Evidence-Based Medicine

Highlights On
Evidence-Based Medicine
By
Prof. Tawfik A. M. Khoja
MBBS, DPHC, FRCGP, FFPH, FRCP (UK)
Family and Community Medicine Consultant (Primary Health Care)
Director General, Executive Board for HMC/GCC
Member of the American Academy of Family Medicine
Member of the American Collage of Executive physicians
Member of the Board of Trustees of IUHPE
Member of the Advisory Board of WAPS
Chairperson of the Saudi Society for Evidence Based Health Care
Dr. Noha A. Dashash
MBBS,DPHC,ABFM,SBFM
Consultant Family Physician
Deputy Director of Primary Health Care, Jeddah Governorate
Supervisor of the EBM Jeddah Working Group
Member of the Board of Directors,
Saudi Society for Evidence Based Health Care
Trainer, Postgraduate Joint Program of Family & Community Medicine, Jeddah
Dr. Lubna A. Al-Ansary
MBBS, MSc, FRCGP
Associate Professor and Consultant,
Deputy Chairperson of the Saudi Society for Evidence Based Health Care
Member, Executive Council, National and Gulf EBM Committee
Member, National Family Safety Program
Member, Executive Council, National Society for Human Rights
Dept of Family and Community Medicine,
College of Medicine, King Saud University, Riyadh, Suadi Arabia
Dr. Abdullah Alkhenizan
MBBS, CCFP, ABHPM, DCEpid
Consultant Family Medicine
Assistant Clinical Professor
Secretary General of the Saudi Society for Evidence Based Health Care
Member, of the National and Gulf Center for EBM
Sixth Edition
Rabi’II 1431H / April 2010G
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© Excutive Board of the Health Ministers› Council, 2010
King Fahd National Library Cataloging-in-publication Data
Khoja, Tawfik Ahmed
Highlights on evidence based medicine./ Tawfik Ahmed Khoja;
Noha Ahmed Dashash-6 - Riyadh, 2010
89 P. ; 24 Cm.
ISBN: 603-90062-3-9
1- Medicine 2- Evidence Based Medicine - Saudi Arabia
I- Noha Ahmed Dashash (co.author)
II- Title
616.75 dc 1430/1040
L.D. No. 1430/1040
ISBN 603-90062-3-9
Executive Board
Of the
Health Ministers’ Council
For Cooperation Council States
Tel.: 00966 1 4885262 - Fax: 00966 1 4885266
P.O.box 7431 Riyadh 11462
E-mail: sgh@sgh.org.sa
www.sgh.org.sa
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Index
Contents
Page No.
- Preface to the Sixth Edition................................................ 7
- Introduction.................................................................................. 9
- What is Evidence-Based Medicine.................................... 11
- Why is Evidence-Based Medicine...................................... 12
- Forms of evidence..................................................................... 13
- Hierarchy of evidence............................................................... 14
- Strength of recommendation taxonomy.............................. 15
- Steps of EBM............................................................................... 20
- Asking answerable questions................................................ 20
- Clinical Scenario........................................................................ 20
- Searching for the best evidence............................................ 20
- Critically appraising the evidence........................................ 21
- Critical appraisal........................................................................ 21
- Applying the evidence to individual patient care............. 22
- Evaluating the process............................................................. 22
- The Logic Behind EBM.............................................................. 22
- Analyzing Information............................................................... 23
- Advantages and disadvantages in practicing EBM......... 23
- Suggestive Guideline................................................................ 25
- At the Central Level................................................................... 25
- At the Peripheral......................................................................... 25
- Implementation of the strategies........................................... 26
- Glossary of Terms in EBM....................................................... 27
- Evidence-Based Medicine Resources ................................ 53
- References for further readings............................................. 59
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Preface to the Sixth Edition
Praise be to Allah and Peace and Blessings on the
most honorable of the Messengers and the last of
the prophets Mohammad, Peace be Upon Him.
Six years ago, when we issued the first edition of
the booklet (Highlights on Evidence-based Medicine)
it was meant to be an introductory book to the concept
of Evidence-based Medicine that is why we were very keen to make it
simple, palatable and in both Arabic and English language for the readers
to whom the subject is still new or unknown. The booklet surpassed all
expectations and the first as well as the second editions were gone very
fast, although produced in large quantity.
The great demand for the second edition was the real motive for us to
update it and carry on the message of dissemination of the concept of
EBM, and evidence based healthcare as well as evidence-based public
health, not only in the Kingdom of Saudi Arabia but also in the Gulf region,
Arab Region and EMRO.
In this edition you will fine topics like hierarchy of evidence and the SORT
(Strength of Recommendations Taxonomy) supported with the concepts
of how to assess quality of evidence and how to assess consistency of
evidence access studies. Steps of EBM were presented in an elaborate
but simple and clear way.
Despite these additions, the booklet is still retaining its simplicity,
clearness as well as its informativeness. This makes it – we hope – more
readable in the EBM and EBHC field.
I hope that this booklet will realize the objective for which it has been
produced, i.e. acting as a sort of an appetizer for those who want to know
more about this discipline, and helping in dissemination of evidencebased
practices in all helathcare fields. and medical / health education as
well as continuous professional development.
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I would like to express my gratitude and appreciation to my colleagues
Dr.Noha A. Dashash, Dr. Lubna A. Al-Ansary and Dr. Abdullah Alkhenizan
for the dedicated efforts and the valuable assistance in preparing this
booklet.
I realize that our vision for practising EBM and EBHC has transformed
from dream to reality, hoping that we could fulfill our mission, and
could offer a handy reference for everybody in the field. to build up the
Evidence-based public health culture.
On the other hand, we hope that the booklet will inspire health workers
in general and the healthcare authorities in particular to disseminate the
concept and implement it is all healthcare facilities.
I do pray to Almighty Allah, the Lord of Universe to crown all
our efforts with rightedness and success.
Prof. Tawfik A M Khoja
MBBS,DPHC, FRCGP,FFPH, FRCP(UK)
Family and Community Medicine Consultant (Primary Health Care)
Director General Executive Board, HMC/GCC
Chairperson of the Saudi Society for Evidence Based Health Care
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EVIDENCE-BASED MEDICINE
Introduction
t is worth to mention that practicing according to the results of clinical studies
and experiments is not a new concept in clinical practice. Ibn Al-Razi (Rhazes
865-925) described the best clinical practice as: “the practice that has been
agreed up on by practitioners and supported by experiments”. In addition he
was the first scientist to recognize the need for a comparison group in clinical
studies. Ibn sina (Avicenna 981-1037) listed several requirements for studies
evaluating new medications. These principles include the need for the drug to
be tested on a well defined disease, the effect of the drug must be seen to occur
constantly in many cases, and the study must be done on humans, for testing a
drug on a lion or a horse might not prove anything about its effect on humans.
All these principles are still valid in the era of evidence based medicine. In
1992 a group of researchers from McMaster University started to use the term
“Evidence-Based Medicine”. They wrote a series of articles in collaboration
with the Journal of The American Medical Association (JAMA) where they
established the principles of the concept of evidence based medicine.
Evidence-based medicine (EBM) is a relatively new approach to the teaching
and practice of medicine. Historically, physicians› clinical decision-making was
based on the knowledge received during their medical training and experiences
gained through individual patient encounters i.e. opinion-based.
Evolution of epidemiology, and subsequently clinical epidemiology, resulted
in methods that allowed the objective critique of therapies used in clinical
practice. Epidemiologic principles were applied to problems encountered
in clinical medicine and an increasing number of clinical trials and medical
journals emerged.
The past two decades have witnessed an acceleration of the information
explosion and with it the volume of medical publications. The importance of
keeping updated is emphasized even more, given that the half life of medical
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knowledge is extremely short. Clinicians face the difficult task of keeping
track of a large amount of new and potentially important information. Although
every one knows this, reports continue to demonstrate that the time devoted for
reading among physicians can not by any means be enough to fill this gap.
On the other hand the Continuing Medical Education (CME), as a means of
keeping physicians up-to-date was growing, moving from lectures by experts
to small group learning, tutorials and interactive feedback sessions. However
studies have shown that CME had limited impact on modifying physician
performance. A legitimate concern is that many physicians will fail to recognize
new and necessary changes in practice and patient care will suffer as doctors
become outdated and their performance deteriorates over time.
Clinicians and health care workers face clinical questions on daily basis,
regarding patient care. These could be about the interpretation of diagnostic
tests, harm associated with treatments they provide, prognosis of a disease in
a specific patient and the effectiveness of a preventive or therapeutic agent.
Using traditional methods they get less than a third of the answers. Clinicians
need simple yet scientifically sound ways to get answers to there questions.
Existing research has many flaws. Archie Cochrane, the late British
epidemiologist, estimated that only 15 to 20% of medical practice is based
on scientific, statistically sound research. Much of our medical practice is
based on either experiences of seniors or research of unknown validity. In
fact, most of what we practice is based on ‘logic’ coming from knowing human
biology, physiology and pathophysiology. For example, we treat arrhythmias
leading to death, after coronary events in order to prevent death. We patch
eyes of patients with corneal abrasions to protect them and enhance healing.
However, when properly designed studies were performed looking specifically
at important outcomes that matter to patients, it turned out that our logic didn’t
really help patients. In the first situation, randomised controlled trials showed
that treating arrhythmia improved ECG’s but in increased death. Similarly, in the
second case, patients with their eyes patched had longer healing durations than
those treated conservatively. Studies looking at pathophysiologic outcomes
are known as DOE’s (Disease Oriented Evidence), whereas studies looking at
important clinical outcomes are known as POEM’s (Patient Oriented Evidence
that Matters).
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The practice of evidence-based medicine requires an understanding of simple
and basic clinical epidemiology, as well as excellent communication skills,
patience, and a commitment to provide the patient with the knowledge required
to make informed choices. It is important that physicians become familiar with
the meaning of EBM and its role in influencing the provision of care and use of
health resources.
What is Evidence-Based Medicine
Evidence-based medicine has been defined by David Sackett, as «the
conscientious, explicit, and judicious use of current best evidence in making
decisions about the care of individual patients», to aid the delivery of optimum
clinical care to patients.
