Tinnitus Retraining Therapy (TRT)
Uitgangsvraag
Wat zijn de (on)gunstige effecten van tinnitus retraining therapie (TRT) bij patiënten met chronische subjectieve tinnitusklachten?
Aanbeveling
Verricht bij patiënten met chronische tinnitusklachten geen tinnitus retraining therapie als onderdeel van klinische behandeling.
Overwegingen
Voor- en nadelen van de interventie en de kwaliteit van het bewijs
Er is een literatuuronderzoek verricht naar de effectiviteit van tinnitus retraining therapy (TRT) ten opzichte van afwachten, placebo of sham controle, of gebruikelijke zorg bij patiënten met chronische subjectieve tinnitusklachten. Er is één RCT uitgewerkt die de vergelijking tussen TRT en wachtlijst controle onderzocht. Daarnaast zijn er twee RCTs en één systematische review uitgewerkt die de vergelijking tussen TRT en gebruikelijke zorg onderzochten. De bewijskracht voor de cruciale uitkomstmaat ‘tinnituslast’ is zeer laag en de bewijskracht wat betreft de belangrijke uitkomstmaten ontbreekt. Hier ligt dus een kennislacune.
Tinnitus retraining therapie (TRT)
Er is onvoldoende bewijs voor een klinisch relevant effect van TRT op tinnituslast, en de resultaten zijn tegenstrijdig.
Waarden en voorkeuren van patiënten (en evt. hun verzorgers)
Tinnitus is een veelvoorkomend, complex symptoom, waarvoor op dit moment wereldwijd geen medische oplossing bestaat. Huidige behandelingen richten zich vaak op vermindering van de tinnitushinder. Ook komt tinnitus vaak voor met andere aandoeningen waar gerichte behandelingen voor zijn. Denk aan gehoorverlies (te behandelen met hoortoestellen en/of implantaten) en stemmingsklachten (depressie/angst, te behandelen in overleg met psychiater/psycholoog). De invasiviteit van een behandeling moet worden afgewogen tegen de ernst van de last die een patiënt met tinnitus ondervindt. Tinnitus patiënten die meer tinnitushinder ervaren zullen vaker open staan voor invasievere behandelingen dan patiënten die minder hinder ervaren.
De Goal Attainment Scale (Wagenaar, 2024) laat zien dat patiënten, los van individuele doelen, vijf gemeenschappelijke behandeldoelen hebben:
- Het verkrijgen van controle waardoor er beter met tinnitus kan worden omgegaan
- Het verbeteren van het welzijn en zich minder depressief of angstig voelen
- Het verbeteren van slaap
- Het verminderen van de negatieve effecten van tinnitus op het gehoor
- Het verbeteren van het begrip van tinnitus
Het is voor patiënten van belang dat een behandeling voor tinnitus invloed heeft op een of meerdere van bovenstaande behandeldoelen.
Kosten (middelenbeslag)
De kosten van tinnitus voor de maatschappij zijn door Maes (2013) onderzocht. Zij berekenden de medische kosten op € 1544 per patiënt per jaar (95%CI € 679-2649), en de maatschappelijke kosten op € 5315 per patiënt per jaar (95%CI € 1319-9001). Mede door het chronische karakter van tinnitusklachten, en door de hoge prevalentie zijn deze kosten substantieel te noemen. De kans is dan ook groot dat interventies die ernstige tinnitusklachten mogelijk verminderen uiteindelijk ook kosteneffectief zullen zijn. Dat geldt in het bijzonder bij non-invasieve interventies die geen beroep hoeven te doen op de relatief hoge kosten van operatieve medisch-specialistische zorg. Wetenschappelijke studies naar de kosteneffectiviteit zullen echter moeten uitwijzen of de bereikte effecten niet alleen klinisch relevant maar ook de investering waard zijn.
Aanvaardbaarheid, haalbaarheid en implementatie
Gezien de ernst van de klachten en de forse impact die tinnitus op het dagelijks leven kan hebben, staan een relatief groot deel van de patiënten open voor allerlei typen interventies om hun klachten te verminderen (Tyler, 2012). Tinnitus wordt vaak ervaren als een relatief complex probleem en het gebrek aan eenvoudige behandelingen leidt bij patiënten tot frustratie en soms zelfs tot machteloosheid. Ongeveer 30-40% van de patiënten staat zelfs open voor operatieve, invasieve interventies (Smit, 2018); ook indien ze daarvoor zelf zouden moeten betalen.
Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies
De prevalentie van tinnitusklachten is hoog, met daarbij een forse impact op kwaliteit van leven voor een deel van de patiënten. De behoefte aan een interventie om de klachten te verminderen is dan ook hoog. Op basis van het verrichte literatuuronderzoek is er echter onvoldoende bewijs voor een klinisch relevant effect van TRT op tinnituslast, en de resultaten zijn tegenstrijdig.
Onderbouwing
Achtergrond
Momenteel zijn er meerdere behandelingen of combinaties hiervan beschikbaar voor de behandeling van tinnitus. Deze module richt zich op de effectiviteit van tinnitus retraining therapie (TRT) bij patiënten met chronische subjectieve tinnitusklachten.
Conclusies
Tinnitus burden (critical)
TRT vs. wait-list control
THI
|
Very low GRADE |
The evidence is very uncertain about the effect of TRT on tinnitus burden (THI) when compared with wait-list control in adult patients with chronic subjective tinnitus.
Source: Henry, 2016 |
TRT vs. care as usual
|
Very low GRADE |
The evidence is very uncertain about the effect of TRT on tinnitus burden when compared with care as usual in adult patients with chronic subjective tinnitus. Source: Bauer, 2017; Phillips, 2010; Scherer, 2019 |
Quality of life (important)
|
No GRADE |
No evidence was found regarding the effect of TRT on quality of life when compared with watchful waiting, placebo/sham control, or care as usual in adult patients with subjective chronic tinnitus. Source: - |
Serious adverse events (important)
|
No GRADE |
No evidence was found regarding the effect of TRT on serious adverse events when compared with watchful waiting, placebo/sham control, or care as usual in adult patients with subjective chronic tinnitus. Source: - |
Samenvatting literatuur
Description of studies
Phillips (2010) performed a systematic review to assess the efficacy of Tinnitus Retraining Therapy (TRT) in the treatment of tinnitus. One randomized controlled trial was included which compared TRT with care as usual (tinnitus masking) in patients with tinnitus. The databases Cochrane ENG Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and reference lists of identified publications were searched until 26 August 2009. Studies including adults (>16 years) complaining of tinnitus, where the patients received TRT vs placebo, TRT vs no treatment, or TRT vs drug/other therapy were included in the analysis. Studies that investigated patients with pulsatile tinnitus or tinnitus in association with otosclerosis, Ménière’s disease or tumours of the cerebellopontine angle were excluded. In total, one study was included. The study compared an intervention group receiving TRT with a control group receiving usual care (tinnitus masking with other sounds). The following relevant outcome measure was reported: tinnitus burden (THI, THQ, TSI).
Henry (2016) performed a randomized controlled study to evaluate whether tinnitus masking (TM) and tinnitus retraining therapy (TRT) decreased tinnitus severity more than the two control groups: an attention-control group that received tinnitus educational counseling (and hearing aids if needed) (TED) and the 6-month-wait-list control (WLC) group. In total, 148 veterans who experienced sufficiently bothersome tinnitus were randomized into one of the four groups. For this literature analysis, we included the TRT group and the WLC group. The TM group consists of 42 patients, the TRT group consists of 34 patients, and the WLC group consists of 33 patients. The follow-up period of the study was six months. The study reported the following relevant outcome measure: tinnitus burden (THI).
