Study characteristics

Methods

5‐arm trial with 3 to 6 weeks duration of treatment and 6 weeks duration of follow‐up

Participants

Location: Solomon Islands, 15 villages around Munda

Setting of recruitment and treatment: Helena Goldie Hospital, Munda; patients identified through community screening February 1985 to March 1986

Sample size:

• Number randomised: 134 children (184 ears)

• Number completed: as above (no loss to follow‐up mentioned)

Participant (baseline) characteristics:

• Age: mean 5.4 ± 3.1 years group 1: 5.2, group 2: 6.3, group 3: 5.3, group 4: 5.0, group 5: 5.1)

• Gender (F/M): 49 (36.6%)/85 (63.4%)

• Main diagnosis: chronic suppurative otitis media with presence of otorrhoea for more than 3 months and tympanic membrane perforation

• High‐risk population: yes

  • Cleft palate (or other craniofacial malformation): not reported (NR)

  • Down syndrome: NR

  • Indigenous groups (Australian Aboriginals/Greenland natives): yes (Solomon Islands) ‐ study noted prevalence is 3.8% for under 15‐year olds

  • Immunocompromised: NR

• Diagnosis method:

  • Confirmation of perforated tympanic membrane: yes (confirmed by otoscopic examination)

    • Central and tubotympanic perforations: 176 (130 were large (> ¼ ear drum); 46 were small)

    • Marginal tympanic perforations: 4

  • Presence of mucopurulent discharge: NR

  • Duration of symptoms (discharge): mean age at CSOM onset: 1.5 ± 1.0 years; discharge for more than 3 months (inclusion criteria)

• Other important effect modifiers:

  • Alternative diagnosis of ear discharge: NR

  • Number who have previously had grommets inserted: NR

  • Number who have had previous ear surgery: NR

  • Number who had previous antibiotic treatment for CSOM: NR

Inclusion criteria:

• Children under 15 years old with CSOM (defined as presence of otorrhoea for more than 3 months and tympanic membrane perforation) living in Munda or principal villages

Exclusion criteria:

• None listed

Interventions

Group 1 (n = 31, 40 ears): Sofradex ear drops (0.5% w/v of framycetin sulphate, 0.050% w/v of dexamethasone and 0.005% w/v of gramicidin) (no details on volume or frequency of administration), PLUS oral clindamycin (15 mg/kg/day) into 3 divided oral daily doses, PLUS aural toilet 4 times per day using cotton wool wisps twisted onto orange sticks. Treatment duration = 6 weeks.

Group 2(n = 31, 41 ears): Sofradex ear drops (0.5% w/v of framycetin sulphate, 0.050% w/v of dexamethasone and 0.005% w/v of gramicidin) (no details on volume or frequency of administration), PLUS aural toilet 4 times per day using cotton wool wisps twisted onto orange sticks. Treatment duration = 6 weeks.

Group 3(n = 24, 32 ears): 2% boric acid in 20% alcohol (3 drops after cleaning using intermittent tragal depression to assist middle ear permeation) given 4 times per day, PLUS aural toilet using cotton wool wisps twisted onto orange sticks. Treatment duration = 6 weeks.

Group 4(n = 19, 26 ears): aural toilet 4 times per day using cotton wool wisps twisted onto orange sticks. Treatment duration = 6 weeks.

Group 5(n = 29, 41 ears): no treatment.

All treatments administered by parents.

Concurrent treatment: parents were instructed to encourage nose blowing, forbid swimming and insert cotton wool/Vaseline ear plugs before washing.

For each child in groups 2 to 5 one of the authors stayed in the village for the first 3 days of treatment to provide parental tuition and supervision. This was continued by a nurse aid who remained until the medical team returned after 3 weeks. If the ear was then dry, the clinical response was judged good, ototopical solutions continued for 1 further week only and aural toilet and clindamycin stopped. If the ear was still discharging, all treatment modalities were continued until the second assessment after 6 weeks.

Outcomes

Outcomes of interest in the review:

Primary outcomes:

• Complete resolution of ear discharge, measured at 2 to 4 weeks and after 4 weeks. Unclear if otoscopically confirmed.

