Evidence-Based Medicine

PFCM
LEVEL 2 Dep’t of Family Medicine Residents, NMMC
November 29, 2019

OUTLINE - Those are random questions that doctors usually ask. But
the most important question is, how we find the
INTRODUCTION ................................................................. 1 answers?
INTRODUCTION TO EVEIDENCE-BASED MEDICINE .................... 1
o Most common source of information
THE FIVE “A” ......................................................................... 1
OBJECTIVES ....................................................................... 1
▪ Our colleagues
WHY ELECTRONIC LITERATURE SEARCH? ........................................... 1 ▪ Experiences
WHAT IS MEDLINE? ................................................................. 1 o Next most common source of information
WHAT TO ACCESS ................................................................... 1 ▪ Books (at least 5 to 10 years old
WHAT DO WE DO WITH OUR OUTPUT? ..................................... 1 o When there isn’t anyone around and there aren’t any
WHY DO WE NEED TO GO THROUGH ALL THESE? ....................... 1 books, and you do not have experience, and we DO not
WHAT IS EBM? ................................................................... 2 need to get an answer FAST
THE EVIDENCE-BASED MEDICINE PRACTITIONER .................................. 2 ▪ Electronic Literature
ADVANTAGES OF EBM........................................................... 2
THE EBM APPROACH ............................................................. 2 THE FIVE “A”
USER’S GUIDE..................................................................... 2
EVIDENCE-BASED MEDICINE ........................................................ 2 1. Ask questions
2. Acquire information/evidence
APPRASING AN ARTICLE ON THERAPEUTICS JOURNAL 3. Appraise evidence
REPORT ............................................................................. 2
4. Apply to patient
DEVELOPING A CLINICAL QUESTION .................................. 2 5. Assess if effective
HOW DO I DEVELOP A CLINICAL QUESTION? ....................................... 2
INFORMATION MASTERY RESOURCES, BY TYPE: ................................... 2 OBJECTIVES
THE PICO QUESTION COMPONENTS ............................................... 2
1. To identify and contrast the old and new paradigms
DISEASE-ORIENTED EVIDENCE AND PATIENT-ORIENTED for medical decision making
EVIDENCE THAT MATTERS .................................................. 3
2. To define Evidence Based-Medicine
THE PATIENT IS WHAT MATTERS ................................................... 3
3. To Enumerate the uses of Evidence Based-Medicine
CHARACTERISTICS OF DOES AND POEMS ........................................ 3
4. To appraise an article on therapy using the user’s
BIOSTATISTICS FOR HIGH VALUE TESTING AND TREATMENT guides
.......................................................................................... 3
LEARNING OBJECTIVES ........................................................ 3
WHY ELECTRONIC LITERATURE SEARCH?
BRIEF REVIEW OF BIOSTATISTICAL CONCEPTS ......................... 3
ROLE OF DIAGNOSTIC TESTS ........................................................ 3 - Books in the library are at least 5 to 10 years old, and MOST
LIKELIHOOD RATIOS: WHAT DO THEY MEAN? ...................................... 3 are obsolete
USING LIKELIHOOD RATIOS.......................................................... 4 - Most books cannot cope with information upsurge
USING FAGAN’S NOMOGRAM ......................................................... 4
- There is an estermated 500,000 to 1 M publication each year
LIKELIHOOD RATIOS ................................................................. 4
EXAMPLES OF COMMON DISEASE, TESTS AND LIKELIHOOD RATIOS ............... 4 - We need to separate the what from the chaff?
USING LIKELIHOOD RATIOS: SMALL GROUP EXERCISE ............................. 5
ROLE OF SCREENING TESTS ......................................................... 5 WHAT IS MEDLINE?
COMMON HARMS ASSOCIATED WITH SCREENING .................................. 5
SCREENING CASCADE ................................................................ 5
- A medical database maintained by the U.S. National Library
VALUE FRAMEWORK .................................................................. 5 of Medicine
SCREENING VALUE CASES ........................................................... 5 - More than 3500 journals are included in the MEDLINE and
SCREENING SMARTER ................................................................ 5 around 30,000 articles are indexed each month
BIOSTATICAL PRINCIPALS IN TREATMENT ........................................... 5 - More than 6 million have been entered since 1966
INTERPRETING THERAPEUTIC STATISTICS .......................................... 5
MOST USUEFUL TERMS FOR TREATMENT OPTIONS.................................. 6
COST-EFFECTIVENESS ............................................................... 6 WHAT TO ACCESS
COST-EFFECTIVENESS OF SELECTED TREATMENTS ................................. 6 - www.nim.nih.gov
SUMMARY ............................................................................. 6 - www.NEJM.com
- www.BMJ.com
- www.freemedicaljournals.com
INTRODUCTION - www.medscape.com
INTRODUCTION TO EVEIDENCE-BASED MEDICINE
- Doctors are life-long learners WHAT DO WE DO WITH OUR OUTPUT?
- How many times does a clinical question crop up in a day? - When you have the article, appraise it using the User’s Guide
o When you do your rounds? to Appraising the Literature (JAMA, 1995)
o When in the clinical? - Weight the evidence afforded by the article
o When you attend conferences?
o When driving home
WHY DO WE NEED TO GO THROUGH ALL THESE?
- Doctors as NO LESS THAN EIGHT questions daily
o What is the best regimen? - Old Paradigm
o What is the probability of the cure? - We seek answers from the following:
o Was my diagnosis correct? o Colleagues or our own experience
o Is there any alternative? o Books
o What was the right dose? o Authorities
o Common sense

