EVIDENCE based MEDICINE

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EVIDENCE based MEDICINE
I N T R O D U C T I O N T O

• BY
• Dr. Mohamed Abdelhafez

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History of EBM !

• The ideas behind it are far from new - it is to
  be hoped that clinicians have to some extent
  always used the evidence (at least as they saw
  it!) to support their treatment of patients

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History of EBM !

• "Believe nothing
• Merely because you have been told itOr because
  it is traditionalOr because you yourself have
  imagined it.Do not believe what your teacher
  tells youMerely out of respect for the
  teacher But whatever after due examination and
  analysisYou find conducive to the good, the
  benefitThe well-being of all thingsThat
  doctrine believe and cling toAnd take it as your
  guide." 

Buddha, 3rd Century BC 
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History of EBM !

• "Those who are enamoured of practice without
  science are like a pilot who goes into a ship
  without rudder or compass and never has any
  certainty where he is going. Practice should
  always be based upon a sound knowledge of
  theory."Leonardo da Vinci, Notebooks,
  1508-1518.

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History of EBM !

• The first recorded clinical trial dates back to
  more than 2000 years by Daniel of Judah compared
  the health effects of a vegetarian diet (the
  intervention) with those of the Royal Babylonian
  diet (control group) over a ten-day period.

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History of EBM !

• The Book of Daniel records (1.15-16) that
• "At the end of the ten days their appearance was
  better and their bodies healthier than all the
  young men who had been eating the royal
  delicacies. So the warden removed their
  delicacies and the wine from their diet and gave
  them a diet of vegetables instead."

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History of EBM !

• Despite the dramatic findings of the study , the
  trial had obvious deficiencies by contemporary
  methodological standards (allocation bias) but
  the publication has remained influential over two
  millennia."

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History of EBM !

• Frederick II (1194-1250) who was interested in
  the effects of digestion.
• He fed two knights identical meals then sent one
  to bed and the other out hunting .
• The King had both knights killed so that he could
  examine their stomach contents and concluded the
  sleeping knight had evidence of better progress
  with digestion.

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History of EBM !

• The first reported controlled therapy trial took
  place in the United Kingdom in 1747.
• Since the early 1600s, many people had felt that
  citrus fruits might reduce the incidence of
  scurvy during long ocean voyages.

James Lind studied sailors with scurvy and
evaluated six potential treatments one of which
involved using citrus fruits. The two sailors who
received the citrus treatment got better as Lind
reported.
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Methods of Practicing Medicine

• Knowledge (Study).
• Clinical experience (Practice).
• Reading (Non systematic way).
• Expert and peer opinion.
• Logic

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Knowledge

• The knowledge decreases with time after graduation

The Slippery Slope
Knowledge of best care
r0.54 plt0.001
Years since graduation
5 10 15 20
Shin et al CMAJ 1993
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Experience

• There always new developments in medicine.
• Difficult to catch up.

New Techniques
New Drugs
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Reading

• Traditional Text Books are always outdated.

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Reading

• Quantity of journals and articles makes it
  impossible to keep updated.

20,000 biomedical journals 5,000 articles/day
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Ask an Expert

• There is always more than one expert opinion.

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Logic

• Logic doesnt always lead to the right
  conclusion.

sun
earth
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Conclusion

• The best way to practice medicine is to be based
  on the best available evidence together with our
  experience and patient preferences.

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What is EBM ?
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What is EBM ?

• The development of evidence-based medicine has
  been rapid over the past 10 years, and has been
  led by Professor
• David Sackett.

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What is EBM ?

• It is the integration of best research evidence
  with clinical experience and patient values .
• Sackett,2000

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Practicing Medicine Without Evidence
BACK TO SLEEP

• In the 1980s studies found a dramatic drop in
  SIDS among children sleeping on their backs.

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Practicing Evidence Based Medicine

• Assess and examine your patient.
• Construct a well built clinical question derived
  from the case.
• Select the appropriate resource(s) and conduct a
  search.
• Appraise that evidence for its validity and
  applicability.
• Integrate that evidence with clinical expertise,
  patient preferences and apply it to practice.
• Evaluate your performance with this patient.

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Steps of Practicing EBM
Assess Your patient
Ask a clinical question
Acquire the best evidence
Apply the evidence to the patient care
Evaluate your performance
Appraise the evidence
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Step I Assess Your Patient

• History
• Physical examination
• Investigations
• Determine the problem

After this we will start to construct a clinical
question built on the problem
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Step II Ask Clinical Question

• There are 2 types of clinical questions
• Background question.
• Foreground question.