Secondary outcomes:

• NR

Funding sources

"This study was made possible by a research grant from the Medical Research Council of New Zealand"

Declarations of interest

No information provided

Notes

Unit of randomisation: person

Methods for including patients bilateral disease: counting bilateral ears separately

RCT was part of a larger epidemiological study. Hearing loss was measured for the epidemiological study but not specifically for the RCT. Results are not presented by those who have CSOM and those who do not.

Only treatment groups 4 and 5 were relevant for this review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "Children from 15 villages with 184 diseased ears were randomly allocated into five treatment groups."

Comment: insufficient information about sequence generation method.

The largest group had 1.6 times (31 patients/41 ears) the number of participants compared to the number in the smallest group (19 patients/26 ears), with a larger number of patients (31 each) in the more effective treatment groups.

Unit of randomisation unclear although it is likely to be by person; results reported by percentage of affected ears.

Allocation concealment (selection bias)

Unclear risk

Comment: no details about allocation concealment are provided in the paper.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: blinding is not specifically stated.

The treatment arms involved dry mopping compared to no treatment – blinding of these interventions is impossible.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: no clear information about who assessed that the ears were "dry" versus "still discharging" ‐ whether this was done by patients or the medical team. No report of otoscopic examination for outcome. Therefore, in the absence of blinding, this is likely high‐risk.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Comment: no dropouts or missing data reported; no statements about missing data.

Selective reporting (reporting bias)

Unclear risk

Comment: no protocol was available on clinicaltrials.gov. The level of reporting is extremely low.

Outcome was reported as two categories: "improved" versus "no change" as opposed to "dry ear" versus others. This definition was not provided, and it was unclear whether "improved" means "dry ear" or a reduction of discharge.

Insufficient information to permit judgement of 'low‐risk' or 'high‐risk'.

Study characteristics

Methods

2‐arm, non‐blinded, parallel‐group RCT, with up to 15 days duration of treatment and 3 to 6 months duration of follow‐up

Participants

Location: Turkey, 1 site

Setting of recruitment and treatment: university hospital department of otolaryngology, March to September 1994

Sample size: 80 people (95 ears)

• Number randomised: 40 (47 ears) in clinic aural toilet group, 40 (48 ears) in self aural toilet group

• Number completed: 40 (47 ears) in clinic aural toilet group, 40 (48 ears) in self aural toilet group

Participant (baseline) characteristics:

• Age: mean 26.5 years (range: 21 months to 70 years)

• Gender (F/M): 35 (44%)/45 (56%)

• Main diagnosis: the title and abstract of the paper indicate 'chronic suppurative otitis media' but the methods section only uses 'otorrhoea' of at least 6 weeks duration. No information about perforated tympanic membrane within the results.

• High‐risk population: none

  • Cleft palate (or other craniofacial malformation): not reported (NR)

  • Down syndrome: NR

  • Indigenous groups (Australian Aboriginals/Greenland natives): NR

  • Immunocompromised: NR

• Diagnosis method:

  • Confirmation of perforated tympanic membrane: NR

  • Presence of mucopurulent discharge: NR

  • Duration of symptoms (discharge): "at least 6 weeks duration between March to September 1994". Unclear whether this is total or since onset of symptoms

• Other important effect modifiers:

  • Alternative diagnosis of ear discharge: not explicitly reported but at least 5/80 (6%) were diagnosed with cholesteatoma.

  • Number who have previously had grommets inserted: NR

  • Number who have had previous ear surgery: NR

  • Number who had previous antibiotic treatment for CSOM: NR

Inclusion criteria:

• Otorrhoea "of at least six weeks duration between March and Sept 1994."

Exclusion criteria:

• NR

Interventions

Intervention (n = 40, 47 ears): daily external ear channel aspiration. Ciprofloxacin drops administered by clinic personnel, continued until otorrhoea resolved or for 15 days.

Comparator group(n = 40, 48 ears): external ear canal aspiration and topical treatment administration by clinic personnel only for the first day (visit). Subsequently administered, by patients (no details about whether patients we told/taught to do any aural toileting). Patients asked to return to clinic as soon as otorrhoea resolved.