Bauer (2017) performed a randomized controlled trial to compare treatment outcomes for chronic bothersome tinnitus after Tinnitus Retraining Therapy (TRT) versus standard of care treatment (SC) and to determine the longevity of the effect over an eighteen-month period. Adults (age eighteen to 75 years) suffering from moderate to severe tinnitus (THI score >36) were eligible for inclusion. Tinnitus criteria were: chronic (>one year), non-pulsate, continuous, sensorineural hearing loss with subjective impairment, symmetric sensorineural hearing loss amenable to amplification within limits of ReSound combination device. Exclusion criteria were: tinnitus amenable to medical or surgical treatment, subjective complaints of hyperacusis, loudness discomfort levels (LDL) less than 100 dB SPL on live-voice testing, prior tinnitus treatment, residence outside a 60-mile radius of Springfield Illinois, Beck Depression Inventory total score >30; endorsing suicide or self-harm on BDI item #9, unwilling to wear prescribed devices, participate in educational counselling, return for follow-up over eighteen months, currently using hearing aids or use within the preceding six months. In total, 38 patients were eligible for inclusion, of which nineteen patients received TRT and nineteen patients received standard of care treatment. The follow-up period of the study was eighteen months, with follow-up measurements at six, twelve and eighteen months. The study reported the following relevant outcome measure: tinnitus burden (THI, TFI).
Scherer (2019) performed a randomized placebo-controlled trial to compare the efficacy of TRT and its components, sound therapy and tinnitus-specific educational counselling, with the standard of care in reducing the negative effect of tinnitus on quality of life. Active-duty and retired military personnel and their dependents were enrolled. Eligible study participants had subjective distressing tinnitus of at least 1 year’s duration and no evidence of a medical cause as determined by study-certified physicians. All participants had functionally adequate hearing sensitivity that did not routinely require amplification. Other eligibility criteria included no treatment for tinnitus within the past year and a score of 40 or more on the tinnitus questionary (TQ), indicated moderately severe effect of tinnitus on quality of life. The exclusion criteria were not reported. In total, 100 patients were eligible for inclusion, of which 51 patients received TRT and 49 patients received standard of care treatment. The follow-up period of the study was eighteen months, with follow-up measurements at three, six, twelve and eighteen months. The study reported the following relevant outcome measure: tinnitus burden (THI, TQ, TFI, VAS).
Results
Tinnitus burden (critical)
TRT vs. wait-list control
Tinnitus Handicap Inventory (THI)
One study reported the outcome measure tinnitus burden measured by THI (Henry, 2016).
Henry (2016) reported that patients who received tinnitus retraining therapy (n=34) had a mean THI change at 3 months follow-up? of -8.37 (95% CI -13.25 to -3.49), compared to 4.65 (95% CI -0.31 to 9.60) in wait-list control patients (n=33). The mean difference was -13.02 (95% CI -19.98 to -6.06), in favour of tinnitus retraining therapy. This difference is considered clinically relevant.
Henry (2016) reported that patients who received tinnitus retraining therapy (n=34) had a mean THI change at 6 months follow-up? of -11.07 (95% CI -16.98 to -5.15), compared to 3.09 (95% CI -2.91 to 9.10) in wait-list control patients (n=33). The mean difference was -14.16 (95% C I -22.58 to -5.73), in favour of tinnitus retraining therapy. This difference is considered clinically relevant.
TRT vs. care as usual
Tinnitus Handicap Inventory (THI)
Three studies reported the outcome measure tinnitus severity measured by THI (Bauer, 2017; Phillips, 2010; Scherer, 2019). Due to differences in outcome reporting, the results were not pooled.
Bauer (2017) reported THI at six, twelve and eighteen months.
The patients who received TRT (n=19) had a mean THI at six months of 26.4 (SD ± 14.1), and the patients who received standard of care treatment (n=19) had a mean THI at six months of 35.8 (SD ± 15.7). The difference in THI between the groups was -9.40 (95% CI -18.89 to 0.09), in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients who received TRT (n=19) had a mean THI at twelve months of 18.6 (SD ± 10.9), and the patients who received standard of care treatment (n=19) had a mean THI at twelve months of 30.7 (SD ± 15.4). The difference in THI between the groups was -12.10 (95% CI -20.58 to -3.62), in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients who received TRT (n=19) had a mean THI at eighteen months of 17.3 (SD ± 12.3), and the patients who received standard of care treatment (n=19) had a mean THI at eighteen months of 33.4 (SD ± 20.5). The difference in THI between the groups was -16.10 (95% CI -26.85 to -5.35), in favour of the patients who received TRT. This difference is considered clinically relevant.
Phillips (2010) reported improvement in THI at eighteen months for patients with a moderate tinnitusproblem, big problem, and very big problem.
The patients in the moderate problem group who received TRT (n=not reported (NR)) had an improvement in THI at eighteen months of 18.2, and the patients who received tinnitus masking (n=NR) had an improvement in THI at eighteen months of 4.6. The difference in improvement between the groups was 13.6, in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients in the big problem group who received TRT (n=NR) had an improvement in THI at eighteen months of 29.2, and the patients who received tinnitus masking (n=NR) had an improvement in THI at eighteen months of 16.7. The difference in improvement between the groups was 12.5, in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients in the very big problem group who received TRT (n=NR) had an improvement in THI at eighteen months of 50.4, and the patients who received tinnitus masking (n=NR) had an improvement in THI at eighteen months of 10.3. The difference between the groups was 40.1, in favour of the patients who received TRT. This difference is considered clinically relevant.
Scherer (2019) reported THI at three, six, twelve and eighteen months.
The patients who received TRT (n=40) had a mean THI at three months of 30.5 (SD ± 17.0), and the patients who received standard of care treatment (n=42) had a mean THI at three months of 36.3 (SD ± 17.7). The difference in THI between the groups was -5.80 (95% CI -13.31 to 1.71), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=32) had a mean THI at six months of 25.8 (SD ± 16.4), and the patients who received standard of care treatment (n=38) had a mean THI at six months of 33.4 (SD ± 18.4). The difference in THI between the groups was -7.60 (95% CI -15.76 to 0.56), in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients who received TRT (n=34) had a mean THI at twelve months of 29.2 (SD ± 17.4), and the patients who received standard of care treatment (n=30) had a mean THI at twelve months of 26.4 (SD ± 14.6). The difference in THI between the groups was 2.80 (95% CI -5.04 to 10.64), in favour of the patients who received standard of care treatment. This difference is not considered clinically relevant.
The patients who received TRT (n=34) had a mean THI at eighteen months of 31.5 (SD ± 20.5), and the patients who received standard of care treatment (n=37) had a mean THI at eighteen months of 29.2 (SD ± 17.2). The difference in THI between the groups was 2.30 (95% CI -6.54 to 11.14), in favour of the patients who received standard of care treatment. This difference is not considered clinically relevant.
Tinnitus Handicap Questionnaire (THQ)
One study reported the outcome measure tinnitus severity measured by THQ (Phillips, 2010).
Phillips (2010) reported improvement in THQ at eighteen months for patients with moderate problem, big problem, and very big problem.
The patients in the moderate problem group who received TRT (n=NA) had an improvement in THQ at eighteen months of 489, and the patients who received tinnitus masking (n=NA) had an improvement in THQ at eighteen months of 178. The difference in improvement between the two groups was 311, in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients in the big problem group who received TRT (n=NA) had an improvement in THQ at eighteen months of 799, and the patients who received tinnitus masking (n=NA) had an improvement in THQ at eighteen months of 256. The difference in improvement between the two groups was 543, in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients in the very big problem group who received TRT (n=NA) had an improvement in THQ at eighteen months of 1118, and the patients who received tinnitus masking (n=NA) had an improvement in THQ at eighteen months of 300. The difference between the two groups was 818, in favour of the patients who received TRT. This difference is considered clinically relevant.
