This systematic review was registered on PROSPERO (CRD42020168004) on 5 February 2020. We have prepared this protocol in accordance with the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA-P) statement (Additional file 1).
Type of studies
Randomized trials and quasi-randomized or prospective controlled clinical trials that have tested TCM with or without western medicine for NCIP will be included. There will be no restrictions for blinding, follow-up or publication status. Publications in English and Chinese will be included.
Type of participant
Patients diagnosed with pneumonia caused by 2019-nCoV without immediately life-threatening co-morbidities will be included. There will be no restrictions with respect to gender, age or ethnicity.
Type of interventions
Traditional Chinese herbal medicine involving extracts from herbs, single or mixture herbal formulas regardless of their compositions or forms. TCM combined with one or more other pharmacological intervention will also be included. There will be no restrictions with respect to dosage, frequency or duration of treatment.
Type of comparators
There will be no restrictions with respect to the type of comparator. The comparators are likely to include western medical therapies, supportive care and other therapeutic methods.
Type of outcome measurements
Our primary outcomes will be survival at the end of treatment and at the end of follow-up, and time and rate of the patient becoming negative for the coronavirus. We will also assess the following outcomes at the end of treatment and at the end of follow up: days to absence of fever; symptom score (based on fever, fatigue, cough, difficulty in breathing, poor appetite, etc.); duration of each symptom; pulmonary function; inflammation index; results of chest CT; length of stay in hospital; use (including dosage and duration) of corticosteroid; quality of life; and adverse events. If other outcomes are reported in the eligible studies, these will be extracted and reported but we will give particular attention to the possibility of selective reporting bias when using any such outcomes in our review.
(1) Suspected or misdiagnosed NCIP patients; (2) Patients with severe basic diseases that are likely to lead to death within the trial follow-up period; (3) Duplicated data or data that cannot be extracted; (4) Full text cannot be obtained.
Databases and search strategy
We will search electronic databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database (Wanfang Data) using keywords related to novel coronavirus, NCIP and TCM. The full search strategy for PubMed is provided in Additional file 2 and similar strategies will be applied to the other electronic databases. Reference lists of relevant trials and reviews will be searched. We will manually search grey literature such as conference proceedings and academic degree dissertations, and trial registries (both through the WHO International Clinical Trials Registry Platform (ICRP) and on the websites of national registries).
After removing duplicates, the retrieved records will be checked independently by two reviewers (XL and DZ), who will apply the eligibility criteria based on the title and abstract. Where a study is potentially eligible, the full-text will be obtained and checked independently by two reviewers (XL and DZ) to identify the eligible studies. Any disagreements will be discussed and resolved in discussion with a third reviewer (JL).
Two independent reviewers (YL and LG) will extract data with a predefined extraction template, which includes the following items: (1) General information: first author, title, journal, year of publication, country, funding source, study design, etc. (2) Characteristics of patients: age, gender, stage and severity of disease, comorbidity, etc. (3) Characteristics of intervention: protocol of Chinese herbal medicine (types, dosage, frequency, duration etc.), protocol of comparators (types, dosage, frequency, duration etc.). (4) Characteristics of trial: sample size (numbers recruited, randomized or allocated to the interventions by another method, followed up and analyzed), generation of randomization sequence, allocation concealment, blinding, etc. (5) Outcomes: all outcomes, main conclusions, adverse events, etc. The original authors will be contacted to request missing data where necessary. Extracted information will be cross checked. Any disagreements will be discussed and resolved in discussion with a third reviewer (YZ).
Assessment of risk of bias
Two independent reviewers (YL and DZ) will assess the risk of bias of the included studies. We will follow the guidance in the latest version of Cochrane Handbook for systematic reviews of interventions when choosing and using tools to assessing risk of bias for randomized and on-randomized trials. Any disagreements will be discussed and resolved in discussion with a third reviewer (RJ).
Statistical analyses will be conducted using RevMan software (version 5.3.5) and R software (version 3.6.1). If possible, analyses for all outcomes will be done by intention-to-treat. We will perform analyses to provide effect estimates for dichotomous data and continuous data, with 95% confidence intervals. We will use risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data. If subsets of included studies are sufficiently homogeneous, we will perform meta-analysis for all outcomes. Heterogeneity will be detected by using a standard Chi-square test with a significance level of P < 0.10. The I2 statistic will be applied to quantify inconsistency across studies and to assess the impact of heterogeneity on the meta-analyses. Fixed-effects model will be used if there is small statistical heterogeneity among studies (I2 < 50%, P > 0.10). Otherwise, random-effects model will be used.
If an adequate number of studies are identified, we will perform subgroup analysis for the following variables: age; patients with or without other diseases; and NCIP stage at which the TCM was given.
We will also consider analyses for other subgroups as reported in the included studies, but we will give particular attention to the possibility of selective reporting bias when using any such subgroups in our review.
To check the robustness of pooled outcome results, we will carry out sensitivity analysis to explore the influence of studies with high risk of bias.
We will test for publication bias using the funnel plot or other corrective analytical methods, depending on the number of clinical trials included in our review.
Quality of evidence
Two independent reviewers (DLZ and JL) will assess the quality of evidence for each outcome with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Each outcome will be assessed for each of the five aspects: limitations, inconsistency, indirectness, imprecision, and publication bias. They will be rated as high, moderate, low, or very low level quality.