Evidence-based medicine can be practiced by the integration of individual
clinical expertise with the best available clinical evidence from systematic
research and patient values and circumstances.
Simply put, EBM means applying the best information to manage patient
problems, diagnosis, prognosis, harm, patient safety …etc. It is based on the
assumption that: 1) medical literature, and thus useful information about patient
care, is growing at an alarming rate; and 2) in order to provide best care for
patients, doctors must be able to continuously upgrade their knowledge, i.e.
by accessing, appraising, interpreting and using medical literature in a timely
fashion.
Best
Clinical
Evidence
Clinical
Expertise
Patient’s
Values &
Circumstances
Fig. 1. Practice of Evidence Based Medicine
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What is the problem Why is there a need for EBM Don›t we already practice
medicine fairly uniformly based on a common fund of evidence.
Bottom line: we are now often practicing medicine based on clinical judgment
that is not well informed by the best evidence of medical research – a slippery
slope to diminished affectivity and/or compromised competence.
Why evidence-based medicine
The first reaction of any doctor to EBM is likely to be «Well, of course that›s
what I always do.» The second response, perhaps more thoughtful and certainly
more honest, will be a degree of confusion: «What does it really mean How
does one actually do evidence based medicine Surely there is not enough
time What kind of doctor am I if my medicine is not evidence based»
Some doctors perceived EBM as diminishing the role of clinical acumen and
experience, fearing that the «art» of decision-making will be lost. It should
be noted that EBM neither excludes the vital role played by experience, nor
advocates the replacement of sound clinical judgment. The practice of EBM
means integrating individual clinical expertise with the best available external
clinical evidence from systematic research. EBM respects clinical skills while
emphasizing the need to develop new skills in information management.
Health care professional of the, whether physicians, nurses, pharmacists or
others, require a basic understanding of steps for seeking out, assessing and
applying the most useful information in concert with patients› preferences.
Although we need new evidence daily, we usually fail to get it. The result is that
both our up-to-date knowledge and our clinical performance deteriorate with
time. Trying to overcome clinical entropy through traditional CME programs
doesn›t improve our clinical performance. A different approach to clinical
learning has been shown to be effective in keeping practitioners up to date:
EBM
The premise of EBM is a simple one, that excellence in patient care correlates
with the use of the best currently available evidence, and that physicians require
a unique set of skills which are not part of traditional medical education, in
order to access and utilize this information.
In EBM, Systematic Reviews are considered the best source of evidence.
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A systematic review is a critical assessment and evaluation of research
(not simply a summary) that attempts to address a focused clinical question
using methods designed to reduce the likelihood of bias. When it includes a
quantitative strategy for combining the results of included studies into a single
pooled or summary estimate, it is called a Meta-Analysis. It is a process of
‹merging› data of similar smaller studies to obtain the ‹power› of a larger study
which can assist in drawing firmer conclusions. This indeed, is the «simplified»
rationale for evidence-based medicine.
This study type is of particular importance when research findings contradict
each other and obscure the true picture. Therefore, by pooling together all
the results of various research studies, the sample size can, in effect, be
increased.
Although pooling together the results of a number of trials will provide a greater
weight of evidence, it is still important to examine meta-analyses critically:-
• Was a broad enough search strategy used
MEDLINE, for instance, covers only about a quarter of the world›s biomedical
journals.
• Do the results all or mostly point in the same direction
A meta-analysis should not be used to produce a positive result by
averaging the results of, say, five trials with negative and ten trials with
positive findings.
• Are the trials in the meta-analysis all small trials
If so, be very cautious.
Forms of evidence
Evidence is presented in many forms, and it is important to understand the
basis on which it is stated. The value of evidence can be ranked according to
the following classification in descending order of credibility:
I. Strong evidence from at least one systematic review of multiple welldesigned
randomized controlled trials.
II. Strong evidence from at least one properly designed randomized controlled
trail of appropriate size.
III. Evidence from well - designed trials such as non-randomised
trials, cohort studies, time series or matched case-controlled studies.
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IV. Evidence from well-designed non-experimental studies from more than
one center or research group.
V. Opinions of respected authorities, based on clinical evidence, descriptive
studies or reports of expert committees.
Hierarchy of Evidence
When searching for an answer for questions on therapeutic and preventive
interventions, a Systematic Review of Randomized Control Trials (RCT) is
considered the best study type. If such a study was not found, the next level of
evidence would be a single RCT. Again if not found, the next level of evidence
would be a cohort study (which is an observational study). If not found we
would have to go to lower levels of evidence (from weaker study designs) until
we reach «Expert Opinion», which is considered the lowest level of evidence.
This highlights one of the fundamentals of EBM evidence which is ‹Evidence is
graded by Strength›. Figure 2, illustrates the hierarchy of evidence (for therapy
and prevention).
Fig. 2. Hierarchy of Evidence.
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Strength of Recommendation Taxonomy (SORT)
AFP uses the Strength-of-Recommendation Taxonomy (SORT), defined below,
to label key recommendations in clinical review articles. In general, only key
recommendations are given a Strength-of-Recommendation grade. Grades
are assigned on the basis of the quality and consistency of available evidence.
Table 1 shows the three grades recognized.
As the table indicates, the strength-of-recommendation grade depends on the
quality and consistency of the evidence for the recommendation. Quality and
consistency of evidence are determined as indicated in Table 2 and Table 3.
An alternative way to understand the significance of a strength-ofrecommendation
grade is through the algorithm generally followed by authors
and editors in assigning grades based on a body of evidence (figure 1). While
this algorithm provides a general guideline authors and editors may adjust the
strength of recommendation based on the benefits, harms, and costs of the
intervention being recommended.
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TABLE 1. Strength-of-Recommendation Grades
Strength of
recommendation
A
B
C
Basis for recommendation
Consistent, good-quality patient-oriented evidence*
Inconsistent or limited-quality patient-oriented
evidence*
Consensus, disease-oriented evidence,* usual practice,
expert opinion, or case series for studies of diagnosis,
treatment, prevention, or screening
* Patient-oriented evidence measures outcomes that matter to patients:
morbidity, mortality, symptom improvement, cost reduction, and quality of
life.
Disease-oriented evidence measures intermediate, physiologic, or
surrogate end points that may or may not reflect improvements in patient
outcomes (e.g., blood pressure, blood chemistry, physiologic function,
pathologic findings).
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TABLE 2. Assessing Quality of Evidence
Study quality
Level 1: good-quality
Patient oriented
evidence
Level 2: limitedquality
patientoriented
evidence
Level 3:
other evidence
Diagnosis
Validated clinical
decision rule SR / meta -
analysis of high -quality
studies
High-quality diagnostic
cohort study*
Invalidated clinical
decision rule
SR / meta - analysis of
lower quality studies or
studies with inconsistent
findings
Lower quality diagnostic
cohort study or
diagnostic case -control
study
Treatment / prevention /
screening
SR/meta-analysis or RCTs with
consistent findings
High-quality individual RCT**
All-or-none study***
SR/meta-analysis of lower
quality clinical trials or of
studies with inconsistent
findings
Lower quality clinical trial
Cohort study
Case-control study
Prognosis
SR / meta - analysis
of good-quality
cohort studies
Prospective cohort
study with good
follow-up
SR/meta-analysis of
lower quality cohort
studies or with
inconsistent results
Retrospective cohort
study or prospective
cohort study with
poor follow-up
Case-control study
Consensus guidelines, extrapolations from bench research, usual practice,
opinion, disease-oriented evidence (intermediate or physiologic outcomes only), or
case series for studies of diagnosis, treatment, prevention, or screening
* High-quality diagnostic cohort study: cohort design, adequate size, adequate
spectrum of patients, blinding, and a consistent, well-defined reference
standard.
** High-quality RCT: allocation concealed, blinding if possible, intention-totreat
analysis, adequate statistical power, adequate follow-up (greater
than 80 percent).
*** In an all-or-none study, the treatment causes a dramatic change in
outcomes, such as antibiotics for meningitis or surgery for appendicitis,
which precludes study in a controlled trial.
(SR = systematic review; RCT = randomized controlled trial)
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TABLE 3.
Studies
Assessing Consistency of Evidence Across
Consistent
Inconsistent
Most studies found similar or at least coherent conclusions
(coherence means that differences are explainable).
or
If high-quality and up-to-date systematic reviews or
meta-analyses exist, they support the recommendation
Considerable variation among study findings and lack of
coherence
or
If high-quality and up-to-date systematic reviews or
meta-analyses exist, they do not find consistent evidence
in favor of the recommendation..
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Strength of Recommendation Based on a Body of Evidence
Is this a key recommendation for clinicians
regarding diagnosis or treatment that merits a
label
Yes
Is the recommendation based on patientoriented
evidence (i.e., an improvement in
morbidity, mortality, symptoms, quality of life,
or cost)
Yes
Is the recommendation based on expert opinion,
bench research, a consensus guideline, usual
practice, clinical experience, or a case series
study
No
Is the recommendation based on one of the
following
• Cochrane Review with a clear
recommendation
• USPSTF Grade A recommendation
• Clinical Evidence rating of Beneficial
• Consistent findings from at least two goodquality
randomized controlled trials or a
systematic review/meta-analysis of same
• Validated clinical decision rule in a relevant
population
• Consistent findings from at least two
good-quality diagnostic cohort studies or
systematic review/meta-analysis of same
No
Yes
Yes
Yes
No
Recommendation
not needed
Strength of
Recommendation = C
Strength of
Recommendation = A
Strength of
Recommendation = B
Figure 1. Assigning a Strength-of-Recommendation grade based on a body of evidence.
(USPSTF = U.S. Preventive Services Task Force)
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Steps of EBM
There are five steps in practicing EBM «5 A’s»:
1. Ask: Asking answerable questions.
2. Acquire: Searching for the best evidence.
3. Appraise: Critically appraising the evidence.
4. Apply: Applying the evidence to individual patient care, and,
5. Asses: Evaluating the process.
Asking answerable questions
The practicing physician is always faced with the dilemma of how best to
answer the clinical questions either arising, for example, from failure of therapy
or from the inquisitive patient. By extension questions could also come from
diverse areas that have stake in health care delivery.