Tinnitus Questionnaire (TQ)
One study reported the outcome measure tinnitus severity measured by TQ (Scherer, 2019).
Scherer (2019) reported TQ at three, six, twelve and eighteen months.
The patients who received TRT (n=40) had a mean TQ at three months of 39.4 (SD ± 16.6), and the patients who received standard of care treatment (n=42) had a mean TQ at three months of 43.5 (SD ± 16.7). The difference in TQ between the groups was -4.10 (95% CI -11.31 to 3.11), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=32) had a mean TQ at six months of 34.8 (SD ± 16.5), and the patients who received standard of care treatment (n=38) had a mean TQ at six months of 40.4 (SD ± 14.8). The difference in TQ between the groups was -5.60 (95% CI -13.00 to 1.80), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=34) had a mean TQ at twelve months of 35.7 (SD ± 16.9), and the patients who received standard of care treatment (n=30) had a mean TQ at twelve months of 35.8 (SD ± 14.7). The difference in TQ between the groups was -0.10 (95% CI -7.84 to 7.64), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=34) had a mean TQ at eighteen months of 39.0 (SD ± 19.2), and the patients who received standard of care treatment (n=37) had a mean TQ at eighteen months of 37.3 (SD ± 16.8). The difference in TQ between the groups was 1.70 (95% CI -6.72 to 10.12), in favour of the patients standard of care treatment. This difference is not considered clinically relevant.
Tinnitus Functional Index (TFI)
Two studies reported the outcome measure tinnitus burden measured by TFI (Bauer, 2017; Scherer, 2019). Since only two studies reported the outcome measure, the results were not pooled.
Bauer (2017) reported TFI at six, twelve and eighteen months.
The patients who received TRT (n=19) had a mean TFI at six months of 30.0 (SD ± 14.3), and the patients who received standard of care treatment (n=19) had a mean TFI at six months of 43.2 (SD ± 19.3). The difference in TFI between the groups was -13.20 (95% CI -24.00 to -2.40), in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients who received TRT (n=19) had a mean TFI at twelve months of 26.2 (SD ± 15.2), and the patients who received standard of care treatment (n=19) had a mean TFI at twelve months of 47.5 (SD ± 23.6). The difference in TFI between the groups was -21.30 (95% CI -33.92 to -8.68), in favour of the patients who received TRT. This difference is considered clinically relevant.
The patients who received TRT (n=19) had a mean TFI at eighteen months of 24.4 (SD ± 21.7), and the patients who received standard of care treatment (n=19) had a mean TFI at eighteen months of 44.1 (SD ± 19.7). The difference in TFI between the groups was -19.70 (95% CI -32.88 to -6.52), in favour of the patients who received TRT. This difference is considered clinically relevant.
Scherer (2019) reported TFI at three, six, twelve and eighteen months.
The patients who received TRT (n=40) had a mean TFI at three months of 43.1 (SD ± 17.6), and the patients who received standard of care treatment (n=42) had a mean TFI at three months of 49.8 (SD ± 17.6). The difference in TFI between the groups was -6.70 (95% CI -14.32 to 0.92), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=32) had a mean TFI at six months of 38.6 (SD ± 18.3), and the patients who received standard of care treatment (n=38) had a mean TFI at six months of 44.7 (SD ± 19.1). The difference in TFI between the groups was -6.10 (95% CI -14.88 to 2.68), in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients who received TRT (n=34) had a mean TFI at twelve months of 38.6 (SD ± 17.4), and the patients who received standard of care treatment (n=30) had a mean TFI at twelve months of 37.6 (SD ± 20.9). The difference in TFI between the groups was 1.00 (95% CI -8.49 to 10.49), in favour of the patients who received standard of care treatment. This difference is not considered clinically relevant.
The patients who received TRT (n=34) had a mean TFI at eighteen months of 40.1 (SD ± 19.6), and the patients who received standard of care treatment (n=37) had a mean TFI at eighteen months of 41.6 (SD ± 23.4). The difference in TFI between the groups was -1.50 (95% CI -11.51 to 8.51), in favour of the patients who received TRT. This difference is not considered clinically relevant.
Tinnitus Severity Index (TSI)
One study reported the outcome measure difference in tinnitus burden measured by TSI at eighteen months for patients with moderate problem, big problem, and very big problem (Phillips, 2010).
The patients in the moderate problem group who received TRT (n=NA) had an improvement in TSI at eighteen months of 7.5 points, and the patients who received tinnitus masking (n=NA) had an improvement in TSI at eighteen months of 1.6 points. The difference in improvement between the two groups was 5.9, in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients in the big problem group who received TRT (n=NA) had an improvement in TSI at eighteen months of 12.1 points, and the patients who received tinnitus masking (n=NA) had an improvement in TSI at eighteen months of 6.7 points. The difference in improvement between the two groups was 5.4 points, in favour of the patients who received TRT. This difference is not considered clinically relevant.
The patients in the very big problem group who received TRT (n=NA) had an improvement in TSI at eighteen months of 19.7 points, and the patients who received tinnitus masking (n=NA) had an improvement in TSI at eighteen months of 4.8 points. The difference between the two groups was 14.9 points, in favour of the patients who received TRT. This difference is considered clinically relevant.
Quality of life (important)
None of the included studies reported the outcome measure quality of life.
Serious adverse events (important)
None of the included studies reported the outcome measure serious adverse events.
Level of evidence of the literature
Tinnitus burden (critical)
TRT vs. wait-list control
THI
The level of evidence for tinnitus burden measured by THI was based on an RCT and therefore starts high. The level of evidence was downgraded by three levels because of study limitations (risk of bias, -1), and because of a very small sample size (imprecision, -2). The level of evidence is therefore graded as very low.
TRT vs. care as usual
THI, TFI
The level of evidence for tinnitus burden measured by THI was based on RCTs and therefore starts high. The level of evidence was downgraded by three levels because of study limitations (risk of bias, -1), because of a small sample size (imprecision, -1), and because of conflicting results (inconsistency, -1). The level of evidence is therefore graded as very low.
THQ, TQ, TSI
The level of evidence for tinnitus burden measured by THQ was based on RCTs and therefore starts high. The level of evidence was downgraded by three levels because of study limitations (risk of bias, -1), and because of a very small sample size (imprecision, -2). The level of evidence is therefore graded as very low.
Quality of life (important)
The level of evidence for quality of life could not be established as no studies reported this outcome measure.
Serious adverse events (important)
The level of evidence for adverse events could not be established as no studies reported this outcome measure.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question:
What are the (un)favorable effects of tinnitus retraining therapy compared to watchful waiting, placebo/sham control, or care as usual in adult patients with chronic subjective tinnitus on tinnitus burden, quality of life and serious adverse events?
| P: patients | adult patients with chronic subjective tinnitus (≥3 months) |
| I: intervention | tinnitus retraining therapy |
| C: control | watchful waiting, placebo/sham control, or care as usual |
| O: outcome measure | tinnitus burden, quality of life, serious adverse events. |
Relevant outcome measures
The guideline development group considered tinnitus burden as a critical outcome measure for decision making; and quality of life and serious adverse events as important outcome measures for decision making.
