EVIDENCE BASED MEDICINE A new approach to clinical care and research

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EVIDENCE BASED MEDICINEA new approach to
clinical care and research
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OBJECTIVES OF THE SESSION

• Recognize the concepts and principles of EBM.
• Identify the important of EBM as an essential
  part of clinical practice.
• Discuss the Skills needed for EBM practice.
• Recall the five steps approach to EBM practice.

• Identify the application of EBM in clinical
  practice.
• Discuss the barriers to practice EBM
• Provide some examples of EBM practice

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Pause for Thought For three minutes

• Why this session is important?
• What is EBM
• What are the
• Benefits ??
• First alone then 2-3 in group

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a test1st ?
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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
(Check all that apply)

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis Reports

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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
EXCELLLENT!

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis Reports

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BUT Past knowledge and practice might be
outdated or inadequate
Up to date Knowledge
Clinical skills and Experience
Graduate Medical School
Practiced Physician
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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
FANTASTIC!

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis reports

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BUT This evidence may be biased, outdated,
incorrect, or not applicable to your patient
JOURNALS (1987 to present)
ARTICLES
ADVERTISEMENTS
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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
WONDERFUL!

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis reports

Mutual Respect Shared Goals Better
Cooperation and Compliance
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The patient should be involved in all important
decisions But this is NOT always an easy task!
And conflicts WILL occur!
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No salt? Lose weight? Forget it! Just give me a
pill!
I WONT take that medicine The side effects are
INTOLERABLE!
But doctor, I DO want to have children!
And conflicts WILL occur!
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No salt? Lose weight? Forget it! Just give me a
pill!
I WONT take that medicine The side effects are
INTOLERABLE!
But doctor, I DO want to have children!
Education about current alternatives and risks is
often needed for both the Patient and the Doctor!
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Ill discuss those risks with my husband.
Yes, Id like to try that new medication!
Wow I never knew that high blood pressure could
be so dangerous at my age!
Education about current alternatives and risks is
often needed for both the Patient and the Doctor!
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An important rule in Evidence Based Medicine It
STARTS with the patient and ENDS with the patient.
The patients preferences MUST be considered!
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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
WOW!!! SUPERB!!!

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis reports

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In the practice of Evidence Based Medicine, it is
the physicians duty to find the best and most
current information and apply it judiciously for
the benefit of the patient.
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But A practice based exclusively on science and
math is effective only if your patients are
robots or clones!
Dont forget to allow for individual human
differences and personal preferences!
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WHAT IS THE BASIS OF YOUR MEDICAL PRACTICE?
If you checked all 4 items

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis reports

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CONGRATULATIONS!
You are practicing EVIDENCE BASED MEDICINE!

1. Training, clinical experience and consultation
   with other professionals
2. Convincing evidence (non-experimental) from
   articles, case reports, product literature, etc.
3. Preferences of the patient
4. Active search of Randomized Controlled Trials,
   Systematic Reviews, Meta-Analysis reports

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EVIDENCE BASED MEDICINEA new approach to
clinical care and research

1. Definition of EBM
2. Basic Steps
3. Trials, Studies and Reports
4. Pros, Cons and Limitations
5. EBM Library
6. Advanced EBM

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What is Evidence Based Medicine?
And where did it come from?
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A BRIEF HISTORY 1980s McMasters University in
Ontario, Canada Dr. David Sackett and colleagues
proposed Evidence Based Medicine (EBM) as a new
way of teaching, learning and practicing
medicine. Dr. Sackett defines EBM as The
conscientious, explicit, and judicious use of
current best evidence in making decisions about
the care of individual patients.
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• "Evidence-based medicine is the integration of
  best research evidence with clinical expertise
  and patient values." Sackett, D. L.
  (2000). Evidence-based medicine How to practice
  and teach EBM(2nd ed.). Edinburgh New York
  Churchill Livingstone.

