Study registration
The methodology to perform this systematic review was developed according to recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement [9]. The corresponding Checklist of PRISMA-P can be found in Additional file 1.This protocol is currently registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42019123047.
Eligibility criteria
Inclusion criteria
Types of studies Randomized controlled trials will be included. Chinese herbal medicine does not include combination drugs with western medicine, etc.There are no restrictions on blinding, follow-up or publishing status. Both Chinese and English publications are available.
Types of participants According to the European guidelines for the classification of CRS, CRS can be divided into patients with nasal polyps (CRSwNP) or patients without nasal polyps (CRSsNP)[3].Inclusion criteria for CRS need to meet EPOS 2012 definition specifications[2].Among them, some patients with cystic fibrosis, myxosinusitis, malignant polyps, eosinophilic fungal sinusitis, allergic fungal sinusitis, inverted papilloma and primary ciliary dyskinesia will be excluded.
Types of interventions Chinese herbal medicines, including herbal extracts, single or mixed herbal formulas, regardless of composition or form. Chinese herbal medicines combined with one or more other drug interventions will also be included. There is no limit to the dosage, frequency, duration or follow-up time of treatment.
Type of comparators There will be no restrictions with respect to the type of comparator. The comparators are likely to include western medicine, placebo, acupuncture, surgical treatment and other treatments.
Type of outcome measurements Our primary outcomes include main symptom efficacy score (including nasal obstruction, runny nose, sneezing, dizziness and pain et al), treatment-related adverse events and health-related quality of life scores(such as the SinoNasal Outcome Tes-22(SNOT-22) or SNOT-20). Secondary outcomes include total nasal symptom score,recurrence rate, endoscopic score (depending on the population, either nasalpolyps size score, e.g. Lund-Kennedy), computerised tomography(CT) scan scores (e.g.Lund-Mackay) and Visual Analogue Score(VAS).If other results are reported in a qualified study, they will be extracted and reported, but when we use any of these results in our review, special attention will be paid to the possibility of selectively reporting deviations.
Exclusion criteria
The exclusion criteria were as follows: (1) it was not a randomized controlled trial; (2) it could not obtain complete data after repeated literature or contact with the original author; (3) it was not an original literature.
Databases and search strategy
The systematic search will be conducted with English and Chinese. The database for electronic retrieval includes: Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), PubMed, Embase, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang database (Wanfang Data) .All databases will be searched from the build database to May 6, 2019 using a predetermined search strategy.The full search strategy for PubMed is provided in Additional file 2, and similar strategies will be applied to other electronic databases. A reference list of relevant tests and reviews will be searched.Related conference papers, journal references and magazines without electronic version will be manually searched to identify all gray literatures.The search words will be modified to adapt to different databases.Furthermore, potentially relevant studies will be identified by manual search of reference list of included trials and review articles.
Study selection
The two reviewers (SH and LL) will screen the titles and abstracts retrieved from the database with unified standards one by one to check whether the required qualified tests are included. If the filter topic or summary is related to the review topic, they will be evaluated in full one by one. In the screening process, if there are differences, we will focus on the inclusion and exclusion criteria, or the third author (XZ) will decide.Dtails of the entire selection procedure will be shown in a flow chart (see figure 1).
Data extraction and management
The two reviewers (SH and LL) will collect data through standardized template format, extract data one by one from the included experiments, and resolve disputes through consultation or discussion with the third author (XZ). If the data and information required in the article are incomplete, we will contact the author of the experiment to complete the required information.
We will extract the following data from each included trial: the basic characteristics of the study literature (author, year of publication and journal), the trial design method (including random method, assignment concealment or not), the patient characteristics (total sample size, average age, gender, race, course of disease, eligibility criteria), the experimental group and the control group (intervention, number of patients in each group, number of shedding) , follow-up time, adverse reactions).
Dealing with missing data
When the data is lost or the information is incomplete, two independent reviewers(SH and LL)will contact the relevant author by email or phone tracking to obtain the missing data. If there is a lack of data in the end, we will analyze the data based on the principle of intention to treat (ITT)[10].We can use standard error, precise P-value or 95% confidence interval (CI) to approximate the standard deviation[11].Considering that there may be differences in the quality of medical literature, sensitivity analysis will be conducted for relevant data if necessary.
Assessment of risk of bias in included studies
Cochrane's "bias risk" assessment tool [12] will be used to assess bias risk in randomized controlled trials. The bias assessment of the randomized controlled trials included mainly includes the following aspects:Selection bias (e.g. method generated by random assignment sequence and assignment concealment), implementation bias (e.g. double blind for participants and implementers), measurement bias (e.g. blind for result evaluation), loss bias (e.g. reasonable analysis for loss data), publication bias (e.g. existence of selective report) and others Source bias. All the included test biases are divided into three grades of "low", "high" and "unclear", which shall be completed or noted according to the specific situation. Two reviewers(XZ and YF) will evaluate independently and any differences will be resolved through discussion or by a third author (SH).
Data synthesis
Statistical analyses will be performed using RevMan 5.3.5 software (The Cochrane Collaboration).Pooled risk ratio (RR) with 95% confidence interval (CI) of dichotomous outcomes will be used to report effect estimates.Continuous data will be presented as mean difference (MD) with 95% CI. If different measurement scales are used, standardized mean difference (SMD) will be performed to analyze continuous data.The heterogeneity of different experimental studies was analyzed by Chi-square test and I2 statistics[13]. According to Cochrane system evaluation, when the P-value of the Chi-square test is greater than 0.10 or I2 < 50%, the heterogeneity difference of related research is acceptable.If studies included are homogeneous in the field of extracted information, fixed-effect model will be used. When the P-value of the Chi-square test in this study is ≤ 0.10 or I2 ≥ 50%, it is considered that the statistical heterogeneity is high, and the collected literature is further screened for quality. In order to find out the source of heterogeneity in experimental study, sensitivity analysis, subgroup analysis or meta regression analysis will be carried out on the basis of age, course of disease, treatment time, CRS type, dose difference and other factors. For the research with high heterogeneity, the random effect model can be used to evaluate the effect amount.