Data Sources and Search
Ten journals, namely Journal of the American Medical Association (JAMA), British Medical Journal (BMJ), Lancet, New England Journal of Medicine (NEJM), Annals of Internal Medicine, JAMA Pediatrics, Lancet Child & Adolescent Health, Journal of the America Academy of Child and Adolescent Psychiatry, Archives of Disease in Childhood-Fetal and Neonatal and Pediatrics were systematically searched from 1 January 2015 to 7 June 2020 in PubMed. We selected the top ten journals According to the impact factors in the PEDIATRICS and MEDICINE, GENERAL & INTERNAL in JCR 2019 (Journal Citation Reports) respectively. The search terms were “pediatric*”, “paediatric*”, “child*”, “infant*”, “adolescent*”, “baby”, “babies”, “trottie*”, “youth*”, “kids”, “toddler*”, “pre-school*”, “preschool*”, “kindergarten*”, “kinder-garten*”, “girl*”, “boy*”, “student*”, “junior*”, “juvenile*”, “neonat*”, “newborn*”, “teenager*”, “pubescent”, “preterm”, “puberty”, “young*”; “cluster”, “crossover trial”, “cluster-crossover trial”, “cluster crossover trial”, “cluster-randomized”, “cluster randomized”, “cluster-randomised”, “cluster randomised”, “cluster RCT”.
Selection Criteria
Studies fulfilling all the following criteria were considered eligible: (1) the study was a cRCT; (2) the study subject was about newborn, infant, toddler, child, and adolescent; and (3) studies published in Chinese or English.
The following types of studies were excluded: (1) conference proceedings, abstracts, letters, or protocols; (2) studies for which the full text was not available; (3) studies were duplicated; and (4) RCTs at the individual level.
Study Selection
After eliminating duplicates, four researchers independently in pairs in two steps as described below. Before the formal selection, a training exercise of a random sample of 200 citations was conducted to ensure the reliability and feasibility of selection, until adequate agreement on the selecting methods was reached. Firstly, the titles and abstracts of the records were independently screened by four researchers based on selection criteria, and then the full texts of potential suitable articles were retrieved for further assessment. Disagreements were resolved by discussion or consultation with a third researcher.
Data Extraction
Using a pre-developed data extraction form, six researchers independently in pairs extracted study characteristics including: (1) Basic information: publication year, title, journal of publication, country of the first author, funding, conflicts of interest, study topic, ICD-11 classification, the country in which the study was conducted, study setting, and whether multi-center; (2) Study design: whether the trial registered, wrote a protocol, published protocol, had a diagram, conducted repeat observations, conducted evaluator training, conducted additional analyses, distinguished primary and secondary outcome indicators (yes or no), and type of intervention, number of centers, number of participants.
Quality of Evidence Assessment
Six researchers independently evaluated the methodological quality of included studies using the Cochrane risk of bias assessment tool [5] in pairs. Disagreements are resolved by consensus or consultation with a third researcher. The overall Cochrane ROB tool grades methodological quality of included studies as high, low, and unclear [6, 7] according to the risk of bias of following 8 items: sequence generation (randomization) , allocation concealment, blinding of participant, blinding of personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting and other sources of bias. See Table 1 The grade of ROB for details.
Table 1 The grade of ROB
The grade of methodological quality
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Conditions
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High Quality
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Two or more of the five key items a have low bias, and three common items b without high bias.
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Low Quality
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One or less of the five key items with low bias, and regardless of other common items.
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Unclear
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Other conditions.
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a: The five key items included sequence generation, allocation concealment, blinding of participant , blinding of personnel , blinding of outcome assessors.
b: three common items were incomplete outcome data, selective outcome reporting, and other sources of bias.
Statistical Analysis
We established the database with Microsoft Excel 2019 software, and descriptive statistics were performed by SPSS software, version 25.0 (Statistical Package for the Social Sciences version 25.0). Qualitative variables were described by absolute numbers (percentages). Quantitative variables were expressed as mean ± standard deviation (SD). We then conducted chi-square test to assess the associations between study factors and rates of ROB. A difference was considered statistically significant effect when the P-value equal to or less than 0.05.
Financial Support
The funding source had no role in design of study, the collection, analysis, interpretation, and the decision to approve publication of the finished manuscript.
Ethical Approval
Not applicable. All the work was developed using published data.