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- New Paradigm EVIDENCE-BASED MEDICINE

- We seek answers from the following: - Is it valid?
o Colleagues or our own experience - What are the results?
o Books o Authorities - Is it applicable to my patient?
o Common sense
o Evidence APPRASING AN ARTICLE ON THERAPEUTICS JOURNAL
REPORT
- Case scenario
WHAT IS EBM? - Research Question
- Evidence Based-Medicine is the judicious use of current best - Search
evidence in making decisions about the care of individual - Title
patients - Source
- Integrating one’s own clinical experience or expertise with - Authors
the results of medical research into clinical practice - Appraisal

THE EVIDENCE-BASED MEDICAL PRACTITIONER DEVELOPING A CLINICAL QUESTION

HOW DO I DEVELOP A CLINICAL QUESTION?
- Two types of question
o Background question
o Foreground question
- Background questions
o ask “who, what, where, when, why , or how about a
single disease drug, intervention, or concept
- Think of these as basic questions you might find from a
testbook or a general EBM resource
o Eg., prevalence, ddx, pathophys, sensitivity/specificity of
a test, dosing/adverse reactions
ADVANTAGES OF EBM
- Some possibilities/suggestions
- To doctors: o For diabetic kidney disease
o Lifelong learning ▪ What is the mechanism?
o Continuing professional development ▪ What is the pathology
o Keeping up-to-date o How an ACEI work to lower BP?
- To patients o What labs should I check for someone on an ACEi
o Better quality of care ▪ Potassium? Creatinine?
o Cost-effective care ▪ How often?
o Better outcomes o What are the side effects of using an ACEi in patients
- To the health care system: with high blood pressure?
o Better utilization of health care resources
INFORMATION MASTERY RESOURCES, BY TYPE:
THE EBM APPROACH
Background questions
- Basic clinical
- EBM background

Foreground Questions
- General Resources
o Guidelines
- Research studies

THE PICO QUESTION COMPONENTS

P – Problem and Population

- What is the disease or condition?
- What the important characteristics of my patient?

I – Intervention
- What is the intervention I am looking for?
USER’S GUIDE - Is it realistic (availability, cost, convenience, etc?
- Therapy or Prevention - Is this different from how I currently practice?
- Diagnosis
- Harm and Causation C – Comparison
- Prognosis - What is the alternative to the intervention
- Clinical Practice Guideline
- Overview
O – Outcome
- Cost-Effectiveness
- Is it something patients care about?
- Or is it something only physiologists/pharamcists care
about?
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Sensitivity
DISEASE-ORIENTED EVIDENCE & PATIENT-ORIENTED “Be sensitive to those who have disease”
EVIDENCE THAT MATTERS
THE PATIENT IS WHAT MATTERS
Disease-Oriented Evidence (DOE)
- Measures outcome that are markers for disease
- “Silent numbers”

Patient-Oriented Evidence That Matters (POEMS)

- Measure outcomes that our patients care about
- They have the potential to change the way we practice! Specificity
“Negative people get specific”
CHARACTERISTICS OF DOES AND POEMS
Disease-Oriented Evidence (DOE)
- Pathophysiology
o Lab Values
o Biochemical Markers
- Pharmacology
o Plaque Size
o Blood Pressure
Positive Predictive Value
- Etiology

Patient-Oriented That Matters (POEMs)

- Morbidity
o Symptoms
o Daily functions
- Mortality
- Quality of life
o As perceived by the patient Negative Predictive Value

