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CLINICAL DILEMMA TREE

TREAT

DIAGNOSIS Wait-and-see

BASIC CONCEPTS OF TEST

EVIDENCE-BASED MEDICINE
M A . R O S A R I O “ C H E R RY ” B E R N A R D O - L A Z A R O , M D , M B A H , F PA F P
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UNCERTAINTIES, Diagnostic Threshold/Test Threshold:

Measures of Treatment Effect
PROBABILITIES AND • BELOW which one RULES OUT the disease;
Relative Risk (RR) = Rt/Rc

THRESHOLDS
Absolute Risk Reduction (ARR) = Rc-Rt
• ABOVE which one REQUEST for further
testing TREAT Relative Risk Reduction (RRR) = 1-RR
Number Needed to Treat = 1/ARR

Where do we get these

DIAGNOSIS Wait-and-see values?

Measures of Diagnostic Test

Accuracy
Treatment Threshold TEST Sensitivity=TP/TP+FN
• ABOVE which one decides to TREAT even Specificity=TN/TN+FP
without the benefit of a diagnostic test
Likelihood Ratios: LR+ and LR-
• BELOW which one decides to do DIAGNOSTIC
TEST before treating
Source: Stern, S.; Cifu, A.; Altkorn, D. (2010) Symptom to Diagnosis. An Evidence-Based Guide.
McGraw-Hill Companies, Inc.
LR(+)=Sn/(1-Sp)
LR(-)= (1-Sn)/Sp
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SOURCES OF EVIDENCES WHY STUDY EBM?

•CLINICAL TRIALS AND REGISTRIES Clinicians face various clinical dilemmas

•META-ANALYSIS AND SYSTEMATIC REVIEWS

•CLINICAL PRACTICE GUIDELINES
But there are still a lot of these in the web…
…How do we know which ones are of quality?
Various of sources of information
 Lectures, seminars, conventions, friends
 Millions of published reports, journal articles and studies published per year
 No control over the QUALITY of information
Choosing BEST available evidence for patient care is important

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WHAT IS
EVIDENCE-BASED MEDICINE?
Evidence-based medicine
(EBM) is the conscientious, How do we go about applying EBM in
explicit and judicious use Clinical Decision Making?
of current best evidence in
making clinical decisions THE EBM PROCESS
about the care of the
individual patient.
- Dr. David Sackett

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EBM: 5 KEY STEPS

ASSESS: INTERVIEW AND EXAMINE THE PATIENT
1. ASK: Convert your clinical dilemma from the patient
encounter to a focused research question
The practice of EBM is usually triggered by patient encounters
2. ACQUIRE: Search the literature and online databases for
applicable research data
in any part of your patient encounter (SOAP), you can generate
3. APPRAISE: Critically appraise the evidence gathered questions about the effects of therapy, the utility of diagnostic tests, the
with regard to its validity and relevance prognosis of disease or the etiology of disorders.
4. APPLY: Integrate appraisal knowledge about the unique
aspects of the patient (including the patients preferences Now, try to recall a clinical dilemma you had with a patient or a clinical
about the possible outcomes) encounter.
5. ASSESS: Interview and examine the patient
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EXAMPLES OF CLINICAL DILEMMA

IN PATIENT ENCOUNTERS ASK: CONVERT YOUR CLINICAL DILEMMA
•Your auntie asked you if Vitamin B-complex is effective in treating
TO A FOCUSED RESEARCH QUESTION
numbness since it was mentioned in commercials (e.g.Mel Tiangco,
Gloria Diaz for B-complex)
At some point in assessing the patient, physicians may have
•Your patient at the health center wanted to ask if he can give Solmux clinical dilemma.
or Carbocisteine for his child who was having cough. You know that
it’s not part of IMCI but you wanted to know if there is evidence for it.
The next step is to convert this dilemma into an answerable
or focused research question.
•Your yaya who has put on some weight over the summer asked you if
drinking anything with L-carnithine could make her lose weight.

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TYPES OF CLINICAL QUESTIONS COMPONENTS OF A

FOCUSED (FOREGROUND) QUESTION
BACKGROUND FOREGROUND QUESTION
Population
QUESTION
Asks for basic information or Asks about decisions and actions
related to patient care
Intervention
general knowledge of disease,
disease process, tests, treatment,
etc. FOUR components:
▪ P – Population or Problem
Two components
 Root (what, how…)
▪ I – Intervention
▪ C – Comparison (if applicable) +/- Co-Intervention
 Verb (causes, prevents) ▪ O –Outcome
Examples:
 How do you insert IV catheter?
▪ M - Methodology
Outcome
Methodology
 What causes UTI?

