1. GRADE profile: Betahistine for Ménière's disease.
| Certainty assessment | Number of participants | Effect | Certainty | Comment | ||||||||
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Betahistine | Placebo/no treatment | Relative (95% CI) | Absolute (95% CI) | ||
| Improvement in vertigo frequency (follow‐up: range 6 months to ≤12 months; assessed with: Self‐rated improvement in either frequency or severity of vertigo) | ||||||||||||
| 1 | randomised trials | very seriousa | not serious | seriousb,c | seriousd,e | none | 24/35 (68.6%) | 16/35 (45.7%) | RR 1.50 (0.98 to 2.29) | 229 more per 1000 (from 9 fewer to 590 more) | ⊕⊝⊝⊝ Very low | |
| Improvement in vertigo frequency (follow‐up: range >12 months; assessed with: AAO‐HNS 1995 class A, B or C) | ||||||||||||
| 1 | randomised trials | seriousf | not serious | seriousg | seriousd,e | none | 28/30 (93.3%) | 27/32 (84.4%) | RR 1.11 (0.93 to 1.32) | 93 more per 1000 (from 59 fewer to 270 more) | ⊕⊝⊝⊝ Very low | |
| Improvement in vertigo frequency: sensitivity analysis for complete/substantial improvement (follow‐up: range 6 months to ≤ 12 months; assessed with: AAOO 1972 class A, B or C (complete resolution of vertigo) | ||||||||||||
| 1 | randomised trials | serioush | not serious | seriousb,i | very seriousj | none | 3/5 (60.0%) | 1.0% | Peto OR 13.08 (1.01 to 170.31) | 107 more per 1000 (from 0 fewer to 622 more) | ⊕⊝⊝⊝ Very low | |
| 10.0% | 492 more per 1000 (from 1 more to 850 more) | |||||||||||
| Improvement in vertigo frequency: sensitivity analysis for complete/substantial improvement (follow‐up: range > 12 months; assessed with: AAO‐HNS 1995 class A or B) | ||||||||||||
| 1 | randomised trials | seriousf | not serious | seriousg | seriousd,e | none | 27/30 (90.0%) | 21/32 (65.6%) | RR 1.37 (1.04 to 1.81) | 243 more per 1000 (from 26 more to 532 more) | ⊕⊝⊝⊝ Very low | |
| Vertigo global score (follow‐up: range 3 months to < 6 months; assessed with: geometric mean of monthly imbalance score) | ||||||||||||
| 1 | randomised trials | seriousk | not serious | not serious | very seriousd,l | none | 17 | 17 | — | MD 0.7 points higher (6.67 lower to 8.07 higher) | ⊕⊝⊝⊝ Very low | |
| Vertigo frequency (follow‐up: range 3 months to < 6 months; assessed with: number of attacks per month) | ||||||||||||
| 2 | randomised trials | seriousm | not serious | not serious | very seriousd,e,n | none | 60 | 57 | — | MD 1.90 attacks per month lower (3.05 lower to 0.74 lower) | ⊕⊝⊝⊝ Very low | |
| Vertigo frequency (follow‐up: range 6 months to ≤ 12 months; assessed with: average number of attacks in 30 days) | ||||||||||||
| 1 | randomised trials | seriouso | not serious | not serious | very seriousd,l | none | 142 | 72 | — | MD 0.63 attacks per 30 days higher (4.07 lower to 5.33 higher) | ⊕⊝⊝⊝ Very low | |
| Serious adverse events | ||||||||||||
| 1 | randomised trials | seriouso | not serious | not serious | very seriousd,l | none | 26/146 (17.8%) | 11/74 (14.9%) | RR 1.20 (0.63 to 2.29) | 30 more per 1000 (from 55 fewer to 192 more) | ⊕⊝⊝⊝ Very low | |
| Change in disease‐specific health‐related quality of life (follow‐up: range 6 months to ≤ 12 months; assessed with: Dizziness Handicap Inventory (mean score per question); scale from: 0 to 4) | ||||||||||||
| 1 | randomised trials | seriouso | not serious | not serious | seriousd | none | 114 | 56 | — | MD 0.06 points higher (0.17 lower to 0.29 higher) | ⊕⊕⊝⊝ Low | |
| Change in disease‐specific health‐related quality of life (follow‐up: range > 12 months; assessed with: Functional Level Scale, score 1 or 2) | ||||||||||||
| 1 | randomised trials | seriousf | not serious | seriousg | seriousd,e | none | 29/30 | 23/32 | RR 1.34 (1.07 to 1.69) | 244 more per 1000 (from 50 more to 496 more) | ⊕⊝⊝⊝ Very low | |
| Change in hearing: continuous data only (follow‐up: range 3 months to < 6 months; assessed with: hearing threshold with pure tone audiometry) | ||||||||||||
| 1 | randomised trials | seriousk | not serious | not serious | seriousd,e | none | 18 | 17 | — | MD 10.1 dB HL higher (1.13 lower to 21.33 higher) | ⊕⊕⊝⊝ Low | |
| Change in hearing: continuous data only (follow‐up: range 6 months to ≤ 12 months; assessed with: change in PTA) | ||||||||||||
| 1 | randomised trials | seriouso | not serious | not serious | very seriousd,p | none | 79 | 34 | — | MD 2.64 dB higher (1.66 lower to 6.94 higher) | ⊕⊝⊝⊝ Very low | |
| Change in hearing: continuous data only (follow‐up: range > 12 months; assessed with: hearing threshold with PTA) | ||||||||||||
