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Clinical Problem Solving an introduction to Evidence-Base

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Title: Clinical Problem Solving an introduction to Evidence-Base


1
Clinical Problem Solving an introduction to
Evidence-Based Medicine basics

2
Lecture overview
  • Objectives
  • EBM skills for practicing medicine
  • Asking
  • Acquiring
  • Assessing
  • Applying

3
Objectives
  • Define evidence-based medicine (EBM)
  • Explain why we use EBM
  • Compare with expert-based medicine
  • How are we misled by
  • Surrogate outcomes
  • Personal observation
  • Pathophysiologic reasoning
  • Describe the tools of EBP
  • Construct a well-built clinical question

4
What is Evidence-Based Medicine (EBM)?
  • Using the best available evidence for making
    decisions about health care

5
What is important to read in the medical
literature
  • Things that
  • Have patient oriented outcomes
  • Answer a patient-care question
  • Might change your practice
  • Are on a topic you have been following
  • People are talking about and you want to know
    more
  • You find interesting POEM or DOE
  • Patient-oriented evidence that matters vs
  • disease-oriented evidence

6
Intro EBM (I)
  • Evidence-based medicine (EBM) requires the
    integration of the best research evidence with
    our clinical expertise and our patients unique
    values and circumstances
  • EBM, 2006, Straus et al

7
Why learn EBM / EBP?
8
  • Good education teaches us to become both
    producers of knowledge
  • discerning consumers of what other people claim
    to know.

9
Helps you find the truth in face of
pharmaceutical marketing
Cal Ripkin, Jr. is not hypertensive and is not
taking PRINIVIL
Its always in the fine print.
10
Value of Learning EBM Short-Term Trial
  • A controlled trial of teaching critical appraisal
    of clinical literature conducted among medical
    students
  • Experimental group of students worked with
    clinical tutors who had
  • Taken course in clinical appraisal
  • Evaluated specialty-specific articles on
    diagnostic tests and treatments
  • Control group of students worked with usual
    clinical tutors
  • Bennett et al. JAMA. 19872572451-2454.

11
Value of Learning EBM Short-Term Trial (cont)
  • Students in experimental group made greater
    number of correct diagnostic and treatment
    decisions and were better able to justify their
    decisions
  • Students in control group were more likely to
    make incorrect decisions after their tutorial
    than before it
  • Students in the control group had become more
    accepting of recommendations from authority
    figures
  • Bennett et al. JAMA. 19872572451-2454.

12
The Patient
  • Patient is a 27-year-old woman with severe right
    lower quadrant pain.
  • initial peri-umbilical pain x 2 days migrating
    yesterday to current site.
  • Loss of appetite. No vomiting, diarrhea no bowel
    movement
  • no known infectious exposure/
  • suspicious ingestions, or recent travel

13
  • First, do no harm.
  • How do we know
  • that we are not?

14
Standard medical practice for hot, moist diseases
15
Louis Study of Bloodletting
Day of 1st bleeding
Averages
Duration of illness
Number of bleedings
16
Pierre Louis (1787-1872)Inventor of the numeric
method and the method of bservation
Discovered in 1828 that patients who were bled
did worse than those who werent
17
Many advances in medicine with uncontrolled use
  • PCN for life-threatening disease
  • Insulin for type I diabetes
  • Treatment of malignant hypertension

18
Traditional Guides to Medical Practice
  • Pathophysiology and pharmacology
  • Foundation of medical practice
  • Do what makes sense
  • Expert opinion
  • In training learning at the bedside from the
    master clinician
  • In practice lectures and seminars with thought
    leaders
  • Clinical experience
  • Successes, outcomes, and adverse events in our
    own practice

19
Cardiac Arrhythmia Suppression Study
1498 subjects with suppressible arrhythmias
post-MI RANDOMIZED
Placebo
Treatment
7.7
Mortality
3.0
20
Problems With the Traditional Approach
  • Physiology may not predict clinical response
  • Beta-adrenergic blockade in heart failure
  • Encainide for post-MI arrhythmia
  • Estrogen replacement for cardioprotection
  • Expert opinion
  • Only as good as the expert
  • May be affected by biases and conflicts of
    interest
  • Clinical experience
  • Dramatic clinical experiences may unduly
    influence our practice patterns
  • May not take account of recent medical literature
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-BasedClinical
    Practice. Chicago, IL American Medical
    Association 2001.