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POPULATION INTERVENTION
Any diagnostic or therapeutic intervention or management (what
•This pertains to group of patients that is similar your patient you want to do or give to the patient):
which maybe in terms of characteristics, primary problem, oDrug (e.g.antibiotic, pain reliever)
disease or co-existing conditions.
oDiagnostic test (e.g. ultrasound, CT scan, blood exam,
mammography)
•Sometimes the age, sex or race of the patient might be relevant oSurgical procedure (eg. laparoscopy, mastectomy)
to the diagnosis or treatment of the disease. oNon-pharmacologic interventions (e.g. diary, counseling, text
messages)

•Examples: elderly patients, patients with dyspnea, smokers... Exposure factors that could influence the prognosis of the patient
oage, co-existing problems, asbestos, cigarette smoking
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COMPARATIVE INTERVENTION OUTCOME

•What you hope to accomplish, measure, improve or affect.
•Maybe included if two (2) drugs or diagnostic tests are to be
compared
•Two kinds of outcome:

•Examples:  Clinical outcome

• Intervention: Ultrasound (vs) Comparative Intervention: CT scan
• Intervention: 5-days antibiotic (vs) Comparative Intervention: single-dose  Surrogate outcome

•Clinical questions do NOT always need to have a specific

comparison.
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TWO KINDS OF OUTCOMES COMPONENTS OF A

FOCUSED (FOREGROUND) QUESTION

Clinical outcome is the real clinical endpoint or true Population

health outcome of interest especially for the patient
▪E.g. relief of symptoms, morbidity, mortality Intervention
+/- Co-Intervention
Surrogate outcome is a measure of effect of a certain
intervention that may correlate the real clinical outcome Outcome
but doesn't necessarily have a guaranteed relationship.
 Eg. Decrease in liver enzymes (may not necessarily correlate with Methodology
resolution of liver cirrhosis).

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PICO: PUTTING THEM TOGETHER STUDY METHODOLOGY AND

POPULATION INTERVENTION COMPARATOR OUTCOME
TYPOLOGY FOR QUESTION BUILDING
Tips for Starting with your Ask "Which Ask "What is the Ask "What can I
building patient, ask "How main main alternative to hope to Methodology pertains to the type of study that is
would I describe a intervention am I compare with the accomplish?" or appropriate for your question.
group of patients considering?" intervention?" "What could this
similar to mine?" Be specific. Again, be specific. exposure really  If your question is on therapy, what will be the appropriate
Balance precision affect?" method?
with brevity. Again, be If your question is on diagnosis then the appropriate study is
specific.
what?
Example “Among obese “…would taking "... when compared "... lead to weight Once you have created a question, it is helpful to think about what type of
patients,… L-carnithine.. with placebo ..." reduction…
question you are asking, as it will affect where you look for the answer and
what type of research you can expect to provide the answer.

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STUDY METHODOLOGY HIERARCHY OF STUDY DESIGNS

TYPE OF QUESTION TYPE OF STUDY
Etiology Case-control or Cohort
The causes of disease and their modes of operation Study
Diagnosis: Diagnostic validation
Signs, symptoms or tests for diagnosing a disorder study Best study
Prognosis: depends on the
Cohort study
The probable course of disease over time TYPE OF
Treatment:
Randomized Controlled QUESTION
Selection of effective treatments which meet your
Trial
patient’s values
Cost-Effectiveness:
Is one intervention more cost-effective than Economic evaluation
another?
Quality of Life:
Qualitative study
What will be the quality of life of the patient?
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WHAT RESEARCH QUESTIONS CAN YOU

COMPONENTS OF A FORMULATE OUT OF THESE CLINICAL DILEMMA?
FOCUSED (FOREGROUND) QUESTION
•Your auntie asked you if Vitamin B-complex is effective in treating
Population
numbness since it was mentioned in commercials (e.g.Mel Tiangco,
Gloria Diaz for B-complex)

Intervention
•Your patient at the health center wanted to ask if he can give Solmux
+/- Co-Intervention or Carbocisteine for his child who was having cough. You know that
it’s not part of IMCI but you wanted to know if there is evidence for it.
Outcome
Methodology •Your yaya who has put on some weight over the summer asked you if
drinking anything with L-carnithine could make her lose weight.

