This document summarizes evidence-based medicine (EBM) and its application in pediatrics. EBM involves systematically searching medical literature, critically appraising evidence, and applying results to practice. While EBM is growing in pediatrics, more adoption is still needed. The key steps of EBM are asking answerable clinical questions, searching efficiently using databases like PubMed and limiting to clinical trials, critically appraising evidence, and applying to practice. Resources like Cochrane Library provide high-quality systematic reviews and evidence syntheses to help pediatricians practice EBM.

1. Review Article
Iran J Pediatr
Sep 2010; Vol 20 (No 3), Pp: 261-268
Evidence Based Medicine in Pediatric Practice: Brief Review
Hamid-Reza Kianifar1; MD, Javad Akhondian1; MD, Mehri Najafi-Sani2, MD,
and Ramin Sadeghi*3,4, MD
1. Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, IR Iran
2. Department of Pediatric Gastroenterology, Tehran University of Medical Sciences, Tehran, IR Iran
3. Evidence based medicine committee, Mashhad University of Medical Sciences, Mashhad, IR Iran
4. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
Received: Oct 14, 2009; Final Revision: Jan 02, 2009; Accepted: Jan 18, 2010
Abstract
Practicing medicine according to the best evidence is gaining popularity in the medical
societies. Although this concept, which is usually called Evidence Based Medicine (EBM) has
been explained in many resources, it has not been addressed enough in pediatrics. In this
review, we briefly explained Evidence Based Medicine approach and its applications in
pediatrics in order to help the pediatricians to efficiently integrate EBM into their daily practice.
Iranian Journal of Pediatrics, Volume 20 (Number 2), September 2010, Pages: 261-268
Key Words: Evidence-based medicine; Child; Critical appraisal; Pediatrics
Introduction
Evidence Based Medicine (EBM) is integrating
the best available evidence in the medical
literature into the daily medical practice[1,2].
This term was first introduced by Guyatt in 1991
and consists of systematic search of the
literature for the best available evidence, critical
appraisal of the retrieved literature, applying the
results in the medical practice and finally
evaluating the efficacy of the approach[3].
Due to a large volume of published medical
literature, the task of finding the best evidence is
very time consuming and is not considered cost
effective by many. It is reported that inadequate
time is the main obstacle for incorporating the
best evidence into the daily medical practice[4,5].
In Evidence Based Medicine (EBM) practice, a
standard method is used for searching the
literature and appraising the found evidence.
This approach can significantly decrease the
time needed for incorporating the evidence into
the daily practice.
EBM has four steps which are shown in Table
1. These steps can make the final results more
reproducible compared to the traditional
practice in medicine and actually this is the main
difference between these two approaches.
Applying EBM in pediatrics is growing and the
pediatricians are getting more involved with this
concept, however this figure is far from
perfect[6,7]. There are several resources
(including web-based medical literature) for
EBM practice in pediatrics which we explain in
* Corresponding Author;
Address: Nuclear Medicine Research Center, Imam Reza Hospital, Ebn Sina Street. Mashhad, IR Iran
E-mail: sadeghir@mums.ac.ir
© 2010 by Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, All rights reserved

2. 262 EBM in Pediatric Pr actice; HR Kianifar, et al
Table 1: Steps of Evidence Based Medicine practice
Step I: Asking an answerable question
Step II: Searching for the best evidence
Step III: Critical appraisal of the found literature
Step IV: Applying evidence in the daily practice
brief in this review. We also briefly reviewed the
steps of EBM. The main focus of our review
would be clinical trials.
1) Asking an answerable question (PICO
approach)
The cornerstone of EBM is framing an
answerable question. If this question is not
structured well, the other steps will not be
successful. Having this fact in mind, especial
attention should be placed in this step[8,9].
Asking an answerable question is putting our
clinical question in a frame which can be used in
the search engines in a simple manner.
