Introduction to

1
Introduction to Evidenced Based Medicine
Module 1
2
Module 1 Intro to EBM

• Objectives
• Define "Evidence Based Medicine"
• Describe the need for EBM
• List 3 components of Evidence-based decisions
• Explain the concept of "hierarchy of evidence"
• List reasons why the hierarchy of evidence is not
  absolute
• Describe the 4 steps of the "EBM process"
• Explain the rationale behind the 3 "broad
  questions" that can be used to evaluate any
  source of evidence.

3
What is EBM?

• Definitions
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

4
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

5
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

6
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

7
What is EBM?
8
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

9
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

10
What is EBM?

• Philosophy ("conscientious, explicit,
  judicious...")
• "enlightened skepticism." Don't believe all
  you're told.
• "Printed word bias. This occurs when a study is
  overrated because of undue confidence in
  published data." (Alejandro Jadad, Randomized
  Controlled Trials A Users' Guide, 1998)
• q.v. "prestigious journal bias," "non-prestigious
  journal bias," "prominent author bias," "famous
  institution bias" ...
• Rigorous, intellectually exacting approach
  "intuition, unsystematic clinical experience, and
  pathophysiologic rationale are of themselves
  insufficient grounds for clinical decision
  making." (Users' Guide p. 4)
• "A formal set of rules must complement medical
  training and common sense..." (p. 4)
• "EBM places a lower value on authority than the
  traditional medical paradigm does." (p. 4)

11
What is EBM?

• Key components
• "The integration of best research evidence with
  clinical expertise and patient values (David
  Sackett, et al. Evidence-based Medicine. How to
  Practice and Teach EBM, 2000)
• "The conscientious, explicit, and judicious use
  of current best evidence in making decisions
  about the care of individual patients..." (Gordon
  Guyatt, M.D., et al. Users' Guides to the Medical
  Literature, 2002)

12
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

13
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

• increasing pressure to
• demonstrate effectiveness of interventions
• utilize the most cost effective measures
• How do you know what really works or is the most
  effective?

14
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

15
Why EBM?
Delay of "bench-to-bedside" research Primary
literature. Original research that generates new
data. Secondary literature. Material published
based on primary literature.

• No new data is generated
• Existing data is made more accessible
• "Four "Ss"
• pre-Selected studies particularly relevant
  studies are culled from the body of primary
  literature.
• Systematic Reviews Particularly relevant studies
  are summarized (in a systematic way to avoid
  bias).
• Synopses Primary findings are re-organized and
  interpreted for pedagogical reasons (e.g.,
  textbooks).
• Systems Primary findings are re-organized and
  interpreted to practical reasons (e.g. decision
  support, practice guidelines)

16
Why EBM?
Delay of "bench-to-bedside" research
Primary Literature
Secondary Research
Years-to-Decades
Routine Clinical Practice
17
Why EBM?
Delay of "bench-to-bedside" research
Primary Literature
Thrombolytic Drugs for acute MI
6 years from the first Systematic Reviews of RCTs
until most review articles and textbooks
recommended their use. (Antman, Lau, et al. JAMA
1992)
Secondary Research
Routine Clinical Practice
18
Why EBM?
Delay of "bench-to-bedside" research
Primary Literature
Aspirin after acute MI
Not recommended by expert opinion until 6 years
after the first systematic review. (Antman, Lau,
et al. JAMA 1992)
Secondary Research
Routine Clinical Practice
19
Why EBM?
Delay of "bench-to-bedside" research
Bed rest after back injury or surgery
Primary Literature

• Studies in the 1940's showed no advantages for
  complete bed rest after surgery
• Instead, DVT, bedsores. osteoporosis, and
  pneumonia identified as problems.
• Ideas about bed rest remain entrenched...
• e.g., 80 of neurological units in UK still
  insist on bed rest, despite 17 years of evidence
  showing no value

