title: Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.
abstract: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus.
  
  
  
  Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded.
  
  
  
  Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used.
  
  
  
  Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments.
  
  
  
  The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.
authors.affiliation: National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham, NG1 5DU, UK. deborah.hall@nottingham.ac.uk.|Otology and Hearing Group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, NG7 2UH, UK. deborah.hall@nottingham.ac.uk.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
authors.affiliation: ENT Department of Hospital Cuf Infante Santo - Nova Medical School, Travessa do Castro 3, 1350-070, Lisbon, Portugal.
authors.forename: Haula
authors.initials: H
authors.lastname: Haider
authors.affiliation: Department of Otorhinolaryngology, Charite University Hospital, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Agnieszka J
authors.initials: AJ
authors.lastname: Szczepek
authors.affiliation: Institute of Biomagnetism and Biosignalanalysis, University Hospital Münster, Malmedyweg 15, 48149, Münster, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Lau
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rabau
authors.affiliation: National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham, NG1 5DU, UK.|Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Jones-Diette
authors.affiliation: Service ORL et CCF, Consultation Acouphène et Hyperacousie, Hôpital Européen G. Pompidou, 20, rue Leblanc, 75015, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Londero
authors.affiliation: Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institutet, Von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Edvall
authors.affiliation: Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institutet, Von Eulers väg 8, 171 77, Stockholm, Sweden.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cederroth
authors.affiliation: Department of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics, |Medical University of Lodz, 90-549 Lodz, 113 Zeromskiego Street, Lodz, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Mielczarek
authors.affiliation: Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Universiteitssingel 40, PO Box 616, 6200, MD, Maastricht, The Netherlands.|Adelante, Centre of Expertise in Rehabilitation and Audiology, Zandbergsweg 111, 6432 CC, Hoensbroek, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuller
authors.affiliation: Department of Otorhinolaryngology, IBSAL, University Hospital of Salamanca, Paseo San Vicente 58-182, 37007, Salamanca, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Batuecas-Caletrio
authors.affiliation: Tinnitus Center, Charite University Hospital, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Brueggemen
authors.affiliation: National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham, NG1 5DU, UK.|Otology and Hearing Group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Thompson
authors.affiliation: Laboratory of Adaptive and Integrative Neuroscience, Centre National de la Recherche Scientifique, Fédération de Recherche 3C, Aix-Marseille Université, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Norena
authors.affiliation: Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Universiteitssingel 40, PO Box 616, 6200, MD, Maastricht, The Netherlands.|Adelante, Centre of Expertise in Rehabilitation and Audiology, Zandbergsweg 111, 6432 CC, Hoensbroek, The Netherlands.
authors.forename: Rilana F F
authors.initials: RF
authors.lastname: Cima
authors.affiliation: National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham, NG1 5DU, UK.|Otology and Hearing Group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Rajnikant L
authors.initials: RL
authors.lastname: Mehta
authors.affiliation: Tinnitus Center, Charite University Hospital, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Mazurek
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D006801:Humans; D012107:Research Design; D014012:Tinnitus / Q000628:therapy*; D016896:Treatment Outcome
keywords: Adult otolaryngology; Audiology; Clinical trials; Methods