In order to be able to search for evidence regarding a particular clinical issue, a
proper answerable question must be formulated. This is not always as easy as
it may seem. It can be done by making sure the question contains four areas
abbreviated by the acronym PICO. ‘P’ stands for the description of patient
or population; ‘I’ for the intervention, ‘C’ for the comparison group; ‘O’ for the
outcome.
Clinical Scenario
Ibrahim is a 60 years old businessman, with no prior history of any cardiovascular
event. He presented to your clinic for follow up, he wanted your advice about
using aspirin, as it was recommended for one of his friends, who had a heart
attack recently.
Formulation a clinical question:
* Patient / Population : Primary prevention
* Intervention : Aspirin
* Comparison : Placebo
* Outcome : Prevention of Cardiovascular events
Searching for the best evidence
Considering the time lapse between writing a book and the book hitting the
stand, may be five years in some cases- by which time some information might
have become obsolete, books cannot be considered as the best source of
evidence. They are good for teaching purposes reference to a limited extent
and it needs update regularly.
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In order to obtain the best evidence, an electronic-based search of answers to
the formulated questions in sources of «ready made» evidence, is the easiest
and fastest way. These sources include the Cochrane Library, Best Evidence,
ACP Journal Club, Clinical Evidence; Infopoems, DARE and others. The main
obstacle against using these resources is cost of subscription (that they are
not free).
If these sources are not available or if the answers of the search question
was not found in them, one would have to search sources of primary evidence
(original articles and systematic reviews). These articles can be found in
electronic databases (e.g. Medline, EMBASE, SAM) and Electronic journals
(e.g. Bandolier, Journal of Evidence Based medicine, JAMA, NEJM, Lancet,
BMJ etc.).
Critically appraising the evidence
The practitioner needs to develop a sorting strategy in reviewing the available
literature so as to remove relevant from irrelevant materials. Then he should
decide whether the article is well conducted and can be used or not.
Several checklists have been developed to help make this process easy,
systematic and more or less reproducible. Usually they focus on three man
areas; validity, results and applicability. Validity or closeness to truth usually
examines the methodology of the article
Critical appraisal
For any clinician, the real key to assessing the usefulness of a clinical study
and interpreting the results to an area of work is through the process of critical
appraisal. This is a method of assessing and interpreting the evidence by
systematically considering its validity, results and relevance to the area of
work considered.
The Critical Appraisal Skills helps health service professionals and decisionmakers
develop skills in appraising evidence about clinical effectiveness. Its
process uses three broad issues that should be considered when appraising a
review article:
• Are the results of the review valid
• What are the results
• Will the results help locally
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Next, the magnitude of the results and its significance are evaluated. Finally,
one should look to the applicability of these results to his/her patients.
Questions asked in this process include:
a) Is the outcome of the study a «patient oriented evidence that matters»
(POEM) or a «disease oriented evidence» (DOE)
b) Does the study population correspond to your practice population
c) What method is described to answer the research question
d) How will this study impact on your practice
Applying the evidence to individual patient care
EBM will modify individual patient care, leading to the use of proven therapies
and diagnostic tests only where data exists to support their use, to the
withdrawal of those which are unproven, and to closer scrutiny of those for
which clear evidence for continued use is lacking. As physicians become more
aware, patients become better educated and a more equitable physicianpatient
relationship follows.
Evaluating the process
A periodic review of the process will show how well a clinical question has
been answered and advise as to its replicability either in the same or another
setting. The more EBM is used, the more the challenges to the practitioner and
the more the experience gained.
The Logic Behind EBM
To make EBM more acceptable to clinicians and to encourage its use, it is best to turn a
specified problem into answerable questions by examining the following issues:
• Person or population in question.
• Intervention given.
• Comparison (if appropriate).
• Outcomes considered.
For example: Is an elderly man given nicotine patches more likely to stop
smoking than a similar man who is not
Next, it is necessary to refine the problem into explicit questions and then
check to see whether the evidence exists. But where can we find the information
to help us make better decisions
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The following are all common sources:
• Personal experience – for example, a bad drug reaction.
• Reasoning and intuition.
• Colleagues.
• Bottom drawer (pieces of paper lying around the office, and son on).
• Published evidence.
Analyzing information
In using the evidence it is necessary to:
• Search for and locate it.
• Appraise it.
• Store and retrieve it.
• Ensure it is updated.
• Communicate and use it.
Every clinician strives to provide the best possible care for patients. However,
given the multitude of research information available, it is not always possible
to keep abreast of current developments or to translate them into clinical
practice. One must also rely on published papers, which are not always tailored
to meet the clinician›s needs.
Advantages and disadvantages in practicing EBM
Advantages
• Clinicians upgrade their knowledge base;
• It improves clinicians› understanding of research and its methods;
• It improves confidence in managing clinical situations;
• It improves computer literacy and data searching skills;
• It allows group problem solving and teaching;
• Juniors can contribute as well as seniors;
• For patients, it is a more effective use of resources;
• It allow better communication with the patient about the rationale behind
treatment;
• It improves our reading habit;
• It leads us to ask questions, and then to be skeptical of the answers: what
better definition is there of sciences
• Wasteful practices can be abandoned;
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• Evidence-based medicine presupposes that we keep up-to-date, and
makes it worthwhile to take trips around the perimeter of our knowledge;
• Evidence-based medicine opens decision making processes to patients.
EBM forms part of the multifaceted process of assuring clinical effectiveness,
the main elements of which are:
- Production of evidence through research and scientific review.
- Production and dissemination of evidence-based clinical guidelines.
- Implementation of evidence-based, cost-effective practice through
education and management of change.
- Evaluation of compliance with agreed practice guidance and patient
outcomes – this process includes clinical audit.
Disadvantages
• It takes time to learn the methods and to put them into practice;
• There is the financial cost of buying and maintaining equipment;
• Medline and other electronic databases are not always comprehensive;
• Authoritarian practitioners may find these methods threatening.
• How do we balance cost and quality in healthcare
• Where should investments be made that improve care in a
cost effective way
• How do we engage patients more responsibility in
their care
• How do we maintain and enhance the professional integrity
of the caring professions
• How do we narrow the gap between knowledge and
practice
The practice of evidence-based medicine is the starting
point for answering these overarching questions.
Evidence-based medicine is not cookbook medicine; it is
a basis for the next generation of health delivery in
the Gulf States.
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(Suggestive Guideline)
STRATEGIC PLANNING IN THE GCC STATES
FOR EVIDENCE-BASED MEDICINE
Strategies
Considering possible strategies to be adopted in promoting evidence-based
health care (EBHC) in the GCC states, the following theoretical frameworks can
be helpful in setting up activities at the central and peripheral levels of health
care delivery:
• Establishment of a national committee for EBM.
• Advocacy (seek legal and political support for EBM).
• Identify sources of financial support (government, organized private
sector, donor agencies etc.).
• Establishment of a reference e-library.
• Launching of a local website dedicated to EBM.
• Training (trainers, trainees).
• Organize workshops and courses on EBM.
At the Central Level:
I- Establishment of a reference e-library:
a) Vital introductory books (10-15 classical books) on how to practice and
teach EBM.
b) Basic important sources of evidence online and in print viz. the Cochrane
library; Best Evidence; ACP Journal Club, Diagnostic Strategies for
common medical problems (ed. Black et al) and Clinical Evidence.
c) EBM websites; electronic databases (Medline, EMBASE, SAM,
UP TO DATE etc.); electronic journals (JAMA, New England Journal of
Medicine, The Lancet, British Medical Journal, etc.).
II- Develop a local EBM website which is updated regularly.
III- Establish a core of national and regional trainers. Can be facilitated by
international, regional and national experts in the field of EBM.
At the Peripheral (Regional/ District/ PHCC) level:
I- Provide easy access to the e-library within the locality, with travel time not
exceeding 15-30 minutes.
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II- Publish a regular newsletter that is directed towards health providers. Part
of the newsletter may be written in Arabic. The newsletter may include:
- EB fact sheets/cards.
- Critically appraised clinical practice guidelines.
- Selection from available EBM resources with recommendations for
clinical care.
- Questions and evidence-based answers.
- Provision of distant learning program.
- Updating the MOH manuals, protocols and guidelines with the best
available evidence.
- Organize weekend courses/workshop (4-5 per year, facilitated
by the core trainers, 50-200 health care professionals may be trained
each year).
- Establish a rapport with local drug companies for facilitation
and sponsorship.
Implementation of the strategies
The national committee is expected to play a leading role in implementing
the outlined strategies. Members of the committee should be drawn from the
ministry of health, university medical schools and EBM-related organizations.
Their task would include advocacy, setting the structure right, sourcing for
finance, securing the services of skilled personnel (computer programmers,
feeding of scientific materials, secretarial support etc.), liaison with the ministry
of health, the universities and other relevant institutions, curriculum design,
development of EBM continuing medical education programmes, problembased
education, vocational training and future improvement in teaching
methodology.
Medical schools are expected to consider the adoption of EBM curriculum. The
faculty should be versed not only in EBM but also in best-evidence medical
education ‹BEME›, reference BEME collaboration website, and the umbrella of
this concept extended to Evidence Based Health Care.
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GLOSSARY OF TERMS
IN EVIDENCE-BASED MEDICINE
This glossary in intended to provide explanation and guidance as to the
meanings of EBM term (a simple definition).
A
Absolute risk (AR)
The probability that an individual will experience the specified outcome during
a specified period. It lies in the range 0 to 1, or is expressed as a percentage.
In contrast to common usage, the word “risk” may refer to adverse events (such
as myocardial infarction) or desirable events (such as cure).
Absolute risk increase (ARI)
The absolute difference in risk between the experimental and control groups
in a trial. It is used when the risk in the experimental group exceeds the risk in
the control group, and is calculated by subtracting the AR in the control group
from the AR in the experimental group. This figure does not give any idea of
the proportional increase between the two groups: for this, relative risk (RR) is
needed.
Absolute risk reduction (ARR)
The absolute difference in risk between the experimental and control groups
in a trial. It is used when the risk in the control group exceeds the risk in the
experimental group, and is calculated by subtracting the AR in the experimental
group from the AR in the control group. The arithmetic difference in risk or
outcomes between treatment and control groups,. Example: if mortality is 30
percent in controls and 20 percent with treatment, ARR is 30-20=10 percent.