A priori, the working group defined the outcome measures as follows:
- Care as usual as defined by the authors (see description of studies);
- Tinnitus burden measured with single- (NRS) or multi-item questionnaires (e.g. THI, TQ, TFI, VAS impact, intrusiveness); Tinnitus burden includes aspects such as impact on daily life, distress and disability (de Ridder, 2021).
- Quality of life in general;
- Serious adverse events.
The working group defined the following differences as a minimal clinically (patient) important:
- THI: 7 points (Fuller, 2020).
- TFI: 13 (Meikle, 2012)
- TSI: 15% (Langguth, 2023)
- TQ: 8 (Zeman, 2012)
- VAS score: 15 points on a 100-points scale, 1.5 on a 10-points scale (Adamchic, 2021)
- Quality of life: 10%
- Serious adverse events: 25% (RR < 0.8 or RR > 1.25).
If different measurement instruments were pooled, then differences were defined as: a trivial effect (standardized mean difference (SMD) = 0 to 0.2), a small effect (SMD = 0.2 to 0.5), a moderate effect (SMD = 0.5 to 0.8), and a large effect (SMD >0.8).
Search and select (Methods)
In the original search for the guideline Tinnitus – Behandeling van patiënten met tinnitus (2016), Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 1979 until January 2014. This resulted in 471 hits. Studies were selected based on the following criteria: systematic reviews and RCT’s that compared tinnitus treatments with watchful waiting (placebo) in adult patients with chronic subjective tinnitus. In total, 26 studies were included based on title and abstract screening. After reading the full text, one systematic review was included regarding tinnitus retraining therapy (Philips, 2010).
For this update, the databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 01-01-2014 until 02-05-2022 (SR’s) and 07-07-2022 (RCT’s). The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 363 hits. Studies were selected based on the following criteria: systematic reviews and RCT’s that compared tinnitus retraining therapy with watchful waiting, placebo, or sham control in adult patients with chronic subjective tinnitus. In total, seven studies were initially selected based on title and abstract screening. After reading the full text, four studies were excluded (see the table with reasons for exclusion under the tab Methods), and three studies were included. Combining the original search and this update, three studies and one systematic review were included in the literature analysis (Bauer, 2017; Henry, 2016; Phillips, 2010; Scherer, 2019).
Results
Four studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.
Referenties
- Adamchic I, Langguth B, Hauptmann C, Tass PA. Psychometric evaluation of visual analog scale for the assessment of chronic tinnitus. Am J Audiol. 2012 Dec;21(2):215-25. doi: 10.1044/1059-0889(2012/12-0010). Epub 2012 Jul 30. PMID: 22846637.
- Bauer CA, Berry JL, Brozoski TJ. The effect of tinnitus retraining therapy on chronic tinnitus: A controlled trial. Laryngoscope Investig Otolaryngol. 2017 May 28;2(4):166-177. doi: 10.1002/lio2.76. PMID: 28894836; PMCID: PMC5562945.
- Fuller T, Cima R, Langguth B, Mazurek B, Vlaeyen JW, Hoare DJ. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2020 Jan 8;1(1):CD012614. doi: 10.1002/14651858.CD012614.pub2. PMID: 31912887; PMCID: PMC6956618.
- Henry JA, Stewart BJ, Griest S, Kaelin C, Zaugg TL, Carlson K. Multisite Randomized Controlled Trial to Compare Two Methods of Tinnitus Intervention to Two Control Conditions. Ear Hear. 2016 Nov/Dec;37(6):e346-e359. doi: 10.1097/AUD.0000000000000330. PMID: 27438870.
- Langguth B, De Ridder D. Minimal Clinically Important Difference of Tinnitus Outcome Measurement Instruments-A Scoping Review. J Clin Med. 2023 Nov 15;12(22):7117. doi: 10.3390/jcm12227117. PMID: 38002730; PMCID: PMC10671865.
- Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, Myers PJ, Newman CW, Sandridge S, Turk DC, Folmer RL, Frederick EJ, House JW, Jacobson GP, Kinney SE, Martin WH, Nagler SM, Reich GE, Searchfield G, Sweetow R, Vernon JA. The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012 Mar-Apr;33(2):153-76. doi: 10.1097/AUD.0b013e31822f67c0. Erratum in: Ear Hear. 2012 May;33(3):443. PMID: 22156949.
- Phillips JS, McFerran D. Tinnitus Retraining Therapy (TRT) for tinnitus. Cochrane Database Syst Rev. 2010 Mar 17;2010(3):CD007330. doi: 10.1002/14651858.CD007330.pub2. PMID: 20238353; PMCID: PMC7209976.
- Tinnitus Retraining Therapy Trial Research Group; Scherer RW, Formby C. Effect of Tinnitus Retraining Therapy vs Standard of Care on Tinnitus-Related Quality of Life: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2019 Jul 1;145(7):597-608. doi: 10.1001/jamaoto.2019.0821. PMID: 31120533; PMCID: PMC6547112.
- Wagenaar O, Gilles A, Van Rompaey V, Blom H. Goal Attainment Scale in tinnitus (GAS-T): treatment goal priorities by chronic tinnitus patients in a real-world setting. Eur Arch Otorhinolaryngol. 2024 Feb;281(2):693-700. doi: 10.1007/s00405-023-08134-2. Epub 2023 Jul 25. PMID: 37488402.
- Zeman F, Koller M, Schecklmann M, Langguth B, Landgrebe M; TRI database study group. Tinnitus assessment by means of standardized self-report questionnaires: psychometric properties of the Tinnitus Questionnaire (TQ), the Tinnitus Handicap Inventory (THI), and their short versions in an international and multi-lingual sample. Health Qual Life Outcomes. 2012 Oct 18;10:128. doi: 10.1186/1477-7525-10-128. PMID: 23078754; PMCID: PMC3541124.
Evidence tabellen
Evidence table for systematic reviews
|
Study reference |
Study characteristics |
Patient characteristics |
Intervention (I) |
Comparison / control (C)
|
Follow-up |
Outcome measures and effect size |
Comments |
|
Phillips, 2010
Individual study characteristics deduced from Philips, 2010 |
SR of RCTs
Literature search up to August 2009
A: Henry, 2006
Study design: Randomised controlled trial
Setting and country: Patients were recruited from a cohort of US military veterans.
Source of funding: Not reported. |
Inclusion criteria: Military veterans (>16 years) complaining of tinnitus.
Exclusion criteria: Patients with pulsatile tinnitus or tinnitus in association with otosclerosis, Méniè’e's disease or tumours of the cerebellopontine angle.
1 study included.
Important patient characteristics at baseline: N, mean age: A: 123 patients, age not reported.
Gender: A: 95% male
Groups comparable at baseline? Not reported. |
Intervention:
A: Tinnitus retraining therapy (TRT): a form of educational counselling and sound therapy given according to a specific protocol.
|
Control:
A: Tinnitus masking (TM)
|
End-point of follow-up: A: 18 months
For how many participants were no complete outcome data available? A: 12 patients The statistical methods used for analysis allowed for missing data elements, however 5 participants had missing predictor data such that they could not be included in the final analysis.
|
Tinnitus severity Defined as tinnitus severity, using THI, THQ and TSI for patients in three groups (moderate problem, big problem, very big problem).
Improvement in THI, THQ and TSI Moderate problem THI I: 18.2 C: 4.6 THQ I: 489 TSI I: 7.5 C: 1.6
Big problem THI I: 29.2 THQ I: 799 C: 256 TSI I: 12.1 C: 6.7
Very big problem THI I: 50.4 C: 10.3 THQ I: 1118 C: 300 TSI I: 19.7 C: 4.8 |
Risk of bias (high, some concerns or low): Tool used by authors:
A: High (sequence generation, allocation concealment, blinding)
|
Evidence table for RCTs
|
Study reference |
Study characteristics |
Patient characteristics 2 |
Intervention (I) |
Comparison / control (C) 3
|
Follow-up |
Outcome measures and effect size 4 |
Comments |
|
Bauer, 2017 |
Type of study: Randomized controlled trial
Setting and country: Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Funding: Funded by the Tinnitus Research Consortium.
