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Placeboresponder in randomisierten, kontrollierten Medikamentenstudien des Fibromyalgiesyndroms

Systematische Übersicht und Metaanalyse

Placebo responders in randomized controlled drug trials of fibromyalgia syndrome

Systematic review and meta-analysis

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Zusammenfassung

Hintergrund

Die Überlegenheit der Verum- gegenüber der Scheinmedikation beim Fibromyalgiesyndrom (FMS) ist minimal. Eine Placebotherapie von funktionellen somatischen Syndromen (FSS) wie dem FMS wird diskutiert. Wir bestimmten die Höhe der Placeboresponseraten in FMS-Medikamentenstudien, um zu überprüfen, ob weitere Forschung über die Placebobehandlung von FSS gerechtfertigt ist.

Material und Methoden

In CENTRAL, MEDLINE, SCOPUS sowie in den Datenbanken des U.S. National Institute of Health und von Pharmaceutical Research and Manufacturers of America wurde nach randomisierten, doppelblinden placebokontrollierten Medikamentenstudien mit einem Paralleldesign und einer Dauer ≥12 Wochen bei FMS-Patienten von Beginn bis 31. Dezember 2010 gesucht. Die Placeboresponseraten wurden durch die gepoolte Schätzung der Anzahl von Patienten mit einer 30%igen oder 50%igen Schmerzreduktion bestimmt.

Ergebnisse

Es wurden 30 Studien mit 3846 Patienten unter Placeboeinnahme eingeschlossen. Die gepoolte Schätzung der 30%igen Schmerzreduktionsrate lag bei 30,8% [95%-Konfidenzintervall (KI): 29,4–32,3%], die gepoolte Schätzung der 50%igen Schmerzreduktionsrate betrug 18,8% (95%-KI: 17,5–20,1%). Die gepoolte Schätzung des relativen Risikos einer 30%igen Schmerzreduktion Verum- vs. Scheinmedikament lag bei 1,38 (95%-KI: 1,27–1,49). Die gepoolte Schätzung des relativen Risikos einer 50%igen Schmerzreduktion Verum- vs. Scheinmedikament betrug 1,57 (95%-KI: 1,36–1,81).

Schlussfolgerung

Die Höhe der Placeboresponseraten in Medikamentenstudien des FMS ist substanziell. Wirksamkeit, Sicherheit und Kosten von für das FMS empfohlenen Medikamenten und offener Placebogabe sollten in großen multinationalen Studien, die von öffentlichen Institutionen gefördert werden, überprüft werden.

Die englische Volltextversion dieses Beitrags ist in SpringerLink (unter „Supplemental“) verfügbar.

Abstract

Background

The superiority of true drug treatment over placebo in reducing symptoms of fibromyalgia syndrome (FMS) is small. Drug placebo treatment of functional somatic syndromes (FSS) such as FMS has been discussed. We determined the magnitude of placebo responders in drug trials with FMS patients to substantiate further research on placebo treatment of FSS.

Material and methods

CENTRAL, MEDLINE, Scopus, and the databases of the U.S. National Institutes of Health and the Pharmaceutical Research and Manufacturers of America were searched for randomized, double-blind, placebo-controlled trials with a parallel design and treatment duration of ≥ 12 weeks in FMS patients from inception to 31 December 2010. The magnitude of placebo responders was assessed by the pooled estimate of patients with a 30% and 50% reduction in pain.

Results

Thirty studies with 3,846 patients on placebo were included. The pooled estimate of a 30% placebo pain reduction was 30.8% (95% confidence interval (CI) 29.4–32.3%) and of a 50% placebo pain reduction was 18.8% (95% CI 17.5–20.1%). The pooled estimate of the risk ratio of 30% pain reduction by true drug versus placebo was 1.38 (95% CI 1.27–1.49). The pooled estimate of the risk ratio of 50% pain reduction by true drug versus placebo response was 1.57 (95% CI 1.36–1.81).

Conclusion

The magnitude of responders to placebo in drug trials of FMS is substantial. The efficacy, safety, and costs of drugs recommended for FMS therapy and open-label placebo should be compared in large multinational trials sponsored by public institutions.