21
Paradigms of Medicine
Expert Based Evidence Based
Pathophysiological reasoning Clinical Studies
Personal observation Best evidence available
Expert based guidelines Evidence based guidelines
22
Seven alternatives to EBMHumorous approach from
BMJ
Basis Marker Unit
Evidence RCT Odds ratio
Eminence White hair Optical dentistry
Vehemence Level of stridency Decibels
Eloquence Smoothness Adhesion score
Providence Religious fervor International units of piety
Diffidence Level of gloom Sighs
Nervousness Litigation phobia level Bank Balance
Confidence Bravado No sweat
BMJ 19993191618-1618
23
Integrates Evidence With
  • Clinical expertise
  • Experience
  • Judgment
  • Patient values and preferences
  • Quality of life
  • Costs
  • Other important factors

24
Clinical Expertise
Patient Values and Preferences
Best Available Evidence
Quality of Life
Costs
25
Focus Treatment Diagnosis
26
The Patient
  • Patient is a 27-year-old woman with severe right
    lower quadrant pain.
  • initial peri-umbilical pain x 2 days migrating
    yesterday to current site.
  • Loss of appetite.
  • No vomiting, diarrhea no bowel movement
  • no known infectious exposure/ suspicious
    ingestions, or recent travel

27
Patient exam
  • VS BP 120/78 P 16 RR 12 T 98.8
  • Chest CTA. CV RRR s M/R/G
  • ABD NML exam x decreased bowel tones and
    definite right lower quadrant pain, specifically
    at McBurneys point.
  • no heptomegaly nor splenomegaly (enlarged liver
    or spleen). She has no rebound pain or involuntary

28
The Five As
  1. Ask the right question
  2. Acquire the evidence
  3. Appraise the evidence
  4. Apply the evidence
  5. Assess its impact

29
Concern
  • Case discussion 27 year old woman with right
    lower quadrant (RLQ) abdominal pain
  • Background information available from textbooks-
  • What typically presents as RLQ pain
  • What is the clinical course of the different
    diagnoses
  • Specifically, what is typical presentation of
    appendicitis
  • Foreground information
  • How good is a CT scan for appendicitis?

30
Formulating the Question
31
Formulating the Question
  • An ideal question
  • Focused enough to be answerable
  • Pertinent to clinical scenario
  • Framed as
  • Population receiving an
  • Intervention (test or treatment) as Compared to
    other test/treatment or placebo associated with
  • Outcome (disease or improvement)

32
PICOS
  • P roblem/population
  • I ntervention
  • C omparison
  • O utcome
  • S tudy design

33
Examples of tough questions
  • Should I screen men for prostate cancer?
  • Who is a good candidate for hormone replacement
    therapy?
  • Are angiotensin receptor blockers now first-line
    for hypertension?

34
Examples of better questions
  • Would a PSA test reduce mortality in a 65
    year-old asymptomatic man?
  • What is the reduction in fracture risk associated
    with hormone replacement therapy?
  • Is losartan more effective than atenolol at
    preventing cardiovascular events in middle-aged
    hypertensive diabetic women?

35
PICOS
  • PICOS for confirmatory diagnosis of appendicitis
  • P 27 year old woman with symptoms suggestive of
    appendicitis
  • I CT Scan
  • C Ultrasound
  • O Accurate diagnosis without undue delay
  • S ??