Conflicts of interest: The authors have no financial relationships or conflicts of interest to disclose. |
Inclusion criteria: Adults (age 18 to 75 years), moderate to severe tinnitus (THI score >36), Tinnitus criteria: chronic (>1 year), non-pulsate, continuous, sensorineural hearing loss with subjective impairment, symmetric sensorineural hearing loss amenable to amplification within limits of ReSound combination device.
Exclusion criteria: Tinnitus amenable to medical or surgical treatment, subjective complaints of hyperacusis, loudness discomfort levels (LDL) less than 100 dB SPL on live-voice testing, prior tinnitus treatment, residence outside a 60-mile radius of Springfield Illinois, Beck Depression Inventory total score >30; endorsing suicide or self-harm on BDI item #9, unwilling to wear prescribed devices, participate in educational counselling, return for follow-up over 18 months, currently using hearing aids or use within the preceding 6 months.
N total at baseline: N=38 I: 19 C: 19
Important prognostic factors2: Age 18-50: I: 3 C: 3 Age 51-65: I: 14 C: 11 Age 66-75: I: 2 C: 5
Gender (% male): I: 13 (68) C: 13 (68)
Duration of tinnitus problem -1-2 years I: 1 C: 1 -2-3 years I: 4 C: 0 -3-5 years I: 0 C: 3 -more than 5 years I: 14 C: 15
Groups were comparable at baseline. |
Intervention: Tinnitus retraining therapy (TRT)
TRT counselling sessions one-on-one, using a standardized TRT powerpoint presentation, distributed over three 1 hour sessions. The counselling content was based on Jastreboff’s neurophysiologic model and consisted of information on hearing mechanisms and theories and examples of how hearing loss and emotional reactions lead to bothersome tinnitus. TRT participants received binaural open fit receiver-in-the-canal combination devices (ReSound, model Live 9 TS [62] RITE, Bloomington, MN) correctly fit to their audiogram by the study audiologist (JEB). Participants were instructed on device use and had control over amplification volume only. The broadband noise volume was set by the study audiologist (JLB) at the direction of the participant to an audible but comfortable level that was less loud than their tinnitus. |
Control: Standard of Care treatment (SC)
Participants in the SC control group received general aural rehabilitation counselling distributed over three 1 hour sessions, using a standardized SC powerpoint presentation. Aural rehabilitation counseling was comprised of information on mechanisms of hearing, hearing health, coping, and listening strategies. SC participants were fitted with binaural combination devices, identical to those fitted to the TRT group, but with the sound generator feature inactivated by the study audiologist. |
Length of follow-up: 18 months: follow-up measurements at 6, 12 and 18 months.
Loss-to-follow-up: I: n=0 C: n=1 (5.3%)
Incomplete outcome data: I: n=0 C: n=3 (15.8%) Reasons: -could not tolerate amplification (n=2) -unknown (n=1) |
Tinnitus burden (mean ± SD) THI Entry I: 46.7 ± 14.7 C: 49.3 ± 15.5
THI 6 months I: 26.4 ± 14.1 C: 35.8 ± 15.7
THI 12 months I: 18.6 ± 10.9 C: 30.7 ± 15.4
THI 18 months I: 17.3 ± 12.3 C: 33.4 ± 20.5
TFI Entry I: 62.0 ± 17.8 C: 72.1 ± 14.1
TFI 6 months I: 30.0 ± 14.3 C: 43.2 ± 19.3
TFI 12 months I: 26.2 ± 15.2 C: 47.5 ± 23.6
TFI 18 months I: 24.4 ± 21.7 C: 44.1 ± 19.7
Adverse events No adverse events.
|
|
|
Henry, 2016 |
Type of study: RCT
Setting and country: four-site clinical trial, USA.
Funding and conflicts of interest: Funding was provided by grants from Veterans Affairs Rehabilitation Research and Development (RR&D) Service (C2887R and C3214R), with general support from the Veterans Health Administration.
The authors have no conflicts of interest to disclose. |
Inclusion criteria: Veterans who experienced sufficiently bothersome tinnitus. Patients were screened with the tinnitus-impact screening interview which includes 8 questions.
Exclusion criteria: Not described.
N total at baseline: Intervention TRT: 34 Control: 33
Important prognostic factors2: For example age ± SD: I TRT: 60.1 (10.1) C: 61.2 (8.8)
Sex: I TRT: 97.1% M C: 97.0% M
Groups comparable at baseline? Subjects in the four groups did not differ significantly on the baseline demographic or clinical characteristics listed in Table 2 |
Describe intervention (treatment/procedure/test):
Tinnitus retraining therapy (TRT)
Subjects receiving TRT were fitted with ear-level sound generators (aka “maskers”), hearing aids, or combination instruments. The fitting protocol for these subjects was mostly the same as in the preceding study. A minor difference was that toward the beginning of the previous study, TRT subjects who had hearing thresholds that would typically be associated with hearing aid candidacy were fitted with ear-level sound generators if they reported no subjective problem with hearing. Those subjects usually complained of difficulty hearing while wearing the sound generators, so we began suggesting combination instruments for subjects who did not complain of hearing problems but had enough hearing loss to be considered a hearing aid candidate. For the present study, all TRT subjects who did not complain of hearing problems, but whose hearing thresholds reflected hearing aid candidacy were advised to try combination instruments. The TRT subjects with normal hearing, or with hearing loss mild enough that they would not be considered candidates for amplification under normal circumstances, were fitted with ear-level sound generators. |
Describe control (treatment/procedure/test):
6-month-wait-list control (WLC) group.
For the WLC group, we considered extending the duration of no treatment beyond 6 months. This was decided against, however, because it would force Veterans to wait at least 1 year for treatment. In our previous study (Henry et al. 2006b), significant benefit was observed within 3 months for both treatment groups, with even greater improvement at 6 months. Six months of no treatment would therefore be sufficient to control for the treatment variable. WLC subjects completed outcome assessments at 0, 3, and 6 months, ensuring three equally spaced data collection points during the no-treatment period. At 6 months, these subjects were informed of their treatment-group assignment—as determined at baseline—and started treatment. |
Length of follow-up: The total follow-up of the study was 18 months. However as the wait-list-control was only 6 months, we used only 6 months of follow-up in this literature review.
Loss-to-follow-up at 6 months Intervention TRT: 6 Control: 1 Reasons (describe): not described.
Incomplete outcome data: Intervention TRT: 0 Control: 0 Reason: skipped visit, missing 6 months outcomes.
|
Outcome measures and effect size (include 95%CI and p-value if available):
TRT vs wait-list-control THI at 3 months TRT: -8.37 (-13.25 to -3.49) WLC: 4.65 (-0.31 to 9.60)
THI at 6 months: TRT: -11.07 (-16.98 to -5.15) WLC: 3.09 (-2.91 to 9.10).
THI at 3 months (mean difference, 95%CI) TRT versus WLC: -13.02 (-19.98 to -6.06)
THI at 6 months TRT versus WLC: -14.16 (-22.58 to -5.73)
Quality of life Not reported.
Adverse events Not reported.