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Step II Ask Clinical Question

• Background question
• General knowledge about a disorder.
• Components Question root what, how, where,
  etc verb disorder or intervention.
• Examples What causes hypertension ?How do we
  tap ascites ?

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Step II Ask Clinical Question

• Foreground question
• Specific knowledge about a disorder.
• Components Patient or problem Intervention,
  prognostic factor, or exposure Comparison
  Outcome
• Examples In patients with tense ascites is
  tapping superior to diuretic therapy in
  controlling ascites.

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Types Of Clinical Question
Background
Foreground
Percentage of questions
Experience
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Step II Ask Clinical Question

• In practicing EBM we use Foreground questions.
• We construct the question according to four
  components PICO
• Patient or problem
• Intervention, prognostic factor, or exposure
• Comparison
• Outcome

PICO
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Step II Example for Clinical Question

• Pauline is a new patient who recently moved to
  the area to be closer to her son and his family.
  She is 67 years old and has a history of
  congestive heart failure brought on by several
  myocardial infarctions.

PICO
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Step II Example for Clinical Question

• She has been hospitalized twice within the last 6
  months for worsening of heart failure. At the
  present time she remains in normal sinus rhythm.
  She is extremely diligent about taking her
  medications (enalapril, aspirin and simvastatin)
  and wants desperately to stay out of the
  hospital. She lives alone with several cats.

PICO
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Step II Example for Clinical Question

• You think she should also be taking digoxin but
  you are not certain if this will help keep her
  out of the hospital. You decide to research this
  question before her next visit.

PICO
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Step II Example for Clinical Question
The structure of the question might look like
this
Patient / Problem
congestive heart failure, elderly
Intervention
digoxin
Comparison
none, placebo
PICO
Outcome
primary reduce need for hospitalization
secondary reduce mortality
In elderly patients with congestive heart
failure, is digoxin effective in reducing the
need for rehospitalization?
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Step II Ask Clinical Question

• Two additional elements of the well-built
  clinical question are the type of question and
  the type of study. This information can be
  helpful in focusing the question and determining
  the most appropriate type of evidence.

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Step II Ask Clinical Question

• The most common types of questions related to
  clinical tasks are

Diagnosis
how to select and interpret diagnostic tests .
Therapy
how to select treatments to offer patients that
do more good than harm and that are worth the
efforts and costs of using them
Prognosis
how to estimate the patient's likely clinical
course over time and anticipate likely
complications of disease
Harm/Etiology
how to identify causes for disease (including
iatrogenic forms)
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Step II Ask Clinical Question

• Type of Study

The Evidence Pyramid
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The Hierarchy of Research

• NOW, we will understand the study design

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WAKE UP !!!
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The Hierarchy of Research
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The Hierarchy of Research
A

• DESCRIPTIVE STUDIES

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A Descriptive Studies

• Case reports and series
• Case series and case reports consist either of
  collections of reports on the treatment of
  individual patients, or of reports on a single
  patient.
•  Case series and case reports, since they use no
  control group with which to compare outcomes,
  have no statistical validity .

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A Descriptive Studies

• Case reports and series

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The Hierarchy of Research

• COMPARATIVE STUDIES

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The Hierarchy of Research
B

• OBSERVATIONAL STUDIES

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The Hierarchy of Research
B

• OBSERVATIONAL STUDIES
• I. Cohort Study

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B Observational Studies

• I. Cohort Study
• A Cohort Study is a study in which patients who
  presently have a certain condition and/or receive
  a particular treatment (exposed) are followed
  over time and compared with another group who are
  not affected by the condition (controls).
• Its a prospective study.

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B Observational Studies

• I. Cohort Study

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B Observational Studies

• I. Cohort Study
• Advantages
• Ethically safe.
• Subjects can be matched.
• Can establish timing and directionality of
  events.
• Eligibility criteria and outcome assessments can
  be standardized.
• Administratively easier and cheaper than RCT.

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B Observational Studies

• I. Cohort Study
• Disadvantages
• The controls may be difficult to identify.
• Exposure may be linked to a hidden confounder.
• Blinding is difficult.
• Randomization not present.
• For rare disease, large sample sizes or long
  follow-up necessary.