36
Important Outcomes
  • Patient Oriented Outcomes
  • outcomes patients actually care about
  • Death (overall or disease-specific)
  • Heart attacks, strokes, amputations, bed sores,
    broken hips, renal failure, etc.
  • Ability to perform activities of daily living
  • Versus
  • Disease oriented outcomes
  • Biochemical, physiologic, pharmacologic, or
    laboratory measures

37
Comparing DOE and POE
Example Disease-Oriented Evidence Patient-Oriented Evidence that Matters Comment
Antiarrhythmic Therapy Drug X ? PVCs on ECG Drug X increases mortality POE contradicts DOE
Type 2 Diabetes Aggressive Tx with insulin or oral agents can keep BS low Aggressive Tx does not reduce mortality or prevent most complications POE contradicts standard teaching
Prostate Screening PSA screening detects prostate cancer early Does PSA screening ? mortality? DOE exists, but POE is unknown
Shaughnessy AF, Slawson DC. Getting the Most from
Review Articles A Guide for Readers and Writers.
American Family Physician 1997 (May
1)552155-60.
38
Background versus foreground information
  • Case discussion 27 year old woman with right
    lower quadrant (RLQ) abdominal pain
  • Background information available from textbooks-
  • What typically presents as RLQ pain
  • What is the clinical course of the different
    diagnoses
  • Specifically, what is typical presentation of
    appendicitis
  • Foreground information
  • How good is a CT scan for appendicitis?

39
Steps of EBM-5 As
  • Ask
  • Acquire
  • Appraise
  • Apply
  • Assess

40
Finding Evidence Sources (I)
  • Primary research database (articles)
  • PubMed (aka MEDLINE), Pyschlit, CCTR
  • Secondary research databases (synthesis)
  • Cochrane Library, Clinical Evidence, InfoPOEMS,
    UpToDate
  • Tertiary resources (meta search engines,
    databases of databases)
  • TRIP (Translating Research Into Practice),
    PrimeEvidence

41
Finding Evidence Sources
  • PubMed
  • 16 million peer reviewed biomedical articles
    indexed (note can use PubMed limits to search on
    particular populations, study types, etc.)
  • Cochrane Library
  • 3000 clinical systematic reviews (gold standard
    database)
  • Clinical Evidence
  • 2500 tsystematic reviews of treatment classified
    by likelihood of benefit
  • InfoPOEMS (www.infopoems.com)
  • 3000 regularly updated entries, Patient Oriented
    Evidence the Matters (POEM), 100 journals
    monitored
  • UpToDate
  • 70,000 pages, evidence based clinical information
    resource, 3000 authors, 350 journals monitored,
    peer reviewed
  • TRIP
  • Meta-search of 55 sites of evidence based
    information

42
Finding Evidence Searching
  • Convert clinical question to searchable question
    (e.g. PICOS)
  • Choose the database you want to search (e.g.
    PubMed)
  • Apply filters to restrict your search (e.g.
    PubMed limits linked to PICOS such as gender,
    age, study type limits)
  • Assess result (e.g. using systematic review
    worksheet)
  • Decide if you have enough information to make a
    decision
  • If not then refine steps 1-3 until you either
    have an answer or decide there isnt enough
    evidence to make an evidence based decision

43
Appraising the Evidence
44
Assess the Evidence
  • Is the study valid?
  • Validity is defined as relative freedom from bias
    and confounding factors
  • What are the results?
  • What is the outcome and how was it measured?
  • What is the magnitude of the effect?
  • Are the results statistically significant?
  • Do the results apply to my patient?
  • Does my patient resemble those in the study?
  • Were all outcomes relevant to my patient
    evaluated?
  • Are there other factors (eg, cost, availability)
    that limit applicability to my patient?
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001

45
Objectives
  • Understand difference between observational and
    experimental studies
  • For 2 major study designs (randomized controlled
    trial and cohort study) describe
  • How the study is designed
  • Advantages and disadvantages of design
  • How to assess validity
  • How to assess results
  • How to assess applicability

46
Experimental vs Observational Studies
  • In experimental studies, the investigator
    controls subjects exposure to intervention
  • Example randomized controlled trial (RCT)
  • In observational studies, investigator does not
    control the exposure it occurs naturally or is
    initiated by patients or their physicians
  • Examples cohort study, case-control study
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

