TARGET 2000.

Study characteristics
Methods	3‐arm, multicentre, parallel‐group RCT with 2‐year follow‐up Randomised by child For this review we have included data relevant to the comparison of ventilation tube insertion with watchful waiting. Additional data on adenoidectomy are relevant to a companion review (MacKeith 2023).
Participants	Location: UK, 11 sites Setting of recruitment and treatment: otorhinolaryngology departments Study dates: April 1994 to January 1998 Sample size: Number randomised: 376 (126 bilateral VT (VTs), 128 VT with adenoidectomy (VTs + ad), 122 watchful waiting (WW)) Number completed: 321 (109 bilateral VT (VTs), 109 VT with adenoidectomy (VTs + ad), 103 watchful waiting (WW)) Participant (baseline) characteristics: Age (mean (SD) months): VTs 62.5 (10.2), VTs + ad 64.5 (10.3), WW 62.9 (10.4) Gender: VTs males 60/126 (48%), females 66/126 (52%); VTs + ad males 61/128 (48%), females 67/128 (52%); WW males 62/122 (51%), females 60/122 (49%) Hearing threshold at baseline (at visit 2) (mean (SD) dB): VTs 32.2 (6.0), VTs + ad 31.7 (6.4), WW 33.5 (6.4) AOM episodes (> 6 per year): VTs 5/126 (4%), VTs + ad 5/127 (4%), WW 8/122 (7%) Inclusion criteria: Children aged between 3.25 and 6.75 years Referred primarily for otological or hearing reasons First visit, with no previous ear or adenoid surgery Bilateral type B + B or B + C2 tympanogram combination Better ear HL > 20 dB HL averaged across 0.5 kHz, 1 kHz, 2 kHz and 4 kHz and air‐bone gap > 10 dB Criteria met on 2 qualifying visits separated by a 12‐week period of watchful waiting Exclusion criteria: Children with cranio‐facial structural abnormalities, severe systemic disease (e.g. diabetes) and non‐OME ear disease (e.g. perforation) Where consultant or parent was unduly concerned over a child’s speech/language, behaviour, otalgia or nose/throat problems, the child could be managed outside TARGET Previous VT/adenoid surgery, outside age limits, not accompanied by parent/guardian, other medical exclusion, significant family language problems, parent refusing to take part in study, child unable/unwilling to do audiometry, administrative problems, family/social reasons and protocol mishaps, particularly early in the trial
Interventions	Bilateral VTs: Bilateral Shepard VTs were inserted following myringotomy and fluid aspiration Bilateral VT with adenoidectomy: Bilateral ventilation tubes were inserted, as above, and adenoidectomy was performed by curettage Watchful waiting: Children were not allocated to any surgery. However, over the 2‐year follow‐up period, 57% of participants in this group actually underwent surgery.
Outcomes	Mean final hearing threshold Air conduction thresholds at 0.5 kHz, 1.0 kHz, 2.0 kHz and 4.0 kHz in each ear at every visit were summarised as the 4‐frequency average binaural hearing thresholds Mean change in hearing from baseline Adverse events: Perforation Haemorrhage Tympanosclerosis Functioning VT
Funding sources	Medical Research Council; Trial Registration Number: ISRCTN35793977
Declarations of interest	Authors reported "None to declare"
Notes	Research integrity checklist: No retraction notices identified Prospective registration not applicable for earliest publications (published before 2010). Registration was noted for the most recent publication. Baseline characteristics were not excessively similar between the groups Plausible loss to follow‐up was reported No implausible results Numbers allocated to each group are not identical
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"For each centre, the first five children were randomised according to a computer‐generated random number sequence. Thereafter, the minimisation procedure balanced the treatment allocations across four dichotomous factors: boy, girl; <5.25, >5.25 years old at initial visit; manual, non‐manual occupation of head of household and baseline hearing <25 dB HL, >25 dB HL."
Allocation concealment (selection bias)	Low risk	"Randomisation was performed by telephone call from the nurse ⁄ research assistant to the statistician at the MRC Institute of Hearing Research and allocation immediately communicated to the parent,” and “This basis of minimisation was not divulged to centres and may be regarded as completely concealed.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	No information provided on blinding of participants and personnel. There is a strong possibility that participants and personnel could identify which treatment a participant received and hence change their behaviour as a result.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	“Audiometry was performed by audiologists, independently of the otolaryngologist and research nurse. Clinic pressures meant that these testers, whilst not blinded in the strictest sense, were not aware of the child’s allocation, nor in a position to be influenced by such information were it present.”
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Losses to follow‐up were 55/376 randomised (14.6%) overall with 19/122 (15.6%) in the medical management group, 17/126 (13.5%) in the VT group and 19/128 (14.8%) in the VT + Ad group. Complete data were available for only 76/122 (62.3%), 85/126 (67.5%) and 92/128 (71.9%) in the medical management, VT and VT + Ad groups, respectively. Reasons for loss to follow‐up after randomisation were not reported.
Selective reporting (reporting bias)	Unclear risk	The trial entry on ISRCTN registry states that “general health, economic impact, behavioural assessment and quality of life” would be assessed. Data on these are published (no economic data) but no details given of the scales used to assess the outcomes.
Other bias	High risk	The trial registration was retrospectively published, raising the possibility of publication bias. In addition, this was an MRC funded, multicentre trial and yet not all outcomes stated in the trial registration were published.