Alternate Clinical Question

- After developing a “best” case based PICO questions, the
next step is exploring other searchable clinical queries
o These are a lsit of flexible alternative questions since the
answer to your precise question may not match the
current scientific literature
o Typically the alternatives involve reasonable variation of
your interventions/comparison Diagnostic Testing

BIOSTATISTICS FOR HIGH VALUE TESTING AND

TREATMENT
LEARNING OBJECTIVES
• Explain basic statistical concepts for diagnostic
testing: sensitivity and specificity, predictive values,
and likelihood ratios.
• Describe the impact o pretest probability and test
characteristics on clinical decision making.
• List the elements of a high value screening test.
• Link these basic statistical concepts to the practice of
high value care.
• Apply the following statistical tools to make high value
treatment decisions: risk ratios, absolute and relative
measures, and numbers needed.
BRIEF REVIEW OF BIOSTATISTICAL CONCEPTS
- Sensitivity: The ability to detect people who do have disease
- Specificity: The ability to detect people who do not have
disease
- Positive Predictive Value: The likelihood that a person with
a positive test result actually has disease
- Negative Predictive Value: The likelihood that a person with
a negative test result truly does not have disease
ROLE OF DIAGNOSTIC TESTS
- To reduce uncertainty regarding a specific patient’s
diagnosis
- Generally most appropriate in the presence of intermediate
(10% to 90%) pretest probability of a disease (e.g., Centor
criteria for Strep pharyngitis)
- Test characteristics (i.e., likelihood ratios) should be
considered before ordering a test to help determine whether
a given test would significantly change posttest probability
(and thus affect management)
LIKELIHOOD RATIOS: WHAT DO THEY MEAN?
- Likelihood ratios combine the sensitivity and specificity of a
test with pretest probability of disease in a specific patient,
avoiding the need to perform statistical calculations based
on test characteristics and prevalence data.
o LR+ = sensitivity / (1-specificity)
o LR- = (1-sensitivity) / specificity

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- They provide a sense of how “powerful” a test is in

influencing our pretest probability of disease.
- Likelihood ratios may be positive [LR(+)], which are used
when assessing for the presence of disease when a test
result is positive, and negative [LR(-)], which are used when
excluding disease with a negative test result.
- Likelihood ratios may also be calculated sequentially with
serial testing, if needed.

USING LIKELIHOOD RATIOS

1. Use the estimated pretest probability of disease as an
anchor on the left side of the graph.
2. Draw a straight line through the known likelihood
ratio, either (+) or (-).
3. Where this line intersects the graph on the right
represents the posttest probability of disease.

LIKELIHOOD RATIOS
- A likelihood ratio of 1 indicates that the test has no influence
on the pretest probability; a likelihood ratio >1 increases the
pretest probability, and a likelihood ratio <1 decreases the
pretest probability.

- In general:
o A LR(+) of 10 increases the pretest probability by ~45%
o A LR(+) of 5 increases the pretest probability by ~30%
o A LR(+) of 2 increases the pretest probability by ~15%
o A LR(-) of 0.5 decreases the pretest probability by ~15%
o A LR(-) of 0.2 decreases the pretest probability by ~30%
o A LR(-) of 0.1 decreases the pretest probability by ~45%

- Even if specific LR calculations are not performed for a

patient, simply knowing the LR of a test helps in making
testing decisions.

EXAMPLES OF COMMON DISEASE, TESTS AND

LIKELIHOOD RATIOS
USING FAGAN’S NOMOGRAM
1. Designate your pretest probability on left line (X); example
= 28%
2. Draw a line to the LR+ (or LR-) for the test (O); example
LR+ = 4
3. Draw a straight line through the two points and extend it to
the right side to determine posttest probability (where this
line intersects the graph on the right represents the posttest
probability of disease = 65%)

