Abstract

Background

Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient.

Methods

Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT.

Discussion

The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results.

Trial registration

ClinicalTrials.gov NCT04663828. The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Details

Title
The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT)
Author
Simoes, Jorge Piano 1   VIAFID ORCID Logo  ; Schoisswohl, Stefan 2 ; Schlee, Winfried 3 ; Basso, Laura 4 ; Bernal-Robledano, Alberto 5 ; Boecking, Benjamin 6 ; Cima, Rilana 7 ; Denys, Sam 8 ; Engelke, Milena 4 ; Escalera-Balsera, Alba 9 ; Gallego-Martinez, Alvaro 9 ; Gallus, Silvano 10 ; Kikidis, Dimitris 11 ; López-Escámez, Jose A. 12 ; Marcrum, Steven C. 13 ; Markatos, Nikolaos 11 ; Martin-Lagos, Juan 14 ; Martinez-Martinez, Marta 14 ; Mazurek, Birgit 6 ; Vassou, Evgenia 11 ; Jarach, Carlotta Micaela 10 ; Mueller-Locatelli, Nicolas 14 ; Neff, Patrick 15 ; Niemann, Uli 16 ; Omar, Hafez Kader 16 ; Puga, Clara 16 ; Schleicher, Miro 16 ; Unnikrishnan, Vishnu 16 ; Perez-Carpena, Patricia 9 ; Pryss, Rüdiger 17 ; Robles-Bolivar, Paula 9 ; Rose, Matthias 18 ; Schecklmann, Martin 4 ; Schiele, Tabea 6 ; Schobel, Johannes 19 ; Spiliopoulou, Myra 16 ; Stark, Sabine 6 ; Vogel, Carsten 17 ; Wunder, Nina 4 ; Zachou, Zoi 11 ; Langguth, Berthold 4 

1  University of Regensburg, Department of Psychiatry and Psychotherapy, Regensburg, Germany (GRID:grid.7727.5) (ISNI:0000 0001 2190 5763); University of Twente, Department of Psychology, Health and Technology, Enschede, The Netherlands (GRID:grid.6214.1) (ISNI:0000 0004 0399 8953) 
2  University of Regensburg, Department of Psychiatry and Psychotherapy, Regensburg, Germany (GRID:grid.7727.5) (ISNI:0000 0001 2190 5763); Universität der Bundeswehr München, Department of Psychology, Neubiberg, Germany (GRID:grid.7752.7) (ISNI:0000 0000 8801 1556) 
3  University of Regensburg, Department of Psychiatry and Psychotherapy, Regensburg, Germany (GRID:grid.7727.5) (ISNI:0000 0001 2190 5763); Eastern Switzerland University of Applied Sciences, Institute for Information and Process Management, St. Gallen, Switzerland (GRID:grid.510272.3) 
4  University of Regensburg, Department of Psychiatry and Psychotherapy, Regensburg, Germany (GRID:grid.7727.5) (ISNI:0000 0001 2190 5763) 
5  Hospital Universitario Virgen de Las Nieves, Universidad de Granada, Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994) 
6  Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin, Tinnitus Center, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662) 
7  KU Leuven University, Health Psychology, Faculty of Psychology and Educational Sciences, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); Adelante, Tinnitus Center of Expertise, Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands (GRID:grid.419163.8) (ISNI:0000 0004 0489 1699); Maastricht University, Experimental Health Psychology, Faculty of Psychology and Neurosciences, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
8  KU Leuven University, Research group Experimental Otorhinolaryngology (ExpORL), Department of Neurosciences, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); University Hospitals of Leuven, Department of Otorhinolaryngology, Head and Neck surgery, Leuven, Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) 
9  Hospital Universitario Virgen de Las Nieves, Universidad de Granada, Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994); GENYO, Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Granada, Spain (GRID:grid.470860.d) (ISNI:0000 0004 4677 7069) 
10  Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (GRID:grid.4527.4) (ISNI:0000000106678902) 
11  National and Kapodistrian University of Athens, Medical School, Department of Otorhinolaryngology, Head and Neck Surgery, Athens, Greece (GRID:grid.5216.0) (ISNI:0000 0001 2155 0800) 
12  Hospital Universitario Virgen de Las Nieves, Universidad de Granada, Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994); GENYO, Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Granada, Spain (GRID:grid.470860.d) (ISNI:0000 0004 4677 7069); University of Granada, Department of Surgery, Division of Otolaryngology, Faculty of Medicine, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994); University of Sydney, Meniere’s Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
13  University Hospital Regensburg, Department of Otolaryngology, Regensburg, Germany (GRID:grid.411941.8) (ISNI:0000 0000 9194 7179) 
14  Instituto de Investigacion Biosanitaria Granada, ibs.GRANADA, Hospital Universitario San Cecilio, Department of Otolaryngology, Granada, Spain (GRID:grid.459499.c) 
15  University of Regensburg, Department of Psychiatry and Psychotherapy, Regensburg, Germany (GRID:grid.7727.5) (ISNI:0000 0001 2190 5763); University Hospital Zurich, University of Zurich, Department of Otorhinolaryngology, Head & Neck Surgery, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); École Polytechnique Fédérale de Lausanne (EPFL), Neuro-X Institute, Geneva, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); University of Salzburg, Centre for Cognitive Neuroscience, Salzburg, Austria (GRID:grid.7039.d) (ISNI:0000000110156330) 
16  Otto Von Guericke University Magdeburg, Knowledge Management and Discovery Lab (KMD), Faculty of Computer Science, Magdeburg, Germany (GRID:grid.5807.a) (ISNI:0000 0001 1018 4307) 
17  University of Würzburg, Institute of Clinical Epidemiology and Biometry, Würzburg, Germany (GRID:grid.8379.5) (ISNI:0000 0001 1958 8658) 
18  Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin, Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662) 
19  University of Applied Sciences, Institute DigiHealth, Neu-Ulm, Germany (GRID:grid.466058.9) 
Pages
472
Publication year
2023
Publication date
Dec 2023
Publisher
Springer Nature B.V.
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13063-023-07303-2
ProQuest document ID
2841213366
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.