Classically the clinical question is divided into
four parts: 1- Patients or Population which is
referred to the specific group the patient or
population belong to. 2- Intervention which is
the kind of treatment or procedure we want to
know its efficacy. 3- Comparison which is the
standard treatment for comparing the effect of
Intervention. 4- Outcome which is the intended
outcome we expected to have by our interven-tion.
"PICO" is the acronym for this 4 part
question which consists of the first letters of
Patients, Intervention, Comparison and
Outcome.
Example:
Assume that you are working in a general
hospital as a pediatrician. A 2.5 year old boy
presented with acute non-bloody diarrhea. You
want to know if probiotics such as Lactobacilius
species are effective in decreasing the duration
of diarrhea compared to oral re-hydration
treatments (ORT).
The PICO format question of this clinical
scenario is depicted in Table 2. It is
recommended to structure the final question in a
single sentence.
2) Searching for the best evidence
There are several resources (mostly web-based)
which can be very effective in searching for the
best available evidence. An efficient search
strategy is indispensable for pediatricians to
save time and energy. It is recommended by
Haynes to categorize the medical resources
according to a hierarchy[10,11].
This hierarchy from bottom to top consists of
"Studies", "Syntheses", "Synopses", "Summaries",
and "Systems" (Fig. 1). This is usually called "5S"
hierarchy. When one moves from "studies"
towards "Systems", the quantity of the evidence
would decrease and the quality would increase.
Fig. 1: The hierarchy of evidence according to Haynes RB. (Reproduced with permission from the
publisher)[10]

3. Iran J Pediatr; Vol 20 (No 3); Sep 2010 263
Table 2: PICO question of the patient
Patient or
Population A 2.5 year old boy with acute non-bloody diarrhea
Intervention Probiotic therapy with Lactobacillus species
Comparison Oral Re-hydration Therapy (ORT)
Outcome Decreased duration of diarrhea
Question
In a 2.5 year old boy with non-bloody diarrhea, how effective is probiotic
therapy with Lactobacillus species compared to Oral Re-hydration Therapy
(ORT) for decreasing the duration of diarrhea?
Individual "Studies" are at the bottom of
the hierarchy. Searching in this field is
time-consuming and needs critical appraisal of
retrieved articles. Several databases regularly
index the individual studies. The most
famous databases are Medline's pubmed
(www.ncbi.nlm.nih.gov/pubmed), SCOPUS
(www.scopus.com), and ISI web of knowledge
(www.isiknowledge.com). Only Pubmed is freely
available online. For academic pediatricians, the
other two databases are also available through
Athens system.
For searching these databases, the PICO
question should be structured with Boolean
operators. For example the PICO-based search of
the example mentioned above would be
something as follows: (Child OR Toddler OR
Pediatric) AND (Diarrhea) AND (Probiotic OR
Lactobacillus) AND (Duration OR frequency).
This search yielded 102 articles in Pubmed on
20 Sep 2009, which shows that many studies are
available in this regard. However reading this
large amount of articles is very time-consuming
and the quality if each article is not apparent
either.
An easy way to decrease the amount of
literature is using the limit section of Pubmed.
For example limiting the above-mentioned
search to "clinical trials" would yield only 59
studies. Another useful tip in searching is
"Clinical Queries" section of Pubmed services.
Using this service for our search yielded 57
studies. As is obvious, the number of studies is
still large.
Complete explanation of searching in the
medical databases is beyond the scope of this
review. Readers can consult several articles on
this topic[12-15].
"Syntheses" are in the next level of evidence
hierarchy. This level contains systematic reviews
of special medical topics. Systematic review is a
kind of review which systematically searches for
all primary studies considering a specific clinical
scenario, appraises, and summarizes them. Meta-analysis
is a kind of systematic review which
quantitatively summarizes and analyses all
relevant studies[8]. Although databases such as
Medline and SCOPUS index systematic reviews,
the most efficient way to find these articles is
databases dedicated to systematic reviews. The
Cochrane library (www.cochrane.org) is the
most famous in this regard.
