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Introduction to
Systematic Review
and Meta-analysis
Image taken from https://communications-marketing.ed.ac.uk/about-us
Introduction
• What is the difference between a systematic
review and meta-analysis?
• Systematic review – A review of
methods and results from all individual
studies which focus on a particular
research question and conform to a set
criteria
• Meta-analysis – Involves use of special
statistical methods to obtain overall
single estimate, by combining the results
of all individual studies
Step 1: Research Question
• P – Patient, problem or population
• I – Intervention
• C – Comparison, control or comparator
• O – Outcome(s) (e.g. pain, fatigue, nausea, infections, death)
Step 2: Data Resources
Data Resources
Published
Literature
• Core
• Specific
Grey Literature
Step 2: Data Resources – Core
Core Resources
Cochrane Library
 Cochrane Reviews
 Registry of Clinical Trials
Intervention & diagnostic reviews
Critically appraised and re-structured abstracts
Global registry of clinical trials
Medline
 Ebsco, Ovid or PubMed
Major medical literature database, produced by US National
Library of Medicine.
Embase Strong on European studies, pharmacological literature,
conference abstracts. Both Medline and Embase are
complementary and essential for searching core clinical topics.
Web of Knowledge Large multidisciplinary databases with citation searching.
Biomedical sciences, social science, conferences.
SCOPUS Large multidisciplinary database with citation searching.
Step 2: Data Resources – Specific
Subject Specific Resources
CINAHL Plus with Full Text Nursing and allied health
PsycInfo Psychology & psychiatry
EMERALD Management, health services, social sciences
ERIC Education
Global Health Public health, international health, grey literature
Health Business Elite Healthcare administration and management
PEDro Physiotherapy
TOXLINE Effects of drugs and chemicals
Westlaw Irish legal materials, including statutes and case law
Step 2: Data Resources – Grey Literature
Grey Literature sources
 NLM (National Library of Medicine, US) - http://www.ncbi.nlm.nih.gov
 National Information Center on Health Services Research and Health Care Technology (NICHSR) http://www.nlm.nih.gov/nichsr/db.html
 Health Services & Sciences Research Resources (HSRR) https://hsrr.nlm.nih.gov/
 US National Institutes of Health Icite Index to Preprintshttps://icite.od.nih.gov/
 Indexes the main biomedical and social science preprint datbasess: arXiv, bioRxiv, ChemRxiv, medRxiv, Research Square, and SSRN.
Institutional repositories: scholarly collections from academic and professional organisations
 OpenDOAR: Directory of Repositories http://www.opendoar.org/
 Bielefeld Base: European research resources http://www.base-search.net/Search/Advanced
 Lenus: HSE Ireland health documentation http://www.lenus.ie/hse/
 RCSI: research repository https://repository.rcsi.com/
Theses
 EThOS http://ethos.bl.uk/ UK theses.
 DART-Europe http://www.dart-europe.eu/ European theses.
 Networked Digital Library of Theses and Dissertations http://search.ndltd.org/
Clinical Trials
 Cochrane Central Registry of Clinical Trials (access via library website)
 ClinicalTrials.gov https://clinicaltrials.gov/
 National Institutes of Health, US ISRCTN Registry http://www.isrctn.com/ global registry of trials
 WHO International Clinical Trials Registry Platform (ICTRP) http://www.who.int/ictrp/en/
Step 3: Data Extraction
Jacknunn, CC BY-SA 4.0, via Wikimedia Commoms
• Search strategy
• In PubMed for instance, PubMed
saves the search strategy as one
long string : Search (deep vein
thrombosis) AND (aspirin) AND
(travel OR aircraft OR airplane)
• MESH (Medical Subject Headings)
• Boolean Operators—AND, OR,
and NOT
Step 4: Assess the Data Eligibility
• Ideally two independent investigators
• Any disagreement is resolved by a 3rd reviewer
• PRISMA flow diagram
• Templates are available - http://www.prisma-
statement.org/PRISMAStatement/FlowDiagram.aspx
• Flow diagrams can also be generated using a Shiny App
available at
https://www.eshackathon.org/software/PRISMA2020.html
Step 5: Combine and Analysis Data
• Qualitative assessment
• JADAD Score for RCT
• Newcastle-Ottawa Scale
for non-RCT
• Cochrane bias assessment
tool
• Publication bias
• Funnel plot
• Quantitative assessment
• Forest plot
Step 5: Combine and Analysis Data
• Forest plot
• Funnel plot
Forest plot
James Grellier, CC BY-SA 3.0, via Wikimedia Commons
The Vertical represents the
‘Line of no effect’
The horizontal line across each box represents the
95% confidence interval. Shorter line are more
precise. If the CI includes 1, the effect is not
significant
The diamond shape represents the pooled outcome
of all the studies. The width of the diamond shape
corresponds to the confidence interval of the result
The square box
indicates the
size of the study
Funnel plot
• The funnel plot is a test for publication bias.