47
RCTs
  • Generally held to be the optimal methodology for
    determining benefit or harm

Treatment
Outcome
Eligible Patients
Randomization
Outcome
Control
Guyatt et al. Users' Guides to the Medical
Literature A Manual for Evidence-Based Clinical
Practice. Chicago, IL American Medical
Association 2001.
48
RCTs Advantages
  • Treatment and control groups are likely to have
    similar distribution of known and unknown
    prognostic factors (potential confounders)
  • Outcomes are determined prospectively in a
    standardized, systematic fashion
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

49
RCTs Disadvantages
  • Costly to perform
  • Size limitations make detection of rare events
    difficult (eg, adverse medication effects)
  • Eligibility restrictions may reduce applicability
    to real patients
  • Cannot be ethically performed if exposure is
    expected to cause harm (eg, smoking)
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

50
RCTs Disadvantages
  • Costly to perform
  • Size limitations make detection of rare events
    difficult (eg, adverse medication effects)
  • Eligibility restrictions may reduce applicability
    to real patients
  • Cannot be ethically performed if exposure is
    expected to cause harm (eg, smoking)
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

51
Assessing the Validity of RCTs
  • Was randomization concealed?
  • Were patients analyzed in groups to which they
    were randomized?
  • Were patients in treatment control groups
    similar with respect to prognostic factors?
  • Were patients, clinicians, outcome assessors, and
    data analysts aware of allocation?
  • Were groups treated equally?
  • Was follow-up complete?
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

52
Assessing the Results of an RCT
  • Magnitude of result How large was the treatment
    effect?
  • Relative risk and odds ratio
  • Absolute risk reduction and number needed to
    treat (NNT)
  • Statistical significance
  • P value
  • Confidence interval How precise was estimate of
    treatment effect?
  • Clinical significance
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

53
Assessing the Results of an RCT
  • Magnitude of result How large was the treatment
    effect?
  • Relative risk and odds ratio
  • Absolute risk reduction and number needed to
    treat (NNT)
  • Statistical significance
  • P value
  • Confidence interval How precise was estimate of
    treatment effect?
  • Clinical significance
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

54
Calculating the Risk Ratio and Number Needed to
Treat (NNT)
Treatment (n 1000)
100 have the outcome
Risk 0.1, or 10 (100/1000)
Control (n 1000)
120 have the outcome
Risk 0.12, or 12 (120/1000)
Risk ratio 0.1/0.12 0.83, or 83
Absolute risk reduction 0.12 - 0.1 0.02, or 2
NNT 1/0.02 50
Guyatt et al. Users' Guides to the Medical
Literature A Manual for Evidence-Based Clinical
Practice. Chicago, IL American Medical
Association 2001.
55
Assessing the Applicability of an RCT
  • Were the study patients similar to my patient?
  • Eligibility criteria
  • Table 1 data (baseline characteristics)
  • Were all clinically important outcomes
    considered?
  • Are the likely treatment benefits worth the
    potential harm and costs?
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

56
Cohort Studies
  • Similar to RCTs, except that assignment to
    intervention is not random

Outcome
Exposed
Eligible Patients
Choice or Happenstance
Not Exposed
Outcome
Guyatt et al. Users' Guides to the Medical
Literature A Manual for Evidence-Based Clinical
Practice. Chicago, IL American Medical
Association 2001.
57
Cohort Studies Advantages
  • Outcomes are determined prospectively in a
    standardized, systematic fashion
  • Often includes a larger, more diverse population
    than those eligible for or included in RCTs
  • Can be used to assess effects of harmful
    exposures (eg, smoking)
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001

58
Cohort Studies Disadvantages
  • Costly to perform
  • Size limitations make detecting rare events
    difficult
  • Exposure and control groups are likely to differ
    in factors that may affect outcomes
  • Control of confounding through statistical
    analysis may be inadequate
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

59
Assessing the Validity of a Cohort Study
  • Were the exposed and control groups similar in
    all known determinants of outcome?
  • Did the analysis adjust for potential
    differences?
  • Were the outcomes measured in the same way in the
    groups being compared?
  • Was follow-up sufficiently complete?
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

60
Assessing the Results of a Cohort Study
  • How strong is the association between exposure
    and outcome?
  • Risk ratio or odds ratio
  • Absolute risk increase or number needed to harm
    (NNH)
  • Statistical significance
  • P value
  • Confidence interval How precise was estimate of
    risk?
  • Clinical significance
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

61
Assessing the Applicability of a Cohort Study
  • Were the study patients similar to the patient
    under consideration in my practice?
  • Should I attempt to stop the exposure?
  • Guyatt et al. Users' Guides A Manual for
    Evidence-Based Clinical Practice. Chicago, IL
    American Medical Association 2001 to the Medical
    Literature.