TRT vs tinnitus education (TED) THI at 3 months TRT: -8.37 (-13.25 to -3.49) TED: -2.20 (-6.75 to 2.35)
THI at 6 months TRT: -11.07 (-16.98 to -5.15) TED: -7.12 (-12.63 to -1.61)
THI at 12 months TRT: -11.71 (-18.54 to -4.89) TED: -9.60 (-15.97 to -3.24)
THI at 18 months TRT: -13.50 (-20.32 to -6.69) TED: -7.98 (-14.34 to -1.62)
THI at 3 months (mean difference, 95%CI) TRT vs TED: -6.17 (-12.85 to 0.50)
THI at 6 months (mean difference, 95%CI) TRT vs TED: -3.94 (-12.03 to 4.14)
THI at 12 months (mean difference, 95%CI) TRT vs TED: -2.11 (-11.45 to 7.22)
THI at 18 months (mean difference, 95%CI) TRT vs TED: -5.53 (-14.85 to 3.80) |
Authors’ conclusion: Audiologists who provided interventions to Veterans with bothersome tinnitus in the regular clinic setting were able to significantly reduce tinnitus severity over 18 months using TM, TRT, and TED approaches. These results suggest that TM, TRT, and TED, when implemented as in this trial, will provide effectiveness that is relatively similar by 6 months and beyond. |
|
Scherer, 2019 |
Type of study: Randomized clinical trial
Setting and country: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Funding: The Tinnitus Retraining Therapy Trial (TRTT) project is supported by awards from the National Institute of Deafness and Other Communication Disorders. The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Conflicts of interest: Dr. Scherer received grants from the National Institute on Deafness and Other Communication Disorders during the conduct of the study. Dr. Formby received grants from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders during the conduct of the study. |
Inclusion criteria: Active-duty and retired military personnel and their dependents were enrolled. Eligible study participants had subjective distressing tinnitus of at least 1 year’s duration and no evidence of a medical cause as determined by study-certified physicians. All participants had functionally adequate hearing sensitivity that did not routinely require amplification. Other eligibility criteria included no treatment for tinnitus within the past year and a score of 40 or more on the TQ, indicated moderately severe effect of tinnitus on quality of life.
Exclusion criteria: Not reported.
N, total at baseline: N total = 100 I: 51 C: 49
Important prognostic factors2: Age ± SD: I: 5.1.1 ± 12.6 C: 49.9 ± 10.0
Gender (% male): I: 34 (66.7%) C: 36 (73.5%)
Tinnitus duration, years (mean ± SD): I: 10.9 ± 8.9 C: 13.0 ± 11.4
Groups were comparable at baseline. |
Intervention: Tinnitus Retraining Therapy (TRT)
TRT, including tinnitus-specific educational counselling (synonymous with directive counselling) (TC) and low-level broadband sound therapy (ST) implemented with ear-level SGs. |
Control: Standard of care
A patient-centered counselling protocol that aligned with current military care and recommended practice guidelines. |
Follow-up duration: 18 months, follow-up measurements at 3, 6, 12 and 18 months.
Loss-to-follow-up: N total = 18 (18%) Intervention: N=13 (25.5%)
Control: N=5 (10%)
No apparent differences in baseline characteristics of participants who withdrew compared with those who remained.
Incomplete outcome data: No incomplete outcome data. |
Outcome measures: Tinnitus Questionnaire (TQ) baseline: Intervention: 56.4 ± 11.9 Control: 54.6 ± 11.2
TQ 3 months: Intervention: 39.4 ± 16.6 Control: 43.5 ± 16.7
TQ 6 months: Intervention: 34.8 ± 16.5 Control: 40.4 ± 14.8
TQ 12 months: Intervention: 35.7 ± 16.9 Control: 35.8 ± 14.7
TQ 18 months: Intervention: 39.0 ± 19.2 Control: 37.3 ± 16.8
Tinnitus Functional Index (TFI) baseline: Intervention: 48.1 ± 17.6 Control: 53.5 ± 17.3
TFI 3 months: Intervention: 43.1 ± 17.6 Control: 49.8 ± 17.6
TFI 6 months: Intervention: 38.6 ± 18.3 Control: 44.7 ± 19.1
TFI 12 months: Intervention: 38.6 ± 17.4 Control: 37.6 ± 20.9
TFI 18 months: Intervention: 40.1 ± 19.6 Control: 41.6 ± 23.4
Tinnitus Handicap Inventory (THI) baseline: Intervention: 37.8 ± 13.0 Control: 38.6 ± 18.7
THI 3 months: Intervention: 30.5 ± 17.0 Control: 36.3 ± 17.7
THI 6 months: Intervention: 25.8 ± 16.4 Control: 33.4 ± 18.4
THI 12 months: Intervention: 29.2 ± 17.4 Control: 26.4 ± 14.6
THI 18 months: Intervention: 31.5 ± 20.5 Control: 29.2 ± 17.2
VAS (10-point) baseline: Intervention: 6.2 ± 2.2 Control: 6.3 ± 2.1
VAS 3 months: Intervention: NA
VAS 6 months: Intervention: 4.5 ± 2.4
VAS 12 months: Intervention: 4.1 ± 2.1 Control: 4.5 ± 2.5
VAS 18 months: Intervention: 4.4 ± 2.4 |
|
Risk of bias table for intervention studies (randomized controlled trials; based on Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University)
|
Study reference
(first author, publication year) |
Was the allocation sequence adequately generated?
Definitely yes Probably yes Probably no Definitely no |
Was the allocation adequately concealed?
Definitely yes Probably yes Probably no Definitely no |
Blinding: Was knowledge of the allocated interventions adequately prevented?
Definitely yes Probably yes Probably no Definitely no |
Was loss to follow-up (missing outcome data) infrequent?
Definitely yes Probably yes Probably no Definitely no |
Are reports of the study free of selective outcome reporting?
Definitely yes Probably yes Probably no Definitely no |
Was the study apparently free of other problems that could put it at a risk of bias?