• If there is publication bias, there will be asymmetry at the wide
part of the funnel plot end due to the absence of small negative
studies
• In this case trials missing from the bottom right-hand corner
Figure taken from Mytton, O.T., et al., Systematic review and meta-analysis of the effect of increased
vegetable and fruit consumption on body weight and energy intake. BMC Public Health, 2014. 14(1): p.
886.
Registration and Guidelines
• Register with International prospective register of systematic reviews
• PROSPERO - https://www.crd.york.ac.uk/PROSPERO/
• Follow guidelines and checklists
• Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) - http://prisma-statement.org/
• Meta-analysis of Observational Studies in Epidemiology (MOOSE)
References
• https://s4be.cochrane.org/blog/2016/07/11/tutorial-read-forest-plot/
• Gosall, N.K. and G.S. Gosall, The Doctor's Guide to Critical Appraisal. 2012: PasTest.
• Harris, M. and G. Taylor, Medical Statistics Made Easy. 2003: CRC Press.
• Mytton, O.T., et al., Systematic review and meta-analysis of the effect of increased
vegetable and fruit consumption on body weight and energy intake. BMC Public
Health, 2014. 14(1): p. 886.
Acknowledgment
• Slide 2 was shared by Dr. Rachna Rohilla (PGIMER Chandigarh)

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OER_s1220738.pptx

  • 1. Introduction to Systematic Review and Meta-analysis Image taken from https://communications-marketing.ed.ac.uk/about-us
  • 2. Introduction • What is the difference between a systematic review and meta-analysis? • Systematic review – A review of methods and results from all individual studies which focus on a particular research question and conform to a set criteria • Meta-analysis – Involves use of special statistical methods to obtain overall single estimate, by combining the results of all individual studies
  • 3. Step 1: Research Question • P – Patient, problem or population • I – Intervention • C – Comparison, control or comparator • O – Outcome(s) (e.g. pain, fatigue, nausea, infections, death)
  • 4. Step 2: Data Resources Data Resources Published Literature • Core • Specific Grey Literature
  • 5. Step 2: Data Resources – Core Core Resources Cochrane Library  Cochrane Reviews  Registry of Clinical Trials Intervention & diagnostic reviews Critically appraised and re-structured abstracts Global registry of clinical trials Medline  Ebsco, Ovid or PubMed Major medical literature database, produced by US National Library of Medicine. Embase Strong on European studies, pharmacological literature, conference abstracts. Both Medline and Embase are complementary and essential for searching core clinical topics. Web of Knowledge Large multidisciplinary databases with citation searching. Biomedical sciences, social science, conferences. SCOPUS Large multidisciplinary database with citation searching.
  • 6. Step 2: Data Resources – Specific Subject Specific Resources CINAHL Plus with Full Text Nursing and allied health PsycInfo Psychology & psychiatry EMERALD Management, health services, social sciences ERIC Education Global Health Public health, international health, grey literature Health Business Elite Healthcare administration and management PEDro Physiotherapy TOXLINE Effects of drugs and chemicals Westlaw Irish legal materials, including statutes and case law
  • 7. Step 2: Data Resources – Grey Literature Grey Literature sources  NLM (National Library of Medicine, US) - http://www.ncbi.nlm.nih.gov  National Information Center on Health Services Research and Health Care Technology (NICHSR) http://www.nlm.nih.gov/nichsr/db.html  Health Services & Sciences Research Resources (HSRR) https://hsrr.nlm.nih.gov/  US National Institutes of Health Icite Index to Preprintshttps://icite.od.nih.gov/  Indexes the main biomedical and social science preprint datbasess: arXiv, bioRxiv, ChemRxiv, medRxiv, Research Square, and SSRN. Institutional repositories: scholarly collections from academic and professional organisations  OpenDOAR: Directory of Repositories http://www.opendoar.org/  Bielefeld Base: European research resources http://www.base-search.net/Search/Advanced  Lenus: HSE Ireland health documentation http://www.lenus.ie/hse/  RCSI: research repository https://repository.rcsi.com/ Theses  EThOS http://ethos.bl.uk/ UK theses.  DART-Europe http://www.dart-europe.eu/ European theses.  Networked Digital Library of Theses and Dissertations http://search.ndltd.org/ Clinical Trials  Cochrane Central Registry of Clinical Trials (access via library website)  ClinicalTrials.gov https://clinicaltrials.gov/  National Institutes of Health, US ISRCTN Registry http://www.isrctn.com/ global registry of trials  WHO International Clinical Trials Registry Platform (ICTRP) http://www.who.int/ictrp/en/
  • 8. Step 3: Data Extraction Jacknunn, CC BY-SA 4.0, via Wikimedia Commoms • Search strategy • In PubMed for instance, PubMed saves the search strategy as one long string : Search (deep vein thrombosis) AND (aspirin) AND (travel OR aircraft OR airplane) • MESH (Medical Subject Headings) • Boolean Operators—AND, OR, and NOT
  • 9. Step 4: Assess the Data Eligibility • Ideally two independent investigators • Any disagreement is resolved by a 3rd reviewer • PRISMA flow diagram • Templates are available - http://www.prisma- statement.org/PRISMAStatement/FlowDiagram.aspx • Flow diagrams can also be generated using a Shiny App available at https://www.eshackathon.org/software/PRISMA2020.html
  • 10. Step 5: Combine and Analysis Data • Qualitative assessment • JADAD Score for RCT • Newcastle-Ottawa Scale for non-RCT • Cochrane bias assessment tool • Publication bias • Funnel plot • Quantitative assessment • Forest plot
  • 11. Step 5: Combine and Analysis Data • Forest plot • Funnel plot
  • 12. Forest plot James Grellier, CC BY-SA 3.0, via Wikimedia Commons The Vertical represents the ‘Line of no effect’ The horizontal line across each box represents the 95% confidence interval. Shorter line are more precise. If the CI includes 1, the effect is not significant The diamond shape represents the pooled outcome of all the studies. The width of the diamond shape corresponds to the confidence interval of the result The square box indicates the size of the study
  • 13. Funnel plot • The funnel plot is a test for publication bias. • If there is publication bias, there will be asymmetry at the wide part of the funnel plot end due to the absence of small negative studies • In this case trials missing from the bottom right-hand corner Figure taken from Mytton, O.T., et al., Systematic review and meta-analysis of the effect of increased vegetable and fruit consumption on body weight and energy intake. BMC Public Health, 2014. 14(1): p. 886.
