Strengthening Medical Laboratory Research:

The Meta-analysis Approach

Idris Nasir Abdullahi, Ph.D., FIBMS (UK)

Roles of Medical Laboratory Scientists

❖Laboratory investigations for:

❑Diagnosis
❑Assessment of prognosis
❑Treatment evaluation
❑Research, Innovation and
Development
Medical Laboratory Research

❖Studies biological processes of;

✓ human health
✓ disease, and
✓ the mechanisms that underlie them

❖ Ultimate goal
✓improve human health and well-being
✓understand and prevent diseases
✓developing new treatments, and enhancing healthcare
Systematic
Review and
Meta-
analysis
Research Related to Laboratory Analyses

❖Epidemiological ❖Clinical
❑Cross-sectional ❑Surgery
❑Transplantation
❖Preclinical ❑Gene therapy
❑Anatomy
❑Physiology ❖Genomics
❑Pharmacology ❑NGS
❑Microbiology ❑Metagenomics
❑Pathology ❖Translational
❑Biochemistry etc. ❑Vaccinology
❑Phage therapy
Era of Data
Science

All data from these research can be summarized by meta-analysis!

 Both are Interrelated

No meta-analysis without a systematic review

What’s a Systematic Review?

“A review of the evidence on a clearly formulated

question that uses systematic and explicit methods to
identify, select and critically appraise relevant primary
research, and to extract and analyze data from the
studies included in the review.”

Source: Cochrane Collaboration

Rapid growth

PubMed search
Up to 15/04/2025:
Systematic review 3,89,512 hits
Meta-analysis >400,000 hits

Up to 1/1/1990:
Systematic review 300,994 hits
Meta-analysis 845
 Steps of a systematic review

1 Formulate research question

2 Develop review protocol

3 Initiate search strategy

4 Apply inclusion /exclusion criteria

5 Quality appraisal

6 Data abstraction

7 Analysis

8 Interpret findings
 Systematic Review in context
Traditional Systematic Meta-
review Review analysis
Author An A team A team
individual
Search Individual Based on a Based on a
strategy protocol protocol
Summary Author’s Qualitative Quantitative
Conclusion judgement from
Statistical
inference
 Systematic review

❖Driven by evidence-based medicine and Cochrane

collaboration

❖Advantages:
✓Reduces bias
✓Replicable
✓Resolves controversy between conflicting findings
✓Provides reliable basis for decision making
Use of meta-analysis as a prelude to clinical trials

Define pre-trial expected effect sizes

❖Sample size estimation
❖Determine effect estimates in key subgroups (e.g.
based on gender, race/ethnicity or age)
❖Identify sources of heterogeneity in prior studies
❖Addressing these sources in design phase of new
trial
Use of meta-analysis in study designs
that are not clinical trials
1. Observational studies
(e.g. case control, cohorts, cross-sectional
prevalence studies, etc.)

2. Studies evaluating diagnostic tests

(sensitivity, specificity, predictive value)

3. “IPD” = individual patient data studies

4. Qualitative studies (meta-ethnography)

Resources required for systematic reviewing

❖Can be time-consuming

❖Team science (to reduce bias)

❖Bibliographic software (e.g., EndNote)

❖Statistical software (if appropriate)

Formulate research question
FINER criteria for research question

Feasible
Interesting
Novel
Ethical
Relevant
 Components of a research question (PICOT)
Patient:
Disease or condition
Stage, severity
Demographic characteristics (age, gender, etc.)
Intervention (or “Exposure”):
Type of intervention or exposure
Dose, duration, timing, route, etc.
Comparison:
Absence of risk or treatment
Placebo or alternative therapy
Outcome:
Risk or protective
Dichotomous or continuous
Type: mortality, morbidity, quality of life, etc.
Studies Suitable for Metaanalysis

❖RCTs

❖Cohort

❖Case-control

❖Cross-sectional
 Formulation of an etiology question

Exposure Outcome

Is smoking a risk factor for lung cancer?

Patient Exposure

Are people who smoke regularly at a greater risk of developing

lung cancer as compared to those who do not smoke?

Outcome Comparison
+ cohort & case-control studies
Develop review protocol
Protocol
❖Background
❖Objectives
❖Pre-determined selection criteria
❖Planned search strategy
❖Proposed method of synthesis of findings

Establishment of an advisory group

Register the protocol with PROSPERO

Search Strategy
Where to locate studies

PubMed
Web of Science
EMBASE
Scopus
Hinari
Google Scholar
 Additional sources to identify
studies for Metaanalysis
❖ Reference lists of retrieved articles
❖ Manual searching of relevant publications
❖ Experts in the field
❖ Corresponding or first authors of published
studies identified for the systematic review
Example of PubMed search
Title: Interaction between 5-HTTLPR genotype, stressful life
events and depression

Search terms:
Life stress
Life event
Depression
Depress
Serotonin transporter
5-HTTLPR
Interaction
Moderation
Apply inclusion /exclusion
criteria
Inclusion/exclusion criteria
P - Population