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SELECTED TOOLS FOR FINDING THE EVIDENCE IN EBM

ACQUIRE: SEARCH THE LITERATUR E Evidence-Based Comprehensive electronic database that Subscription required. Available
AND ONLINE DATABASES FOR APPLICABLE RESEARCH DATA Medicine Reviews combines and integrates: Cochrane
Database of Systematic Reviews, ACP
through medical center libraries and
other institutions
www.ovid.com
Journal Club, The Database of Abstracts of
Reviews of Effectiveness
•What Search Engine would you use? (Google, yahoo, bing, Cochrane Library Collection of EBM databases, including the Subscription required. Abstracts of
emed, Pubmed?) www.cochrane.org Cochrane Database of Systematic Reviews-
full articles reviewing specific health care
systematic reviews available free
online. Some countries have funding
topics. to provide free access to all
residents

•Select the appropriate resources and conduct a search ACP Journal Club Collection of summaries of original studies
and systematic reviews. Published
Subscription required.
www.acpjc.org
bimonthly.

Clinical Evidence Monthly updated directory of concise Subscription required. Free access
•PUBMED comprises more than 19 million citations for biomedical articles www.clinicalevidence.co overviews of common clinical interventions. for United Kingdom and developing
countries.
from MEDLINE and life science journals. m
MEDLINE National Library of Medical database with Free via Internet
www.nlm.nih.gov citations back to 1966.
Source: Page 25, Table 3-3, Harrison’s 19th Edition

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APPRAISE: CRITICALLY APPRAISE 4 COMPONENTS OF

THE EVIDENCE GATHERED WITH REGARD TO ITS
VALIDITY AND RELEVANCE APPRAISAL TOOLS
•Application of rules of evidence to a study to o RELEVANCE Does this study address a clearly focused
assess completeness of reporting methods question?
and procedures, conclusions, compliance with Does the study answer a particular
ethical standards, etc. question similar to my own?
•Careful, exact examination and judgement of o VALIDITY Did the study use valid methods to
address this question?
literature for a set of stated clinical objectives.
o RESULTS What are the results?
•Application principles of analysis to identify Are the valid results of this study
Each component has
unbiased and valid studies reported in important?
Questions answerable
literature. o APPLICABILITY Are these valid, important results by
applicable to my patient or population? ❑ YES
•Exclusion of research studies that are poorly Will the results be helpful to me? ❑ NO
designed. ❑ UNCLEAR

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DIAGNOSTIC STUDY CR-AP

RELEVANCE: Does the study answer a RESULTS: What are the results? Are the
particular question similar to my own? results valid?
Measures of Diagnostic Test Accuracy
VALIDITY: Did the study use valid methods to • Sensitivity=TP/TP+FN
address this question?
• Specificity=TN/TN+FP
1. Was the diagnostic test evaluated in a
representative spectrum of patients (like • Likelihood Ratios: LR+ and LR-
those in whom it would be used in
practice)? • LR(+)=Sn/(1-Sp)
2. Was the reference standard applied • LR(-)= (1-Sn)/Sp
regardless of the index test result?
APPLICABILITY: Will the results help me
3. Was there an independent, blind in caring for my patients?
CRITICAL APPRAISAL
comparison between the index test and
an appropriate reference ('gold') standard

(CR-AP) IN A NUTSHELL
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RESULTS: WHAT ARE THE RESULTS?

DISEASE STATE
or GOLD STANDARD RESULT

Present Absent
(+) (-) Measures of Diagnostic
Test Accuracy
POSITIVE
Positive True Positives False Positives Sensitivity=TP/TP+FN
PREDICTIVE VALUE
(+) (TP) (FP)
DIAGNOSTIC (PPV) (TP/TP+FP)
Specificity=TN/TN+FP
TEST RESULT Negative False Negatives True Negatives
NEGATIVE
(-) (FN) (TN)
PREDICTIVE VALUE Likelihood Ratios: LR+ and
(NPV) (TN/FN+TN) LR-
SENSITIVITY SPECIFICITY
LR(+)=Sn/(1-Sp)
(TP/TP+FN) (TN/FP+TN) LR(-)= (1-Sn)/Sp
CBL CBL