  • 14. Registration and Guidelines • Register with International prospective register of systematic reviews • PROSPERO - https://www.crd.york.ac.uk/PROSPERO/ • Follow guidelines and checklists • Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) - http://prisma-statement.org/ • Meta-analysis of Observational Studies in Epidemiology (MOOSE)
  • 15. References • https://s4be.cochrane.org/blog/2016/07/11/tutorial-read-forest-plot/ • Gosall, N.K. and G.S. Gosall, The Doctor's Guide to Critical Appraisal. 2012: PasTest. • Harris, M. and G. Taylor, Medical Statistics Made Easy. 2003: CRC Press. • Mytton, O.T., et al., Systematic review and meta-analysis of the effect of increased vegetable and fruit consumption on body weight and energy intake. BMC Public Health, 2014. 14(1): p. 886.
  • 16. Acknowledgment • Slide 2 was shared by Dr. Rachna Rohilla (PGIMER Chandigarh)

Editor's Notes

  1. Hi Everyone. I am presenting this short PowerPoint presentation on Introduction to Systematic Review and Meta-analysis as part of the assignment on Digital Education module of the Postgraduate Certificate in Clinical Academic Practice (PgCAP)
  2. First of all, what is Systematic Review and Meta-analysis A systematic review identifies, appraises, synthesises and interprets data into a refined conclusion that meets pre-specified eligibility criteria to answer a given research question. Meta-analysis, on the other hands, is a subset of systematic review. It combines the results of multiple scientific studies using a systematic review software (For example, Review Manager or RevMan). There are 5 distinctive stages of systematic review Defining Research Question Searching for relevant data sources Extraction of relevant data Assess the eligibility of the data Analyses and combine data
  3. Step 1 - Defining an answerable question and agreeing an objective method is required to design a useful systematic review Clinical reviews of quantitative data are often structured using the acronym PICO, which stands for 'Population or Problem', 'Intervention or Exposure', 'Comparison' and 'Outcome'
  4. Step 2 - Planning how the review will search for relevant data from research that matches certain criteria is a decisive stage in developing a rigorous systematic review.  Resources can be either published literature or grey literature We will look at the examples of each next
  5. One of the published literature is CORE resources Some examples are listed here
  6. Published literature can also be SPECIFIC to the subject of interest Some examples are listed here
  7. Grey literature sources can be sought in various websites, repositories, theses, and clinical trials
  8. Step 3 Relevant data are 'extracted' from the data sources according to the review method
  9. Step 4 This stage involves assessing the eligibility of data for inclusion in the review, by judging it against criteria identified at the first stage.
  10. Last stage is analysing and combining data can provide an overall result from all the data. We have got Qualitative assessment and Quantitative assessment The Qualitative assessment can be done using JADAD score, Newcastle-Ottawa Scale, Cochrane bias assessment tool and a Funnel plot for publication bias. For Quantitative assessment - a forest plot (also called a blobbogram) should be used
  11. We would now learn how to interpret forest flot. Funnel flot is useful to detect publication bias
  12. Firstly, It is important to register with PROSPERO prior to starting the process of conducting a systematic review Secondly, remember to follow the guidelines and checklist This includes PRISMA guideline which consists of a 27-item checklist and a four-phase flow diagram The PRISMA statement can be found on the PRISMA website The MOOSE group has also published a checklist containing specification for reporting of meta-analysis of observational studies in epidemiology.
  13. Here is the references
  14. I would like to thanks Dr. Rachna Rohilla who has kindly share one of her slide in this presentation. Many thanks.