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Evidence Synthesis

Meta-Analysis

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🧠 What is a Meta-Analysis?

A meta-analysis is a structured, quantitative method of synthesizing data from multiple independent primary studies that address a common research question. It is typically conducted as part of a systematic review, providing a statistical estimate of the overall effect size, while accounting for variations across studies. Meta-analyses are widely used in clinical medicine, public health, and health policy to inform evidence-based decision-making.

Meta-analytic techniques enhance the precision of effect estimates, assess consistency among findings (heterogeneity), and identify potential sources of between-study variability. The process adheres to a rigorous methodological framework to minimize bias and ensure reproducibility.

  • Purpose: To statistically integrate results from individual studies to derive a pooled effect estimate with increased statistical power.
  • Common Applications: Treatment efficacy, diagnostic test accuracy, risk factor associations, and prevalence estimates.
  • Foundational Principle: Greater cumulative knowledge emerges from the systematic aggregation and analysis of multiple studies than from any single study alone.

🗂️ Methodological Framework: Conducting a Meta-Analysis

  1. 1. Formulate a Precise Research Question
    Use the PICO (Population, Intervention, Comparator, Outcome) framework to ensure clarity and focus. A well-defined question guides the eligibility criteria, search strategy, and analysis plan.
  2. 2. Develop and Register a Protocol
    A priori registration is strongly recommended to promote transparency and reduce risk of bias. Register protocols via PROSPERO or follow the PRISMA-P guidelines. Protocols should detail:
    • Eligibility criteria (inclusion/exclusion)
    • Search strategy and databases
    • Risk of bias tools
    • Statistical methods and planned subgroup analyses
  3. 3. Conduct a Comprehensive Literature Search
    Design a robust, reproducible search strategy in collaboration with a health sciences librarian. Use a combination of controlled vocabulary (e.g., MeSH, Emtree) and keywords across multiple databases (e.g., PubMed/MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO). Record:
    • Search strings and filters applied
    • Dates of search and updates
    • Gray literature sources (e.g., clinical trial registries, dissertations)
  4. 4. Study Selection and Screening
    Conduct title/abstract screening followed by full-text review. Use software like Rayyan or Covidence for blinded, dual-reviewer screening. Resolve conflicts via consensus or third-party adjudication.
  5. 5. Critical Appraisal and Risk of Bias Assessment
    Apply validated tools appropriate for the study designs included:
    • RoB 2 – Randomized controlled trials
    • ROBINS-I – Non-randomized studies
    • Newcastle-Ottawa Scale – Observational studies
    • QUADAS-2 – Diagnostic accuracy studies
    Document and report risk of bias assessments to inform sensitivity analysis and interpretation of results.
  6. 6. Data Extraction
    Extract relevant quantitative and qualitative data using standardized templates. Include:
    • Study identifiers (authors, year, journal)
    • Population characteristics
    • Intervention and comparator details
    • Outcome measures (continuous, dichotomous, time-to-event)
    • Effect sizes, confidence intervals, and standard errors
    Use dual, independent data extraction to reduce errors.
  7. 7. Statistical Synthesis
    Perform meta-analysis using software such as:
    • RevMan – User-friendly for Cochrane-style reviews
    • R (metafor, meta packages) – Highly flexible, publication-grade analysis
    • Stata – Comprehensive statistical capabilities
    Key steps:
    • Choose an appropriate model (fixed-effect vs. random-effects)
    • Assess heterogeneity using Cochran’s Q and I² statistics
    • Investigate outliers and influence using sensitivity analyses
    • Explore subgroup or meta-regression analyses, if applicable
  8. 8. Assess Publication Bias
    Use funnel plots, Egger’s test, or Begg’s test to detect potential publication bias. Consider small-study effects and selective outcome reporting.
  9. 9. Interpret Results in Context
    Discuss the strength and applicability of findings. Interpret confidence intervals, heterogeneity, and quality of evidence using tools like GRADE.
  10. 10. Report According to PRISMA Guidelines
    Ensure full reporting using the PRISMA 2020 checklist and flow diagram. Include:
    • Comprehensive methods and search strategy
    • Study selection and risk of bias tables
    • Forest plots and other visual summaries
    • Transparent discussion of limitations

🛠️ Tools & Software for Meta-Analysis

Tool Function Link
RevMan Cochrane's review manager for systematic reviews RevMan
R (metafor/meta) Advanced meta-analysis scripting in R metafor
Stata Statistical computing with meta-analysis commands Stata Meta
Covidence Systematic review management (screening, extraction) Covidence
Rayyan Collaborative abstract and full-text screening Rayyan

📚 Key Resources and Guidance Documents