Types of studies

Randomised controlled trials (RCTs) and quasi-RCTs (the group allocation was not purely random but rather determined by a factor such as a birth date, a hospital record number or an alternation) will be included. Cluster RCTs, case studies, case series, qualitative studies and uncontrolled trials will be excluded. Trials that do not provide detailed results will also be excluded. Dissertations and abstracts will be included if these contain sufficient details for critical evaluation. No language restriction will be imposed. If we encounter languages other than English, Korean and Chinese, we will either contact the original authors or obtain a translation of the manuscript from professional service.

Types of participants

The studies that evaluated patients who had a diagnosis of OME will be included. The diagnostic criteria for OME should be based on the criteria of the American Academy of Pediatrics (AAP) and the American Academy of Otolaryngology and Head and Neck Surgery (AAOHNS).5 We will exclude studies of patients with ventilation tubes present, patients with an anatomical deformity or patients with other chronic immunocompromised states.

Types of interventions

We will include those trials using the oral administration of herbal medicine alone or as a combined therapy of the oral administration of herbal medicine with a conventional therapy versus the same conventional therapy. Herbal medicine is defined as a single herb, an individually prescribed herbal formula or herbal products extracted from natural herbs. There is no limitation on the number of herbs used, the dosage, the forms of medication or the duration of the treatment. We will include only the oral administration of the medication.

Types of outcome measures

The following outcome measures will be assessed based on analyses of the data obtained in the included trials

Electronic searches

Electronic search will be conducted using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, the Allied and Complementary Medicine Database (AMED) and the Cochrane Central Register of Controlled Trials (CENTRAL). We will also search three Chinese databases (China Network Knowledge Infrastructure (CNKI), Wangfang Data and VIP Information) and five Korean databases (KoreaMed, the Research Information Service System (RISS), Oriental Medicine Advanced Searching Integrated System (OASIS), DBPIA and the Korean Studies Information Service System (KISS)).

Searching other resources

Ongoing studies will be sought in the meta-Register of Controlled Trials (mRCT; http://www.controlled-trials.com/mrct), Clinical trials.gov (http://www.clinicaltrials.gov) and the WHO International Clinical Trials Registry platform (ICTRP; http://apps.who.int/trialsearch/), all of which list ongoing trials. The bibliographic references of all of the included trials will be reviewed to identify other relevant studies. We will also contact the authors of the trial studies and experts in the field.

Search strategy

The strategies for searching The Cochrane Library, MEDLINE and EMBASE databases are presented in online supplementary appendix 1. These strategies will be modified for use with other databases.

Selection of studies

Two of the review's authors (MJS and YHK) will independently screen the titles and abstracts of the searched studies, perform the study selection and record their decisions on a standard eligibility form. The arbitrator (MSL) will decide on the study selection when a consensus cannot be reached. The details of selection process will be shown in PRISMA flow diagram (figure 1).

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Figure 1

Study selection flow diagram.

Data extraction and management

Two of the authors (MJS and YHK) will independently extract the data using a standard data extraction form and resolve disagreements through discussion before analysis. When the reported data are insufficient or ambiguous, two of the authors (Y-EK and HWL) will contact the corresponding authors of the clinical trials by email or telephone to request additional information or clarification.

Assessment of risk of bias in the included studies

We will independently assess the risk of bias in the eligible studies according to the criteria described in the Cochrane Handbook V.5.1.0, which include random sequence generation, allocation concealment, blinding of participants and personnel, blinding of the outcome assessment, incomplete outcome data, selective reporting and other sources of bias.28 The quality of the study will be classified as low, unclear or high risk of bias. If necessary, we will contact the authors of eligible trials for clarification. Any differences in opinion will be resolved by discussion or arbitration involving a third author.

Measures of the treatment effect

For continuous data, we will use the mean difference (MD) to measure the treatment effect at a 95% CI. We will convert other forms of data into MDs. In the case of outcome variables with different scales, we will use the standard MD with a 95% CI. For dichotomous data, we will present the treatment effects as a relative risk or risk difference with 95% CIs. Based on these results, we will calculate the associated numbers needed to treat.

Unit of analysis issues

Data from parallel-group studies will be included for meta-analysis. If there are cross-over trials, the first phase of the data will be adopted for analysis.

Managing missing data

We will request missing data from the original authors, whenever possible. If it is not possible to do this, we will only analyse the available data.

Assessment of heterogeneity

If a meta-analysis is possible, we will use the I² statistic to quantify the inconsistencies among the included studies. An I² value of >50% will be considered indicative of substantial heterogeneity.29 If heterogeneity is observed, we will conduct a subgroup analysis to explore its possible causes.29

Assessment of reporting biases

We will prepare funnel plots to assess the reporting biases if sufficient studies are available (at least 10 trials).30 However, funnel plot asymmetry is not the same as publication bias; therefore, we will attempt to distinguish the different possible reasons for the asymmetry, such as small-study effects, poor methodological quality and the true heterogeneity of the included studies.30 ,31

Data synthesis

Data synthesis for comparable trials with comparable outcomes will be performed using Review Manager (RevMan), V.5.2.6.

Subgroup analysis and investigation of heterogeneity

If the data are available, a predefined subgroup analysis will be conducted to assess the heterogeneity of different studies, including the following:

1. Laterality of OME: bilateral OME versus unilateral OME;

2. Duration of OME: any duration of OME versus persistent OME (lasting for more than 2 or 3 months);

3. Duration of treatment;

4. Type of herbal medicine;

5. Type of control;

6. Type of age group (participants aged over 18 years vs children aged 2 years or more vs children younger than 2 years).

Sensitivity analysis

Sensitivity analysis will principally be performed as follows:

1. Sample size (eg, more or less than 40 participants in each group);

2. Low risk of bias (eg, allocation concealment or the blinding of participants/assessors).