IN TROD U CTION

SYSTEMATIC
TO

AND
REVIEWS
META-ANALYSES
Learning Outcomes
• An Introduction to Narrative Reviews,
Systematic Reviews and Meta-Analyses
• Overview of Steps of Conducting a
Systematic Review
• Formulating A Research Question
• When to Update a Systematic Review Topic
• Identifying Common Pitfalls in Topic
Selection
Types of Articles
When conducting a search, there are many articles you may run into
.

• Primary research articles (Why, How, What)

• Review articles
• Case studies

It is imperative to be abLe to
distinguish between these
articles !
Review Articles

“Articles that go through and

summarize the previously
conducted original research on a
topic”
Because you want Identify gaps and
Publications! factual uncertainties

WHY DO SYSTEMATIC
REVIEWS AND
META-ANALYSES?

Comprehensive and To implement the

un-biased summary current best
of existing research evidence more
rapidly
 Trial Trial B Trial C Trial D
A
1 0 0 0 patients 5 0 0 patients 100 patients 50 patients
Published: Published: Published:
Published: 2012
2002 2020 2023

INVOLVED only INVOLVED Asian, INVOLVED INVOLVED only

Asians Black and Caucasian Caucasian Asian

Randomization Randomization Randomization Randomization

BLINDING BLINDING BLINDING BLINDING

CONSORT guidelines CONSORT guidelines CONSORT guidelines CONSORT guidelines

followed: followed: followed: followed:

Drug A is Drug B is Drug B is Drug A is

better for better for better for better for
HTN HTN HTN HTN
The Evidence
Paradox

• 19,000+ RCTs published every year

• Tens of thousands of other clinical
studies
 WHY DO SYSTEMATIC REVIEWS AND
META- ANALYSIS?
"The volume of published material makes it impractical for an
individual clinician to remain up to date on a variety of common
conditions.

This is further complicated when

individual studies report
conflicting conclusions!!
 The doubling time of medical
knowledge

1950 1980 2010

2020
50 years 07 years 3.5 years 2.5
months!
 Types of Review Articles
NARRATIVE SYSTEMATIC META-
REVIEWS REVIEWS ANALYSIS
• Usually a • A focused • A subset of Systematic
broad clinical question clinical
question Reviews
• Search strategy • Well-defined search • All features of a SR
not
specified strategy are present
• Selection criteria not • Pre- • Quantitative
specified determined
selection criteria data
analysis i.e. analysis is
• No appraisal • Critical appraisal used to combine all
or grading and grading of the results from
• Conclusions based on evidence included studies into
a sample of the • Conclusions based on a single result
evidence all available evidence
examples
 Meta-
Analyses

Systematic
Reviews

All reviews
Steps of Conducting
Systematic Reviews
and Meta-AnaLyses
 STEPS TO CONDUCT A
SYSTEMATIC REVIEW
Manuscript
Qualtitative writing
Article and and
screening quantitative submitting
Running a
and data synthesis to a journal
systematic
FRAMING
literature extraction
YOUR
search
RESEARCH
QUESTION 5

4
3
2
1
 Topic
SeLection
 • Topic Selection is the single most crucial step in
any research.
• Journals want to publish topics that are interesting,
novel and clinically relevant. A good topic builds
upon the existing evidence in a meaningful way.
SeLection

You are the editor of a high-impact journal, and you receive

Topic

a
paper titled "Smoking as a Risk Factor for Lung Cancer:
A
Systematic Review and Meta-Analysis". The search strategy,
data extraction, analysis and write-up are all perfect. Would
you publish this
paper?
1) Start broad (by choosing
Choosin a specialty or a disease)
and then narrow down to
g Your a specific topic
Topic

Steps of Topic Selection

Thoroughly check your 2)

topic for novelty,
Refining
homogeneity and clinical
relevance Your
Topic
 Choosing Your Topic

1 2 3 4 5

Select your Read up Formulate

Select a Select a
area of on research
disease available treatment
interest question
treatments
 Your choice should depend
on:
• The field you may want to pursue in
the future
SeLect • An area in which a mentor may be

Your readily available to guide you

• Areas with a lot of new clinical trials

Area coming out tend to be better, e.g.

oncology vs
of surgery

Intere
st
Infectious Cardiology Radiology
Diseases
Choose a disease within your area of
interest.
• The disease of choice should be one that is being
actively researched on, e.g. COVID-19 vs smallpox
• The should have a significant
disease
burden, global heart failure

SeLect
e.g.
cardiomyopathy. vs can
Reviews takutsubo
be done on rare
diseases but prevalent diseases are preferred by

A
journals.