This figure does not give any idea of the proportional reduction between the
two groups: for this, relative risk (RR) is needed.
Allocation concealment
A method used to prevent selection bias by concealing the allocation sequence
from those assigning participants to intervention groups. Allocation concealment
prevents researchers from (unconsciously or otherwise) influencing which
intervention group each participant is assigned to.
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Applicability
The application of the results from clinical trials to individual people. A
randomised trial only provides direct evidence of causality within that specific
trial. It takes an additional logical step to apply this result to a specific individual.
Individual characteristics will affect the outcome for this person.
People involved in making decisions on health care must take relevant
individual factors into consideration. To aid informed decision-making about
applicability, we provide information on the characteristics of people recruited
to trials.
B
Baseline risk
The risk of the event occurring without the active treatment. Estimated by the
baseline risk in the control group.
The base line risk is important for assessing the potential beneficial effects
of treatment. People with a higher baseline risk can have a greater potential
benefit.
Best evidence
Systematic reviews of RCTs are the best method for revealing the effects of
a therapeutic intervention. RCTs are unlikely to adequately answer clinical
questions in the following cases:
1. Where there are good reasons to think the intervention is not likely to be
beneficial or is likely to be harmful;
2. Where the outcome is very rare (e.g. a 1/10000 fatal adverse
reaction);
3. Where the condition is very rare;
4. Where very long follow up is required (e.g. does drinking milk in adolescence
prevent fractures in old age);
5. Where the evidence of benefit from observational studies is overwhelming
(e.g. oxygen for acute asthma attacks);
6. When applying the evidence to real clinical situations (external validity);
7. Where current practice is very resistant to change and/or patients would
not be willing to take the control or active treatment;
8. Where the unit of randomisation would have to be too large (e.g. a nationwide
public health campaign); and
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9. Where the condition is acute and requires immediate treatment. Of these,
only the first case is categorical. For the rest the cut off point when an RCT
is not appropriate is not precisely defined. If RCTs would not be appropriate
we search and include the best appropriate form of evidence.
Bias
Systematic deviation of study results from the true results, because of the
way(s) in which the study is conducted.
Blinding / blinded
A trial is fully blinded if all the people involved are unaware of the treatment
group to which trial participants are allocated until after the interpretation of
results. This includes trial participants and everyone involved in administering
treatment or recording trial results.
Ideally, a trial should test whether people are aware of which group they
have been allocated to. This is particularly important if, for example, one of
the treatments has a distinctive taste or adverse effects. Unfortunately such
testing is rare. The terms single and double blind are common in the literature
but are not used consistently. So a study is blinded if any or all of the clinicians,
patients, participants, outcome assessors, or statisticians were unaware of
who received which study intervention. The double double-blind usually refers
to patient and clinician being blind, but is ambiguous so it is better to state who
is blinded.
C
Case control study
A study design that examines a group of people who have experienced an event
(usually an adverse event) and a group of people who have not experienced the
same event, and looks at how exposure to suspect (usually noxious) agents
differed between the two groups. This type of study design is most useful for
trying to ascertain the cause of rare events, such as rare cancers.
Case control studies can only generate odds ratios (OR) and not relative risk
(RR). Case control studies provide weaker evidence than cohort studies but are
more reliable than case series.
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Case series
It is a report on a series of patients with an outcome of interest. No control
group is involved. Case series provide weaker evidence than case control
studies.
Clinical Practice Guideline
Is a systematically developed statement designed to assist practitioners and
patient make decisions about appropriate health care for specific clinical
circumstances.
Cluster randomisation
A cluster randomised study is one in which a group of participants are randomised
to the same intervention together. Examples of cluster randomisation include
allocating together people in the same village, hospital, or school. If the results
are then analysed by individuals rather than the group as a whole bias can
occur.
The unit of randomisation should be the same as the unit of analysis. Often
a cluster randomised trial answers a different question from one randomised
by individuals. An intervention at the level of the village or primary care
practice may well have a different effect from one at the level of an individual
patient. Therefore, trying to compensate by allowing for intra class correlation
coefficients or some other method may not be appropriate.
Cohort study
Involves identification of two groups (cohorts) of patients, one which did receive
the exposure of interest, and one which did not, and following these cohorts
forward for the outcome of interest. Exposure is likely to cause specified events
(e.g. lung cancer). Prospective cohort studies (which track participants forward
in time) are more reliable than retrospective cohort studies. Cohort study is a
non-experimental study design that follows a group of people (a cohort), and
then looks at how events differ among people within the group. A study that
examines a cohort, which differs in respect to exposure to some suspected
risk factor (e.g. smoking), is useful for trying to ascertain whether exposure is
likely to cause specified events (e.g. lung cancer). Prospective cohort studies
(which track participants forward in time) are more reliable than retrospective
cohort studies.
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Cohort studies should not be included within the Benefits section, unless it is
not reasonable to expect higher levels of evidence.
Completer analysis
Analysis of data from only those participants who remained at the end of
the study. Compare with intention to treat analysis, which uses data from all
participants who enrolled.
Confidence interval (CI)
An estimate of precision. If a study is repeated 100 times, the results will fall
within this range 95 times; the CI quantifies the uncertainty in measurement;
usually reported as 95% CI, which is the range of values within which we can be
95% sure that the true value for the whole population lies.
The 95% confidence interval (or 95% confidence limits) would include 95% of
results from studies of the same size and design in the same population. This
is close but not identical to saying that the true size of the effect (never exactly
known) has a 95% chance of falling within the confidence interval. If the 95%
confidence interval for a relative risk (RR) or an odds ratio (OR) crosses 1,
then this is taken as no evidence of an effect. The practical advantages of a
confidence interval (rather than a P value) is that they present the range of
likely effects.
Controlled clinical trial (CCT)
A trial in which participants are assigned to two or more different treatment
groups. In BMJ Clinical Evidence, we use the term to refer to controlled trials in
which treatment is assigned by a method other than random allocation. When
the method of allocation is by random selection, the study is referred to as a
randomised controlled trial (RCT; see below). Non-randomised controlled trials
are more likely to suffer from bias than RCTs.
Controls
In a randomised controlled trial (RCT), controls refer to the participants in its
comparison group. They are allocated either to placebo, no treatment, or a
standard treatment.
Correlation coefficient
A measure of association that indicates the degree to which two variables
change together in a linear relationship. It is represented by r, and varies
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etween – 1 and +1. When r is +1, there is a prefect positive relationship (when
one variable increases, so does the other, and the proportionate difference
remains constant). When r is –1 there is a perfect negative relationship (when
one variable increases the other decreases, or vice versa, and the proportionate
difference remains constant). This, however, does not rule out a relationship —
it just excludes a linear relationship.
Cost-Benefit Analysis
Converts effects into the same monetary terms as the costs and compares
them.
Cost-Effectiveness Analysis
Coverts effects into health terms and describes the costs for some additional
health gain (e.g. cost per additional MI prevented).
Cost-Utility analysis
Converts effects into personal preferences (or utilities) and describes how
much it costs for some additional quality gain (e.g. cost per additional quality
life-year, or QALY).
Crossover randomised trial
A trial in which participants receive one treatment and have outcomes measured,
and then receive an alternative treatment and have outcomes measured again.
The order of treatments is randomly assigned. Sometimes a period of no
treatment is used before the trial starts and in between the treatments (washout
periods) to minimise interference between the treatments (carry over effects).
Interpretation of the results from crossover randomised controlled trials (RCTs)
can be complex.
Crossover studies have the risk that the intervention may have an effect after
it has been withdrawn, either because the washout period is not long enough
or because of path dependency. A test for evidence of statistically significant
heterogeneity is not sufficient to exclude clinically important heterogeneity. An
effect may be important enough to affect the outcome but not large enough to
be significant.
Crossver Study Design
The administration of two or more experimental therapies one after the other in
a specified or random order to the dame group of patients.
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Crossver-sectional Study
The observation of a defined population at a single point in time or time interval.
Exposure and outcome are determined simultaneously.
Cross sectional study
A study design that involves surveying a population about an exposure, or
condition, or both, at one point in time. It can be used for assessing prevalence
of a condition in the population. Cross sectional studies should never be used
for assessing causality of a treatment.
D
Data pooling
Crude summation of the raw data with no weighting, to be distinguished from
meta-analysis).
Decimal places
We always precede decimal points with an integer. Numbers needing treatment
to obtain one additional beneficial outcome (NNTs) are rounded up to whole
numbers e.g. an NNT of 2.6 would become 3. Numbers needing treatment to
obtain one additional harmful outcome (NNHs) are rounded down to whole
numbers e.g an NNH of 2.3 would become 2. For P values, we use a maximum
of three noughts after the decimal: P < 0.0001. We try to report the number
of decimal places up to the number of noughts in the trial population e.g 247
people, with RR 4.837 would be rounded up to 4.84. We avoid use of more than
three significant figures.
Decision analysis
The application of explicit, quantitative methods that quantify prognosis,
treatment effects, and quality of life and cost in order to analyze a decision
under conditions of uncertainty.
Disability Adjusted Life Year (DALY)
A method for measuring disease burden, which aims to quantify in a single
figure both the quantity and quality of life lost or gained by a disease, risk
factor, or treatment. The DALYs lost or gained are a function of the expected
number of years spent in a particular state of health, multiplied by a coefficient
determined by the disability experienced in that state (ranging from 0 [optimal
health] to 1 [deaths]). Later years are discounted at a rate of 3% per year, and
childhood and old age are weighted to count for less.
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Drillability
Refers to the ability to trace a statement from its most condensed form through
to the original evidence that supports it. This requires not only the data but also
all the methods used in the generation of the condensed form to be explicit and
reproducible. We see it as an important component of the quality of evidencebased
publications.
E
Ecological Survey
Based on aggregated data for some population as it exists at some point or
points in time; to investigate the relationship of an exposure to a known or
presumed risk factor for a specified outcome.
Event
The occurrence of a dichotomous outcome that is being sought in the study
(such as myocardial infarction, death, or a four-point improvement in pain
score).
Event rates
In determining the power of a trial the event rate is more important than the
number of participants. Therefore, we provide the number of events as well as
the number of participants when this is available.
