evidence based medicine

1. Evidence-Based Medicine
Hajer Elkout

2. Outlines…
 What is Evidence-Based-Medicine (EBM)?
 Why do we need EBM?
 The steps of practicing EBM.
 Resources of EBM.
 Trials, studies and reports.
 Who can practice EBM?
 Pros and cons.
 Limitation.
 EBM and guidelines.

3. What is EBM?
‘The process of systematically finding, appraising and
using contemporaneous research findings as a basis
for clinical decisions’.
Rosenberg, Donald 1995
 It is the integration of best research evidence with
clinical expertise and patient values.
Sackett, et al 2001

4.  In the practice of Evidence Based Medicine, it is the
physician’s duty to find the best and most current
information and apply it cautiously for the benefit of
the patient
 BUT….allow for individual human differences and
personal preferences!

5. Evidence based practice
 how accurate are diagnostic tests?
 how strong are prognostic markers?
 how effective are interventions?
 Therapy
 Screening
 Prevention
 by using this evidence:
 more efficiently
 more critically
 more systematically

6. Why bother? Why do we need EBM?

8. McNaughton R, Huet G, Shakir S. BMJ Open 2014;4:e004221.

9. Why?
 New evidence is produced every day which could
make major changes in the way that we care for our
patients.
 Without keeping up-to-date our clinical performance
may deteriorate.
 EBM has been shown to keep doctors up to date
and ultimately improve health care.
 Laws and regulations.
 General public have greater access to health care
information (web, media etc).

10. WHAT IS THE BASIS OF YOUR
MEDICAL PRACTICE?

12. WHAT IS THE BASIS OF YOUR MEDICAL
PRACTICE?
 Clinical experience and consultation with professionals.
BUT… Past knowledge and practice might be outdated or inadequate
 Convincing evidence (non-experimental) from articles, case
reports, product literature, etc.
BUT…This evidence may be biased, outdated, incorrect, or not applicable
to your patient
 Preferences of the patient.
But… This is NOT always an easy task!
 Active search of RCT, Systematic Reviews, Meta-Analysis
Reports.
But… A practice based exclusively on science and math is effective only if

13. How many hours did you spend reading?
 “A 21st century clinician who cannot critically read a
study is as unprepared as one who cannot take a
blood pressure or examine the cardiovascular
system.”
BMJ 2008:337:704-705

15. what skills will you
need to keep up to
date with the best
evidence?
 to find the evidence more efficiently.
 to appraise the quality of the evidence more
effectively.
 to use good quality evidence more systematically.
Must be aware of their responsibility to
maintain their knowledge and skills
throughout there careers.
Students are expected to keep up to
date and to apply knowledge
necessary for good clinical care.

16. What is Evidence-based Practice
 EBP is about asking questions and searching for
answers in the body of medical research, and
having found a likely source of information
appraising the paper for its scientific validity and
then applying the result to your problem.

17. The steps of practicing EBM
‘EBM begins and ends with patients’
1. Ask a focused question.
2. Track down the evidence
3. Critically appraise evidence for its validity, quality,
precision
4. Apply the evidence in practice:
 amalgamate the valid evidence with other relevant
information (values & preferences, clinical/health issues,
& system issues)
 implement the decision in practice.
5. Evaluate your practice.

18. The best question (PICO)
 P = Patient population
 I = Intervention
 C = Comparison
 O = Outcome

19. Patient population/disease The patient population or disease of interest
- age
- gender
- ethnicity
- with certain disorder (e.g., hepatitis)
Intervention The intervention or range of interventions of interest
- Exposure to disease
- Prognostic factor A
- Risk behavior (e.g., smoking)
Comparison What you want to compare the intervention against
- No disease
- Placebo or no intervention/therapy
- Prognostic factor B
- Absence of risk factor (e.g., non-smoking)
Outcome Outcome of interest
- Risk of disease
- Accuracy of diagnosis
- Rate of occurrence of adverse outcome (e.g., death)
PICO: Components of an answerable, searchable question
Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice.
Philadelphia, PA: Lippincott Williams &Wilkins.