| 1 | randomised trials | seriousf | not serious | seriousg | seriousd | none | 30 | 32 | — | MD 1.4 dB HL higher (7.1 lower to 9.9 higher) | ⊕⊝⊝⊝ Very low | |
| Change in hearing: dichotomous data only (follow‐up: range 6 months to ≤ 12 months; assessed with: improvement with pure tone audiometry) | ||||||||||||
| 2 | randomised trials | very seriousq | not serious | seriousb,r | seriousd,e | none | 24/41 (58.5%) | 13/41 (31.7%) | Peto OR 3.14 (1.28 to 7.66) | 276 more per 1000 (from 56 more to 463 more) | ⊕⊝⊝⊝ Very low | |
| Change in tinnitus ‐ 6 to ≤ 12 months (assessed with: MiniTF score; scale from: 0 to 24) | ||||||||||||
| 1 | randomised trials | seriouso | not serious | not serious | seriousd | none | 114 | 54 | — | MD 0.06 lower (1.52 lower to 1.39 higher) | ⊕⊕⊝⊝ Low | |
| Tinnitus (follow‐up: range ≥ 12 months to 0; assessed with: THI; scale from: 0 to 100) | ||||||||||||
| 1 | randomised trials | seriousf | not serious | seriousg | seriousd | none | 30 | 32 | — | MD 0.9 points higher (5.55 lower to 7.35 higher) | ⨁◯◯◯ Very low | |
| Other adverse effects ‐ headache | ||||||||||||
| 4 | randomised trials | seriouss | serioust | not serious | very seriousd,l | none | 62/226 (27.4%) | 31/148 (20.9%) | OR 1.16 (0.69 to 1.95) | 26 more per 1000 (from 55 fewer to 131 more) | ⊕⊝⊝⊝ Very low | |
| Other adverse effects ‐ gastrointestinal disturbance | ||||||||||||
| 4 | randomised trials | seriouss | serioust | not serious | very seriousd,l | none | 79/224 (35.3%) | 41/148 (27.7%) | OR 1.08 (0.65 to 1.78) | 16 more per 1000 (from 78 fewer to 128 more) | ⊕⊝⊝⊝ Very low | |
| Other adverse effects ‐ dry mouth | ||||||||||||
| 2 | randomised trials | seriouss | not serious | not serious | seriousd | none | 2/187 (1.1%) | 3/114 (2.6%) |
OR 0.30 (0.05 to 1.95) |
18 fewer per 1000 (from 25 fewer to 24 more) | ⊕⊕⊝⊝ Low | |
| Other adverse effects ‐ sleep disturbance | ||||||||||||
| 2 | randomised trials | seriousu | not serious | not serious | very seriousd,l | none | 7/164 (4.3%) | 4/91 (4.4%) | RR 1.42 (0.47 to 4.38) | 18 more per 1000 (from 23 fewer to 149 more) | ⊕⊝⊝⊝ Very low | |
AAO‐HNS: American Academy of Otolaryngology – Head and Neck Surgery; AAOO: American Academy of Ophthalmology and Otolaryngology; CI: confidence interval; MD: mean difference; OR: odds ratio; PTA: pure tone average; RR: risk ratio
aHigh risk of bias for five domains in this study, and unclear risk of bias for the remaining two domains.
bThe criteria used for the diagnosis of Ménière's disease were poorly defined, therefore the population may not be appropriate.
cThis outcome was reported as an improvement in either the frequency or severity of attacks, not only frequency.
dOptimal information size was not reached (taken as < 300 events for dichotomous outcomes or < 400 participants for continuous outcomes, as a rule of thumb).
eConfidence interval ranges from a likely trivial effect to potential benefit.
fUnclear risk of bias for several domains, and high risk of bias due to differential use of intratympanic steroids in the intervention and control group.
gAll participants also received intratympanic dexamethasone injections throughout the trial.
hMultiple bias domains unclear, and high risk of selective reporting.
iScoring system for vertigo only considers "complete resolution", not substantial improvement.
jSample size extremely small and confidence interval ranges from potential harm to potential benefit.
kMultiple domains at unclear risk of bias leading to an overall concern about the risk for this trial.
lConfidence interval ranges from potential harm to potential benefit.
mMultiple bias domains rated at unclear risk of bias. High risk of selective reporting bias due to incomplete outcome data for this result.
nNumeric data used in this analysis were estimated due to incomplete reporting in the article.
oHigh risk of attrition bias, and potential for selective reporting.
pData for four‐tone average estimated from reported data at each of the four frequencies.
qHigh risk of bias for multiple domains in both of the included studies.
rThe trial with the largest weight in the analysis assessed the "better hearing side", which may not be appropriate (likely to be the ear without Ménière's disease).
sRisk of bias rated as either high risk or unclear risk for several domains in the studies.
tI2 > 40%.
uThe trial with the largest weight in the analysis has multiple concerns regarding risk of bias.