Secondary Research
Routine Clinical Practice
(Allen C, Glasziou P, Del Mar C. Bed rest a
potentially harmful treatment needing more
careful evaluation. Lancet 1999.)
20
Why EBM?
Delay of "bench-to-bedside" research
Primary Literature
Use of albumin in fluid resuscitation

• Based on physiologic reasoning. Used for gt50
  years for hypovolemia, shock, burns...
• Later RCTs suggested increased mortality in some
  conditions
• Modern, large Systematic Reviews showed possible
  biphasic effect based on dose. (Wilkes, Navickis.
  Ann Int Med 2001)

Secondary Research
Routine Clinical Practice
21
Why EBM?
Delay of "bench-to-bedside" research
"Life Cycle of Translational Research"
Primary Literature
Median time from "initial discovery of a medical
intervention" to a "highly cited article" was 24
years. (Contopoulos-loannidis, Alexiou, et al.
Science 2008)
Secondary Research
Routine Clinical Practice
22
Why EBM?
Median time from "initial discovery" to a "highly
cited article" was 24 years. (Contopoulos-loannidi
s, Alexiou, et al. Life-cycle of translational
research for medical interventions, Science 2008)
23
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

• Early, judicious use of the primary literature
  may help save lives.
• How to decide what constitutes "Judicious" will
  to be explained more as the course progresses.

24
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

25
Why EBM?
Managing the primary literature
26
Why EBM?
Managing the primary literature
100 K
35 K
15 K
27
Why EBM?
Managing the primary literature

• MEDLINE adds 4500 records daily.
• Just within their own fields, physicians would
  need to read 19 articles per day, 365 days per
  year, to keep up with research. (Oxford Center
  for EBM)
• Not all (10) of these articles are considered
  high quality and clinically relevant. (Oxford)

EBM helps you find the most appropriate article
for a specific clinical question.
28
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

Pharmaceutical companies invest considerable
resources to promote products based on skewed or
selective evidence (or emotion appeals through
direct-to-consumer advertising). EBM provides
tools to help alert clinicians to potentially
misleading marketing. (Glasziou, Hayes. The
paths from research to improved health outcomes,
Evidenced Based Nursing, 2005 8(2)36-8.)
29
Why EBM?

• What is the need?
• Cost
• Delay of "bench-to-bedside" research
• Managing the primary literature
• Counter misleading marketing
• Dealing with conflicting results

30
Why EBM?
Dealing with conflicting results?
"My students are dismayed when I say to them
"Half of what you are taught as medical students
will in ten years have been shown to be wrong.
And the trouble is, none of your teachers know
which half." -Sydney Burwell, M.D., Dean, Harvard
Medical School (1956)
Postmenopausal HRT
(Contopoulos-loannidis, Alexiou, et al. Science
2008)
31
Why EBM?
Dealing with conflicting results

• Back-to-Sleep Based on physiologic reasoning,
  Dr. Benjamin Spock recommended that babies sleep
  on their stomach to prevent risk of vomiting and
  choking.
• Later shown to increase the risk of SIDS

32
Why EBM?
Dealing with conflicting results

• Beta-blockers initially avoided after MI due to
  pathophysiologic reasoning that they would
  decrease compensatory sympathetic mechanisms
• Later shown to decrease hospitalization death

33
Why EBM?
Dealing with conflicting results

• Based on 16 cohort studies (and some physiologic
  reasoning) HRT used to be recommended for
  postmenopausal women to reduce the risk of CHD.
• Womens' Health Initiative show it actually
  increased the risk of MI, stroke, and venous
  thromboembolism

34
Why EBM?
Dealing with conflicting results

• Since the 1960s, lidocaine was used for V-fib
  V-tach prophylaxis in patients with acute MI.
• A meta-analysis showed some reduction in V-fib
  V-tach, but a probably increase in actual
  mortality