The Cochrane Library has three sections. The
first section is Cochrane Database of Systematic
Reviews (CDSR). This part indexes the
systematic reviews and meta-analyses which are
prepared by Cochrane groups themselves. CDSR
is the gold standard for systematic reviews. The
second section is Database of Abstracts of
Reviews of Effects (DARE). This is the database
for the other systematic reviews and meta-analyses
published in other journals. Systematic
reviews in DARE need critical appraisal since the
quality of them is not assured completely by
Cochrane library. The third is Cochrane Central
Register of Controlled Trials (CENTRAL). This is
an international collection of Randomized
Controlled Trials (RCT). The Cochrane library is
most efficient for treatment or intervention of
clinical questions.
"Synopses" are the next level of evidence
hierarchy. These are synopses of original studies
and systematic reviews which usually contain a
commentary by an expert on the study results.
Examples of this level of resources are
DARE section of Cochrane library, ACP Journal

4. 264 EBM in Pediatric Pr actice; HR Kianifar, et al
Club (www.acpjc.org), and bandolier
(www.medicine.ox.ac.uk/bandolier/index.html).
In contrast to the previous medical resources,
"Summaries" gather information regarding
several aspects of a clinical question and
summarize "synopses", "syntheses", and
"studies" on a health condition. "Summaries"
usually consider all management options which
can be found in the literature. The best examples
of "summaries" are clinical guidelines.
www.guidelines.gov is a freely available
website which provides numerous clinical
guidelines. NHS clinical knowledge summaries
(www.cks.nhs.uk/home) and EBM textbooks
[such as uptodate (www.uptodate.com)] are
other examples in this regard.
"Systems" are on the top of the evidence
hierarchy. A 'System" would integrate and
summarize all evidence about a clinical scenario
and automatically link a specific patient’s
condition to the relevant information. For more
details, the reader can consult Haynes article on
this topic[10].
Where to find the best evidence
When searching for the best available evidence,
one should search the top of the hierarchy first
and in case of unsuccessful search, should move
toward the bottom. This approach is very time
and cost saving. If you are not familiar enough
with resources mentioned above, several
evidence based "federated search engines" are
available online[10]. Two examples of these
search engines are TRIP database
(www.tripdatabase.com) and SUMsearch
(http://sumsearch.uthscsa.edu). Table 3 shows
some useful websites which provide evidence
based resources.
If you were forced to search among individual
studies (due to lack of resources on the top of
the hierarchy), you will need to know how to
appraise the individual studies and systematic
reviews. The next part of this review briefly
explains this issue.
3) Critical appraisal of the literature
Published studies are not always of high quality.
It is recommended to read the full text of the
found articles since the abstracts can be
misleading and sometimes do not contain
necessary data[16,17]. For each article a level of
evidence can be assigned and only studies with
highest level of evidence should be considered
for application in our clinical situation[12,13,18].
Oxford center for evidence based medicine has
issued tables for levels of evidence of various
study designs[19]. The levels of evidence for
studies of therapeutic design are available in
Table 4.