62
Case-Control Studies
  • In contrast to RCTs and cohort studies,
    participants are selected based on the presence
    of the outcome rather than the exposure
  • Exposure status is determined retrospectively
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

63
Case-Control Studies Design
Select Subjects
Cases (diseased)
Controls(nondiseased)
Exposed
Not Exposed
Observe
Exposed
Not Exposed
Guyatt et al. Users' Guides to the Medical
Literature A Manual for Evidence-Based Clinical
Practice. Chicago, IL American Medical
Association 2001.
64
Case-Control Studies Advantages
  • Much more efficient for investigation of rare
    outcomes
  • Take less time to perform than RCTs or cohort
    studies
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

65
Case-Control Studies Disadvantages
  • Retrospective assessment of exposure may be
    inadequate (recall bias)
  • Can be performed only after outcomes have
    occurred (ie, after damage has already occurred)
  • Selection of appropriate controls may be
    difficult
  • Control of confounding through statistical
    analysis may be inadequate
  • Guyatt et al. Users' Guides to the Medical
    Literature A Manual for Evidence-Based Clinical
    Practice. Chicago, IL American Medical
    Association 2001.

66
Steps of EBM-5 As
  • Ask
  • Acquire
  • Appraise
  • Apply
  • Assess

67
Applying EBM
68
Clinical Expertise
Patient Values and Preferences
Best Available Evidence
Quality of Life
Costs
69
Integrates Evidence With
  • Clinical expertise
  • Experience
  • Judgment
  • Patient values and preferences
  • Quality of life
  • Costs
  • Other important factors

70
Integrates Evidence With
  • Clinical expertise
  • Experience
  • Judgment
  • Patient values and preferences
  • Quality of life
  • Costs
  • Other important factors

71
Therapy Review -
  • VALIDITY
  • Clearly focused question?
  • Randomization
  • Blinding- subjects, providers, investigators
  • Groups similar at start and treated the same
    throughout?
  • Followed in randomized groups and accounted for
    at end? (intention to treat)
  • Enough subjects to minimize chance differences?
  • REUSLTS AND PRECISION
  • What are results? How presented?
  • Certainty precision? (95 CIs)
  • APPLICABILITY
  • Can the results be applied to my patient?
  • All important outcomes addressed?
  • Should there by change in policy?

72
Therapy Intention to treat
  • Subjects are analyzed in the groups they were
    randomized to.
  • Maintains randomization
  • Better reflects real world outcomes
  • Measures efficacy (Will this work?)
  • Detects issues about intervention other than
    effectiveness In the best possible
    circumstances, do they work?

73
Therapy Bias
  • Randomization helps lessen patient bias
  • Self-selection
  • Blinding helps lessen patient and investigator
    bias

74
Therapy What Are the Results ?
  • RR OR RRR
  • ARR
  • NNT / NNH
  • P value/ CI
  • Clinically significant?

75
Therapy What Are the Results ?
  • RR OR RRR
  • ARR
  • NNT / NNH
  • P value/ CI
  • Clinically significant?


76
Therapy Expressing Results
  • Risk outcome event rate
  • number having event
  • number receiving the intervention
  • Relative risk risk in intervention group
  • (RR) risk in control group
  • Relative risk reduction (RRR) 1 - RR

77
Therapy Expressing Results
  • Absolute risk reduction (ARR)
  • difference in risk (control intervention)

78
Therapy Expressing Results
  • Number-needed-to-treat (NNT) 1/ARR
  • in words the number of patients who need to be
    treated to prevent one outcome event from
    occurring in specified time

79
Therapy Example
  • An oncology trial testing a new treatment with
    4-year follow-up for mortality
  • experimental treatment 30
  • control group 50
  • What are the RR, RRR, ARR, NNT?