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• Clinical expertise the clinicians cumulated
  experience, education, and clinical skills
• Patient values The patient brings to the
  encounter his or her own personal and unique
  concerns, expectations, and values.
• Best Research Evidence usually found in
  clinically relevant research that has been
  conducted using sound methodology

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Evidence Based Medicine It is a change in the
way physicians practice medicine, teach and
learn, and handle research. Clinical practice
Based on the best current evidence (not
necessarily on how its always been
done) Patient Care Compassionate,
patient-oriented (less authoritarian) Learning
Teaching Problem-based, problem-solving more
investigative, less know-it-all-by-yesterday Rese
arch More stringent approach, better proof
criteria (more demanding of proof, less room for
error)
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THREE MAJOR COMPONENTS of EBM
PATIENT
Question or Problem
PHYSICIAN
INFORMATION
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THE ADDED DETAILS
PATIENT Values, Concerns Preferences,
Expectations Life predicament
EBM
PHYSICIAN Training Experience Current
Expertise Continued learning Demand for proof
INFORMATION Clinically relevant Proven by
research Best up-to-date evidence
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Isnt this the way we have always practiced
medicine?
Arent these just the same old ingredients
tossed into a new recipe?
When am I supposed to find the time to do that?
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The basic steps of EBM
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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and
  usefulness(validity and relevance)
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• Making a decision, by integrating the
  evidence with your clinical expertise and the
  patients values.
• 5. Evaluate
• The information, intervention, and EBM process

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The Clinical Question
The FIRST step The HARDEST step The MOST
IMPORTANT step!
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FACT We all have informational needs!
That is not a problem!
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• Problems arise
• if we fail to recognize those needs
• if we fail to bridge the information gap
• if we fail to ask the right questions

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Asking good questions is a skill to be learned.
Hmmm Is he about to give me a BONUS?
Or is he about to FIRE me?
Lee, exactly how much time did you spend on that
big project?
It will make life easier for you...
And also for others around you!
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Lee, can you give me an accounting of the extra
time you spent on that project so that I can
charge it back to the client?
Oh sure! Ill have it on your desk by tomorrow!

• A GOOD QUESTION
• Is focused and relevant
• Provides clear communication
• Clarifies your goal or need
• Will reduce the amount of time needed to obtain
  the answer

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Asking Questions
Foreground Questions
Background Questions
Expert
Novice
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The Question

• Background
• Anatomy and Physiology
• Pathophysiology
• Pharmacology and Toxicology
• Differential diagnosis
• Diagnostic testing
• Treatment
• Textbooks, reviews, lectures, experts

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The Clinical Question

• Foreground
• Detailed information
• Patient focus
• Evidence-based process

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WHEN PRACTICING EBM, a good question must also

• Be specific
• Identify the problem, clarifiy the clinical
  issue
• Be answerable
• through the literature
• Contain multiple aspects
• (patient, options, comparisons, etc)

It should NOT involve a question of Personal
Preference or Local Concern.
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EBM QUESTION Should include multiple
factors (Examples) P PATIENT type of patient or
population Ex 47 yr male w/DM2 and cellulitis
toe, 25 yr female w/DVT and chest
pain E EXPOSURE environmental, personal,
biological Ex TB, tobacco, drug, diet,
pregnancy or menopause, MRSA, allergy I INTERVENT
ION clinical intervention Ex medication,
procedure, test, surgery, radiation, drug,
vaccine C COMPARISON compare alternative
treatment Ex other prior, new or existing
therapy O OUTCOME clinical outcome of
interest Ex Reduced death rate in 5 yrs,
decreased infections, fewer hospitalizations
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Scenario and Question

• A healthy adult presents to the clinic inquiring
  about the aspirin that it might prevent heart
  attack ?

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The Question

• In an asymptomatic adult and no risk factors,
  would the use of aspirin reduce the incidence of
  cardiovascular events?

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Aspirin and Primary Prevention

• 1. Patient population.
• 2. Intervention.
• 3. Comparison intervention.
• 4. Outcomes.

