We will strictly abide by the requirements of the “Preferred Reporting Items for Systematic Review and Meta-analysis Protocols” to report the meta analysis.
Protocol and registration
The protocol registration number was INPLASY2020120047.
Type of study.
Studies were randomized controlled trials (RCTs) using Shuanghuanglian injection for viral pneumonia in adult patients. The language will be limited to Chinese or English. Exclude non-RCT, animal experiments,unclear results indicators such as images, and other nonquantitative indicators. For the articles published repeatedly in Chinese and English journals,the latest one published articles were taken.
Type of Participants.
Participants were adults aged 18 years old and older with the diagnosis of viral pneumonia in the general population, regardless of gender, ethnicity, race, and disease stage. Children, patients with severe cardiovascular diseases and mental illnesses, pregnant women, breast stage, and cancer will be excluded.
Interventions included Shuanghuanglian injection alone or in combination with conventional therapy (CT) and/or biological agents for at least 2 weeks. The controls included no treatment, placebo, and CT alone.
The main outcome indicators include: the cure rate,mortality, efficacy, or adverse events confirmed by imaging diagnosis. The secondary outcome indicators include: odds ratio, risk ratio, hazard ratios, standardized incidence ratio, standardized mortality ratio, and associated 95% confidence intervals (CIs).
Data sources and search strategies
We will serch the following databases will be searched: Pubmed, Embase, Web of Science, the Cochrane library, the China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, Chinese Science, and Technology Periodical Database. Collect all the RCTs on the treatment of viral pneumonia with Shuanghuanglian injection. And manually search for references in the related literature. The retrieval time is from the inception of the database to December 10, 2020. The language is limited to Chinese and English. The search strategy for PubMed was listed, which was including all search terms. Other searches will be conducted based on these results, and the search strategy will be modified as required for other electronic databases.
#1 search “viral pneumonia” [Title/Abstract]
#2 Search “Shuanghuanglian injection ” [Title/Abstract]
#3 Search “RCT” [Title/Abstract] OR “randomized controlled trial” [Title/Abstract]
#4 Search “Efficacy” [Title/Abstract] OR “safety” [Title/Abstract]
#5 #1 and #2 and #3 and #4.
Selection of studies
All initial records from the four electronic databases will be imported into the web-based systematic review Rayyan software. Two authors independently complete the following process: according to the above search strategy to complete the process of document retrieval, import documents into Rayyan software. then, according to the inclusion and exclusion criteria, filter the literature by reading the title and abstract. If it is not possible to determine whether the article meets the requirements based on the inclusion and exclusion criteria, then read full text to select. All the procedures will be carried out by 2 independent reviewers and completed a cross-check. Any conflict will be resolved by discussion with the 3rd author. The process of research selection is shown in Fig. 1.
The data will be extracted out by two independent reviewers in accordance with the Cochrane Handbook of Systematic Reviews of Interventions. Two investigators will independently screen all the included studies to extract the following data: name of the first author, publication year, study design, country, intervention, control group, study period, sample size, numbers of outcomes, age at enrollment, sex, duration of follow-up, adjustments, and effect estimates. The reviewers fillthe extracted information into a pre-built Excel table. If necessary, we will contact the trial author for further information.
Dealing with missing data
If there is data loss in the included study, we will contact the original author of the article to obtain the original information. If the missing data is still not available, the existing data will be analyzed and a sensitivity analysis will be performed to address the potential impact of the missing data.
Risk of bias assessment and quality of selected studies
Two researchers independently evaluated the risk of bias in randomized controlled trials in accordance with the Cochrane Handbook of Systematic Reviewers, including the following items: random sequence generation, allocation concealment, blind participants and personnel, blind assessment of results, incomplete result data, selective reports, and other biases. The quality of studies was classified as being at of high, unclear, or low risk of bias. After completion, they would recheck. In the case of a disagreement, they would discuss. If no agreement could be reached, a decision would be made in consultation with researchers from the third party.
Statistical analyses were performed using RevMan 5.3 software. Dichotomous data. The relative
risk (RR) was calculated with 95% confidence intervals (CI). Continuous data. A fixed-effect mean difference (MD) with 95% CI was calculated for outcomes reported in the same scale, and the standardized mean difference (SMD) with 95% CI was calculated for outcomes reported indifference scales.
Assessment of heterogeneity: For the meta-analysis of non-significant heterogeneity, we applied a fixed-effect model (FEM),otherwise, Statistical heterogeneity was calculated using the I2 statistic, and > 50% was considered to be substantial. Subgroup analyses were performed to explore heterogeneity, and a random-effects model was applied.
Subgroup analysis: When heterogeneity is detected, we will judge the source of heterogeneity through subgroup analysis (e.g., different types of Chinese medicines therapies, research quality, publication age, participation population, and length of treatment). In addition, we can also observe the relationship between the effect values and grouping variables.
The Cochrane Collaboration’s Risk of Bias Tool was used to assess bias. Seven domains of risk were assessed: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data, selective reporting, and other bias(baseline balance and funding/conflict of interest). Publication bias for meta-analysis of ≥ 10 studies was also assessed by using funnel plots and Egger test.
Assess the quality of evidence
The evaluation of the strength of the evidence will be based on the grading of recommendations assessment, development, and evaluation system, there are 4 levels of evidence strength: high,
medium, low, or very low.