Table 3: Some free useful online resources for evidence based medicine
Name of the site Internet address Type of
resource
Bandolier www.medicine.ox.ac.uk/bandolier/index.html Synopsis
National guideline clearinghouse www.guidelines.gov Summary
Tripdatabase www.tripdatabase.com Search engine
Sumsearch http://sumsearch.uthscsa.edu Search engine
Cincinnati Children's Hospital
http://www.cincinnatichildrens.org/svc/alpha/h/he
Medical Center
alth-policy/ev-based/default.htm Summary
University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site
www.med.umich.edu/pediatrics/ebm/ Summary
PedsCCM: The Pediatric Critical
Care Website http://pedsccm.org/EBJournal_Club_intro.php Synopsis
Resources for Practicing Evidence-
Based Medicine www.pedsccm.org/EBJournal_Club_intro.php Summary
National library guideline www.library.nhs.uk/GUIDELINESFINDER/ Summary
Pubmed clinical queries www.ncbi.nlm.nih.gov/corehtml/query/static/clinic
al.shtml Search engine
The NHS Clinical Knowledge
Summaries www.cks.nhs.uk/home Summary

5. Iran J Pediatr; Vol 20 (No 3); Sep 2010 265
Table 4: Oxford levels of evidence for therapeutic study designs#
Level Therapy/Prevention, Etiology/Harm
1a Systematic review (SR) (with homogeneity*) of Randomized Controlled Trials (RCTs)
1b Individual RCT (with narrow Confidence Interval)
1c All or none†
2a SR (with homogeneity*) of cohort studies
2b Individual cohort study (including low quality RCT; e.g., <80% follow-up)
2c "Outcomes" Research; Ecological studies
3a SR (with homogeneity*) of case-control studies
3b Individual Case-Control Study
4 Case-series (and poor quality cohort and case-control studies‡)
5 Expert opinion without explicit critical appraisal, or based on physiology, bench research
or "first principles"
# Reproduced with permission from Oxford levels of evidence for therapeutic study designs[19 ]
* Homogeneity of a systematic review means that it is free of worrisome variations (heterogeneity) in the directions
and degrees of results between individual studies. Not all systematic reviews with statistically significant
heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. Studies
displaying worrisome heterogeneity should be tagged with a "-" at the end of their designated level.
† Met when all patients died before the Rx became available, but some now survive on it; or when some patients died
before the Rx became available, but none now die on it.
‡ Poor quality cohort study means one that failed to clearly define comparison groups and/or failed to measure
exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed
individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a
sufficiently long and complete follow-up of patients. By poor quality case-control study we mean one that failed to
clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably
blinded), objective way in both cases and controls and/or failed to identify or appropriately control known
confounders.
While critically appraising an individual study,
two issues are to be addressed: 1- Are the results
valid? 2- What are the results and are the
findings important?
By answering these two fundamental
questions, each study can be assigned to a
specific level of evidence. Several checklists are
available online for this purpose[20,21].
Are the results valid?
The design of each study should be carefully
scrutinized and if met the standards can be
included in our every day practice. Several
questions should be answered in this regard
which can be found in Table 5. When the study
design is proved to be of high quality, the next
step would be to find out what actually the
results are.
What are the results and are the findings
important?
For each therapeutic study, several measures of
effect size are available which are mentioned in
the results section of the studies or can be
calculated easily (A free software is available for
this task[22]). These include: P-values, Relative
Risk (RR), Relative Risk Reduction (RRR),
Absolute Risk Reduction (ARR), Number Needed
to Treat (NNT) and their Confidence Interval
(CI). Table 6 shows the results of a putative
study in a 2×2 format which we use for
expressing the formulas.
Relative Risk (RR): The relative risk means
how likely it is that an event will be seen in the
treatment group compared to the control group
(RR=b/(a+b)/d/(c+d)). An RR of 1 means no
therapeutic effect. When the treatment is
effective RR would be <1.
Absolute Risk Reduction (ARR): It is the
absolute difference in the rates of events
between the treatment and control groups
(ARR=d/(c+d)-b/(a+b)). An ARR of 0 means that
the treatment has no effect.
Relative Risk Reduction (RRR): This is the
most commonly reported measure of treatment
effects (RRR=1-RR). It is the measure of
reduction in the rate of the outcome in the
treatment group compared to the control group.

6. 266 EBM in Pediatric Pr actice; HR Kianifar, et al
Table 5: Questions to be answered for assuring validity of the results of a RCT*
Was the assignment of patients to treatments randomised?
What is best? Where do I find the information?
Centralised computer randomisation is ideal and
often used in multi-centred trials. Smaller trials may
use an independent person (e.g, the hospital
pharmacy) to “police” the randomization.
