Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PROSPERO REGISTRATION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

Innovations in Doctoral Training and Research on Tinnitus:The European School on Interdisciplinary Tinnitus Research (ESIT) Perspective

Tinnitus is a common medical condition which interfaces many different disciplines, yet it is not a priority for any individual discipline. A change in its scientific understanding and clinical management requires a shift toward multidisciplinary cooperation, not only in research but also in training. The European School for Interdisciplinary Tinnitus research (ESIT) brings together a unique multidisciplinary consortium of clinical practitioners, academic researchers, commercial partners, patient organizations, and public health experts to conduct innovative research and train the next generation of tinnitus researchers. ESIT supports fundamental science and clinical research projects in order to: (1) advancing new treatment solutions for tinnitus, (2) improving existing treatment paradigms, (3) developing innovative research methods, (4) performing genetic studies on, (5) collecting epidemiological data to create new knowledge about prevalence and risk factors, (6) establishing a pan-European data resource. All research projects involve inter-sectoral partnerships through practical training, quite unlike anything that can be offered by any single university alone. Likewise, the postgraduate training curriculum fosters a deep knowledge about tinnitus whilst nurturing transferable competencies in personal qualities and approaches needed to be an effective researcher, knowledge of the standards, requirements and professionalism to do research, and skills to work with others and to ensure the wider impact of research. ESIT is the seed for future generations of creative, entrepreneurial, and innovative researchers, trained to master the upcoming challenges in the tinnitus field, to implement sustained changes in prevention and clinical management of tinnitus, and to shape doctoral education in tinnitus for the future

Tinnitus-related fear: Mediating the effects of a cognitive behavioural specialised tinnitus treatment

OBJECTIVE: Cognitive behavioural treatments (CBT) for the reduction of tinnitus complaints have been shown to be effective; however the specific mechanisms of change are yet to be unveiled. Reductions in tinnitus-related fear have been indicated to be an important factor in alleviating tinnitus suffering. The role of tinnitus-related fear has been proposed as a mediator explaining the cognitive behavioural treatment effects on tinnitus severity, tinnitus-related impairment and general quality of life of tinnitus patients. METHODS: A two-group, single-centre RCT was carried out with adult tinnitus patients (n = 492), with 3 follow-up assessments up to 12 months after randomization. Patients were randomly assigned to Usual Care (UC) or Specialised cognitive behavioral stepped Care (SC). A repeated-measures design, with group as a between subjects factor, and time as the within-subject factor, was used in an intention-to-treat analysis. Mixed regressions for assessing mediation effects were performed with general health, tinnitus distress, tinnitus related impairment as the dependent variables and tinnitus related fear as the mediator variable. RESULTS: Tinnitus-related fear appears to mediate part of the treatment benefits of specialized CBT for Tinnitus, as compared to usual care, with respect to increased quality of life ratings, and decreased tinnitus severity and tinnitus related impairments. CONCLUSIONS: The effectiveness of specialized cognitive behavioural treatment approaches for tinnitus might be partly explained by significant reductions in tinnitus-related fear. These results are relevant in that currently, though CBT approaches in tinnitus management have been proven to lead to decreased suffering of tinnitus patients, the psychological mechanisms causing these benefits are still to be discovered

The Fear of Tinnitus Questionnaire:Toward a Reliable and Valid Means of Assessing Fear in Adults with Tinnitus

Objectives: The purpose of this study was to assess the factor structure, reliability, and validity of the Fear of Tinnitus Questionnaire (FTQ); a brief self-report measure of people’s fears about potential cognitive, emotional, behavioral, and social consequences of living with tinnitus. Design: Five hundred eighty-eight Dutch-speaking adults with tinnitus completed an online battery of questionnaires measuring tinnitus-related distress, fear, catastrophizing, and quality of life. The sample was randomly split into two to perform exploratory and Bayesian confirmatory factor analyses. A subsample of participants (n = 144) completed the battery of questionnaires a second time after a 2-week interval to calculate test-retest reliability and conduct a Bland-Altman analysis. Convergent and concurrent validity of the FTQ was assessed with the complete data set and measures of tinnitus-related distress as the outcome. Results: Exploratory factor analyses indicated that single- and three-factor FTQ models were both valid solutions. Posterior predictive p values for the Bayesian confirmatory factor analyses ranged between 0.51 and 0.53 indicating that the respective models were an excellent fit for the data. The FTQ showed excellent test-retest reliability (average value intraclass correlation coefficient (ICC) = 0.92; 95% confidence interval, 0.89–0.95) and in the Bland-Altman analysis, satisfactory agreement between participants’ scores after a 2-week interval. Furthermore, the FTQ demonstrated good internal reliability (α = 0.83, 95% confidence interval, 0.81–0.85) and added statistically significant amounts of variance to models predicting tinnitus-related distress and interference in daily life. Conclusions: The FTQ has good psychometric properties and can be used to assess people’s fear of tinnitus in research or clinical settings. Further work to establish the reliability and validity should be conducted and include an examination of a version of the FTQ that uses Likert-type response scales which might offer improved sensitivity

