Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data

Research article

Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure

Research article

A randomised controlled trial to assess the effectiveness of offering study results as an incentive to increase response rates to postal questionnaires [ISRCTN26118436]

Research article

A priori postulated and real power in cluster randomized trials: mind the gap