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Influenza vaccines licensed in the United States in healthy children: a systematic review and network meta-analysis (Protocol)

Gabriela J Prutsky12*, Juan Pablo Domecq12, Tarig Elraiyah1, Zhen Wang1, Lisa A Grohskopf6, Larry J Prokop5, Victor M Montori124 and Mohammad Hassan Murad13

Author Affiliations

1 Knowledge and Evaluation Research Unit (KER), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

2 Unidad de Conocimiento y Evidencia (CONEVID), Universidad Peruana Cayetano Heredia, 430 Honorio Delgado Ave, San Martin de Porres, Lima 31, Peru

3 Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

4 Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

5 Mayo Clinic Libraries, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

6 Influenza Division, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, USA

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Systematic Reviews 2012, 1:65  doi:10.1186/2046-4053-1-65

Published: 29 December 2012



Influenza is an acute respiratory illness caused by influenza viruses, which occurs in epidemics worldwide every year. Children are an important target for prevention methods, including vaccination. While evidence about the decision on whether to vaccinate healthy children is robust, evidence supporting the decision of which of available vaccines to use remains unclear.

This review will summarize the evidence about the efficacy and safety of the available vaccines for seasonal influenza licensed in the United States for use in healthy children.


An umbrella systematic review (SR) and network meta-analysis will be conducted of randomized controlled trials (RCTs). We will search for SRs to identify parallel RCTs evaluating inactive and/or live attenuated influenza vaccines licensed in the United States for use in healthy children to prevent influenza. Subsequently, we will update the literature search of the selected SRs to the present time to capture recent controlled studies. To complement the work focused on harms, we will also select observational studies focusing on post marketing retrospective studies. Inclusion will not be limited by language, publication date or publication status. To identify additional candidate studies, we will review the reference lists of the eligible primary studies and narrative reviews; we will query the expert members of the Advisory Committee on Immunization Practices and review references from their previous statement. Additionally, we will review the reports from the Institute of Medicine on the adverse effects of vaccines. Two reviewers will independently determine study eligibility and will extract descriptive, methodological (using the Cochrane risk of bias tool for RCTs and the Newcastle–Ottawa scale for observational studies) and efficacy data. When possible, we will conduct meta-analyses and network meta-analyses by combining indirect and direct comparisons.

We will evaluate heterogeneity using the I2 statistic and the agreement of indirect comparisons and direct evidence. We will report the Cochrane Q test to determine the statistical significance of heterogeneity.

The overall quality of evidence will be assessed following the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach.


Our systematic review will allow patients, clinicians, guideline developers and policy makers to make evidence-based choices between the two available vaccine options, by providing information regarding benefits and harms of these types of vaccines.

Influenza; Influenza vaccine; Children; Systematic review