Pragmatic Uncontrolled Study of Specialized Cognitive Behavioral Therapy for Adults With Chronic Tinnitus

OBJECTIVES: Tinnitus is the perception of sound without an external source, affecting quality of life that can cause severe distress in approximately 1 to 3% of the population of people with tinnitus. Randomized controlled trials of cognitive behavioral therapy for tinnitus have demonstrated its effectiveness in improving quality of life, but the effects of their implementation on a large scale in routine practice remains unknown. Therefore, the main purpose of this study was to examine the effects of stepped-care cognitive behavioral therapy for tinnitus delivered in a tertiary audiological center of a regional hospital. Second, we wished to examine predictors of favorable outcome. DESIGN: Four hundred three adults with chronic tinnitus were enrolled in this prospective observational study (at 3 months, N=334, 8 months, N=261; 12 months, N=214). The primary outcome was health-related quality of life as measured by the Health Utilities Index III (HUI-III) at 12 months. Secondary outcomes were self-reported levels of tinnitus-related distress, disability, affective distress and tinnitus-related negative beliefs and fear. Measures were completed pre-intervention at 3 months, 8 months, and 12 months. Multilevel modeling was used to examine effects and their predictors. RESULTS: Younger participants with lower levels of tinnitus distress were more likely to dropout while those with higher tinnitus distress at baseline and quality of life were more likely to receive step 2 of treatment. MLM analyses revealed, with one exception, no relation between any baseline variable and outcome change over time. Most participants' improvement exceeded minimally clinical important difference criteria for quality of life, tinnitus-related handicap, and tinnitus distress. CONCLUSIONS: Results from this large pragmatic study complements those from randomized controlled trials of cognitive behavioral therapy for chronic tinnitus distress and supports its implementation under "real-world" conditions

Pragmatic Uncontrolled Study of Specialized Cognitive Behavioral Therapy for Adults With Chronic Tinnitus

OBJECTIVES: Tinnitus is the perception of sound without an external source, affecting quality of life that can cause severe distress in approximately 1 to 3% of the population of people with tinnitus. Randomized controlled trials of cognitive behavioral therapy for tinnitus have demonstrated its effectiveness in improving quality of life, but the effects of their implementation on a large scale in routine practice remains unknown. Therefore, the main purpose of this study was to examine the effects of stepped-care cognitive behavioral therapy for tinnitus delivered in a tertiary audiological center of a regional hospital. Second, we wished to examine predictors of favorable outcome. DESIGN: Four hundred three adults with chronic tinnitus were enrolled in this prospective observational study (at 3 months, N=334, 8 months, N=261; 12 months, N=214). The primary outcome was health-related quality of life as measured by the Health Utilities Index III (HUI-III) at 12 months. Secondary outcomes were self-reported levels of tinnitus-related distress, disability, affective distress and tinnitus-related negative beliefs and fear. Measures were completed pre-intervention at 3 months, 8 months, and 12 months. Multilevel modeling was used to examine effects and their predictors. RESULTS: Younger participants with lower levels of tinnitus distress were more likely to dropout while those with higher tinnitus distress at baseline and quality of life were more likely to receive step 2 of treatment. MLM analyses revealed, with one exception, no relation between any baseline variable and outcome change over time. Most participants' improvement exceeded minimally clinical important difference criteria for quality of life, tinnitus-related handicap, and tinnitus distress. CONCLUSIONS: Results from this large pragmatic study complements those from randomized controlled trials of cognitive behavioral therapy for chronic tinnitus distress and supports its implementation under "real-world" conditions

Better Together. Group versus individual Cognitive-Behavioral Therapy for tinnitus:A Multiple-Baseline Single-Case Experimental Design

OBJECTIVE: Chronic tinnitus is effectively treated through cognitive-behavioral therapy (CBT). Both group and individual CBT for tinnitus are effective, but no study has directly compared the two. The current study explores group versus individual CBT for tinnitus. DESIGN: A multiple-baseline single-case experimental design was employed to observe changes within/between individual and group treatments. Six participants started a 10-week CBT protocol and were equally divided into individual or group treatment. Participants were exchanged between treatments at random time points. Diary data included 14 variables on tinnitus experience (e.g. annoyance and distraction) and wellbeing (e.g. happiness and stress). Five male participants (59- to 67-year-old) completed treatment. RESULTS: Randomization tests comparing means between individual and group treatments did not reveal significant differences. Analysis of data overlap and trend (Tau-U) revealed minor significant improvements for seven variables (50%) in group treatment as compared to individual treatment. Diminished happiness and activity levels were observed in participants who went from group to individual treatment. CONCLUSIONS: Low effect sizes and homogeneity of sample restrict the generalizability of data. Group CBT indicated potential benefits when compared to individual CBT. Social learning may be an underlying process in group delivery boosting tinnitus recovery. Findings are limited to male patients with chronic disabling tinnitus

