This lecture is an overview of systematic review and Meta-analyses. Recommended for researchers and policy makers.

1. INTRODUCTION TO
SYSTEMATIC REVIEWS
Professor F. E. Afolabi LESI FNAMed, FAMedS
Department of Paediatrics,
College of Medicine, University of Lagos

2. OBJECTIVES
At the end of the session it is expected that participants should:
• Define what a systematic review is and note the differences from a
traditional review.
• Outline the systematic review process.
• Describe how the knowledge can be applied in appraising evidence
for healthcare decision making.
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3. INTRODUCTION: DEFINITION
• Systematic review is a form of
research that provides a summary of
medical reports on a specific clinical
question, using explicit methods to
search, critically appraise, and
synthesize the world literature
systematically. (Sackett, 2000)
• Systematic review is the process of
integrating empirical data towards
producing evidence that guides
decision making.
• A form of observational research
• It is internationalizing what was
previously local.
• It is the summit of clinical research 3
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4. INTRODUCTION: DIFFERENCE WITH
TRADITIONAL REVIEWS
• While traditional review articles or narrative reviews can be useful
when conducted properly, there is evidence that they are usually of
poor quality.
• Authors of narrative reviews often use informal, subjective methods
to collect and interpret studies and tend to be selective in citing
reports that reinforce their preconceived ideas or promote their own
views on a topic.
• They are rarely explicit how they selected, assessed, and analysed the
primary studies, thereby not allowing readers to assess potential bias
in the review process.
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5. WHAT IS THE DIFFERENCE ?
NARRATIVE REVIEW SYSTEMATIC REVIEW
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6. A SYSTEMATIC REVIEW IS……
• EXPLICIT : Objectives, Materials & Methods
• SYSTEMATIC : Literature identification
• TRANSPARENT : Decisions & Criteria
• REPRODUCIBLE : Methods & Conclusions
• UNBIASED
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7. REVIEW TOOLS
• Advisory group (critiques
protocol)
• Good library and librarian
• Printers, photocopiers etc
• Review group (other authors)
• Internet connectivity and
telephones
• Publish timeline for the review
• Funding
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8. STEPS TO THE REVIEW
•The research question
•Assemble the team
•Protocol registration
•The Review
•Publication
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9. THE REVIEW
PROCESS
Formulate question
Comprehensively search for all
potentially relevant studies
Assessment of individual studies for
methodical quality and risk of bias
Analysis of selected studies including
meta-analysis if appropriate
Prepare a critical summary stating aims,
describing and reporting results
Identified studies assessed for inclusion
and justify all excluded studies
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10. THE QUESTION
• A good review is based on a clearly defined answerable question.
• The most relevant question are those raised by patients themselves
or students on treatment problems or dilemmas encountered during
patient care (Intervention/Therapy, Aetiology, Diagnosis,
Prognosis/Prediction)
• The question will guide:
• Inclusion criteria
• Search strategy
• Data to be extracted
•P I C O (T S)
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11. Does high first dose quinine reduce mortality among people with severe
malaria?
High first dose quinine in treating severe malaria
• Population (people with severe malaria)
• Interventions and Comparator (High first dose [loading] vs Uniform dose [no
loading] quinine)
• Outcomes
• Primary - Death,
• Secondary - Fever Clearance Time, Parasite Clearance Time, Coma Recovery Time, Adverse
Events)
• Timing (Duration of the intervention or date of publication)
• Study Design (RCT)
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12. Appropriateness of Research Design
Clinical question Study design
Diagnosis Cross-sectional
Screening Cross-sectional
Aetiology/causation Cohort or Case-Control
Therapy Randomized controlled study (RCT)
Prevention Randomized controlled study (RCT)
Rehabilitation Randomized controlled study (RCT)
Prognosis Longitudinal cohort study
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13. STUDY SEARCH
• Develop a robust search strategy (PUBMED,
MEDLINE, EMBASE, COCHRANE LIBRARY)
• PsychINFO, CINAHL, PEDro, Compedex
• Grey Literature ( Trial registries, regulatory
filings, white papers, government documents)
• Cited reference searches
• Handsearching
• Conference proceedings, Citation index
• Select studies based on agreed protocol
• Title screening & full text reviews
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14. QUESTION HIGH FIRST DOSE QUININE FOR TREATING SEVERE MALARIA
SELECTION
CRITERIA
INTERVENTIONS OUTCOMES PARTICIPANTS STUDY
Loading (High first
dose) vs
No Loading (Uniform
dose)
Death
Coma recovery time
Fever clearance time
Parasite clearance
time
Adverse events
Patients (Adults and
Children) with
Severe Malaria
Randomised
Controlled Trial
SEARCH
STRATEGY
Loading dose
High first dose
Quinine
Index and free text search for:
Malaria
Randomised
Controlled Trial
(ti:ab)
Controlled clinical
trial
Double blind
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15. TEAM DEVELOPMENT
• Initiating author
• Subject matter experts for
the question
• Discuss potential sources of
bias
• Determine the timeline for
the review
• Determine the source of
funding for the review
• Publish the protocol : open
journal, submission to an
ethics board or register with
PROSPERO (International
Prospective Register of Systematic
Reviews)
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16. TEAM ROLES AND ISSUES
Roles
• Initiator and Corresponding Author.
• All must have some form of expertise.