The English full-text version of this article is available at SpringerLink (under “Supplemental”).

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Literatur

  1. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219

    Article  PubMed  Google Scholar 

  2. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  PubMed  CAS  Google Scholar 

  3. Briley M (2010) Drugs to treat fibromyalgia – the transatlantic difference. Curr Opin Investig Drugs 11:16–18

    PubMed  Google Scholar 

  4. Burke JP, Sanchez R, Joshi AV et al (2011) Health care costs in patients with fibromyalgia on pregabalin vs. duloxetine. Pain Pract. DOI 10.1111/j.1533-2500.2011.00470.x

  5. Cochrane AL (1989) Effectiveness and efficiency. Random reflections on health services. Cambridge University Press for British Medical Journal & The Nuffield Provincial Hospitals Trust, Cambridge, S 31

  6. Cremonini F, Ziogas DC, Chang HY et al (2010) Meta-analysis: the effects of placebo treatment on gastro-oesophageal reflux disease. Aliment Pharmacol Ther 32:29–42

    Article  PubMed  CAS  Google Scholar 

  7. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  8. Dorn SD, Kaptchuk TJ, Park JB et al (2007) A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome. Neurogastroenterol Motil 19:630–637

    Article  PubMed  CAS  Google Scholar 

  9. Dworkin RH, Turk DC, Wyrwich KW et al (2008) Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 9:105–121

    Google Scholar 

  10. Dworkin RH, Turk DC, Katz NP et al (2011) Evidence-based clinical trial design for chronic pain pharmacotherapy: a blueprint for ACTION. Pain 152(3 Suppl):107–115

    Article  Google Scholar 

  11. Egger M, Zellweger-Zahner T, Schneider M et al (1997) Language bias in randomised controlled trials published in English and German. Lancet 350:326–329

    Article  PubMed  CAS  Google Scholar 

  12. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F (2010) Biological, clinical, and ethical advances of placebo effects. Lancet 375:686–695

    Article  PubMed  Google Scholar 

  13. Furukawa TA, Cipriani A, Barbui C et al (2005) Imputing response rates from means and standard deviations in meta-analyses. Int Clin Psychopharmacol 20:49–52

    Article  PubMed  Google Scholar 

  14. Häuser W, Petzke F, Sommer C (2010) Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. J Pain 11:505–521

    Article  PubMed  Google Scholar 

  15. Häuser W, Bartram-Wunn E, Bartram C et al (2011) Systematic review: placebo response in drug trials of fibromyalgia syndrome and painful peripheral diabetic neuropathy – magnitude and patient-related predictors. Pain 152:1709–1717

    Article  PubMed  Google Scholar 

  16. Higgins JPT, Green S (2011) Cochrane Handbook for systematic reviews of intervention. Version 5.1.0. http://www.cochrane-handbook.org

  17. Ho VMS (1994) The placebo effect: can we use it better? BMJ 309:69–70

    Article  Google Scholar 

  18. Hróbjartsson A, Kaptchuk TJ, Miller FG (2011) Placebo effect studies are susceptible to response bias and to other types of biases. J Clin Epidemiol 64:1223–1229

    Article  PubMed  Google Scholar 

  19. Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  PubMed  CAS  Google Scholar 

  20. Kaptchuk TJ, Friedlander E, Kelley JM et al (2010) Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One 5:e15591

    Article  PubMed  CAS  Google Scholar 

  21. Kaptchuk TJ, Kelley JM, Conboy LA et al (2008) Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 336:999–1003

    Article  PubMed  Google Scholar 

  22. Kelley JM, Lembo AJ, Ablon JS et al (2009) Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosom Med 71:789–797

    Article  PubMed  Google Scholar 

  23. Mayou R, Farmer A (2002) ABC of psychological medicine: functional somatic symptoms and syndromes. BMJ 325:265–268

    Article  PubMed  Google Scholar 

  24. Moher D, Liberati A, Teztlaff J, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 51:1–7

    Google Scholar 

  25. Moore RA, Smugar SS, Wang H et al (2010) Numbers-needed-to-treat analyses – do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo-controlled chronic low back pain trials. Pain 151:592–597