Disea
COVID-
19
Smallpox se
Tip: If you aren't sure which disease to choose, make a list
of 10 diseases in your area of interest. Try to complete all
the subsequent steps for all of them. You might end up
with 10
topics!
 Get an idea of the established standard of
care for your disease. Are there any new
clinical trials assessing promising treatments
? How are they better than the standard of

Read up care.
If there's no new therapy on the horizon for

on your disease that could potentially beat out

the standard of care, you've probably chosen

avaiLabLe the wrong disease.

treatmen
ts Ivermectin Remdesivir

Tip: Search for your disease on PubMed using

the
clinical trial filter.
The treatment you choose
should:
• Have at least one and preferably
multiple recently published clinical
trials on it
• Should preferably have shown good
efficacy and safety to warrant further
research on it. SeLect
a
treat
ment
 Formulate a research question
following the PICO
Framework
P POPULATION

FormuLate I INTERVENTION
resea rch
question C CONTROL

O OUTCOME OUTCOME

S STUDY
DESIGN
 A comparator The endpoint The study
The The
group which which is design that will
disease of treatment of compared
most clinical be included in
choice: choice: trials have between the your review, e.g.
COVID-19 Ivermectin compared the two drugs, e.g. randomized
intervention viral clearance, clinical trials
to, e.g. placebo time to
sustained
recovery
Our Research Question
Eff ect of Ivermectin Versus PLacebo on ALL-
Cause MortaLity in COVID-19 Patients: A
Systematic Review and Meta-AnaLysis of
Randomized ControLLed TriaLs

Tip: It isn't necessary to defi ne all aspects of PICOS for your review.
Often only P and I are defi ned. "Ivermectin for Treatment of COVID-
19: A Systematic Review and Meta-Analysis" would also be a good
topic.
Pro tip!
To make up a good title, follow the following layout

"INTERVENTION FOR
POPULATION WITH
CONDITION"
Trans Sphenoidal Resection for Patients with
Pituitary Adenoma
Refi ning Your Topic

1 2 3 4

Preliminary
Preliminary
Background search for Consult
search for
search original an
reviews articles expert
You need to learn everything theoretical
there is to know about your topic. For
example:
• What is the mechanism of action of
Ivermectin? You need to know this for
your intro.
• COVID-19 has several different Background
severities.
You might want to consider limiting search
your topic to only mild COVID-19,
but first you need to know what
mild, moderate and severe COVID-19
mean.
• You might want to include time to viral
clearance as an outcome but first you
 Look for other narrative reviews,
systematic reviews and meta-
analyses on your topic.
If you don't find a review article
PreLiminary already done on your topic, you're
good to go!
s e a r c h for
reviews Tip: Run a search using Boolean
operators on PubMed while using
the systematic review filter, e.g.
"COVID-19 AND
Ivermectin"
Before finalising your topic, it's
best to identify at least 3 or
4 studies that would definitely
be included in your review article.
Preliminary
You can go through these studies s e a r c h for
in detail to see the outcomes originaL
being assessed, the interventions
being used and the study articLes
population being considered.
 Always try to get a subject specialist
on board who preferably has prior
experience with systematic reviews
and meta-analyses.
Consult They will be the best judge of the

an clinical relevance and impact of

your topic.
expert Otherwise, the previous steps may
lead you to work on a topic
comparing two therapies for a
disease, only to find out later that
both therapies are redundant
compared to a third option.
1 2 3 4 5
Select your Select Read up on Formulate
Select a
area of a available research
treatment
interest diseas treaatments question
e

Steps of Topic SeLection

1 2 3 4
Preliminary Preliminary Consult
Background search for
search for an
search original
reviews expert
articles
Another ExampLe
Gastroenterology, Endocrinology, Oncology
Area of
Let's choose: Oncology
Interest

Colorectal Carcinoma, Renal Cell Carcinoma, Acute

Disease Lymphoblastic Leukemia
Let's choose: Acute Lymphoblastic Leukemia

Chemotherapy is the standard of care for newly

Reading up diagnosed ALL. HSCT is used in patients who
relapse.
on trials
Before HSCT, patients are given radiation
or chemotherapy.
Total Body Irradiation is a promising option in HSCT,
Treatment but may have safety concerns. Alternatives like chemo
are being considered.
Our Research Question
Total Body Irradiation Versus Chemotherapy
Conditioning in Acute LymphobLastic
Leukemia Patients Undergoing Hematopoietic
Stem CeLL TranspLant: A Systematic
Review and Meta-AnaLysis of Cohort Studies
 Learn about ALL, its presentation, risk factors,
Background
Search
treatment options. Learn about HSCT. Learn
about TBI and chemotherapy types and doses