Common/concurrent treatment in both groups: ciprofloxacin lactate acetate solution, 2 mg/mL, administered twice, with a 5‐minute break in between. If age < 15 years; 3 drops twice daily. If age > 15 years; 5 drops twice daily. Clinical personnel and patients were instructed to wait minutes between the 2 applications.

Outcomes

Outcomes of interest in the review:

Primary outcomes:

• Resolution of ear discharge or "dry ear" (whether otoscopically confirmed or not) measured at between 1 week to 2 weeks. Unclear if otoscopically confirmed.

Secondary outcomes

• Adverse events: hearing

• Adverse events: aural toilet, dizziness

Funding sources

No information provided

Declarations of interest

No information provided

Notes

Unit of randomisation: person

Methods for reporting people with bilateral ear disease: by ear, counting bilateral ears separately

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomised into two groups..."

Comment: no further information available on methods of sequence generation.

Allocation concealment (selection bias)

Unclear risk

Quote: "Patients were randomised into two groups..."

Comment: no further information available about allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: it was not possible to blind since one group had daily treatment in the clinic, whereas the other group was self‐treating at home. This has a risk of bias particularly as they may have been a conflict of interest involved.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote: "... (self‐treated) patients were asked to return to clinic as soon as otorrhoea resolved..." "... treatment (by clinic personnel) continued until otorrhoea resolved."

Comment: there was no description of the involvement of blinded personnel to assess/confirm the resolution of ear discharge. It does not appear that the outcome assessment was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no dropouts were reported. All patients were included in the analysis, including those who went on to surgery.

Selective reporting (reporting bias)

High risk

Comment: no trial protocol was identified in clinicaltrials.gov. The methods section does not detail the outcomes that would be measured in the trial and so it is not clear if all of the outcomes measured were reported. There is a lack of information about how some of the outcomes were measured/defined (e.g. hearing).

Study characteristics

Methods

3‐arm, non‐blinded, cluster‐RCT, with up to 16‐week duration of treatment and follow‐up

Participants

Location: Kiambu district, Central Province, Kenya

Setting of recruitment and treatment: 145 primary schools (December 1991 to June 1992)

Sample size: 524 children (145 schools)

• Number randomised: 221 children in antibiotics plus steroids plus dry mopping group; 201 in dry mopping group, 102 children in 'no specific treatment' group.

• Number completed: at 16‐week follow‐up: 144 children in antibiotics plus steroids plus dry mopping group; 184 in dry mopping group, 73 children in 'no specific treatment' group.

Participant (baseline) characteristics:

• Age: mean age not given. 80% of children were aged 5 to 14 years; 20% were older than 15 years

• Gender (F/M): 241 (46%)/283 (54%)

• Main diagnosis: tympanic membrane perforation associated with purulent otorrhoea that had been present continuously for at least the preceding 2 weeks

• High‐risk population:

  • Cleft palate (or other craniofacial malformation): not reported (NR)

  • Down syndrome: NR

  • Indigenous groups Australian Aboriginals/Greenland natives): 0%

  • Immunocompromised: NR

• Diagnosis method:

  • Confirmation of perforated tympanic membrane: yes (removal of occluding wax or foreign bodies, then otoscopic examination)

  • Presence of mucopurulent discharge: yes, 524/524 (100%)

  • Duration of symptoms (discharge): at least 2 weeks (inclusion criteria)

• Other important effect modifiers:

  • Alternative diagnosis of ear discharge: 0/524 (0%)

  • Number who have previously had grommets inserted: NR

  • Number who have had previous ear surgery: NR (exclusion criteria: "children with previous ear surgery except tympanocentesis or myringotomy")

  • Number who had previous antibiotic treatment for CSOM: NR

Inclusion criteria:

• Children in primary school standards 1 to 8 (typically 4 to 12 years) with tympanic membrane perforation associated with purulent otorrhoea that had been present continuously for at least the preceding 2 weeks

Exclusion criteria:

• Treatment with antibiotics during the preceding 2 weeks

• Previous significant adverse reaction to systemic or topical antibiotics

• Otomycosis

• Failure to view the tympanic membrane

• Complicated otitis media

• Previous ear surgery (other than tympanocentesis or myringotomy)

• Anatomical predisposition to otitis media

• Congenital malformation of external, middle or inner ear

• Another illness that made trial inclusion potentially dangerous to health

• Otorrhoea that was moist but not purulent

Interventions

Dry mopping alone (n = 201): twice daily except at weekends. Mops were individually prepared by ear monitors (trained school children approximately 9 to 10 years old) from orange sticks with cotton wool wrapped tightly round the tip but protruding beyond. Treatment duration: until otorrhoea had stopped or 16 weeks.