20. QuestionTemplates for Asking PICO Questions
Therapy
In __________________, what is the effect of ____________________ on
______________________ compared with __________________?
Etiology
Are _____________ who have ________________ at ______________
risk for/of ____________________ compared with _____________________
with/without ______________________?
Diagnosis or DiagnosticTest
Are (Is) _________________________ more accurate in diagnosing___________
compared with ________________?
Prevention
For _________________ does the use of _______________ reduce the future
risk of ________________ compared with _________________?
Prognosis
Does _______________ influence _________________ in patients who have
__________________?
Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia, PA:
LippincottWilliams &Wilkins.

21. Ask a clinical question:

22. Exaples:
 Etiology: Are 30-50 year old women (P) who have high
blood pressure (I) at increased risk for myocardial
infarction (O) compared with women without high blood
pressure (C)?
 Diagnosis: In middle-aged males with suspected
myocardial infarction (P), are serial 12-lead ECGs (I)
compared to one initial 12-lead ECG (C) more accurate
in diagnosing an acute myocardial infarction (O)?
 Prognosis: For patients 65 years and older (P), how
does the use of an influenza vaccine (I) compared to not
received the vaccine (C) influence the risk of developing
pneumonia (O) during flu season (T)?

23. Clinical case
 P: 6 y/o girl with asthma (step 3)
 I: Adding LABA/ICS combined inhaler
 C: LABA + ICS separate inhalers
 O: asthma control

24. The steps of practicing EBM
‘EBM begins and ends with patients’
1. Ask a focused question.
2. Track down the evidence
3. Critically appraise evidence for its validity, quality,
precision
4. Apply the evidence in practice:
a. amalgamate the valid evidence with other relevant
information (values & preferences, clinical/health issues,
& system issues)
b. implement the decision in practice
5. Evaluate your practice.

25. Find the Best Evidence:
“The Literary Search”
 External - from outside resources (researchers,
experts)
 Current – not out of date, most recent
 High Quality - accurate, precise, effective, safe
 Patient focused - applicable and appropriate for
your individual patient

26. What study design fits it best?
 EXPERIMENTAL TRIALS
 (Answers questions of diagnosis or treatment)
 Randomized Controlled Trials (RCTs)
 Controlled studies
 Blinded vs Open
 OBSERVATIONAL STUDIES
 Descriptive reports
 Retrospective studies
 Cohort studies
 Case Control

28. 0
500000
1000000
1500000
2000000
2500000
Biomedical MEDLINE Trials Diagnostic?
MedicalArticlesperYear
5,000?
per day
2,000
per day
75 per
day
ArticlesPerYear
There is an epidemic of evidence to keep up
with!

29. Literary resources
 Textbooks (caution – most obsolete!)
 Journals (may be outdated)
 Review articles (summaries, abstracts)
 Systematic reviews (prepared in systematic, rigorous
manner) ex: cochrane collection
 Meta-analysis
 Clinical practice guidelines
 Summarized and easily digestible information

30. Electronic resources, databases,
internet
 Bibliographic database: medline, pubmed.
 Medical information services: medscape.
 Review services
 Subjective
 Systematic reviews
 Meta-analysis
 examples: Cochrane,
 Best evidence,
 Up to date

31. To answer the previous question,
208 research paper!!!

32. The steps of practicing EBM
‘EBM begins and ends with patients’
1. Ask a focused question.
2. Track down the evidence
3. Critically appraise evidence for its validity, quality,
precision
4. Apply the evidence in practice:
a. amalgamate the valid evidence with other relevant
information (values & preferences, clinical/health issues,
& system issues).
b. implement the decision in practice.
5. Evaluate your practice.