35
Why EBM?
Dealing with conflicting results
Damned if you do...
...Damned if you don't
36
Why EBM?
Dealing with conflicting results Hierarchy of
Evidence The notion that some study designs are
less susceptible to bias than others, with the
effect that some study results are more likely to
be valid than others. "Study design," "bias,"
and "validity" will be more rigorously explained
later. Casual understanding is sufficient for
now.
37
Hierarchy of Evidence
A Hierarchy of Evidence (strongest type of
evidence on top)
Meta-Analysis Randomized Controlled Trial Cohort
Study Case-Control Study Case Series Single Case
Reports Anecdotal Reports Pathophysiologic
Reasoning Ideas, opinions, etc.
(Petrie A. Statistics in orthopaedic papers.
The Journal of Bone and Joint Surgery 2006
88-B(9)1121-36)
38
Hierarchy of Evidence
Meta-Analysis Randomized Controlled Trial Cohort
Study Case-Control Study Case Series Single Case
Reports Anecdotal Reports Pathophysiologic
Reasoning Ideas, opinions, etc.

• This particular hierarchy is best for
  investigating cause-and-effect (e.g. in making
  treatment decisions).
• Different hierarchies may apply for different
  kinds of investigations
• harm
• prognosis
• diagnosis
• others...
• There is always evidence, even if it is anecdotal
  or based on theory...
• When studies contradict (all else being equal),
  the "higher" study is less likely to be biased.
• Hierarchy is not absolute...

39
Hierarchy of Evidence
Reasons why a "Hierarchy of Evidence" is not
absolute

• Effect size is large
• Unethical to continue Randomized Controlled
  Trials
• RCT's most useful when effect size and risk of
  bias are comparable.
• Mechanism of action is well understood
• Results can be reliably predicted from theory
  rather than experiment.
• e.g. Effectiveness of parachutes

40
Hierarchy of Evidence
Reasons why a "Hierarchy of Evidence" is not
absolute

• Effect size is large
• Unethical to continue Randomized Controlled
  Trials
• RCT's most useful when effect size and risk of
  bias are comparable.
• Mechanism of action is well understood
• Results can be reliably predicted from theory
  rather than experiment.
• e.g. Effectiveness of parachutes
• Large body of consistent observational studies
• Risk of Type I error reduced through replication
  large effect sizes
• e.g., use of insulin in DKA, Pap smears, also
  parachutes

Patient preference or clinical expertise are more
relevant than degree of certainty. (Related to
external validity...) Your patient (or an
outcome of interest) is more similar to that of a
"lower" study than a "higher" study.
41
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

42
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

43
The EBM Process

• Step 1 Ask a well-built clinical question
• Use the Mnemonic PICO
• P Patient characteristics
• age (adult, pediatric)
• sex
• diagnosis or condition
• social situation, resources, values
• setting inpatient, outpatient, rural, tertiary
  care, etc.
• public health issue or individual patient issue?

44
The EBM Process

• Step 1 Ask a well-built clinical question
• I Intervention
• What it is you are considering trying
• Could be a medication, a diagnostic test, or some
  other type of treatment
• Most useful when you need to choose between
  treatment options

45
The EBM Process

• Step 1 Ask a well-built clinical question
• C Comparison
• One of the options you are choosing between
• Sometimes the labeling of one treatment as
  "Intervention" and the other as "Comparison" is
  arbitrary.
• A treatment (or test) can really only be assessed
  in comparison to something else...
• ...Even if the "something else" is "standard
  treatment," "watch-and-wait," or "no treatment."

46
The EBM Process

• Step 1 Ask a well-built clinical question
• O Outcome
• The effect you want to achieve (or avoid)
• Can include treatment effects as well as side
  effects
• Usually, you are interested in one primary
  outcome (even if the primary outcome is fairly
  global such as "quality of life,"
  "functionality," or "hospitalizations."
• Surrogate outcomes Measurements that are not of
  themselves important to patients (e.g., blood
  pressure, bone density, cholesterol level) but
  that are associated with outcomes that are
  important to patients (e.g., stroke, fracture,
  MI).
• Use caution with surrogate outcomes (e.g.,
  Lidocaine use after AMI decreased V-fib but
  increased death.)