Comparator group(n = 102): no specific treatment

Concurrent treatment: the clinical officer removed any occluding wax or foreign body at the start of the trial. All participants received multivitamins. No other concurrent treatment was given.

Children were withdrawn from the trial if antibiotics were prescribed.

Outcomes

Outcomes of interest in the review:

Primary outcomes:

• Complete resolution of ear discharge, measured after 4 weeks (otoscopically confirmed)

Secondary outcomes:

• Hearing

Funding sources

The study was supported by the Overseas Development Administration (UK), the Gatsby Charitable Foundation (UK) and the Thrasher Research Fund (USA).

Declarations of interest

No information provided

Notes

Unit of randomisation: school

Methods for including patients with bilateral disease: each school had one side and for bilateral cases the ear of the school’s assigned side was entered in the trial.

This was a 3‐arm trial:

1. Dry mopping only

2. Dry mopping plus topical antibiotics plus steroids plus systemic antibiotics

3. Control group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Interventions were allocated randomly within each quintuplet, by a random numbers table, in the ratio of two schools for dry mopping, two for dry mopping plus antibiotics, and one control."

Comment: adequate sequence generation.

Allocation concealment (selection bias)

Unclear risk

Quote: "Interventions were allocated randomly within each quintuplet, by a random numbers table, in the ratio of two schools for dry mopping, two for dry mopping plus antibiotics, and one control."

Comments: matching schools were arranged in groups of 5 according to 3 principles: whether situated in a tea or coffee plantation, agro‐ecological zone and numbers of pupils. There is a possibility that the researchers could have influenced the allocation to treatment group. There is no good information relating to the baseline characteristics of the schools in each group.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "Control group received no specific treatment."

"Our inability to mask the treatment allocation may have biased the results."

Comment: the participants and personnel were not blinded to treatment group.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "Some team members believed before the trial started that dry mopping and antibiotics are the most effective treatment for the disease, and that dry mopping alone is not effective. They might therefore have been biased in their clinical examination."

"They therefore knew which treatment was being given. Parents, ear monitors, and teacher‐supervisors of children in the dry‐mopping plus antibiotics group may have realised that antibiotics were being given and assumed that they would be more effective. This treatment might therefore have been given more assiduously than the others."

"Potential biases due to the fact that the study could not be blinded were kept to a minimum by random assignment of teams and changing of team composition each day; by close monitoring of the performance of ear monitors, teacher‐supervisors, and teams; and by the use of clearly defined and easily recognisable outcomes."

Comment: it appears that the outcome assessors were not blinded to treatment group. The primary outcome (clinical resolution) was assessed by physicians and so lack of blinding could have led to bias in the results.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Comment: the paper provides information for the number of children attending each of the 4‐week follow‐ups from 8 weeks to 16 weeks. The number of children who were randomised to dry mopping alone but were not seen at 16 weeks was 57/201 (28%) and the equivalent number in the control group at 16 weeks was 29/102 (28%). The number not attending was similar for both groups although the reasons for non‐attendance were not provided.

Selective reporting (reporting bias)

Unclear risk

Quote: "The average hearing threshold level for each child was calculated with the hearing thresholds for 1dB, 2dB, and 4dB at each visit. The effects of resolution and healing of the eardrum on the hearing threshold were investigated for each treatment group at 8, 12, and 16 weeks by ANOVA."

Comment: the analysis does not appear to look at hearing loss per treatment group. No published protocol was identified through clinicaltrials.gov. The outcomes which were presented in the methods sections are well reported in the results section, although hearing results are not presented by treatment group but by improvement in CSOM.