Event Rate is the proportion of patients in a group in whom an the event is
observed. Thus, if out of 100 patients, the event is observed in 27, the event rate
is 0.27. Control Event Rate (CER) and Experimental Event Rate (EER) are used
to refer to this in control and experimental groups of patients respectively.
Evidence-Based Health Care
Extends the application of the principles of Evidence-Based Medicine ( see
below) to all professions associated with health care, including purchasing and
management.
Evidence-Based Medicine
Is the conscientious, explicit and judicious use of current best evidence
in making decisions about the care of individual patients. The practice of
evidence-based medicine means integrating individual clinical expertise with
the best available external clinical evidence from systematic research.
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Experimental study
A study in which the investigator studies the effect of intentionally altering one
or more factors under controlled conditions.
External validity (generalisabilty)
The validity of the results of a trial beyond that trial.
A randomised controlled trial (RCT) only provides direct evidence of causality
within that trial. It takes an additional logical step to apply this result more
generally. However, practically it is necessary to assume that results are
generalisable unless there is evidence to the contrary. If evidence is consistent
across different settings and in different populations (e.g. across ages and
countries) then there is evidence in favour of external validity. If there is only
evidence from atypical setting (e.g. teaching hospital when most cases are
seen in primary care) then one should be more sceptical about generalising the
results. Generalisability is not just a consequence of the entry requirements for
the trial, but also depends on the population from which the trial population was
drawn (see applicability).
F
Factorial design
A factorial design attempts to evaluate more than one intervention compared
with control in a single trial, by means of multiple randomisations.
False negative
A person with the target condition (defined by the gold standard) who has a
negative test result.
False positive
A person without the target condition (defined by the gold standard) who has a
positive test result.
Fixed effects
The “fixed effects” model of meta-analysis assumes, often unreasonably, that
the variability between the studies is exclusively because of a random sampling
variation around a fixed effect (see random effects below).
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H
Harms
Evidence-based healthcare resources often have great difficulty in providing
good quality evidence on harms. Most RCTs are not designed to assess
harms adequately: the sample size is too small, the trial too short, and often
information on harms is not systematically collected. Often a lot of the harms
data are in the form of uncontrolled case reports. Comparing data from these
series is fraught with difficulties because of different numbers receiving the
intervention, different baseline risks and differential reporting. We aim to
search systematically for evidence on what are considered the most important
harms of an intervention. The best evidence is from a systematic review of
harms data that attempts to integrate data from different sources. However,
because of these difficulties and following the maxim “first one must not do
harm” we accept weaker evidence. This can include information on whether
the intervention has been either banned or withdrawn because of the risk of
harms.
Hazard ratio (HR)
Broadly equivalent to relative risk (RR); useful when the risk is not constant
with respect to time. It uses information collected at different times. The term
is typically used in the context of survival over time. If the HR is 0.5 then the
relative risk of dying in one group is half the risk of dying in the other group.
If HRs are recorded in the original paper then we report these rather than
calculating RR, because HRs take account of more data.
Heterogeneity
In the context of meta-analysis, heterogeneity means dissimilarity between
studies. It can be because of the use of different statistical methods (statistical
heterogeneity), or evaluation of people with different characteristics, treatments
or outcomes (clinical heterogeneity). Heterogeneity may render pooling of data
in meta-analysis unreliable or inappropriate.
Finding no significant evidence of heterogeneity is not the same as finding
evidence of no heterogeneity. If there are a small number of studies,
heterogeneity may affect results but not be statistically significant.
Homogeneity
Similarity (see heterogeneity).
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I
Incidence
The number of new cases of a condition occurring in a population over a
specified period of time.
Inclusion / exclusions
We use validated search and appraisal criteria to exclude unsuitable papers.
Authors are then sent exclusion forms to provide reasons why further papers
are excluded.
Intention to treat (ITT) analysis
Analysis of data for all participants based on the group to which they were
randomised and not based on the actual treatment they received.
Where possible we report ITT results. However, different methods go under
the name ITT. Therefore, it is important to state how withdrawals were handled
and any potential biases, e.g. the implication of carrying last result recorded
forward will depend on the natural history of the condition.
L
Likelihood ratio (L R)
Is the likelihood of a given test result in a patient with the target disorder compared
to the likelihood of the same result in a patient without that disorder.
The ratio of the probability that an individual with the target condition has
a specified test result to the probability that an individual without the target
condition has the same specified test result.
LR>1 indicates and increased likelihood of disease, LR

M
Meta-analysis
A type of systematic review that uses rigorous statistical methods to
quantitatively, summarize o synthesize the results of multiple similar studies. A
statistical technique that summarises the results of several studies in a single
weighted estimate, in which more weight is given to results of studies with
more events and sometimes to studies of higher quality.
We use meta-analysis to refer to the quantitative methods (usually involving
weighting) used to integrate data from trials. This is logically distinct from a
systematic review, which is defined by an explicitly systematic search and
appraisal of the literature. It is also distinct from data pooling, which is based
purely on the raw data.
Morbidity
Rate of illness but not death.
Mortality
Rate of death.
N
Negative likelihood ratio (NLR)
The ratio of the probability that an individual with the target condition has
a negative test result to the probability that an individual without the target
condition has a negative test result. This is the same as the ratio (1-sensitivity/
specificity).
Negative predictive value (NPV)
The chance of not having a disease given a negative test result (not to be
confused with specificity, which is the other way round). NPV is the proportion
of people with a negative test who are free of disease. See also SpPins and
SnNouts.
N-of-1 Trials
The patient undergoes pairs of treatment periods organized so that one period
involved the use of the experimental treatment and one period involves the use
of an alternate or placebo therapy. The patients and physician are blinded,
if possible, and outcomes are monitored. Treatment periods are replicated
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until the clinician and patient are convinced that the treatments are definitely
different or definitely not different.
Negative statements
At what stage does no evidence of an effect become evidence of no effect
If confidence intervals are available then we should aim to indicate in words
the potential size of effect they encompass. If a result is not significant we try
and state if the confidence intervals include the possibility of a large effect
(e.g. “The RCT found no significant effect but included the possibility of a large
harm/ benefit/ harm or benefit”). The exact wording depends on the mean result
and the width of the confidence intervals.
Non-systematic review
A review or meta-analysis that either did not perform a comprehensive search of
the literature and contains only a selection of studies on a clinical question, or
did not state its methods for searching and appraising the studies it contains.
Not significant/non-significant (NS)
Not significant means that the observed difference, or a larger difference, could
have arisen by chance with a probability of more than 1/20 (i.e. 5%), assuming
that there is no underlying difference. This is not the same as saying there is
no effect, just that this experiment does not provide convincing evidence of
an effect. This could be because the trial was not powered to detect an effect
that does exist, because there was no effect, or because of the play of chance.
If there is a potentially clinically important difference that is not statistically
significant then do not say there was a non-significant trend. Alternative
phrases to describe this type of uncertainty include, “Fewer people died after
taking treatment x but the difference was not significant” or “The difference was
not significant but the confidence intervals covered the possibility of a large
beneficial effect” or even, “The difference did not quite reach significance.”
Number needed to harm (NNH)
One measure of treatment harm. It is the average number of people from a
defined population you would need to treat with a specific intervention for a
given period of time to cause one additional adverse outcome. NNH can be
calculated as 1/ARI.
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Number needed to treat (NNT)
NNT is the number of patients who need to be treated to prevent one bad
outcome. It is the inverse of the ARR:
NNT=1/ARR.
The number of patients who need to receive an intervention instead of the
alternative in order for one additional patient to benefit. The NNT is calculated
as: 1/AAR. Example ; if the AAR is 4 percent the NNT=1/4 percent=1/0.04=25.
NNT is one measure of treatment effectiveness. It is the average number of
people who need to be treated with a specific intervention for a given period
of time to prevent one additional adverse outcome or achieve one additional
beneficial outcome. NNT can be calculated as 1/ARR :
1. NNTs are easy to interpret, but they can only be applied at a given level of
baseline risk.
2. How do we calculate NNTs from meta-analysis data The odds ratio (OR)
(and 95% CI) with the AR in the control group can be used to generate
absolute risk (AR) in the intervention group and from there to the NNT. This is
a better measure than using the pooled data, which only uses trial size (not
variance) and does not weight results (e.g. by trial quality). As people can
not be treated as fractions, we round NNTs up and numbers needed to harm
(NNHs) down to the largest absolute figure. This provides a conservative
estimate of effect (it is most inaccurate for small numbers).
3. NNTs should only be provided for significant effects because of the difficulty
of interpreting the confidence intervals for non-significant results. Nonsignificant
confidence intervals go from an NNT to an NNH by crossing
infinity rather than zero.
NNT for a meta-analysis
Absolute measures are useful at describing the effort required to obtain a benefit,
but are limited because they are influenced by both the treatment and also by
the baseline risk of the individual. If a meta-analysis includes individuals with
a range of baseline risks, then no single NNT will be applicable to the people
in that meta-analysis, but a single relative measure (odds ratio or relative risk)
may be applicable if there is no heterogeneity. In BMJ Clinical Evidence, an
NNT is provided for meta-analysis, based on a combination of the summary
odds ratio (OR) and the mean baseline risk observed in average of the control
groups.
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O
Observational studies
Observational studies may be included in the Harms section or in the Comment.
Observational studies are the most appropriate form of evidence for the
Prognosis, Aetiology, and Incidence/Prevalence sections. The minimum data
set and methods requirements for observational studies have not been finalised.
However, we always indicate what kind of observational study, whether case
series, case control, prospective or retrospective cohort study.
Odds
The odds of an event happening is defined as the probability that an event will
occur, expressed as a proportion of the probability that the event will not occur.
Odds are a ratio of events to non-events, e.g, if the event rate for a disease is
0.2 (20 percent), its non-event rte is 0.8 (80%) then its odds are 0.2/0.8=0.25 (see
Odds Ratio).
Odds ratio (OR)
One measure of treatment effectiveness. It is the odds of an event happening
in the experimental group expressed as a proportion of the odds of an event
happening in the control group. Odds Ratio is the odds of an experimental
patient suffering an event relative to the odds of a control patient. The closer
the OR is to one, the smaller the difference in effect between the experimental
intervention and the control intervention. If the OR is greater (or less) than one,
then the effects of the treatment are more (or less) than those of the control
treatment. Note that the effects being measured may be adverse (e.g. death or
disability) or desirable (e.g. survival).