33. Critical appraisal!!
 Interpreting the evidence
 How to read a paper?
 How to do the math?

34.  You do NOT have to become a researcher,
epidemiologist, or statistician to practice EBM.
HOWEVER…
 in order to understand and interpret the evidence
you must have a solid understanding of:
 basic research principles and
 study designs.

35. Quality of medical literature
Journal High Quality Articles
N Eng J Med 17%
Ann Intern Med 13%
JAMA 12%
BMJ 9%
Lancet 8%
About 1/2 of ‘valid’ evidence today is out of date in 5 years
About 1/2 of valid evidence is not implemented
Add a reference

36. Hierarchy of evidence
value of study design to maximize weight and minimize bias
1. Systematic review of all relevant RCTs.
2. At least one properly designed RCT.
3. Well-designed controlled trial without randomization.
4. Well designed cohort or case control studies, preferably.
from >1 center or group.
5. Multiple time series with or without intervention.
6. Opinions of respected authorities.
7. Clinical expertise.
8. Descriptive studies.
9. Reports of expert committees

37. Types of study evidence affects the
quality

38. Going back to our example
 Bensch G, Berger WE, Blokhin BM et al.:One-year efficacy and safety of
inhaled formoterol dry powder in children with persistent asthma Ann.
Allergy Asthma Immunol. 89(2), 180–190 (2002).
 Levenson M: Long-acting b-agonists and adverse asthma events meta-
analysis: Drug Safety and Risk Management Advisory Committee, and
Pediatric Advisory Committee 2008
 Cates Christopher J,Cates Matthew J: Cochrane Database Syst. Rev. (3),
CD006363 (2008).
 Cates CJ, Lasserson TJ, Jaeschke R: Cochrane Database Syst. Rev. (2),
CD006923 (2009).
 Bisgaard H:. Pediatr. Pulmonol. 36(5), 391–398 (2003).
 Plint AC, Russell K, Bjornson CL, Rowe BH: The Cochrane library and
long-acting b-agonist treatment for childhood asthma: an overview of
reviews. Evid. Based Child Health 3, 909–919 (2008)
 US Department of Health and Human Services; NHLBI: Guidelines for the
diagnosis and management of asthma
 MHRA safety alerts: salmeterol and formoterol in asthma management
 Rabe Kf et al: Effect of budesonide in combination with formoterol for
reliever therapy in asthma exacerbations: a randomised controlled,
double-blind study. Lancet 368(9537), 744–753 (2006).

39. How to read a paper?
 Is it reliable?
 Is it valid?
 Is it relevant?
 What is the clinical importance of the study?

40. The good news:
most articles should be ignored
EBM Journal Process
 140+ journals scanned
 60,000 articles
 Is it valid? (<5%)
 Intervention: RCT
 Prognosis: inception cohort
 Etc
 Is it relevant?
 6-12 GPs & specialists asked:
Relevant? Newsworthy?
 < 0.5% selected
Number Needed to Read
to find 1 valid is 20+
Number Needed to Read
to find 1 valid & relevant is
200+

41. How to do the maths?
 Sample size.
 Representative
 Generalisable
 Statistical test used
 P-value and confidence intervals
 Odds ratio and Hazard ratio.
 Sensitivity and specificity.

42. EBM vocabulary for 21st Century Medicine…
ARR
Efficacy
Intention-to-treat
Likelihood ratio
OR
Meta-analysis
DB-RCT
Cost-benefit
Population attributable risk
95% CI
Sensitivity
HR

43. Reminder
 We need another session(s) to talk about:
1. Basic research principles, types of studies, …...
2. Search, retrieve literature from online resources.
3. Critical appraisal of research papers.

44. The steps of practicing EBM
‘EBM begins and ends with patients’
1. Ask a focused question.
2. Track down the evidence
3. Critically appraise evidence for its validity, quality,
precision
4. Apply the evidence in practice:
a. amalgamate the valid evidence with other relevant
information (values & preferences, clinical/health issues,
& system issues)
b. implement the decision in practice.
5. Evaluate your practice.