Better Together. Group versus individual Cognitive-Behavioral Therapy for tinnitus: A Multiple-Baseline Single-Case Experimental Design

OBJECTIVE: Chronic tinnitus is effectively treated through cognitive-behavioral therapy (CBT). Both group and individual CBT for tinnitus are effective, but no study has directly compared the two. The current study explores group versus individual CBT for tinnitus. DESIGN: A multiple-baseline single-case experimental design was employed to observe changes within/between individual and group treatments. Six participants started a 10-week CBT protocol and were equally divided into individual or group treatment. Participants were exchanged between treatments at random time points. Diary data included 14 variables on tinnitus experience (e.g. annoyance and distraction) and wellbeing (e.g. happiness and stress). Five male participants (59- to 67-year-old) completed treatment. RESULTS: Randomization tests comparing means between individual and group treatments did not reveal significant differences. Analysis of data overlap and trend (Tau-U) revealed minor significant improvements for seven variables (50%) in group treatment as compared to individual treatment. Diminished happiness and activity levels were observed in participants who went from group to individual treatment. CONCLUSIONS: Low effect sizes and homogeneity of sample restrict the generalizability of data. Group CBT indicated potential benefits when compared to individual CBT. Social learning may be an underlying process in group delivery boosting tinnitus recovery. Findings are limited to male patients with chronic disabling tinnitus

Fear influences phantom sound percepts in an anechoic room

Aims and hypotheses: In an environment of absolute silence, researchers have found many of their participants to perceive phantom sounds (tinnitus). With this between-subject experiment, we aimed to elaborate on these research findings, and specifically investigated whether-in line with the fear-avoidance model of tinnitus perception and reactivity-fear or level of perceived threat influences the incidence and perceptual qualities of phantom sound percepts in an anechoic room. We investigated the potential role of individual differences in anxiety, negative affect, noise sensitivity and subclinical hearing loss. We hypothesized that participants who experience a higher level of threat would direct their attention more to the auditory system, leading to the perception of tinnitus-like sounds, which would otherwise be subaudible, and that under conditions of increased threat, narrowing of attention would lead to perceptual distortions. Methods: In total, N  = 78 normal-hearing volunteers participated in this study. In general, the study sample consisted of young, mostly female, university students. Their hearing was evaluated using gold-standard pure tone audiometry and a speech-in-noise self-test (Digit Triplet Test), which is a sensitive screening test to identify subclinical hearing loss. Prior to a four-minute stay in an anechoic room, we randomized participants block design-wise in a threat ( N  = 37) and no-threat condition ( N  = 41). Participants in the threat condition were deceived about their hearing and were led to believe that staying in the room would potentially harm their hearing temporarily. Participants were asked whether they perceived sounds during their stay in the room and rated the perceptual qualities of sound percepts (loudness and unpleasantness). They were also asked to fill-out standardized questionnaires measuring anxiety (State-Trait Anxiety Inventory), affect (Positive and Negative Affect Schedule) and noise sensitivity (Weinstein Noise Sensitivity Scale). The internal consistency of the questionnaires used was verified in our study sample and ranged between α  = 0.61 and α  = 0.90. Results: In line with incidence rates reported in the literature, 74% of our participants reported having heard tinnitus-like sounds in the anechoic room. Speech-in-noise identification ability was comparable for both groups of participants. The experimental manipulation of threat was proven to be effective, as indicated by significantly higher scores on a Threat Manipulation Checklist among participants in the threat condition as compared to those in the no-threat condition ( p  < 0.01). Nevertheless, participants in the threat condition were as likely to report tinnitus percepts as participants in the no-threat condition ( p  = 1), and tinnitus percepts were not rated as being louder ( p  = 0.76) or more unpleasant ( p  = 0.64) as a function of level of threat. For participants who did experience tinnitus percepts, a higher level of threat was associated with a higher degree of experienced unpleasantness ( p  < 0.01). These associations were absent in those who did not experience tinnitus. Higher negative affect was only slightly associated with higher ratings of tinnitus unpleasantness ( p  < 0.01). Conclusion: Whereas our threat manipulation was successful in elevating the level of fear, it did not contribute to a higher percentage of participants perceiving tinnitus-like sounds in the threat condition. However, higher levels of perceived threat were related to a higher degree of perceived tinnitus unpleasantness. The findings of our study are drawn from a rather homogenous participant pool in terms of age, gender, and educational background, challenging conclusions that are applicable for the general population. Participants generally obtained normophoric scores on independent variables of interest: they were low anxious, low noise-sensitive, and there was little evidence for the presence of subclinical hearing loss. Possibly, there was insufficient variation in scores to find effects