The Methods should tell you how patients were
allocated to groups and whether or not
randomisation was concealed.
Were the groups similar at the start of the trial?
What is best? Where do I find the information?
If the randomisation process worked (that is,
achieved comparable groups) the groups should be
similar. The more similar the groups the better it is.
There should be some indication of whether
differences between groups are statistically
significant (ie P values).
The Results should have a table of "Baseline
Characteristics" comparing the randomized groups
on a number of variables that could affect the
outcome (ie age, risk factors, etc). If not, there may
be a description of group similarity in the first
paragraphs of the Results section.
Aside from the allocated treatment, were groups treated equally?
What is best? Where do I find the information?
Apart from the intervention the patients in the
different groups should be treated the same, eg
additional treatments or tests.
Look in the Methods section for the follow-up
schedule, and permitted additional treatments, etc
and in Results for actual use.
Were all patients who entered the trial accounted for? – and were they analyzed in the groups to
which they were randomized?
What is best? Where do I find the information?
Losses to follow-up should be minimal – preferably
less than 20%. However, if few patients have the
outcome of interest, then even small losses to follow-up
can bias the results. Patients should also be
analyzed in the groups to which they were
randomized – ‘intention-to-treat analysis’.
The Results section should say how many patients
were randomized (eg Baseline Characteristics table)
and how many patients were actually included in the
analysis. You will need to read the results section to
clarify the number and reason for losses to follow-up.
Were measures objective or were the patients and clinicians kept “blind” to which treatment was
being received?
What is best? Where do I find the information?
It is ideal if the study is ‘double-blinded’ – that is,
both patients and investigators are unaware of
treatment allocation. If the outcome is objective (eg
death) then blinding is less critical. If the outcome is
subjective (eg symptoms or function) then blinding of
the outcome assessor is critical.
First, look in the Methods section to see if there is
some mention of masking of treatments, eg placebos
with the same appearance or sham therapy. Second,
the Methods section should describe how the
outcome was assessed and whether the assessor/s
were aware of the patients' treatment.
* Reproduced with permission from Critical appraisal for therapy articles [20]
Number Needed to Treat (NNT): This is the
number of patients one needs to treat to prevent
one bad outcome or cause one additional good
outcome (NNT=1/ARR). The NNT of 1 means
that the treatment is effective in all patients.
Treatment is less effective for NNT>1.
Confidence Interval: Providing the P-values,
and the above-mentioned indices is not sufficient
enough for interpretation. P-value is only a point
probability that an outcome has occurred by
chance and it does not provide any clue to the
magnitude of effect. One solution to this problem
is confidence intervals (CI) for each effect size
index. When the confidence interval range is
wide, usually the sample size is small and vice
versa[23]. CI can be calculated by a CAT maker
software which is freely available online[22]. Full
explanation of this issue is beyond the scope of
this article. The readers can refer to Cohen J
articles for consultation[24,25].
4) How to apply the best found evidence to
our patients.
The final question in evidence based medicine
would be “Are the results helpful for my
particular patients?” This is a very complicated

7. Iran J Pediatr; Vol 20 (No 3); Sep 2010 267
Table 6: Results of a putative study in a 2×2 format
Number of events
(cured)
Number of patients without
event (not cured)
Treatment Group a b
Control Group c d
matter which is intertwined with socio-economical,
religious, ethical, and many other
issues[26]. For example, using probiotics for
treatment of diarrhea cannot be easily
performed in Iran due to high cost[27]. Pain is a
very important factor to be considered when
treating pediatric patients. Usually less painful
procedures (such as oral treatments) are
preferred for children [28]. Full explanation of this
issue is available elsewhere in the literature[29].
Acknowledgment
The authors wish to thank Oxford Centre for
Evidence-Based Medicine and BMJ Publishing
Group Ltd for granting permission to use their
products.
Conflict of Interest: None
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