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Methodology of Clinical Trials for Tinnitus

  • Michael LandgrebeEmail author
  • Berthold Langguth
  • Florian Zeman
  • Michael Koller
Chapter

Keypoints

  1. 1.

    There is no established methodology for clinical trials of tinnitus treatment.

     
  2. 2.

    Inter-study comparability is difficult due to insufficient characterization of investigated samples and variation of the used assessment and outcome measures.

     
  3. 3.

    Clinical trials in tinnitus should follow standards set by the guidelines of Good Clinical Practice, by the Consort statements, and should be registered in a clinical trial registry.

     
  4. 4.

    The design of the clinical trial depends on the clinical question, which should be answered by the study.

     
  5. 5.

    Placebo-controlled randomized trials represent the gold standard for testing efficacy of treatment approaches. However, in order to save resources, a stepwise approach seems reasonable, which involves pilot open trials as a first step to screen for potentially promising treatments and which is followed in case of positive outcome by randomized controlled trials.

     
  6. 6.

    Due to the heterogeneity of tinnitus, the best possible characterization of the investigated study sample, with respect to clinical or neurobiological characteristics, is highly desirable.

     
  7. 7.

    Outcome criteria for therapeutic trials have to be reliable, valid, specific, and relevant.

     
  8. 8.

    Trial design should be based on statistical estimation of sample sizes and power in order to minimize the risk of type I and type II errors.

     
  9. 9.

    To enhance inter-study comparability, international accepted standards for patient assessment and outcome measurement should be followed.

     
  10. 10.

    Standardization of clinical trial methodology will enhance clinical research in tinnitus by facilitating data comparison across trials and allowing pooled data analyses of multicenter study results in international databases.

     