Preliminary Look for previous review articles on this topic. Run

search for a PubMed search using "ALL AND TBI" with
review articles systematic review filter
 Try to modify your topic to make it
different from the previously published
• Canarticle.
review you modify the Population?
In case of E.g. ALL to pediatric ALL, COVID-19 to
duplication severe COVID-19, Hepatitis A to viral
Hepatitis
of topic, try • Can you modify the Intervention? E.g.
to ciprofloxacin to fluoroquinolones,
tyrosine kinase inhibitors to imatinib,
modify steroids to high dose steroids
yours to • Can you modify the Control?
• Can you modify the Outcome?
ma ke it • Can you modify the Study Design?
different
 Preliminary
Search for
PubMed search using "TBI AND ALL
Original articles AND Pediatric"

A hematologist was consulted who advised to proceed

Consult an with the topic as several centers use TBI whereas
expert others use chemo so optimal therapy remains
to be established
Updating a
Review
There's already Can you modify
the topic by No Is the topic still No Try again with a
a review done changing any clinically relevant? new topic
on your topic of PICOS?
Yes
Yes
Are there sufficient
original articles No Try again with a
Modify your published since
topic but make new topic
the latest
sure it stays systematic review?
clinically
relevant Yes
Are the newer
studies revealing No Try again with a
substantially
new topic
different or novel
findings?
Yes

The topic can

be updated.
 • As new studies are completed, the results of reviews may become out of
date and thereby provide misleading information to decision makers.
Upda tin a Revie

You can consider updating an existing systematic review if:

• The research question remains clinically relevant
w

• There are sufficient original articles published after the latest systematic
review. A general rule of thumb is at least 3 new articles.
• The newer studies report any finding that the previous SR did not
cover
g
 A Quick ExampLe
Outcomes of Catheter Ablation Of Atrial Fibrillation in Patients with
Upda tin a Revie

Hypertrophic Cardiomyopathy : A Systematic Review and Meta-Analysis

EP Europace (Impact Factor 5)
April 2016
g w
 A Quick ExampLe
Outcomes of Catheter Ablation Of Atrial Fibrillation in Patients with
Upda tin a Revie

Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis EP

Europace (Impact Factor 5)
April 2016 Are there sufficient Are the newer
w

original articles studies revealing

published since substantially
Is the topic still
the latest different or novel
clinically relevant?
systematic review? findings?

Outcomes for The new studies

The previous SR
Atrial Fibrillation in report much
included 15
HCM remain poor longer follow up so
studies.
so the topic is still outcome upto 5
Ten new studies
clinically relevant. years following
have been
published since ablation can be
then. assessed.
g
 Pitfalls in
Topic Selection
 Combining AppLes and
Oranges
Safety of systemic hormone repLacement
therapy in breast cancer survivors: a
systematic review and meta-anaLysis

Author No. Of
Randomisation Intervention Result
Name Patients

Fahlen 378 Yes Estradiol Insignificant

Conjugated
Selen 77 No Equine Insignificant
Estrogen
CONCLUSION:
Hormone RepLacement Therapy
Holmberg 442 Yes Estrogen Significant significantLy increased risk of
breast cancer recurrence.

Kenemans 3098 Yes Tibolone Significant

 Garbage In, Garbage
Out
Meta-Analysis of Randomized
6 studies with Controlled Trial of
394 patients
Aspirin for Pregnancy 9364 patients

Positive
Induced Hypertension Negative
Results Results

A Systematic Review is only as good as the studies included in it.

A Systematic Review comprising of few, small poorly done studies
is no bett er than these studies and is worse evidence compared
to a single Large-scale trial.
 The Sweet
Cardiovascular
Spot Ventricular Arrythmias after
Complications Fibrillation After Lung Transplant
After Organ Lung Transplant
Transplant

120 2 studies 20 studies

studies
This topic is This topic is This topic is
too broad! too narrow! just right!

Might be a Might be a Perfect for a

good narrative good letter to SR!
review editor
Thanks
Any questions?