Definitely yes Probably yes Probably no Definitely no |
Overall risk of bias If applicable/necessary, per outcome measure
LOW Some concerns HIGH
|
|
Bauer, 2017 |
Probably yes
Reason: Participants were randomly assigned to balanced treatment arms by a co-investigator, not involved in screening, consent, or assessment. |
Probably yes
Reason: Allocation concealment was maintained by segregating the tasks of recruitment, consent and screening, enrolment, and allocation to separate investigators. |
Probably no
Reason: no information about blinding. |
Definitely no
Reason: loss-to-follow-up was infrequent, 0% in the intervention group, 5.3% in the control group. Missing outcome data was frequent, 0% in intervention group, 15.8% in control group. |
Definitely yes
Reason: The outcome measures mentioned in the abstract are reported in the results section. |
Definitely no
Reason: small sample size, lack of precision in reported hearing loss history |
HIGH (THI and TF) Reason: The study was not blinded, the sample size was very small and missing outcome data was frequent. |
|
Henry, 2016 |
No information;
Reason: Qualifying subjects received an envelope containing their assignment (TRT, TM, TED, and WLC). |
No information;
Reason: Qualifying subjects received an envelope containing their assignment (TRT, TM, TED, and WLC). |
Definitely no;
Reason: study participants and personnel was not blinded. |
Definitely no;
Reason: Loss to follow-up was more than 10% in the intervention groups. |
Definitely yes
Reason: All relevant outcomes were reported. |
Definitely no;
Reason: the study size was too small. |
HIGH (THI)
Reason: The primary outcome measure (THI) is subjective, as the study is not blinded this could result in bias. |
|
Scherer, 2019 |
Definitely yes
Reason: The randomization schedule was generated using a computer-generated random permutation with random blocking and stratification. |
Definitely yes
Reason: Audiologists ordered SGs directly from the manufacturer, General Hearing Instruments Inc. Each SG was identified as conventional or placebo by serial number in a schedule prepared prior to trial initiation and provided to General Hearing Instruments Inc. At randomization, the order form provided only the serial number of the assigned device to ensure blinding to SG type |
Probably yes
Reason: patients and audiologists were blinded. |
Definitely no
Reason: Loss-to-follow-up was more than 10% in both the intervention and the control group. |
Definitely yes
Reason: All relevant outcomes (mentioned in the abstract) were reported. |
Definitely no
Reason: Missed visits and withdrawals, mostly in TRT group, smaller sample size than planned, lack of study clinician expertise in providing TRT at study outset, inclusion of active-duty military personnel and their dependents so applicability in civilian population may can be questioned. |
Some concerns (TQ, THI, TFI)
Reason: High loss-to-follow-up, questionable generalizability, lack of expertise in TRT. |
Table of excluded studies
|
Reference |
Reason for exclusion |
|
Formby C, Yang X, Scherer RW. Contributions of Counseling and Sound Generator Use in Tinnitus Retraining Therapy: Treatment Response Dynamics Assessed in a Secondary Analysis of a Randomized Trial. J Speech Lang Hear Res. 2022 Feb 9;65(2):816-828. doi: 10.1044/2021_JSLHR-21-00210. Epub 2022 Jan 24. PMID: 35073492; PMCID: PMC9132149. |
Secondary analysis of Scherer (same data), therefore Scherer 2019 is included. |
|
Grewal R, Spielmann PM, Jones SE, Hussain SS. Clinical efficacy of tinnitus retraining therapy and cognitive behavioural therapy in the treatment of subjective tinnitus: a systematic review. J Laryngol Otol. 2014 Dec;128(12):1028-33. doi: 10.1017/S0022215114002849. Epub 2014 Nov 24. PMID: 25417546. |
The systematic review does not contain a meta-analysis, evidence table or risk of bias assessment. |
|
Han M, Yang X, Lv J. Efficacy of tinnitus retraining therapy in the treatment of tinnitus: A meta-analysis and systematic review. Am J Otolaryngol. 2021 Nov-Dec;42(6):103151. doi: 10.1016/j.amjoto.2021.103151. Epub 2021 Jun 27. PMID: 34303210. |
Different comparison: TRT with medication versus medication alone. |
|
Luyten TR, Jacquemin L, Van Looveren N, Declau F, Fransen E, Cardon E, De Bodt M, Topsakal V, Van de Heyning P, Van Rompaey V, Gilles A. Bimodal Therapy for Chronic Subjective Tinnitus: A Randomized Controlled Trial of EMDR and TRT Versus CBT and TRT. Front Psychol. 2020 Sep 10;11:2048. doi: 10.3389/fpsyg.2020.02048. PMID: 33013517; PMCID: PMC7511540. |
Different comparison: EMDR with TRT versus CBT and TRT. |
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 19-11-2024
Laatst geautoriseerd : 19-11-2024
Geplande herbeoordeling : 19-11-2025
Algemene gegevens
De ontwikkeling van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodules is in 2020 een multidisciplinaire cluster ingesteld. Dit cluster bestaat uit vertegenwoordigers van alle relevante organisaties die betrekking hebben op de zorg voor patiënten met gehoorproblemen.
Het cluster Otologie bestaat uit meerdere richtlijnen, zie hier voor de actuele clusterindeling. De stuurgroep bewaakt het proces van modulair onderhoud binnen het cluster. De expertisegroepsleden worden indien nodig gevraagd om hun expertise in te zetten voor een specifieke richtlijnmodule. Het cluster Otologie bestaat uit de volgende personen:
Clusterstuurgroep
- Dr. H. (Hilke) van Det-Bartels, voorzitter cluster otologie, KNO-arts, Isala, Zwolle, NVKNO (tot en met oktober 2023)
- Drs. M. (Monique) Campman-Verhoeff, voorzitter cluster otologie, KNO-arts, Treant Zorggroep, Emmen (vanaf november 2023)
- Dr. E. (Erik) van Spronsen, voorzitter cluster otologie, KNO-arts, Amsterdam UMC locatie AMC, Amsterdam
- Drs. R.M. (Robert) van Haastert, KNO-arts, Dijklander Ziekenhuis, Purmerend
- Dr. A.L. (Diane) Smit, KNO-arts, UMC Utrecht, Utrecht
- Drs. M.J. (Thijs) Vaessen, Oogarts, Deventer Ziekenhuis, Deventer
- Dr. Y.J.W. (Yvonne) Simis, Klinisch fysicus, audioloog, Amsterdam UMC locatie VUmc, Amsterdam (tot augustus 2023)
- Dr. ir. F.L. (Femke) Theelen, Audioloog, Amsterdam UMC, Amsterdam (vanaf augustus 2023)
- Drs. S.A.H. (Sjoert) Pegge, Radioloog, Radboudumc, Nijmegen
Betrokken clusterexpertisegroep
- Dr. A.L. (Diane) Smit, KNO-arts, UMC Utrecht, Utrecht
- Dr. R. (Rutger) Hofman, KNO-arts, UMCG, Groningen
- Dr. C.A. (Katja) Hellingman, KNO-arts, Maastricht UMC, Maastricht
- Dr. E.L.J. (Erwin) George, Klinisch fysicus-audioloog, Maastricht UMC, Maastricht
- M. (Michael) Huinink, patiëntvertegenwoordiger, Stichting Hoormij·NVVS (tot en met mei 2023)
- Drs. O.V.G. (Olav) Wagenaar, klinisch neuropsycholoog, Rijndam revalidatie (vanaf januari 2024)
- Ir. C.W.M. (Chris) van den Dries, patiëntvertegenwoordiger, Stichting Hoormij·NVVS (vanaf februari 2024)
Met ondersteuning van
- Dr. R. (Romy) Zwarts-van de Putte, adviseur, Kennisinstituut van Medisch Specialisten
- Drs. E.R.L. (Evie) Verweg, junior adviseur, Kennisinstituut van Medisch Specialisten
Belangenverklaringen
De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle clusterstuurgroepleden en actief betrokken expertisegroepleden (fungerend als schrijver en/of meelezer bij tenminste één van de geprioriteerde richtlijnmodules) hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoeksfinanciering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een richtlijnmodule worden wijzigingen in belangen aan de projectleider doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase. Een overzicht van de belangen van de clusterleden en betrokken expertisegroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.
