This study will follow the Cochrane Collaboration and will follow the Preferred Systematic Evaluation and Meta-Analysis Protocol Checklist for reporting item.we have registered the Meta-analysis protocol under the CRD42023465975 number on the International Prospective Register of Systematic Reviews (PROSPERO) website.
Types of participants
The diagnostic criteria are derived from the Chinese Guidelines for the Classification, Diagnosis, and Treatment of Pulmonary Nodules (2016 edition) [12], the Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 edition)[13], and the Fleischner Guidelines[1], or other widely recognized diagnostic criteria.Moderate-risk solid pulmonary nodules are defined by diameters ranging from 5 to 15 mm and the absence of significant malignant CT findings. When dealing with multiple nodules, priority is given to the largest and most dangerous ones.
Types of outcomes
The inclusion criteria for the literature must encompass at least one of the following indicators:
(1) size and number of pulmonary nodules, involving chest CT examinations before and after treatment; utilizing the patient's chest CT report to determine nodule diameter and number;in cases of multiple pulmonary nodules, selecting the largest nodule or the one with the maximum diameter and highest risk of morphological malignancy as the observation indicator.
(2)The malignant risk score indicator refers to the Mayo predictive model recommended by the guidelines to assess malignant risk[14]. Alternatively, refer to other recognized models such as the Brock model[15], VA model[16].
The Mayo prediction model equation is:
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Probability of Malignancy(P) = e x/(1 + e x);
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x=-6.8272+(0.0391×Age) + (0.7917×Cigarettes) ་ (1.3388 × Cancer) ་ (0.1274 × Diameter) ་ ( 1.0407 × Spiculation) ་ (0.7838 × upper).
Formulae note: e is the base of the natural logarithm; where age is in years; diameter is in mm; history of smoking (with or without cessation) is counted as 1, and none as 0; presence of a burr is counted as 1, and none as 0; location in the upper lobes of the lungs is counted as 1, and all others are counted as 0; and a history of a previous extrathoracic malignant tumor greater than 5 years, and malignant tumors are counted as 1, and none are counted as 0.
(3)The clinical efficacy (total effective rate) index is determined by referring to the guiding principles for clinical research of new Chinese medicine[17]:clinical cure, signifying the disappearance of nodules on chest CT; apparent effect, indicating smaller and lighter nodules on chest CT with a volume reduction rate of ≥ 50% ; effective, denoting smaller and lighter nodules on chest CT with a volume reduction rate of ≥ 25% and < 50% ;ineffective,identified when there is little change in nodule volume on chest CT, with a volume reduction rate of < 25%, unchanged volume, or progression (evidenced by the appearance of malignant CT signs such as lobulation,burr,pleural pulling,vacuoles,etc.).
The volume reduction rate is calculated as follows: (pre-treatment volume - post-treatment volume) / pre-treatment volume × 100%. The total effective rate is determined by the formula: (number of clinically cured cases + number of cases with apparent effect + number of effective cases) / total number of cases × 100%. Additionally, adverse events caused by TCM will be documented in these studies.
Search strategies
We will explore randomized controlled trials (RCTs) focusing on TCM treatment for Pulmonary Nodules across seven databases:PubMed,Web of Science, The Cochrane Library,CNKI,Wangfang, CBM, and VIP database.We will employ Medical Subject Headings (MeSH) and various keywords, either individually or in combination, during the search. The search terms will be customized according to each specific database, with the search scope adjusted as needed. After conducting several preliminary searches, the search strategies will be finalized. For instance, the PubMed search strategy details are outlined in Table 1. In Chinese databases, the search will be conducted using Chinese characters with similar meanings.To ensure the integrity and rigor of the article, We will also from the world health organization's international clinical trial register platform (https://www.who.int/clinical-trials-registry-platform) and Chinese clinical trial register platform (http://www.chictr.org.cn) is Conducted randomized controlled trials.
Table 1
Search strategy used in PubMed database
No. | Search terms |
#1 | Pulmonary nodules[MeSH] |
#2 | Solitary nodules[All Fields] |
#3 | Ground glass nodule[All Fields] |
#4 | Solitary Lung Nodules[All Fields] |
#5 | #1 OR #2 OR #3 OR #4 |
#6 | Traditional Chinese Medicine[MeSH] |
#7 | TCM[[ti,ab]] |
#8 | #6 OR #7 |
#9 | Clinical trials [MeSH] |
#10 | Randomized controlled trial [ti,ab] |
#11 | Controlled clinical trial [ti,ab] |
#12 | Randomly [ti,ab] |
#13 | #9 OR #10 OR #11 OR #12 |
#14 | #5 AND #8 AND #13 |
Study selection process
Following predetermined criteria, two reviewers (M-XR and W-HH) independently conducted the screening and data extraction for relevant studies. The initial screening involved reviewing the titles and abstracts of the studies to exclude obviously irrelevant ones. The remaining studies were then carefully reviewed again to eliminate those not meeting the inclusion and exclusion criteria, resulting in the final selection of included studies. In cases of disagreements between the two reviewers, resolutions were achieved through discussions with the authors (L-LS).Information such as published authors, publication year, sample size, interventions, treatment cycles, outcome indicators, and methodology of the included studies was summarized and recorded in an Excel file. The flowchart outlining the entire study selection procedure is presented in Fig. 1.
Risk of bias assessment
Two authors (M-XR and W-HH) independently assessed the quality of the final included literature using the Cochrane Risk of Bias Tool[18]. In instances of disagreement, resolutions were reached through discussions with the reviewers (L-LS).The evaluation encompassed six aspects: (1) random sequence generation, (2) deviations from intended interventions, (3) missing outcome data, (4) outcome measurement, (5) selection of reported results, and (6) overall bias. Each included document was rated as 'Low risk', 'uncertain risk', or 'high risk' by the evaluators.
Sensitivity analysis
Indicators demonstrating notable heterogeneity will be analyzed to identify potential sources of variation, and the stability of the results will be evaluated through either sensitivity analysis or subgroup analysis. Outcomes from the sensitivity analyses, including factors like sample size, methodological pitfalls, and missing data, will be condensed into a summary table. After excluding studies that led to unstable outcomes, we will explore the study design and potential factors contributing to the instability in the Discussion section.