DIAGNOSTIC STUDY CR-AP RCT CR-AP

RELEVANCE: Does the study answer a
particular question similar to my own?
VALIDITY: Did the study use valid methods to
address this question?
1. Was the diagnostic test evaluated in a
representative spectrum of patients (like
those in whom it would be used in
practice)?
2. Was the reference standard applied
regardless of the index test result?
3. Was there an independent, blind
comparison between the index test and
an appropriate reference ('gold') standard
of diagnosis?
RESULTS: What are the results? Are the RELEVANCE: Does the study answer a particular RESULTS: What are the results?
results valid? question similar to my own?
VALIDITY: Are the methods of the study valid? •Relative Risk (RR) = Rt/Rc
Measures of Diagnostic Test Accuracy
• Sensitivity=TP/TP+FN 1. Was the assignment of patients to treatment
•Absolute Risk Reduction (ARR) = Rc-Rt
randomized?
• Specificity=TN/TN+FP
2. Were the groups similar at the start of the trial? •Relative Risk Reduction (RRR) = 1-RR;
• Likelihood Ratios: LR+ and LR-
3. Aside from the allocated treatment, were the
• LR(+)=Sn/(1-Sp) •Number Needed to Treat = 1/ARR
groups treated equally?
• LR(-)= (1-Sn)/Sp
4. Were all patients who entered the trial accounted
for? And were they analyzed in the groups to
APPLICABILITY: Will the results help me APPLICABILITY: Will the results
in caring for my patients? which they were randomized? help me in caring for my patients?
5. Were measures objective or were the patients
and clinicians kept “blind” to which treatment was
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RCT CR-AP META-ANALYSIS CR-AP

RELEVANCE: Does the study answer a particular
question similar to my own?
VALIDITY: Are the methods of the study valid?
1. Was the assignment of patients to treatment
randomized?
2. Were the groups similar at the start of the trial?
3. Aside from the allocated treatment, were the
groups treated equally?
4. Were all patients who entered the trial accounted
for? And were they analyzed in the groups to
which they were randomized?
5. Were measures objective or were the patients
and clinicians kept “blind” to which treatment was
being received?
RESULTS: What are the results?
•Relative Risk (RR) = Rt/Rc
•Absolute Risk Reduction (ARR) = Rc-Rt
•Relative Risk Reduction (RRR) = 1-RR;
•Number Needed to Treat = 1/ARR
APPLICABILITY: Will the results
help me in caring for my patients?
RELEVANCE: Does the study answer a particular question similar to my
own?
VALIDITY: Are the results valid?
1. 1. Is it unlikely that important, relevant studies were missed?
2. Were the criteria used to select articles for inclusion appropriate?
3. Were the included studies sufficiently valid for the type of question
asked?
RESULTS: Look for Forest Plot; Note precision and homogeneity
APPLICABILITY: Will the results help me in caring for my patients?
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EYEBALLING META-ANALYSIS CR-AP

HOMOGENEITY
RELEVANCE: Does the study answer a particular question similar to my
•With the ‘eyeball’ test one looks for own?
overlap of the confidence intervals of the VALIDITY: Are the results valid?
trials with the summary estimate. 1. 1. Is it unlikely that important, relevant studies were missed?
•In the example above note that the 2. Were the criteria used to select articles for inclusion appropriate?
dotted line running vertically through the
3. Were the included studies sufficiently valid for the type of question
combined odds ratio crosses the asked?
horizontal lines of all the individual
studies indicating that the studies are RESULTS: Look for Forest Plot; Note precision and homogeneity
homogenous. APPLICABILITY: Will the results help me in caring for my patients?
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CPG CR-AP APPLY THE EVIDENCE

USING AGREE INSTRUMENT
o Go back to the patient and together decide
CBL note on Alignment with Components whether you will apply the evidence or not.
DOMAIN COMPONENTS of Appraisal Tools After all, EBM consist of not just the evidence
and clinician’s judgement but more
I Scope and Purpose Relevance importantly, the patient’s preference and
II Stakeholder Involvement * values
III Rigor and Development Validity o Ask the patient to follow-up so you can
assess whether the intervention worked or
IV Clarity of Presentation Results not.
V Applicability Applicability o In assessing the results of the application of
the evidence can lead you to another cycle of
VI Editorial Independence ** practicing evidence-based medicine
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CBL CBL

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