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. 2008 Dec;138(12):2297–2306. doi: 10.3945/jn.108.097154

TABLE 2.

Systematic review steps and examples from nutrition-related topics1

Examples
Systematic review step Vitamin D and bone health (10) Soy and health outcomes (12) (n-3) Fatty acids and arrhythmogenic mechanisms (13)
Form multidisciplinary research team (in addition to systematic review methodologists and systematic review sponsors) Domain experts in nutrition, endocrinology, pediatrics, and biochemistry Domain experts in soy research and relevant health areas Domain experts in (n-3) fatty acids research and cardiac electrogenesis and arrhythmia outcomes
Develop analytic framework Related intakes, serum 25(OH)D, active form [1,25(OH)D] and bone health Not available Different for whole animal, intact animal isolated organ and cell, and cell culture studies
Develop and refine key questions Serum 25(OH)D and bone health Soy formulations, doses, and purposes in trials Evidence from whole animal studies that (n-3) fatty acids affect arrhythmogenic outcomes
Intake or sun exposures and serum 25(OH)D Whole soy or soy constituents and heath outcomes
Vitamin D intakes and BMD, fractures, or falls; variation with age, ethnicity, geography, BMI Dose-response of soy forms or constitutions Evidence from cell culture and tissue studies that (n-3) fatty acids directly affect cell organelles involved in electrogenesis
Sunlight and 25(OH)D without ↑ skin cancer Frequency and type of adverse effects
Intakes related to toxicities Dose-response of whole soy and constituents on safety
Define eligibility criteria Some questions limited to RCT Inclusions: subjects ≥13 y; RCT, cohorts, cross-over and nonrandomized comparison studies; ≥5 subjectsin soy arm; any health condition; quantification of soy intake; outcomes of interest; ≥4-wk duration Inclusions: experiments of (n-3) fatty acids and arrhythmia, intermediate mechanisms of arrhythmia, and electrogenesis
Some questions included prospective cohorts, case-control, and before-after studies.
One question restricted to existing systematic reviews Exclusions: letters or abstracts; mechanisms related to eicosanoids, enzymes, receptors, membrane composition, fluidity, or phospholipids; nonmammalian animals or cell lines; no relevant outcomes; no (n-3) fatty acids intervention; reviews; safety assessments
Included studies that assessed vitamin ergocalciferol or cholecalciferol with or without calcium supplementation
Excluded studies that used calcium with vitamin D as a control arm unless a placebo was available as a comparator; vitamin D preparations calcitriol or alphacalcidol; studies on the efficacy of vitamin D for the treatment of secondary causes of osteoporosis or for treatment of vitamin D-dependent rickets Exclusions: soy mixed with other ingredients; soy enteral feedings; reviews; nontrial observational studies; animal or in vitro studies; ingested soy not quantified; insignificant amounts of soy; no intake data
Identify search terms and strategy 130 key terms 33–63 key terms per search 64 search terms
Screen abstracts according to eligibility criteria 6566 unique records ∼4800 abstracts 1807 abstracts
Articles retrieved for evaluation 1447 reports 599 full text articles 274 articles
Extract data from articles which met inclusion criteria 167 articles 178 articles 89 articles
Construct evidence and summary tables 18 summary tables 86 summary tables 31 summary tables
Assess methodological quality, applicability Jadad scale for RCT 3 categories (A,B,C) of methodological quality 4 categories for fatty acid and/or level of fat in the comparison diet
Good, fair, or consistent rating for observational studies 3-category applicability grade
Perform meta-analyses, as appropriate Meta-analysis of RCT that assessed interventions, populations, and outcomes Meta-analysis for several cardiovascular outcomes Meta-analyses for whole animal studies
Meta-regression of differences across studies and dose-responses For isolated organ and cell studies, qualitative data summary
Synthesize results, write report, have report reviewed Report written by EPC; peer review by TEP members and external reviewers Report written by EPC; peer review by TEP members and external reviewers Report written by EPC; peer review by TEP members and external reviewers
1

EPC, evidence-based practice center; FA, fatty acid; RCT, randomized controlled trial; TEP, technical expert panel; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)D, 1,25-dihydroxyvitamin D.