When events are rare the OR is analagous to the relative risk (RR), but as event
rates increase the OR and RR diverge.
The ratio of events to non-events in the intervention group over the ratio of
events to non-events in the control group.
Odds reduction
The complement of odds ratio (1-OR), similar to the relative risk reduction (RRR)
when events are rare.
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Open label trial
A trial in which both participant and assessor are aware of the intervention
allocated.
Outcomes
This generally means mortality, morbidity, quality of life, ability to work, pain,
etc. Laboratory outcomes are avoided if possible. Even if there is a strong
relationship between a laboratory outcome marker and a clinical outcome it is
not automatic that it will hold under new conditions. Outcomes that are markers
for clinically important patient centred outcomes are often called surrogate
outcomes (e.g. ALT concentrations are a proxy for liver damage following
paracetamol overdose).
P
PICOt
Population, intervention, comparison, and outcome, all with a time element
(PICOt). The current reporting requirements of systematic reviews are: how
many RCTs, how many participants in each, comparing what with what, in what
type of people, with what results. Each variable needs a temporal element,
(how old are the participants, how long is the treatment given for, when is the
outcome measured). In the future, we hoping to have a brief description in the
text with full details accessible from the website.
Placebo
A substance given in the control group of a clinical trial, which is ideally identical
in appearance and taste or feel to the experimental treatment and believed
to lack any disease specific effects. In the context of non-pharmacological
interventions, placebo is usually referred to as sham treatments.
Placebo is not the same as giving no treatment and can induce real physiological
changes. Whether it is appropriate to compare the experimental with placebo
or no treatment depends on the question being asked. Where possible we
report on the specific intervention given as a placebo. We include, if available,
information is available on whether participants or clinicians could distinguish
between placebo and the intervention.
POEMs
The acronym POEMs stands for Patient-Oriented Evidence that Matters, and
refers to summaries of valid research that is relevant to physicians and their
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patients. POEMs are selected from research published in more than 100 clinical
journals. Each month, a team of family physicians and educators reviews these
journals and identifies research results that are important and can be applied
to day-to-day practice. The valid POEMs are summarized, reviewed, revised,
and compiled into InfoRetriver, part of the InfoPOEMs, Inc. POEMs have to meet
three criteria: they address a question that primary care physicians face in daytoday
practice; they measure outcomes important to physicians and patients,
including symptoms, morbidity, quality of life, and mortality; and they have the
potential to change the way physicians practice. Studies that do not meet
these criteria cannot be POEMs.
Types of Studies Selected:
• Studies of treatments must be randomized, controlled trials.
• Studies of diagnostic tests, such as in a laboratory or as part of the physical
examination.
• Only systematic reviews, including meta-analyses, are considered rather
than nonsystematic reviews.
• Studies of prognosis that identify patients before they have the outcome
of importance and are able to follow-up at least 80 percent of the study
population.
• Decision analysis involves choosing an action after formally and
logically weighing the risks and benefits of the alternatives.
• Qualitative research findings are reported if they are highly relevant,
although specific conclusions will not be drawn from the research.
Positive likelihood ratio (LR+)
The ratio of the probability that an individual with the target condition has a
positive test result to the probability that an individual without the target
condition has a positive test result. This is the same as the ratio (sensitivity/1-
specificity).
Positive predictive value (PPV)
The chance of having a disease given a positive test result (not to be confused
with sensitivity, which is the other way round.
PPV is the proportion of the people with a positive test who have disease. Also
called the post-test probability of disease after positive test See also SpPins
and SnNouts.
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Posttest Probability
The proportion of patients with that particular test result who have the target
disorder (posttest odds/{1+ posttest odds}).
Power
A study has adequate power if it can reliably detect a clinically important
difference (i.e. between two treatments) if one actually exists. The power of a
study is increased when it includes more events or when its measurement of
outcomes is more precise.
We do not generally include power calculations, but prefer to provide confidence
intervals (CIs) and leave it to readers to say if this covers a clinically significant
difference. If no CIs are available a power calculation can be included assuming
it is adequately explained.
Pragmatic study
An RCT designed to provide results that are directly applicable to normal practice
(compared with explanatory trials that are intended to clarify efficacy under
ideal conditions). Pragmatic RCTs recruit a population that is representative
of those who are normally treated, allow normal compliance with instructions
(by avoiding incentives and by using oral instructions with advice to follow
manufacturers instructions), and analyse results by “intention to treat” rather
than by “on treatment” methods.
Predictive value
(positive and negative)
Pretest probability
PV+
PV-
Percentage of patients with a positive
or negative test for a disease who do
or do not have the disease in question.
Portability of disease before a test is
performed.
Pre-test probability / prevalence
The proportion of people with the target disorder in the population at risk at a
specific time (point prevalence) or time interval (period prevalence).
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Prevalence
The proportion of people with a finding or disease in a given population at a
given time.
Publication bias
Occurs when the likelihood of a study being published varies with the results
it finds. Usually, this occurs when studies that find a significant effect are
more likely to be published than studies that do not find a significant effect, so
making it appear from surveys of the published literature that treatments are
more effective than is truly the case.
Can occur through both preference for significant (positive) results by journals
and selective releasing of results by interested parties. A systematic review can
try and detect publication bias by a forest plot of size of trial against results.
This assumes that larger trials are more likely to be published irrespective of
the result. If a systematic review finds evidence of publication bias this should
be reported. Often publication bias takes the form of slower or less prominent
publication of trials with less interesting results.
P value
P-value is the probability of obtaining the same or more extreme data assuming
the null hypothesis of no effect; p-values are generally (but arbitrarily) considered
significant if p

Quasi randomised
A trial using a method of allocating participants to different forms of care that
is not truly random; for example, allocation by date of birth, day of the week,
medical record number, month of the year, or the order in which participants are
included in the study (e.g. alternation).
R
Randomised
We aim to provide an explanation of how a trial is quasi-randomised in the
Comment section.
Random effects
The “random effects” model assumes a different underlying effect for each
study and takes this into consideration as an additional source of variation,
which leads to somewhat wider confidence intervals than the fixed effects
model. Effects are assumed to be randomly distributed, and the central point of
this distribution is the focus of the combined effect estimate.
We prefer the random effects model because the fixed effects model is
appropriate only when there is no heterogeneity—in which case results
will be very similar. A random effects model does not remove the effects of
heterogeneity, which should be explained by differences in trial methods and
populations.
Randomised controlled trial (RCT)
RCT a group of patients is randomized into an experimental group and a
control group. These groups are followed up for the variables/outcomes of
interest. A trial in which participants are randomly assigned to two or more
groups: at least one (the experimental group) receiving an intervention that
is being tested and an other (the comparison or control group) receiving an
alternative treatment or placebo. This design allows assessment of the relative
effects of interventions.
Regression analysis
Given data on a dependent variable and one or more independent variables,
regression analysis involves finding the “best” mathematical model to describe
or predict the dependent variable as a function of the independent variable(s).
There are several regression models that suit different needs. Common forms
are linear, logistic, and proportional hazards.
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Relative risk (RR)
The number of times more likely (RR > 1) or less likely (RR < 1) an event is
to happen in one group compared with another. It is the ratio of the absolute
risk (AR) for each group. It is analogous to the odds ratio (OR) when events are
rare.
We define relative risk as the absolute risk (AR) in the intervention group
divided by the AR in the control group. It is to be distinguished from odds ratio
(OR) which is the ratio of events over non-events in the intervention group over
the ratio of events over non-events in the control group. In the USA, odds ratios
are sometimes known as rate ratios or relative risks.
Relative risk increase (RRI)
The proportional increase in risk between experimental and control participants
in a trial.
Relative risk reduction (RRR)
Is the percent reduction in events in the treated group event rate (EER) compared
to the control group event rate (CER).
RRR= (CER-EER)/CER*100
The percentage difference in risk or outcomes between treatment and control
groups. Example: if mortality is 30 percent in control and 20 percent with
treatment, RRR is (30-20)/30=33 percent.
The proportional reduction in risk between experimental and control participants
in a trial. It is the complement of the relative risk (1-RR).
Risk Ratio
Is the ratio of risk in the treated group (EER) to the risk in the control group
(CER): RR=EER/CER.RR is used in randomized trials and cohort studies.
S
Sensitivity (Sn)
Percentage of patients with disease who have appositive test for the disease
in question.
Sensitivity is the proportion of people with disease who have a positive test.
See also SpPins and SNNouts.
Sn is the chance of having a positive test result given that you have a disease
(not to be confused with positive predictive value (PPV) which is the other way
around.
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Sensitivity analysis
Analysis to test if results from meta-analysis are sensitive to restrictions on
the data included. Common examples are large trials only, higher quality trials
only, and more recent trials only. If results are consistent this provides stronger
evidence of an effect and of generalisability.
Sham treatment
An intervention given in the control group of a clinical trial, which is ideally
identical in appearance and feel to the experimental treatment and believed
to lack any disease specific effects (e.g. detuned ultrasound or random
biofeedback).
Placebo is used for pills, whereas sham treatment is used for devices,
psychological, and physical treatments. We always try and provide information
on the specific sham treatment regimen.
Significant
Significance comes in 2 varieties:
Statistical significance is when the p-value is small enough to reject the null
hypothesis of no effect; where clinical significance is when the effect size is large
enough to be potentially considered worthwhile by patients. By convention,
taken to mean statistically significant at the 5% level. This is the same as a 95%
confidence interval not including the value corresponding to no effect.
SnNout
When a sign/test has a high sensitivity, a negative result rules out the diagnosis;
e.g. the sensitivity of a history of ankle swelling for diagnosis ascites is 92
percent, therefore, is a person does not have a history of ankle swelling, it is
highly unlikely that the person has ascites.
Specificity (Sp)
Percentage of patients ( or the proportion of people) without (free of) disease
who have a negative test for the disease in question. See also SpPins and
SnNouts.