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The Hierarchy of Research
B

• OBSERVATIONAL STUDIES
• II. Case Control Study

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B Observational Studies

• II. Case Control Study
• Case control studies are studies in which
  patients who already have a certain condition are
  compared with people who do not.
•  Its a retrospective study

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B Observational Studies

• II. Case Control Study

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B Observational Studies

• II. Case Control Study
• Advantages
• Quick and cheap.
• Only feasible method for very rare disorders or
  those with long lag between exposure and outcome.
• Fewer subjects needed than cross-sectional
  studies.

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B Observational Studies

• II. Case Control Study
• Disadvantages
• Reliance on recall or records to determine
  exposure status.
• Confounders.
• Selection of control groups is difficult.
• Potential bias recall, selection.

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B Observational Studies

• Relative Risk
• factor
• RR

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B Observational Studies RR

• Relative risk is a measure of how much a
  particular risk factor (say cigarette smoking)
  influences the risk of a specified outcome (say,
  death by age 70)

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B Observational Studies RR

• For example, a relative risk of 2 associated with
  a risk factor means that persons with that risk
  factor have a 2 fold increased risk of having a
  specified outcome compared to persons without
  that risk factor.

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B Observational Studies RR

• A relative risk of 0.5 means that persons with
  that risk factor have half the risk of the
  specified outcome (a protective effect) compared
  to persons without the risk (protective) factor.

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B Observational Studies RR

• In Cohort study we can calculate the RR.
• In Case-control study we calculate OR (odds
  ratio) instead.OR is about equal to the RR.
• N.B. We cant calculate RR in case-control
  studies.

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B Observational Studies RR

• The Two by Two Table

Outcome
ve
- ve
ve
A
B
C
Factor
- ve
D
F
G
H
I
J
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B Observational Studies RR
In Cohort study RR AR
Absolute Risk in exposure group
Absolute Risk in non-exposure group
No. of outcome
Total No.
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B Observational Studies RR
In Case-control study OR Odds of exposure

Odds of exposure in the cases
Odds of exposures in the controls
No. of exposed
No. of unexposed
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B Observational Studies RR
In Cohort study RR (A/C) / (D/G)
In Case-control study OR (A/D) / (B/F)
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Examples for RR OR

• EXAMPLE I

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Examples I

• In a study about the association of smoking and
  lung cancer, 6000 participants were enrolled.
• 2000 were smokers and 4000 were non-smokers.
• During 10 years of follow up, 100 of the smokers,
  and 100 of non-smokers developed lung cancer.

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Examples I
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Examples I

• What is this study design ?
• What is absolute risk and relative risk of
  developing lung cancer with smoking?

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Examples I
Absolute risk of lung cancer among smokers 100
/ 2000 Absolute risk of lung cancer among
non-smokers 100 / 4000 Relative Risk 2 Lung
cancer increases by 2 fold with smoking.
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Examples for RR OR

• EXAMPLE II

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Examples II

• In a hypothetical study in which 200 cases of
  lung cancer were compared with 200 controls
  regarding their smoking habits. The history of
  smoking was inquired.
• 127 of the lung cancer patients were smokers.
• 79 of control group were smokers.

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Examples II
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Examples II

• What is this study design ?
• What is odds ratio ?
• What association between smoking and lung cancer,
  you conclude from this study?

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Examples II

• Odds of exposure among cases 127 / 73
• Odds of exposure among controls 79 / 121
• Odds Ratio 2.66
• Smoking increases the probability of having lung
  cancer by 2.66 fold.

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The Hierarchy of Research
B

• OBSERVATIONAL STUDIES
• III. Cross Sectional Study

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B Observational Studies

• III. Cross Sectional Study
• A study in which the exposure and outcome are
  determined simultaneously.
• Thus the cause and effect relationship between
  the two cant be clearly established.
• It is Snap Shot in Time study

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B Observational Studies

• III. Cross Sectional Study
• Advantages
• Cheap and simple.
• Ethically safe.

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B Observational Studies

• III. Cross Sectional Study
• Disadvantages
• Establishes association at most, not causality
• Recall bias susceptibility
• Confounders may be unequally distributed
• Neyman bias
• Group sizes may be unequal.

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The Hierarchy of Research
C

• EXPERIMENTAL STUDIES
• RCT

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WAKE UP !!!
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C The RCT

• The Gold Standard Of Clinical Research

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C The RCT

• Randomized controlled trial is one in which
• Patients are randomly assigned to two or more
  groups
• One or more intervention groups and one control
  group
• Followed up in time
• The outcomes are compared.

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C The RCT

• Randomized controlled trial

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C The RCT

• Advantages
• The least biased Design.
• Blinding more likely
• Randomization facilitates statistical analysis.