I - Intervention

C - Comparison (if necessary)

O - Outcome

T - Type of study (if necessary)

Exclusion criteria
❖Keep log of excluded studies

❖Note reasons for exclusion

❖Have eligibility checked by more than one

reviewer

❖Develop strategy to resolve disagreements

Meta-analysis Statistics
Meta-analysis Software

❖Comprehensive Metaanalysis

❖Cochrane Review Manager (RevMan)

❖OpenMeta [Analyst]

❖NetMetaXL

❖Stata
Synthesizing the Data
 Forest Plot
Meta Analysis
Study name Statistics for each study Event rate and 95% CI
Event Lower Upper
rate limit limit Z-Value p-Value
Peng et al (2019) 0.944 0.495 0.997 1.947 0.052
Rebelo et al (2018) 0.082 0.031 0.198 -4.639 0.000
Pulss et al (2017) 0.001 0.000 0.004 -9.932 0.000
Lengliz et al (2021) 0.057 0.014 0.202 -3.850 0.000
Ghazali et al (2020) 0.004 0.001 0.018 -7.639 0.000
Menthil-Murugan et al (2019)0.011 0.001 0.151 -3.172 0.002
De coster et al (2022) 0.000 0.000 0.005 -5.705 0.000
Yousfi et al (2016) 0.023 0.009 0.060 -7.400 0.000
Atterby et al (2019) 0.003 0.001 0.013 -8.029 0.000
Budel et al (2020) 0.032 0.008 0.120 -4.732 0.000
Milenkov et al (2021) 0.002 0.000 0.014 -6.190 0.000
Zou et al (2021) 0.049 0.036 0.064 -19.462 0.000
Zurfluh et al (2015) 0.001 0.000 0.007 -6.986 0.000
Chen et al (2022) 0.157 0.133 0.185 -16.835 0.000
Shen et al (2018) 0.011 0.008 0.015 -29.251 0.000
Mahmoodi et al (2020) 0.007 0.002 0.021 -8.558 0.000
Al-Mir et al (2021) 0.083 0.040 0.165 -6.074 0.000
Li et al (2024) 0.043 0.019 0.091 -7.462 0.000
Yen et al (2022) 0.004 0.002 0.010 -12.186 0.000
0.016 0.008 0.035 -10.313 0.000
-1.00 -0.50 0.00 0.50 1.00

Favours A Favours B

Pooled prevalence of CARBR E. coli in healthy humans,

Meta Analysis

pets, and livestock was 1.6% (95% CI, 0.8%-3.5%)

Random effects meta-analysis of studies of nitrogen dioxide
exposure and new-onset asthma in children.
Phylogenomic analysis of 50 publicly available COLR and CARBR- E. coli
mapped against the reference strain, E. coli str. K-12 substr. MG1655.
Geographical locations with cholera cases and their transmission route

Legend
Few imported cases (< 20 cases)

Moderate cases (20-100 cases)

High cases (5000-25000 cases)

High cases (10000-100000 cases)

Bidirectional transmission
Unidirectional transmission
Is there heterogeneity?

Yes

Deal with
heterogeneity?
(e.g. subgroup
analysis)
 Sub-group analyses: Influence of Year of Studies on
Heterogeneity
Category Temporal No. of Pooled Heterogeneit Cochrane P OR (95% CI) P value
trend studies prevalence y Cochrane Q value
pooled (%)
VANR-E. 2005-2010 8 5 162.2 <0.0001 1
faecium

2011-2015 9 1.6 14.2 0.077 0.11 (0.08-0.17) <0.0001

2016-2020 14 1.5 243.8 <0.0001 0.21 (0.21-0.37) <0.0001

2021-2024 5 0.7 31.5 <0.0001 0.12 (0.07-0.19) <0.0001

VANR-E. 2005-2010 8 1.3 8.8 0.270 1

faecalis

2011-2015 9 0.5 10.1 0.258 0.25 (0.11-0.56) 0.0008

2016-2020 14 0.8 81.3 <0.0001 1.05 (0.58-1.89) 0.8767

2021-2024 5 0.7 9.5 0.049 0.77 (0.36-1.64) 0.0112

Interpret findings
 Issues to consider
❖Publication bias
❖Search bias
✓ Language
✓ Geographical scope
Publication Bias
❖Arises from including studies which show positive results
while studies with non-significant or negative results are
least included
❖The most used method to examine publication bias is the
funnel plot
Egger’s test
Interpretation of results

❖Strength of the evidence

❖Explanations of effectiveness
❖Applicability
❖Trade-offs between benefits and harms
❖Implications for practice
…Interpreting the finding

❖The findings from the evidence synthesis need to be

discussed and put into context.

❖The quality and heterogeneity of the included studies

should be addressed.

❖The applicability of the findings should be mentioned.

❖For any recommendation generated from a systematic

review, the strengths and weaknesses of evidence
should be highlighted.
Examples of Bioinformatics-based Meta-
analysis!!!

https://pmc.ncbi.nlm.nih.gov/articles/PMC10818522/

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