SpPin
When a sign / test / symptom has a high Specificity, a Positive result rules
in the diagnosis. For example, the specificity of Western plot test for HIV for
diagnosing HIV is 98% therefore if a person does have a positive western plot
test, it rules in the diagnosis of HIV.
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Standardised mean difference (SMD)
SpPin when a sign/test has a high specificity, a Positive result rules in the
diagnosis; e.g. the specificity of fluid wave for diagnosing ascites is 92 percent.
Therefore, it a person has a fluid wave, it is highly likely that the person has
ascites.
A measure of effect size used when outcomes are continuous (such as
height, weight, or symptom scores) rather than dichotomous (such as death or
myocardial infarction).
The mean differences in outcome between the groups being studied are
standardised to account for differences in scoring methods (such as pain
scores). The measure is a ratio; therefore, it has no units.
SMD are very difficult for non-statisticians to interpret and combining
heterogenous scales provides statistical accuracy at the expense of clinical
intelligibility. We prefer results reported qualitatively to reliance on effect sizes,
although we recognise that this may not always be practical.
Statistically significant
Means that the findings of a study are unlikely to have arisen because of
chance. Significance at the commonly cited 5% level (P < 0.05) means that the
observed difference or greater difference would occur by chance in only 1/20
similar cases. Where the word “significant” or “significance” is used without
qualification in the text, it is being used in this statistical sense.
Subgroup analysis
Analysis of a part of the trial/meta-analysis population in which it is thought the
effect may differ from the mean effect.
Subgroup analysis should always be listed as such and generally only
prespecified subgroup analysis should be included. Otherwise, they provide
weak evidence and are more suited for hypothesis generation. If many tests are
done on the same data this increases the chance of spurious correlation and
some kind of correction is needed (e.g. Bonforroni). Given independent data,
and no underlying effect, 1 time in 20 a significant result would be expected
by chance.
Surrogate outcomes
Outcomes not directly of importance to patients and their careers but predictive
of patient centered outcomes.
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Systematic review
A type of review article that uses explicit methods to comprehensively analyze
and qualitatively synthesize information from multiple studies. Aystamatic
Review is a literature review focused on a single question which tries to identify,
appraise, select and synthesis all high quality research evidence relevant to
that question. A review in which specified and appropriate methods have
been used to identify, appraise, and summarise studies addressing a defined
question. It can, but need not, involve meta-analysis.
The present requirements for reporting systematic reviews are search date,
number of trials of the relevant option, number of trials that perform the
appropriate comparisons, comparisons, details on the type of people, follow up
period, and quantified results if available.
T
True negative
A person without the target condition (defined by a gold standard) who has a
negative test result.
True positive
A person with the target condition (defined by a gold standard) who also has a
positive test result.
V
Validity
The soundness or rigour of a study. A study is internally valid if the way it is
designed and carried out means that the results are unbiased and it gives you
an accurate estimate of the effect that is being measured. A study is externally
valid if its results are applicable to people encountered in regular clinical
practice.
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W
Weighted mean difference (WMD)
A measure of effect size used when outcomes are continuous (such as symptom
scores or height) rather than dichotomous (such as death or myocardial
infarction). The mean differences in outcome between the groups being studied
are weighted to account for different sample sizes and differing precision
between studies. The WMD is an absolute figure and so takes the units of the
original outcome measure.
A continuous outcome measure, similar to standardised mean differences but
based on one scale so in the real units of that scale. Ideal ly should be replaced
by a discrete outcome and a relative risk; however, we use WMD if this is not
possible.
* * *
* *
*
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Evidence-Based
Medicine Resources
A- Textbooks
1. Evidence-based medicine: How to practice and teach EBM. Sackett DL
et.al. New York, Churchill Livingstone,1997.
2. Evidence-based medicine: How to practice and teach EBM. Straus et.
al. New York, Churchill Livingstone, 3rd ed.
3. Evidence-based healthcare: How to make health policy and management
decisions. Muir Gray JA. New York, Churchill Livingstone,1997.
4. Towards evidence-based medicine in general practice. Rosser W.
Blacwell Science Inc., 1997.
5. Evidence-Based Family Medicine. Rosser WW, Shafir MS. Hamilton.
B.C. Decker Inc. 1998. [Also available in CD-ROM].
6. The evidence-based primary care handbook. Ed Mark Gabbay. Royal
Society of Medicine Press, 2000.
7. Evidence-Based Practice in Primary Care: Silagy C and Haines A. 2nd
Ed BMJ Books 2001 (Also available in Arabic).
املمارسة املستندة إلى أدلة في الرعاية الصحية األولية حترير أ.د.‏ كريس سيالجي .8
وأ.د.‏ أندروهينز،‏ ترجمة د.‏ لبنى األنصاري،‏ النشرالعلمي واملطابع - جامعة امللك
سعود،‏ ‎1425‎ه / ‎2004‎م
9. Evidence-based public health. Brownson RC, Baker EA, Leet TL,
Gillespie KN. Oxford University Press, New York 2002.
10. Users› Guides to the Medical Literature. Essentials of Evidence-Based
Clinical Practice. Gordon Guyatt, MD. Drummond Rennie, MD. 2002.
11. Users› Guides to the Medical Literature. A Manual for Evidence-Based
Clinical Practice. Gordon Guyatt, MD. Drummond Rennie, MD. 2002.
12. Appraisal of Guidelines for research & evaluation. AGREE instrument
training manual. The AGREE Collaboration, January 2003.
13. Fundamentals of Evidence-Based Medicine basic concepts in easy
language. Prasad K. 1st Ed. Meeta Publishers, New Delhi, 2004.
14. Evidence-Based Practice: A Primer for Health Care Professionals: Dawes
M, Davies M and Gray A. 2nd Ed. Churchill Livivngstone 2005.
15. How to Read a Paper: The Basics of Evidence-Based Medicine:
Greenhalgh T. 3rd Ed. BMJ Books & Blackwell Publishing London 2006.
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16. Evidence-based Medicine Toolkit: Heneghan C and Badenoch D. 2nd
Ed. BMJ Books & Blackwell Publishing London 2006.
B- Reappraised literature [Peer-reviewed publications
which retrieve and appraise articles from prominent
medical journals through rigorous criteria:
• The American College of Physicians Journal Club and Evidence Based
Medicine, a joint venture between ACP and BMJ.
Published six times a year, ACP Journal Club is the critically acclaimed
source to find the most important articles among the thousands
published each year in peer-reviewed journals. ACP Journal Club›s
distinctive format facilitates rapid assessment of each study›s validity
and relevance to your clinical practice.
http://www.acponline.org/journals/acpjc /jcmenu.hun.
• Evidence-Based Nursing.
http://ebn.bmjjournals.com/
• Cochrane Collaboration- An international network of more than 4000
scientists and clinical epidemiologists dedicated to «preparing,
maintaining and disseminating systematic reviews of health care.»
Cochrane Centers exist in Europe and North America, and have been
founded on the principle that summary data in the form of scientifically
conducted review articles (systematic overviews) represent the most
efficient means by which clinicians can quickly access relevant
information.
The Cochrane Library Updated quarterly. It is formed of several separate
databases, including The Cochrane Database of Systematic Reviews
(CDSR), which contains the full text of specially compiled systematic
reviews covering many branches of health care. It also contains the
protocols and progress reports of systematic reviews that are currently
being undertaken; The Database of Abstracts of Reviews of Effectiveness
(DARE) which contains structured abstracts of good quality systematic
reviews already published elsewhere; The Cochrane Controlled Trials
Register (CCTR) which contains the bibliographic details and MEDLINE
abstracts of about two orders of magnitude. A search of the Cochrane
Library searches all the databases, so search results will not all be
systematic reviews. CDSR and DARE form part of EBMR on Ovid Biomed
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(with ACP Journal Club). The Cochrane Library is a good source to try
first.
http://www.update-software.com/cochrane/cochrane-frame.html
• Clinical Evidence
Clinical Evidence (CE) is the continually updated international source
of the best available evidence on the effects of common clinical
interventions, published by the BMJ publishing group. Topics are selected
to cover common or important clinical conditions seen in primary care
or ambulatory settings. It presents clear summaries of evidence, derived
from systematic reviews and randomized controlled trials wherever
possible. Each CE topic is developed following a rigorous process to
ensure relevance and reliability. It is available online or PDA format.
http://www.clinicalevidence.com/
• Essential Evidence Plus:
Formerly InfoPOEMs/ InfoRetriever, is a powerful electronic resource
packed with the content, tools, calculators, podocasts and daily email
alerts fto help clinicians deliver first-contact evidence-based patient
care. InfoPOEMs: The Clinical Awareness System InfoPOEMs is a
searchable database of POEMS (Patient Oriented Evidence that Matters)
from the Journal of Family Practice. POEMS are summaries similar to
ACP Journal Club articles in methodology and format, targeted at family
practitioners. InfoRetriever simultaneously searches the complete
POEMs database (Infopoems) along with 6 additional evidence-based
databases, plus the leading quick-reference tool, to enable rapid lookup
and application of information and tools while you practice. In seconds,
you search the complete POEMs database, 120 clinical decision
rules, 1700+ diagnostic-test and H&PE calculators, the complete set of
Cochrane systematic review abstracts, all USPSTF guidelines plus all
evidence-based guidelines from the National Guidelines Clearinghouse
(NGC), and the Five-Minute Clinical Consult. The information is organized
and presented for immediate application to your practice. There is even
basic drug information and an ICD-9 lookup tool within the application.
http://www.essentialevidenceplus.com/index.cfm
• Evidence-Based Medicine
Available by subscription from the American College of Physicians and
Canadian Medical Association and the BMJ Publishing Group. Published
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imonthly in printed format, and included with ACP Journal Club on a
CD Rom called Best Evidence. Very similar in approach and format to
ACP Journal Club, but covering general practice, surgery, psychiatry,
paediatrics, obstetrics, and gynaecology.
http://www.bmjpg.comidata/ebm.htm
• The Evidence Based Medicine Jeddah Working Group
Provides EBM teaching materials, resources and links. Provides
information on local, regional and international EBM events.
P.O.Box: 15814 Jeddah 21454, KSA. Tel./ Fax: 00966 2 6725232
E-mail: ebmjeddah@yahoogroups.com
http://www.ebmjeddah.org/
• National & Gulf Center for Evidence Based Medicine (NGCEBM)
Post Graduate Training Center-National Guard Health Affairs, King
Abdulaziz Medical City - Riyadh. P.O.Box: 22490 Riyadh 11426, KSA.