45. Apply the evidence in practice
Fancy trials and complex reports won’t help the
patient…
Treatment will!

46. The LABA controversy, the conclusion

47. Implement the decision in practice
 Can the results be extrapolated to your patient?
 Availability of tests/treatment
 Affordability of tests/treatment
 Are there adverse risks?
 Are there alternatives?
 What are the patient preferences?

48. Step 5, evaluate your performance
 Clinical efficacy.
 Cost analysis.
 Patient surveys.
 Mortality/morbidity
rates.

49. Pros and cons of EBM

50. Pros
 Clinicians update knowledge base routinely.
 Improved understanding of research methods.
 Physician becomes more critical in use of data.
 Increased confidence in management decisions.
 Increased computer literacy, data search technology.
 Better reading habits.
 Provides framework for group problem solving, team
generated practice.

51. Cons
 Time consuming
 Information overload
 Time to learn and practice
 Cost to establish resource infrastructure (library,
office, computers, etc).
 May expose your current practice as obsolete or
dangerous (loss of authority and respect).

52. Limitations
Physician attitude: Can be the greatest limitation!
 “It decreases the importance of my clinical expertise”
(that’s a necessary component!)
 “It only applies to those involved in research.”
 “It ignores patient values and preferences.”
 “It’s just another cookbook approach to medicine.”
 “It’s a poorly masked way to cut medical costs.” (cost of
care may actually increase).

53. At the end…….
“DOES EBM REALLY MAKE A
DIFFERENCE?”

54. Guidelines

55. What are clinical practice guidelines?
Clinical practice guidelines are recommendations
for clinicians and consumers about optimal and
appropriate care for specific clinical situations

56. Formal or informal guidelines are the
basis for all clinical practice
 Basis for most clinical decisions
 Foundation of clinical teaching
 Mental short-cuts and memory aids for
common or complex problems
 Primary method to evaluate care patterns
and monitor standards of care

57. When are guidelines needed ?
 Institute of Medicine (IOM) criteria – clinical
practice guidelines are useful when:
 the problem is common or expensive.
 there is great variation in practice patterns.
 there is enough scientific evidence to determine
appropriate and optimal care.
(IOM , 1992)

58. Types of guideline development
approaches
 Single author - expert opinion
 Single author - systematic literature review
 Consensus panel using expert opinion only
 Consensus panel using evidenced-based
approach (AHCPR methodology)
AHCPR: Agency for Health Care Policy and Research

59. Steps in developing guideline
recommendations
 define clinical questions of interest
 develop summary of evidence on:
 clinical efficacy (potential benefits).
 potential harms / projected costs.
 weigh likelihood of benefit versus likelihood of
harms.
 consider costs.
 develop finding /recommendation statements.
 document all aspects of the process.

60. Levels of evidence
Level Type of evidence
I Evidence obtained from at least one randomised
controlled trial or from meta-analysis of randomised
controlled trials
II Evidence obtained from at least one well-designed
controlled study without randomisation
III Evidence obtained from well-designed non-experimental
descriptive studies, such as comparative studies,
correlation studies and case control studies
IV Evidence obtained from expert committee reports or
opinions and/or clinical experience of respected
authorities

61. Grading of recommendations
Grade Recommendation
A (Evidence level I)
Requires at least one randomised controlled trial as part of the body of
literature of overall good quality and consistency addressing the specific
recommendation
B (Evidence levels II, III)
Requires availability of well-conducted clinical studies but not randomised
clinical trials on the topic of recommendation
C (Evidence level IV)
Requires evidence from expert committee reports or opinions and/or
clinical experience of respected authorities. Indicates absence of directly
applicable studies of good quality

64. Task
1. Identify a clinical problem with a patient.
2. Formulate a clinical question using PICO.
3. Search the literature for appropriate article(s).
4. Evaluate the article(s).