80
Therapy Example
  • RR risk of death in experiment/control groups
  • 30/50 0.6 or 60
  • RRR 1 - RR 1-0.6 0.4 or 40
  • ARR risk of death in control experimental
    groups
  • .50 -.30 0.2 or 20
  • NNT 1/ARR 1 0.2
  • 5 patients treated with the experimental
    therapy to prevent one death at 4 years

81
(No Transcript)
82
Therapy Smoking cessation
  • NNT for all methods of delivery 14 (95 CI 13 to
    16)..
  •  
  • N C
    E NNT 95 CI        
  • Chewing gum 16518 12 19 13 (11 to 15)
  • Patch 8283 9 15
    16 (13 to 21)
  • Intranasal spray 887 12 24 8.3
    (5.9 to 14)
  • Inhaler 976 9 17
    12 (8.1 to 26)

83
Therapy Relative Versus Absolute Benefits
  • Consider
  • July 3, 2002 Worldcom stock rose 120 (relative
    increase)
  • The stock rose from 0.10 ? 0.22 (absolute
    increase)

84
Therapy Relative risk reduction versus
absolute risk reduction
  • Baseline risk 10/100 5/100
  • RRR 50 ARR 5 NNT 20
  • Baseline risk 1/100 0.5/100
  • RRR 50 ARR 0.5 NNT 200
  • Baseline risk 0.1/100 0.05/100
  • RRR 50 ARR 0.05 NNT 2000

85
Therapy RRR Lipid Trials
  • 4S WOSCOPS CARE AFCAPS
  • for acute myocardial infarction
  • RRR 27 31 25 40
  • ()
  • NNT 19 42 40 435
  • (5 year)

86
Therapy 95 Confidence Interval
  • Any statistic only an estimate of the true
    value of that statistic.
  • Confidence Interval (CI) gives range within which
    that true value probably lies.
  • 95 CI - if we repeated the experiment with
    similar populations an infinite number of times,
    the results would fall within the CI 95 of the
    time. 95 certain that the true value will fall
    within the 95 CI range.
  • CI gives us an idea of the precision of the
    result, since the narrower the CI is, the more
    certain we can be that the experimental value is
    close to the true value.
  • And, generally, the larger the sample size, the
    narrower the CI

87
  • CI idea of significance, e.g.
  • If the 95 CI for the ARR includes 0, no
    difference between the experimental and control
    groups.
  • If the 95 CI for the RRR or Odds Ratio includes
    1,
  • no difference between the experimental and
    control groups.
  • Similar to P values (e.g., Plt0.05) statistically
    significant
  • CI gives a sense of the size of the differences
    found in the study.
  • e.g., research study - 50 of patients treated
    with Drug A are cured, compared with 45 of
    patients treated with Drug B.
  • ARR I s thus 5.
  • Statistical analysis Plt0.001, statistically
    significant.
  • But if 95 CI of ARR is 0 to 10, indicates
    result is not clinically significant (includes
    0 - no difference).

88
Therapy Statistical Significance ?Clinical
Significance
  • Are the results clinically important?
  • Duration of pharyngitis 8.1 days to 7.4 days
  • Weight 279 lbs to 266 lbs after 3 months
  • Survival increased from 4.5 mos to 5.2 mos with
    100 mortality at 12 months
  • Claudication Increase in walking distance by 34
    ft.

89
Diagnosis Review - Worksheet
  • VALIDITY
  • Clearly focused question?
  • Appropriate reference standard?
  • Reference standard test applied to all
    subjects? (verification bias)
  • Did results of standard influence interpreting
    test results? (review bias)
  • Disease status reported and varied? (spectrum
    bias)
  • Test method reported with sufficient detail to be
    replicated?
  • REUSLTS AND PRECISION
  • What are results?
  • Certainty precision? (95 CIs)
  • APPLICABILITY
  • Can the results be applied to my patient?
  • Are local resources (equipment, expertise, cost)
    sufficient to apply these results?