E-mail: ebm@ngha.med.sa
www.ngha.med.sa/internet/Abunt-NGHA/Centers-noHP/NGCEBM/index.
htm
• Reference Gulf Center for EBM
Arabian Gulf University, College of Medicine and Medical Sciences,
P.O.Box: 22979 Manama, Kingdom of Bahrain. Tel.: 239999 - Fax:
271090.
• Evidence-based Mental Health
Evidence-Based Mental Health is published quarterly by the BMJ
Publishing Group. Evidence-Based Mental Health alerts clinicians
to important advances in treatment, diagnosis, etiology, prognosis,
continuing education, economic evaluation and qualitative research in
mental health. It selects and summarizes the highest quality original and
review articles. Experts in the field comment on the clinical relevance
and context of each study Thereby integrating the best available clinical
evidence with clinical experience.
http://ebmh.bmjjournals.com/
• Evidence-based Cardiovascular Medicine
http://www.harcourt-international.com/journals/ebm/
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C- Resources that will help you to learn more about EBM:
• Centre for Evidence Based Medicine (Oxford University)
http://www.cebm.net/ The site provides information on learning, doing
and teaching EBM as well as the EBM toolbox.
• Centre for Evidence-Based Medicine (University of Toronto).
http://www.cebm.utoronto.ca/ The goal of this website is to help develop,
disseminate, and evaluate resources that can be used to practise and
teach EBM for undergraduate, postgraduate and continuing education
for health care professionals from a variety of clinical disciplines.
• Critical Appraisal skills program (CASP).
CASP is a UK project that aims to help health service decision makers
develop skills in the critical appraisal of evidence about effectiveness,
in order to promote the delivery of evidence-based health care. The
Open Learning Resource, can be used by individuals or groups to
develop knowledge and skills to implement evidence-based health care
effectively in practice. The CD ROM and Workbook learning resource is
aimed at people who do not have wide internet access but want to work
in their own time using an interactive, supported educational tool. The
5 modules introduce the concept of EBM and cover the 5 basic steps
of EBM. Offprints of all the articles and source materials needed to
complete the activities in the resource and a comprehensive glossary
are provided.
• Netting the Evidence:
ScHARR Introduction to Evidence Based Practice on the Internet.
http://www.shef.ac.uk/scharr/ir/netting/ An alphabetical list of databases,
journals, software, organizations, resources for searching, appraising
and implementing evidence.
• An Introduction to Evidence-Based Medicine/ Information Mastery
Course:
A free web-based course (7 modules) prepared by Mark Ebell.
http://www.poems.msu.edu/InfoMastery.
• The Evidence-Based-Health Mailing list:
Organized by the Centre for Evidence-Based Medicine in Oxford.
http://www.jiscmail.ac.uk/lists/evidence-based-health.html
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-58-

References
For further readings
1. Evidence-Based Care Resource Group. Evidence-based medicine: a new
approach to teaching the practice of medicine. JAMA 1992;268(17):2420-
2425.
2. Silagy C, Lancaster T. The Cochrane Collaboration in primary health care.
Fam Pract 1993;10:364-365.
3. Guyatt GH, Rannie D. Users’ Guides to Reading the medical literature:
Editorial. JAMA 1993;270(17):2096-2097.
4. Weatherall, D.J. The Unhumanity of Medicine. British Medical Journal, 1994,
(308) 1671-72.
5. Evidence-Based Care Resource Group. Evidence-Based Care: 1. Setting
Priorities: how important is this problem Can Med Assoc J 1994;150:1249-
1254.
6. Evidence-Based Care Resource Group. Evidence-Based Care: 2. Setting
guidelines: how should we manage this problem Can Med Assoc J
1994;150:1417-1423.
7. Evidence-Based Care Resource Group. Evidence-Based Care: 3. Measuring
performance: how are we managing this problem Can Med Assoc J
1994;150(11):1575-1579.
8. Evidence-Based Care Resource Group. Evidence-Based Care: 4. Improving
performance: how can we improve the way we manage this problem Can
Med Assoc J 1994;150(11):1793-1796.
9. Evidence-Based Care Resource Group. Evidence-Based Care: 5. Lifelong
learning: how can we learn to be more effective Can Med Assoc J
1994;150(12):1971-1973.
10. Ridsdale L. Evidence-Based General Practice. A critical reader. W.B.
Saunders Company Ltd. 1995.
11. Richardson WS, Wilson MC, Nishikawa J, Hayward RSA. The well-built
clinical question: a key to evidence-based decisions. Editorial. ACP J Club
1995 Nov/Dec;123:A12-A13.
12. Ham C, Hunter DJ, Robinson R. Evidence based policymaking. BMJ
1995;310:71-72.
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13. Fahey T, Griffiths S, Peters TJ. Evidence based purchasing: Understanding
results of clinical trials and systematic reviews. BMJ 1995;311:1056-1060.
14. Guyatt GH, Cook DJ, Jaeschke R. How should clinician use the results of
randomized trials Editorial. ACP J Club 1995 Jan/Feb;122:A12-A13.
15. Guyatt GH, Jaeschke R, Cook DJ. Applying the findings of clinical trials to
individual patients. Editorial. ACP J Club 1995 Mar/Apr;122:A12-A13.
16. Cook RJ, Sackett DL. The number needed to treat: a clinically useful
measure of treatment effect. Br Med J 1995;310:452-454.
17. Bero L, Rennie D. The Cochrane Collaboration: preparing, maintaining
and disseminating systematic reviews of the effects of health care. JAMA
1995;274:1935-1938.
18. Freemantle N, Grilli R, Grimshaw J et al. Implementing findings of medical
research: the Cochrane collaboration on effective professional practice.
Quality in Health Care 1995;4:45-47.
19. Evidence-based medicine, in its place. Editorial. Lancet 1995;346:785.
20. Davidoff F, Haynes B, Sackett D, smith R. Evidence-based medicine.
A new journal to help doctors identify the information they need. BMJ
1995;310:1085-1086.
21. Ellis J, Mulligan I, Rowe J, Sackett DL. In patient general medicine is
evidence based. Lancet 1995;346:407-410.
22. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence
based medicine: What it is and what it is not. BMJ 1996;312:71-72.
23. Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based
medicine: how to practice and teach EBM. BMJ 1996; 313:1410 (30
November).
24. Meade MO, Richardson WS., Eds:Mulrow C, Cook DJ. Selecting and
appraising studies for a systematic review. Ann Intern Med 1997; 127:531-
537.
25. Counsell C. Eds: Mulro C, Cook DJ. Formulating questions and locating
primary studies for inclusion in systematic reviews. Ann Intern Med
1997;127:380-387.
26. Bero LA, Jadad AR. How consumers and policymakers can use systematic
reviews for decision making. Ann Intern Med 1997;127:37-42.
27. Cook DJ, Greengold NL, Ellrodt AG, Weingarten SR. The relation between
systematic reviews and practice guidelines. Ann Intern Med 1997;127:210-
216.
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28. Mulrow C, Cook D. Integrating heterogeneous pieces of evidence in
systematic reviews. Ann Intern Med 1997;127(11):989-995.
29. Mulrow C, Langhorne P, Grimshaw J. Eds. Mulro C, Cook DJ. Integrating
heterogenous pieces of evidence in systematic reviews. Ann Intern Med
1997;127:989-995.
30. Brouwers M, Haynes RB, Jadad A, Hayward RSA, Padunsky J, Yang
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Performance Quality Health Care 1997;5:195-201.
31. Ellrodt G, Cook DJ, Lee J, Hunt D, Weingarten S. Evidence –based disease
management. JAMA 1997;278(20):1687-1692.
32. Cook DJ, Mulro CD, Haynes RB: Synthesis of Best Evidence for Clinical
Decisions. Ann Intern Med 1997;126:376-80.
33. Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: Synthesis of best
evidence for clinical decisions. Ann Intern Med 1997;126:376-380.
34. Hunt DL, McKibbon A. Locating and appraising systematic reviews. Ann
Intern Med 1997;126:532-538.
35. Rosser WW, Shafir MS. Evidence-based family medicine. Hamilton: B.C.
Decker Inc., 1998.
36. McColl A, Smith H, White P, field J. General practitioner›s perceptions of
the route to evidence-based medicine: a questionnaire survey. BMJ 1998;
316:361-5.
37. Green L. using evidence-based medicine in clinical practice. Prim care
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38. Kathleen N. Lohr, Kristen Eleazer, Josephine Mauskopf. Review Health
policy issues and applications for evidence-based medicine and clinical
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39. Alastair McColl, Paul Roderick, John Gabbay, Helen Smith, Michael Moore.
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40. Campbell H, Hotchkiss R, Bradshaw N, Porteous M. Integrated care
pathways. Education and Debate. BMJ 1998;316:133-137.
41. Haynes B, Haines A. Barriers and bridges to evidence based clinical
practice, BMJ 1998; 317:276-6.
42. Salisbury C, Bosanquet N, Wilkinson E, Bosanquet A, & Hasler J, The
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43. Jefferson Health System: From editor. Higher Quality at lower cost: Is
evidence-based Medicine the answer. Health policy newsletter January
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44. Stewart A. Evidence-based medicine: a new paradigm for the teaching and
practice of medicine. Annals of Saudi Medicine 1999; 19(1):32-36.
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46. Dawes M, Davies P, Gray A., et al. Evidence-based Practice. A primer for
health care professionals. London, Churchill Livingstone 1999.
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48. Hannay DR. The evidence-based primary care handbook: Review. BMJ
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performance indicators in primary care: a qualitative study. Quality
in Health Care 2000;9: 166-174.
50. Greenhalgh T. How to read a paper. The basics of evidence-based medicine
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51. Rodrigues RJ. Information systems: the key to evidence-based
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55. Silagy C, Haines A (ed). Evidence-based practice in primary care. 2nd
edition. London; BMJ books, 2001.
56. Gray JAM. Evidence-based healthcare: how to make health policy and
management decisions. 2nd edition London: Churchill Livingstone, 2001.
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