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C The RCT

• Disadvantages
• Expensive time and money.
• Volunteer bias.
• Ethically problematic at times.

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C The RCT

• Evaluation of RCTs
• For those who apply conclusions of RCTs in their
  clinical practice, its essential to know how to
  evaluate them properly.
• A biased RCT can be hazardous to medical practice
  and patients.

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C The RCT

• Importance Of Randomization
• Assigning patients at random reduces the risk of
  bias and increases the probability that
  differences (confounders) between the groups can
  be attributed to the treatment.
• Confounder A variable, other than the one
  studied, that can cause or prevent the outcome of
  interest. A confounding variable may be due to
  chance or bias.

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C The RCT

• Importance Of Randomization
• With proper randomization the basic
  characteristics of the participants are similar
  in all the groups.
• These are called balanced groups.
• The only variable will be the intervention.

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C The RCT

• The Double Blind Method
• A double blind study is one in which neither the
  patient nor the physician knows whether the
  patient is receiving the treatment of interest or
  the control treatment.

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C The RCT

• The Double Blind Method

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C The RCT

• Importance Of Blinding
• A double blind study is the most rigorous
  clinical research design because, in addition to
  the randomization of subjects which reduces the
  risk of bias, it can eliminate the placebo effect
  which is a further challenge to the validity of a
  study.

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C The RCT

• Double Blind

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C The RCT

• The placebo effect could be thought of in this
  way
•  
• Patients who believe they are receiving a new
  experimental treatment tend to be more optimistic
  about the outcome.
• Doctors who believe that a patient is receiving a
  new experimental treatment tend to be more
  optimistic about that patient's chances, evaluate
  their state of health more favorably, and
  communicate positive expectations to the
  patients, who in turn try to get better so as to
  prove their doctor right!  

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C The RCT

• Importance Of Blinding
• In a review of acupuncture for back pain
  including both non-blinded and blinded studies
• Non-blinded studies showed a significant relative
  benefit of 1.8
• Double blind studies showed that acupuncture has
  no benefit in pain relief.

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C The RCT

• Prospective, Blind Comparison To A Gold Standard
  Study
• Studies that show the efficacy of a diagnostic
  test.
• This is a controlled trial that looks at patients
  with varying degrees of an illness and
  administers both diagnostic tests, the test under
  investigation and the "gold standard" test to all
  of the patients in the study group.

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C The RCT

• Bias in RCTs
• There are several bias that could affect the RCTs
  including
• Sampling Bias
• Selection Bias
• Ascertainment Bias
• Withdrawal or Drop Out Bias
• Publication Bias

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The Hierarchy of Research
D

• Systematic Reviews
• and
• Meta-Analyses
• TOP OF THE EVIDENCE PYRAMID

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D Systematic Reviews and Meta-Analyses

• A systematic review is a comprehensive survey of
  a topic in which all of the primary studies of
  the highest level of evidence  have been
  systematically identified, appraised and then
  summarized according to an explicit and
  reproducible methodology.

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D Systematic Reviews and Meta-Analyses

• A meta-analysis is a survey in which the results
  of all of the included studies are similar enough
  statistically that the results are combined and
  analyzed as if they were one study.  

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D Systematic Reviews and Meta-Analyses
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D Systematic Reviews and Meta-Analyses

• In general
• a good systematic review or meta-analysis will be
  a better guide to practice than an individual
  article.

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D Systematic Reviews and Meta-Analyses

• Three Main Pitfalls Specific
• To Meta-analysis

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D Systematic Reviews and Meta-Analyses

• It's rare that the results of the different
  studies precisely agree, and often the number of
  patients in a single study is not large enough to
  come up with a decisive conclusion.  

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D Systematic Reviews and Meta-Analyses

• If the authors are interested in supporting a
  particular conclusion, they can include studies
  that support that conclusion and omit studies
  that do not.
• Do the authors explain in their paper exactly on
  what basis they included studies , and do their
  reasons make sense?  

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D Systematic Reviews and Meta-Analyses

• Studies that show some kind of positive effect
  tend to be published more often than those that
  do not. This means that if the authors include
  only published studies, several weak positive
  studies may seem to add up to a strong positive
  result.
• Do weak negative studies exist? This effect is
  known as Publication bias.

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Next Session

• RCT. (Design and Bias)
• Searching the literature.
• Appraising the evidence.
• How to apply the evidence to my patient.

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