    Article  PubMed  Google Scholar 

  26. Moore RA, Eccleston C, Derry S et al (2010) Evidence in chronic pain – establishing best practice in the reporting of systematic reviews. Pain 150:386–389

    Article  Google Scholar 

  27. Newman DH (2008) Hippocrates‘ shadow: secrets from the house of medicine – what doctors don’t know, don’t tell you, and how truth can repair the patient-doctor breach. Simon &Schuster

  28. Pitz M, Cheang M, Bernstein CN (2005) Defining the predictors of the placebo response in irritable bowel syndrome. Clin Gastroenterol Hepatol 3:237–247

    Article  PubMed  Google Scholar 

  29. Sicras-Mainar A, Rejas J, Navarro R et al (2009) Treating patients with fibromyalgia in primary care settings under routine medical practice: a claim database cost and burden of illness study. Arthritis Res Ther 11:R54

    Article  PubMed  Google Scholar 

  30. Staud R, Price DD (2008) Importance of measuring placebo factors in complex clinical trials. Pain 138:474

    Article  PubMed  Google Scholar 

  31. Talley NJ, Locke GR, Lahr BD et al (2006) Predictors of the placebo response in functional dyspepsia. Aliment Pharmacol Ther 23:923–936

    Article  PubMed  CAS  Google Scholar 

  32. Turner JA, Deyo RA, Loeser JD et al (1994) The importance of placebo effects in pain treatment and research. JAMA 271:1609–1614

    Article  PubMed  CAS  Google Scholar 

  33. Vase L, Petersen GL, Riley JL 3rd, Price DD (2009) Factors contributing to large analgesic effects in placebo mechanism studies conducted between 2002 and 2007. Pain 145:30–49

    Article  Google Scholar 

  34. Weimer K, Horing B, Klosterhalfen S, Enck P (2011) Placebo response: in studies on pain and under other clinical conditions. Schmerz 25:325–335

    Article  PubMed  CAS  Google Scholar 

  35. Wissenschaftlicher Beirat der Bundesärztekammer (2010) Stellungnahme des Wissenschaftlichen Beirats der Bundesärztekammer „Placebo in der Medizin“. http://www.bundesaerztekammer.de/downloads/StellPlacebo2010.pdf

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Danksagung

Wir danken Prof. Furukawa (Japan), der uns eine Excel-Formel der Imputationsmethode zur Verfügung gestellt hat.

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Dr. Häuser hat in den vergangenen 3 Jahren von Janssen-Cilag einmalig ein Honorar für einen Vortrag erhalten. Dr. Tölle war in den vergangenen 3 Jahren als Berater und/oder Redner für Astellas, Grünenthal, Eli Lilly & Company, Boehringer Ingelheim Pharmaceuticals, Pfizer, UCB Pharma und Mundipharma tätig. Bei den weiteren Autoren liegt kein Interessenkonflikt vor.

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Authors and Affiliations

  1. Klinik für Innere Medizin 1, Klinikum Saarbrücken gGmbH, Winterberg 1, 66119, Saarbrücken, Deutschland

    W. Häuser, E. Bartram-Wunn & C. Bartram

  2. Klinik für Psychosomatische Medizin und Psychotherapie, Technische Universität München, München, Deutschland

    W. Häuser, E. Bartram-Wunn & C. Bartram

  3. Klinik für Neurologie und Zentrum für Interdisziplinäre Schmerztherapie, Technische Universität München, München, Deutschland

    T.R. Tölle

Authors
  1. W. Häuser
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  2. E. Bartram-Wunn
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  3. C. Bartram
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  4. T.R. Tölle
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Corresponding author

Correspondence to W. Häuser.

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English version of "Placeboresponder in randomisierten, kontrollierten Medikamentenstudien des Fibromyalgiesyndroms. Systematische Übersicht und Metaanalyse" (PDF 0,6 MB)

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Häuser, W., Bartram-Wunn, E., Bartram, C. et al. Placeboresponder in randomisierten, kontrollierten Medikamentenstudien des Fibromyalgiesyndroms. Schmerz 25, 619–631 (2011). https://doi.org/10.1007/s00482-011-1106-4

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