90
Diagnosis 2X2 table Diagnostic test
characteristics
  • Sensitivity
  • Specificity
  • Predictive Value
  • Likelihood Ratios

91
DIAGNOSTIC TEST
D I S E A S E D I S E A S E
Present Absent TOTALS
Test positive True Positive False Positive All positive
Test negative False Negative True Negative All negative
TOTALS All with disease All without disease Entire population
T E S T
92
Diagnosis What are the Results?

D I S E A S E
() (-)
() a b
(-) c d

T E S T
93
Diagnosis What are the Results?

Pt has diseaseDz () Dz (-)
Test() a b
Test(-) c d
94
Diagnosis What are the Results?
Pt has diseaseDz () Dz (-)
Test() a b
Test(-) c d
95
Diagnosis What are the Results?

Dz () Pt does not have disease Dz (-)
Test() a b
Test(-) c d
96
Diagnosis What are the Results?

Pt has diseaseDz () Dz (-)
Test() a b
Test(-) c d

97
Diagnosis What are the Results?

Pt has diseaseDz () Dz (-)
Test() a b
Test(-) c d

TP
FN
98
Diagnosis Sensitivity
  • Sensitivity is proportion of people with disease
    who have a positive test

Dz () Dz (-)
Test() a b
Test(-) c d

TP
FN
Sensitivity (a/ac) (TP/TPFN)
99
Diagnosis What are the Results?

Dz () Pt does not have disease Dz (-)
Test() a b
Test(-) c d

100
Diagnosis What are the Results?

Dz () Pt does not have disease Dz (-)
Test() a b
Test(-) c d

101
Diagnosis What are the Results?
Dz () Pt does not have disease Dz (-)
Test() a b
Test(-) c d

FP
TN
102
Diagnosis Specificity
  • Specificity is proportion of people without
    disease who have negative test

Dz () Dz (-)
Test() a b
Test(-) c d

FP
TN
Specificity (d/bd) (TN/FPTN)
103
Diagnosis Tradeoffs of sensitivity
specificity labeling diabetes
  • Blood sugar
  • 70
  • 100
  • 130
  • 160
  • 200
  • Sensitivity Specificity
  • 98.6 8.8
  • 88.6 69.8
  • 64.3 96.9
  • 47.1 99.8
  • 27.1 100

104
Diagnosis Choosing a test
  • SnNout-
  • A sensitive test, if negative, rules out a
    disease
  • SpPin-
  • A specific test, if positive, rules in a
    disease

105
Diagnosis Sensitivity Specificity
  • Useful for picking a test (test properties)
  • Screening- prefer sensitive test
  • Diagnosis prefer specific test
  • Less help in making diagnosis

106
Diagnosis What are the Results?
  • In patients, what you know are their test
    results- you are trying to determine whether they
    actually have the disease.
  • Positive Predictive Value
  • Of all who tested positive for a disease, the
    proportion that actually has it
  • Negative Predictive Value
  • Of all who tested negative for a disease, the
    proportion that actually does not have it

107
Diagnosis What are the Results?

D I S E A S E
() (-)
() a b
(-) c d

T E S T
108
Diagnosis Positive Predictive Value
  • Proportion of people with a positive test
  • who have a disease
  • PPV
  • a/ab
  • TP/TPFP

Dz () Dz (-)
Test() TP a FP b
Test(-) c d

true positives over all positives
109
Diagnosis Negative Predictive Value
  • Proportion of people with a negative test
  • who dont have a disease
  • NPV
  • d/dc
  • TN/TNFN
  • true negatives
  • over all positives

Dz () Dz (-)
Test() a FP b
Test(-) FN c TN d

110
Diagnosis What are the Results?
  • PPV dependent on prevalence, even when using the
    same test
  • Example Prevalence of a particular disease in a
    population is 50. Sensitivity 90 Specificity
    95
  • PPV a/ab
  • 95