47
The EBM Process

• Outcomes
• Efficacy The effects of an intervention under
  ideal conditions (e.g., a laboratory experiment)
• Most RCT's measure efficacy.
• Effectiveness The effects of an intervention
  under the usual conditions (e.g., in the field)
• RCT's may overestimate effectiveness
• Observational studies may give a better estimate
  of actual effectiveness.
• Efficiency The relative ease (or lack of waste)
  in producing an effect.
• Related to the idea of potency
• Not really an EBM concept, but included here
  since it is another "eff-" word that is commonly
  confused with efficacy and effectiveness.

48
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

49
The EBM Process
Step 2 Search for the Evidence Searching
techniques can be involved and take a lot of
experience and trial error to discover what
works well. These will be covered in more detail
in a later module.

• In searching, you should consider
• What databases are available relevant to my
  question?
• How does each database work? How do you enter
  searches? How can you refine or narrow searches?
• Use your PICO question to choose key words
• What type of article (treatment, harm, diagnosis,
  prognosis, etc.) is most relevant to my question?
• Which articles are of the highest level of
  evidence?

50
The EBM Process

• Step 2 Search for the Evidence
• In general, the highest level of evidence is
  preferred. Emphasize additional criteria when
• You find gt1 article at the highest available
  level of evidence
• Results are inconsistent from article to article
• The patients studied, the clinical setting, or
  the outcome measured are significantly different
  from your PICO question

• In these cases you should especially consider
• Which articles have a clinical setting, patient
  population, or outcome most similar to my PICO
  question?
• Which studies are the most recent?
• How large are the sample sizes?
• How well done are the studies? (Step 3 of the EBM
  process)

51
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

52
The EBM Process
Step 3 Critically appraise the evidence

• "Critically appraise" refers to determining the
  appropriateness of a some evidence (usually a
  journal article) for a particular clinical
  situation.
• Internal validity Refers to the soundness of the
  research methodology
• Does the study measure what it says it is
  measuring?
• Related to efficacy performance under ideal (or
  laboratory) conditions.
• External validity Refers to generalizability of
  the results.
• Related to effectiveness How meaningful are the
  results in real life?
• Three broad questions are use to critically
  appraise an article

• Are the results valid?
• What are the results?
• How can I apply these results to my patient?

53
Critical Appraisal
Are the results valid?

• Traditional wording of this question is
  misleading it's not really about the results.
• It's about the methodology (internal validity)
• Is the methodology sufficiently sound that the
  results can be trusted?
• There are specific criteria than can be used to
  determine the soundness of the methodology.
• Different article types (harm, therapy,
  diagnosis, prognosis) have different criteria
  that are used to determine the soundness of the
  methodology
• These criteria will be explained in future
  sessions.
• Despite the wording, it is not a yes or no
  answer.
• How likely is it that the results are valid?

54
Critical Appraisal
What are the results?

• This question is largely statistically based
• Involves knowing what the various numerical
  results mean.
• Knowing how to interpret results
• These will also be covered in future modules.

How can I apply these results to my patient?

• This question is about external validity
  (generalizability) and effectiveness results
  with real patients in real world settings
• Patients recruited for studies may not be
  characteristic of all patients
• Study subjects are often more motivated or better
  educated than average...
• ...or have fewer comorbidities, or more "classic"
  or less ambiguous diagnoses.

55
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

56
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient

This step is redundant. Same as the 3rd
"critical appraisal" question.
57
The EBM Process

• An approach to clinical decision making that
  systematically incorporates available evidence,
  patient preference, and clinical expertise.
• A four-step process
• Ask a "well-built" clinical question
• Search for the best evidence to answer the
  question.
• Critically appraise the evidence
• Apply the evidence to a particular patient
• Some authors add a fifth step Evaluate your own
  performance.

This step is redundant. Same as the 3rd
"critical appraisal" question.
58
Conclusion What EBM is NOT
These are some of the criticisms you will
sometimes hear about evidenced based medicine.
59
Conclusion What EBM is NOT
60
Conclusion What EBM is NOT