• Who applies search strategy and determines eligibility for inclusion?
• Who extracts? (one person)
• Who cross-checks? (another person)
• Clarification of ambiguity and resolution of differences? (All with the most
senior or the most experienced chairing)
• Who is mentoring who?
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17. RISK OF BIAS ASSESSMENT
BIAS EFFECT
SELECTION BIAS Allocation concealment, sequence generation
PERFORMANCE BIAS Blinding of participants and personnel, Other potential threats to validity
DETECTION BIAS Blinding of outcomes assessment, Other potential threats to validity
ATTRITION BIAS
REPORTING BIAS
Incomplete outcome data
Selective reporting of outcome
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18. META-ANALYSIS
Definition: a quantitative statistical analysis of several separate but
similar experiments or studies in order to test the pooled data for
statistical significance. (Miriam-Webster Dictionary)
• RevMan software
• Relative Risk (binary data)
• Weighted Mean Difference (continuous data)
• Tables (skewed or other data)
• Sub-group analysis to investigate heterogeneity.
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19. RESULT GENERATION & REPORTING
• Concise and direct
• Use of tables
• Plain language summary
• Fixed and random effect sizes
• Identifying and quantifying
heterogeneity
• Meta-analysis report if available
• Assessing publication bias
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20. RESULTS INTERPRETATION (Forest Plot)
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21. CAN SYSTEMATIC REVIEWS BE CONSIDERED
AS ORIGINAL RESEARCH? YES
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23. DECISION MAKING: WHO AND WHY?
• Patient: Understanding treatment options?
• Clinician: Developing guidelines? Deciding best practice in a changing
world with new developments daily?
• Pharmacist: Guiding drug policy in a facility. What drugs should we stock?
• Policy Maker: What would be most cost-effective with dwindling
resources or funds?
• Research funders: Which research has established evidence therefore no
need to fund? Or none or inconclusive evidence and requires funding?
Grantors often require that you have looked for evidence to support grant
applications.
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24. Covid19 and Vaccination during Pregnancy
Prasad et al NATURE COMMUNICATIONS | (2022) 13:2414 | https://doi.org/10.1038/s41467-022-30052
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25. How
thorough?
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26. Results
Overall
Effectiveness
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27. Effect on
Pregnancy
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28. Covid19 and Vaccination during Pregnancy
Interpretation of Findings
• Limitations to the Review: Methods section did not report on different
biases.
• Conclusion: mRNA covid19 vaccines are effective in pregnant women. No
greater negative effects associated with its use either on the mother, her
pregnancy or her baby.
• Implications for practice or policy in purchasing and using vaccines
especially when there is vaccine hesitancy.
• Implications for funders: no need to fund mRNA vaccine research in
pregnancy.
• Caution: Assumption that the virus does not mutate to a more or less
virulent variant.
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29. The Cochrane Collaboration
• An international network of individuals and institutions
committed to preparing, maintaining and disseminating
systematic reviews of the effects of healthcare
interventions
• Founded in Oxford, UK, in 1993
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THE COCHRANE
COLLABORATION
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31. Cochrane logo
• Systematic review in 1989, of steroids given to women
in preterm labour.
• Pooled results showed the intervention reduced the
risk (by 30% - 50%) of babies dying from complications
of immaturity.
• Thousands of deaths could have been prevented, had
the review been conducted earlier in 1972 when 1st
trial was done.
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32. Where can you get help in getting trained?
• Cochrane Nigeria
• Director: Professor Martin Meremikwu, University of Calabar
Cochrane Nigeria Email: cochranenigeria@yahoo.co.uk Tel: +234 8039733998
• Cochrane South Africa
South African Medical Research Council
Email: cochrane.africa@mrc.ac.za Tel: +27 21 938 0256/0508
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33. Any Questions?
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34. CONCLUSION
• Systematic reviews are rigorous and scientifically sound. It is now
being regarded and published as original research in reputable
journals.
• Doing a systematic review is a continuous iterative process. Evidence
is never final.
• It forms the basis of evidence based medicine and are an integral part
of improving clinical practice.
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35. REFERENCES
1. Akobeng A K. Understanding systematic reviews and meta-analysis. Archives of Diseases
in Children 2005, 845-8.
2. Sackett DL, Strauss SE, Richardson WS, et al. Evidence-based medicine: how to practice and
teach EBM. London: Churchill-Livingstone, 2000.
3. Pai M, McCulloch M, Gorman JD, et al. Systematic reviews and metaanalyses: an
illustrated, step-by-step guide. Natl Med J India 2004;17:86–95.
4. McGovern DPB. Systematic reviews. In: McGovern DPB, Valori RM, Summerskill WSM, eds.
Key topics in evidence based medicine. Oxford: BIOS Scientific Publishers, 2001:17–9.
5. McAlister FA, Clark HD, van Walraven C, et al. The medical review article revisited: has the
science improved? Ann Intern Med 1999;131:947–51.
6. Cochrane handbook for systematic reviews of interventions.
7. Prasad et al NATURE COMMUNICATIONS (2022) 13:2414 https://doi.org/10.1038/s41467-
022-30052.
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36. APPRECIATION
• African Community for Systematic Reviews and Meta-
Analyses (ACSRM) in partnership with International
Network for Advancing Science and Policy (INASP)
• Dr. Florence Nkemehule, Faculty of Pharmacy
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