Dz () Dz (-)
Test() a b
Test(-) c d
100 100
90
5
10
95
200
111
Diagnosis PPV prevalence
  • PPV dependent on prevalence using same test
  • Example Prevalence of a particular disease in a
    population is 5. Same test, same sensitivity
    specificity
  • Sensitivity 90 Specificity 95
  • PPV a/ab
  • 47

Dz () Dz (-)
Test() a b
Test(-) c d
10 190
9
10
1
180
200
112
Diagnosis PPV NPV
  • Useful for diagnosis
  • Probability of disease after ( ) or () test
  • Drawbacks
  • Sensitive to prevalence of disease
  • Prevalence of disease in general population may
    not be the same as that of patients you see in
    clinic/ER.
  • Not all test results can be categorized as or
    -.
  • For these reasons, some consider PPV NPV Old
    School.

113
Diagnosis What are the Results?
  • Likelihood Ratios
  • Likelihood Ratio is how much more likely is it
    that someone with this finding has the disease,
    compared to someone who doesnt. It does NOT vary
    with prevalence.
  • Technically, the LR is how much more likely
    someone is to get any positive test result if
    they have disease, compared to someone who
    doesnt.

114
Diagnosis Likelihood ratio
  • LR SENSITIVITY
  • 1 - SPECIFICITY

115
Diagnosis What do all the numbers mean?
  • The Likelihood Ratio is a diagnostic weight
  • It tells you by how much a given diagnostic
    test result will raise or lower the probability
    of having the disorder.
  • Pretest Probability the chance that the pt has
    disease, prior to ordering any tests. This is
    often an estimation based on clinical experience
  • Post-test Probability the chance that the pt has
    disease, given the results of the test

116
Diagnosis What are the Results?
  • What do all the numbers mean?
  • A LR of 1.0 means the post-test probability is
    exactly the same as the pretest probability.
  • A LR gt1.0 increases the probability of having the
    disorder.
  • A LRlt1.0 decreases the probability of having the
    disorder.

117
Diagnosis What are the Results?
  • Likelihood ratios gt10 or lt0.1 generate large
    changes from pre- to post-test probability and
    are generally considered significant.
  • Strong evidence to rule in/rule out a
    diagnosis.
  • Likelihood ratios of 5-10 and 0.1-0.2 generate
    moderate changes in probability.
  • Moderate evidence to rule in/rule out a
    diagnosis.
  • Likelihood ratios of 2-5 and 0.2-0.5 generate
    small changes.
  • Minimal evidence to rule in/rule out a
    diagnosis
  • Likelihood ratios 0.5-2 usually have little effect

118
Figure 1a Likelihood Ratio Nomogram
119
LRs Diagnostic Weights
From Steve McGee, Evidence Based Physical
Diagnosis
120
Table 2a Likelihood Ratios of Tests for the
Diagnosis of Appendicitis
121
Likelihood ratio
  • DVT
  • Homans sign LR 1.5
  • Doppler LR 39
  • ANEMIA
  • Conjunctival rim pallor LR 16.7

122
Summary Diagnostic Test
D I S E A S E D I S E A S E
Present Absent TOTALS
Positive True Positive False Positive ALL Positives
Negative False Negative True Negative ALL Negatives
TOTALS All with disease All without disease Entire population
T E S T
PPV
NPV
Sensitivity
Specificity
123
Explanation
124
Common pitfalls
  • Results reported as relative risk
  • (ex. Migraines, CVA OC)
  • Results that came from recalculating the data
    after trial was done
  • (Post-hoc analysis) (ex. Hot study)
  • Over-interpreting results
  • Relying on just one study (ex. Mg for heart dz),
  • a poor study, or wrong type of study (ex. HRT)
  • Confusing statistical significance with clinical
    significance (ex. Drugs for BPH)
  • Not looking at CIs
  • Not considering who funded study

125
Steps of EBM-5 As
  • Ask
  • Acquire
  • Appraise
  • Apply
  • Assess

126
Core of EBP
  • Supposing is good
  • but finding out
  • is better.
  • Mark Twain
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