Keywords

Tinnitus Clinical trials Placebo Inter-study comparability 

References

  1. 1.
    Friedman, LM, Furberg, CD, DeMets, DL Blindness. 3rd ed. New York: Springer; 1998Google Scholar
  2. 2.
    Langguth, B, Goodey, R, Azevedo, A, Bjorne, A, Cacace, A, Crocetti, A, et al Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, y 2006. Prog Brain Res, 2007; 166:525–36PubMedCrossRefGoogle Scholar
  3. 3.
    MRC Health Services and Public Health research Board. A framework for development and evaluation of RCTs for complex interventions to improve health. London: MRC; 2006Google Scholar
  4. 4.
    Klinkhammer-Schalke, M, Koller, M, Ehret, C, Steinger, B, Ernst, B, Wyatt, JC, et al Implementing a system of quality-of-life diagnosis and therapy for breast cancer patients: results of an exploratory trial as a prerequisite for a subsequent RCT. Br J Cancer, 2008; 99(3):415–22PubMedCrossRefGoogle Scholar
  5. 5.
    Klinkhammer-Schalke, M, Koller, M, Wyatt, JC, Steinger, B, Ehret, C, Ernst, B, et al Quality of life diagnosis and therapy as complex intervention for improvement of health in breast cancer patients: delineating the conceptual, methodological, and logistic requirements (modeling). Langenbecks Arch Surg, 2008; 393(1):1–12PubMedCrossRefGoogle Scholar
  6. 6.
    Lisanby, SH, Gutman, D, Luber, B, Schroeder, C, Sackeim, HA Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Biol Psychiatry, 2001; 49(5):460–3PubMedCrossRefGoogle Scholar
  7. 7.
    Loo, CK, Taylor, JL, Gandevia, SC, McDarmont, BN, Mitchell, PB, Sachdev, PS Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some “sham” forms active? Biol Psychiatry, 2000; 47(4):325–31PubMedCrossRefGoogle Scholar
  8. 8.
    Tyler, RS, Noble, W, Coelho, C Considerations for the design of clinical trials for tinnitus Acta Otolaryngol Suppl, 2006; 556:44–9PubMedCrossRefGoogle Scholar
  9. 9.
    Dobie RA Clinical Trials and Drug Therapy In: Snow JB, editor Tinnitus: Theory and Management Hamilton, USA: BC Decker; 2004; 266–77Google Scholar
  10. 10.
    Cohen J Statistical Power Analysis for the Behavioral Sciences, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum; 1988Google Scholar
  11. 11.
    Kleing, T, Steffens, T, Sand, P, Murthum, T, Hajak, G, Strutz, J, et al Which tinnitus patients benefit from transcranial magnetic stimulation? Otolaryngol Head Neck Surg, 2007; 137(4):589–95CrossRefGoogle Scholar
  12. 12.
    Altman, DG, Schulz, KF, Moher, D, Egger, M, Davidoff, F, Elbourne, D, et al The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med, 2001; 134(8):663–94PubMedGoogle Scholar
  13. 13.
    Moher, D, Schulz, KF, Altman, DG The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet, 2001; 357(9263):1191–4PubMedCrossRefGoogle Scholar
  14. 14.
    International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) adopts consolidated guideline on good clinical practice in the conduct of clinical trials on medicinal products for human use. Int Dig Health Legis, 1997; 48(2):231–4Google Scholar
  15. 15.
    Wei, PBC, Mubiru, S, O′Leary, S Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev, 2006; 25(1):CD003998Google Scholar
  16. 16.
    Landgrebe, M, Binder, H, Koller, M, Eberl, Y, Kleing, T, Eichhammer, P, et al Design of a placebo-controlled, ­randomized study of the efficacy of repetitive transcranial ­magnetic stimulation for the treatment of chronic tinntius. BMC Psychiatry, 2008; 8(1):23PubMedCrossRefGoogle Scholar
  17. 17.
    Chalmers, I, Altman, DG How can medical journals help ­prevent poor medical research? Some opportunities presented by electronic publishing. Lancet, 1999; 353(9151):490–3PubMedCrossRefGoogle Scholar
  18. 18.
    Møller, AR A double-blind placebo-controlled trial of baclofen in the treatment of tinnitus Am J Otol, 1997; 18(2):268–9PubMedGoogle Scholar
  19. 19.
    Mardini, MK Ear-clicking “tinnitus” responding to carbamazepine. N Engl J Med, 1987; 317(24):1542PubMedGoogle Scholar
  20. 20.
    Levine, RA Typewriter tinnitus: a carbamazepine-responsive syndrome related to auditory nerve vascular compression. ORL J Otorhinolaryngol Relat Spec, 2006; 68(1):43–6PubMedCrossRefGoogle Scholar
  21. 21.
    Tyler, R, Coelho, C, Tao, P, Ji, H, Noble, W, Gehringer, A, et al Identifying tinnitus subgroups with cluster analysis. Am J Audiol, 2008; 17(2):S176–84PubMedCrossRefGoogle Scholar
  22. 22.
    Schlee, W, Hartmann, T, Langguth B, Weisz, N Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci, 2009; 10:11PubMedCrossRefGoogle Scholar
  23. 23.
    Hiller, W, Goebel, G Factors influencing tinnitus loudness and annoyance. Arch Otolaryngol Head Neck Surg, 2006; 132(12):1323–30PubMedCrossRefGoogle Scholar
  24. 24.
    Meikle, MB, Stewart, BJ, Griest, SE, Tin, WH, Henry, JA, Abrams, HB, et al Assessment of tinnitus: measurement of treatment outcomes. Prog Brain Res, 2007; 166:511–21PubMedCrossRefGoogle Scholar
  25. 25.
    Tyler, RS, Oleson, J, Noble, W, Coelho, C, Ji, H Clinical trials for tinnitus: study populations, designs, measurement variables, and data analysis. Prog Brain Res, 2007; 166:499–509PubMedCrossRefGoogle Scholar
  26. 26.
    Langguth, B, Kleing, T, Fischer, B, Hajak, G, Eichhammer, P, Sand, PG Tinnitus severity, depression, and the big five personality traits. Prog Brain Res, 2007; 166:221–5PubMedCrossRefGoogle Scholar
  27. 27.
    Newman, CW, Jacobson, GP, Spitzer, JB Development of the tinnitus handicap inventory. Arch Otolaryngol Head Neck Surg, 1996; 122(2):143–8PubMedCrossRefGoogle Scholar
  28. 28.
    Greimel, KV, Leibetseder, M, Unterrainer, J, Albegger, K Can tinnitus be measured? Methods for assessment of tinnitus-specific disability and presentation of the Tinnitus Disability Questionnaire. HNO, 1999; 47(3):196–201PubMedCrossRefGoogle Scholar
  29. 29.
    Beck, AT, Steer, RA Internal consistencies of the original and revised beck depression inventory. J Clin Psychol, 1984; 40(6):1365–7PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Michael Landgrebe
    • 1
    • 2
    Email author
  • Berthold Langguth
  • Florian Zeman
  • Michael Koller
  1. 1.Department of Psychiatry, Psychosomatics, and PsychotherapyUniversity of RegensburgRegensburgGermany
  2. 2.Interdisciplinary Tinnitus ClinicUniversity of RegensburgRegensburgGermany

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