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USING LIKELIHOOD RATIOS: SMALL GROUP EXERCISE
- Use the nomograms and LRs given to come up with the
posttest probability of disease for the cases provided.
- Focus on the diagnostic process:
o Estimate the pretest probability of disease in your
patient.
o Evaluate how testing would influence your pretest
probability of disease using the LR provided and the
nomogram.
o Decide if you think the test is high value based on this
exercise.
- Be prepared to briefly summarize your findings and share
them with the larger group.
ROLE OF SCREENING TESTS
- To detect asymptomatic and early stage disease
- Should be highly sensitive and highly specific to pick up
most cases of true disease and avoid false positives
- Targeted toward populations with a higher disease
prevalence (high positive predictive value)
- Should be relatively safe and cost-effective
- Should screen for diseases in which early identification
and treatment have been demonstrated to improve
clinical outcomes
COMMON HARMS ASSOCIATED WITH SCREENING
- False positive results
o Primary goal of screening: find specific diseases
→Maximize sensitivity at cost of specificity
→ False positives
o Can lead to incorrect labeling, inconvenience, expense,
and physical harm in follow-up tests
- Selection bias (healthy volunteer bias)
- Lead Time bias
o Make diagnosis of disease earlier -> Flase survival
benefit
- Length Time Bias:
o “Overdiagnosis” and “Pseudodisease”
SCREENING CASCADE
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VALUE FRAMEWORK
SCREENING VALUE CASES
- Discuss the following screening cases, and use handout to
guide your decisions:
o 45-year-old woman asking about mammography
o 70-year-old man with ESRD on HD, CAD, COPD, and
uncontrolled DM asking for colonoscopy
o 35-year-old woman, new patient, had a negative Pap
smear 2 years ago, now asks for a repeat Pap test
because “that’s what she’s always had”
SCREENING SMARTER
- Screen less frequently.
- Don’t screen patients with a life expectancy less than 10
years.
- Discuss potential downstream testing with patient before
ordering initial screening test.
- Use higher threshold for positive result.
- Understand basic test characteristics and limitations, as well
as an individual patient’s goals and values.
BIOSTATICAL PRINCIPALS IN TREATMENT
- High value therapeutic decision making requires
understanding the effectiveness of different treatment
options, and balancing potential benefits with both medical
and financial costs.
INTERPRETING THERAPEUTIC STATISTICS
- Absolute risk (AR) or Event Rate (ER): The probability
of an event occurring in a group during a specified time
period.
Patients with event in group/total patients in group
- Relative risk (RR): The ratio of the probability of
developing a disease with a risk factor present to the
probability of developing the disease without the risk factor
present.
Experimental event rate/control event rate
- Absolute risk reduction (ARR):The difference in rates of
events between experimental group (EER) and control group
(CER)
Experimental event rate - control event rate
- Relative risk reduction (RRR): The ratio of absolute risk
reduction to the event rate among controls
Experimental event rate - control event rate/ control
event rate
 [PFCM] Evidence-Based Medicine

• Number needed to treat (NNT): Number of

patients needed to receive a treatment for one
additional patient to benefit
1/absolute risk reduction

• Number needed to harm (NNH): Number of

patients needed to receive a treatment for one
additional patient to be harmed
1/absolute risk increase

MOST USUEFUL TERMS FOR TREATMENT OPTIONS

- Use absolute risk, absolute risk reduction, and
numbers needed whenever possible.
- Relative comparisons may exaggerate uncommon
outcomes. Interventions that reduce the rate of a disease
from 40% to 20% and 4% to 2% each have a relative risk
reduction of 50%. However, the absolute risk reduction
(ARR) for the first case is 20%, whereas the ARR for the
second case is 2%.
- Numbers needed are useful indicators of the clinical impact
of an intervention because they provide a sense of
magnitude expected from the intervention.
- Statistical significance ≠ clinical importance, especially
for large studies with uncommon outcomes.

COST-EFFECTIVENESS

- Quality-adjusted life-year (QALY) is a generic measure of

disease burden, including both the quality and the quantity
of life lived. 1 QALY = 1 year in perfect health
- Measures that cost money but improve health can be further
categorized by their cost,
often measured in dollars per QALY
- QALYs incorporate an estimate of the quantity of life gained
by the intervention, coupled with a more subjective
assessment of the quality of that life affected by the
intervention
- Historically, payers have considered any intervention that
has a cost-effectiveness ratio of
<$100K per QALY as acceptable

COST-EFFECTIVENESS OF SELECTED TREATMENTS

- Cost-saving (ratio <$0): Aspirin for at-risk patients,
childhood immunizations
- 0 to $13,999/QALY: Chlamydia screening, colorectal
screening for all adults >50
- $14,000 to $34,999/QALY: Cervical cancer screening,
hypertension screening for all adults

SUMMARY
- Diagnostic tests should only be used if the result is likely to
significantly affect your certainty of a disease (posttest
probability) and should rely on likelihood ratios for a given
test when available.
- The goals of screening are to detect treatable,
asymptomatic, or early stage disease.
- The limitations, harms, and costs associated with screening
should be considered in the context of the patient’s goals.
- Whenever possible, treatment benefit should be expressed
in terms of absolute risk reduction (not relative risk
reduction).
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