Clusterstuurgroep
Tabel 1. Gemelde (neven)functies en belangen stuurgroep
|
Clusterlid |
Functie |
Nevenfuncties |
Gemelde belangen |
Ondernomen actie |
|
Van Det |
KNO arts Isala Zwolle |
Voorzitter koploperproject, lid kerngroep otologie KNO vereniging, lid klankbordgroep vestibulologie, lid KNO vereniging |
Geen |
Geen restrictie |
|
Spronsen |
KNO-arts, Amsterdam UMC |
Raad van Advies START |
Geen |
Geen restrictie |
|
Vaessen |
Oogarts Deventer Ziekenhuis, Oogarts Streekziekenhuis Koningin Beatrix te Winterswijk |
Geen |
Samen met Sallandse Specialisten Coorporatie aandeelhouder in een drietal |
Geen restrictie |
|
Simis (tot augustus 2023) |
Klinisch Fysicus – Audioloog |
Geen |
Geen |
Geen restrictie |
|
Van Haastert |
KNO-arts Dijklanderziekenhuis Hoorn/Purmerend |
Geen |
Geen |
Geen restrictie |
|
Smit |
KNO arts UMC Utrecht, afdeling KNO |
Medisch adviseur Stichting Hoormij·NVVS, onbetaald |
-Medeaanvrager en onderzoeker van MinT-studie over toepassing van mindfulness bij tinnitus, gefinancierd door HandicapNL |
Geen restrictie, de studie die betrekking heeft op tinnitus is niet gefinancierd door een commerciële partij. |
|
Campman-Verhoeff |
KNO-arts Treant Zorggroep |
Bestuurslid stichting nascholing KNO – onbetaald |
Geen |
Geen restrictie |
|
Pegge |
Radioloog Radboud UMC |
Geen |
Geen |
Geen restrictie |
|
Theelen (vanaf augustus 2023) |
Klinisch Fysicus – Audioloog |
Geen |
Geen |
Geen restrictie |
Clusterexpertisegroep
Tabel 2. Gemelde (neven)functies en belangen expertisegroep
|
Clusterlid |
Functie |
Nevenfuncties |
Gemelde belangen |
Ondernomen actie |
|
Hofman |
KNO-arts UMCG, Groningen |
Geen |
Copromotor van een promovendus die onderzoek doet naar beengeleidingsimplantaten (BCD), onderzoek is gesponsord door Oticon medical. Een BCD helpt niet tegen tinnitus. |
Geen restrictie, geen connectie tussen extern gefinancierd onderzoek en herziene modules. |
|
Hellingman |
KNO-arts/otoloog MUMC+, Maastricht |
Geen |
Geen |
Geen restrictie |
|
George |
Klinisch fysicus-audioloog, Maastricht UMC+ |
- bestuurslid Stichting Opleiding Klinische Fysica (onbetaald) |
ELEPHANT-studie (2018-2022) en RHINO-studie (vanaf 2022), wetenschappelijke research; promovendus grotendeels gefinancieerd door Advanced Bionics, op gebied van optimalisatie van outcomes van cochleaire implantatie. Geen vergoeding voor mijzelf. -Reguliere samenwerking met patientenorganisatie Stichting Hoormij·NVVS, geen boegbeeldfunctie. |
Geen restrictie. Deze studies hebben geen betrekking op de modules die in deze cyclus zijn herzien. |
|
Huinink (tot mei 2023) |
Directeur Grootzakelijk Rabobank Vrijwilliger Stichting Hoormij·NVVS |
Bestuurslid (toezichthouder) Stichting NMCX |
Geen |
Geen restrictie |
|
Wagenaar (vanaf januari 2024) |
Klinisch neuropsycholoog/opleider bij Revalidatiecentrum Rijndam |
'Tinnitus (onbetaald) Columnist Earline (betaald) |
Royalty’s boek EHBOorsuizen Royalty’s online zelf-CGT eHBOorsuizen Financieel belang in TinniVRee Neuropsychologisch verklaringsmodel tinnitus & hyperacusis. EHBOorsuizen FB peersupportgroup |
Geen restrictie, de mogelijke belangen hebben geen betrekking op de modules die in deze cyclus zijn herzien. |
|
Van den Dries (vanaf februari 2024) |
Vrijwilliger bij Stichting Hoormij·NVVS Lid van Commissie Tinnitus en Hyperacusis als belangenbehartiger en voorlichter |
Moderator van de Facebookgroep Eerste Hulp bij Oorsuizen/Tinnitus |
Geen |
Geen restrictie |
Inbreng patiëntenperspectief
Er werd aandacht besteed aan het patiëntenperspectief door deelname van relevante patiëntenorganisaties aan de need-for-update en/of prioritering. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijnmodule is tevens ter commentaar voorgelegd aan alle relevante patiëntenorganisaties in de stuur- en expertisegroep (zie ‘Samenstelling cluster’ onder ‘Verantwoording’) en aan alle patiëntenorganisaties die niet deelnemen aan de stuur- en expertisegroep, maar wel hebben deelgenomen aan de need-for-update (zie ‘Need-for-update’ onder ‘Verantwoording’). De eventueel aangeleverde commentaren zijn bekeken en verwerkt.
Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen
Bij de richtlijnmodule is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).
Module |
Uitkomst raming |
Toelichting |
|
Module [Behandeling van patiënten met tinnitus – Tinnitus Retraining Therapy] |
Geen substantiële financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (>40.000 patiënten), volgt ook uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
AGREE
Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 3.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).
Need-for-update, prioritering en uitgangsvragen
Tijdens de need-for-update fase (voorjaar, 2021) inventariseerde het cluster de geldigheid van de richtlijnmodules binnen het cluster. Naast de partijen die deelnemen aan de stuur- en expertisegroep zijn hier ook andere stakeholders voor benaderd. Per richtlijnmodule is aangegeven of deze geldig is, herzien moet worden, kan vervallen of moet worden samengevoegd. Ook was er de mogelijkheid om nieuwe onderwerpen aan te dragen die aansluiten bij één (of meerdere) richtlijn(en) behorend tot het cluster. De richtlijnmodules waarbij door één of meerdere partijen werd aangegeven herzien te worden, werden doorgezet naar de prioriteringsronde. Ook suggesties voor nieuwe richtlijnmodules werden doorgezet naar de prioriteringsronde. Afgevaardigden vanuit de partijen in de stuur- en expertisegroep werden gevraagd om te prioriteren (zie ‘Samenstelling cluster’ onder ‘Verantwoording’). Hiervoor werd de RE-weighted Priority-Setting (REPS) – tool gebruikt. De uitkomsten (ranglijst) werd gebruikt als uitgangspunt voor de discussie. Voor de geprioriteerde richtlijnmodules zijn door de het cluster concept-uitgangsvragen herzien of opgesteld en definitief vastgesteld.
Uitkomstmaten
Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde het cluster welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. Het cluster waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde het cluster tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.
Methode literatuursamenvatting
Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd indien mogelijk gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.
Beoordelen van de kracht van het wetenschappelijke bewijs
De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding). GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).
Tabel 3. Gradaties voor de kwaliteit van wetenschappelijk bewijs
|
GRADE |
Definitie |
|
Hoog |
|
|
Redelijk |
|
|
Laag |
|
|
Zeer laag |
|
Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in een richtlijnmodule volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).
Overwegingen (van bewijs naar aanbeveling)
Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.
Formuleren van aanbevelingen
De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door het cluster wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. Het cluster heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.
In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.
Tabel 4. Sterkte van de aanbevelingen
|
Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers |
||
|
|
Sterke aanbeveling |
Zwakke (conditionele) aanbeveling |
|
Voor patiënten |
De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet. |
Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. |
|
Voor behandelaars |
De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen. |
Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren. |
|
Voor beleidsmakers |
De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid. |
Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. |
Organisatie van zorg
Bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de richtlijnmodule Organisatie van zorg.
Commentaar- en autorisatiefase
De conceptrichtlijnmodule werd voorgelegd aan alle partijen die benaderd zijn voor de need-for-update fase. De commentaren werden verzameld en besproken met het cluster. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door het cluster. De definitieve richtlijnmodule werd ter autorisatie of goedkeuring voorgelegd aan de partijen die beschreven staan bij ‘Initiatief en autorisatie’ onder ‘Verantwoording’.
Literatuur
Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.
Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.
Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.
Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.
Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.
Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html
Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.
Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.
Wagenaar O, Gilles A, Van Rompaey V, Blom H. Goal Attainment Scale in tinnitus (GAS-T): treatment goal priorities by chronic tinnitus patients in a real-world setting. Eur Arch Otorhinolaryngol. 2024 Feb;281(2):693-700. doi: 10.1007/s00405-023-08134-2. Epub 2023 Jul 25. PMID: 37488402.
Zoekverantwoording
Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.