• Asymptomatic adults with no risk factors

Aspirin
Placebo
Incidence of CV events
In asymptomatic adults no risk factors, would
the use of aspirin reduce the incidence of
cardiovascular events?
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Scenario and Questions (Contd)

• Scenario
• A 32-year-old man, single, teacher in primary
  school, known to have IBS for last 3 years with
  no response to conventional medication. I decided
  to search for effect of TCA in patients with IBS.

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Use of TCA in IBS

• 1. Patient population.
• 2. Intervention.
• 3. Comparison intervention.
• 4. Outcomes.

• Middle age adults with IBS

Using of TCA
dietary fibers, bulking agents and mebeverne
Relieving of symptoms
In middle age adults with IBS, would the use
of TCA reduce the pain and improve symptoms?
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• FRAMING THE QUESTION (Example PICO)
• ELEMENT PROMPTS THE QUESTION
• Patient How would I describe a group of patients
  similar to mine?
• Intervention What main action am I considering?
• Comparison What is/are the other options?
• Outcome What do I (or the patient) want to happen
  (or not happen)?
• Example
• P In kids under age 12 with poorly controlled
  asthma on metered dose inhaled steroids
• I would the addition of salmetrol to the
  current therapy
• C compared to increasing the dose of current
  steroid
• O lead to better control of symptoms without
  increasing side effects?

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• CATEGORY OF QUESTION
• MAJOR CATEGORIES
• Diagnosis
• Prognosis
• Therapy/ Treatment PICO
• Harm (iatrogenic, other) PEO
• MISCELLANEOUS
• Quality of care
• Health economics
• Office Management
• Etc.

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THE PATIENTS QUESTIONS Must be
considered! Often QUALITATIVE (not based on
measureable outcomes) Feelings, ideas,
experiences, preferences, concerns, fears,
beliefs, ethnicity Usually based on LIMITED
BACKGROUND Perception of problem Self-diagnosis T
reatment wanted or needed Alternatives (read,
heard, considered, tried) What is the patient
hoping to avoid? What benefits does the patient
want or need most? Etc.
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QUANTITATIVE vs QUALITATIVE QUESTIONS

• QUANTITATIVE Solid Evidence
• Measurable answer or response
• Necessary for scientific study
• Necessary for the practice of EBM

• QUALITATIVE Quality of Life
• Fuzzy data - Impact on daily life, work,
  family, etc.
• May be very important and influential to
  decisions especially for the patient
• Creates added challenge or twist to practice of
  EBM

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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Some examples

• Questions from our clinics
• What to do with IBS patients?
• Management of premenopousal women.
• How to deal with psychosomatic cases ?
• Guidelines for shifting patient from one drug to
  another ?
• Proper management of IBS ?
• Assessment of ED ?
• Assessment of prostatic enlargement ?
• Assessment of alcohol intake.

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Find the Best EvidenceThe Literary Search
HINT If your desk looks like this, its probably
the LAST place you should start looking!
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Find the Best EvidenceThe Literary Search
The BEST EVIDENCE is External - from outside
resources (researchers, experts) Current not
out of date, most recent High Quality -
accurate, precise, effective, safe Patient
focused - applicable and appropriate for your
individual patient
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• FIVE STEPS TO FINDING THE BEST EVIDENCE
• IDENTIFY NEEDS What type of information is
  needed?
• IDENTIFY RESOURCES Types, Availability,
  Timeliness,Costs?
• SEARCH RETRIEVE Use efficient strategies
• REVIEW Check quality and usefulness of info
• INTERPRET Help patient understand info,
  application

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• WHAT TYPE OF INFORMATION IS NEEDED?
• WHAT CATEGORY IS THE QUESTION?
• Diagnosis
• Prognosis
• Therapy
• Harm

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WHAT STUDY DESIGN FITS IT BEST? There are MANY
study designs! EXPERIMENTAL TRIALS (Answers
questions of diagnosis or treatment) Randomized
Controlled Trials (RCTs) Controlled
studies Blinded vs Open ETC. OBSERVATIONAL
STUDIES Descriptive reports Retrospective
studies Cohort studies Case Control ETC.
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EXAMPLE Randomized Controlled Trials
(RCT) Gold Standard of research Ideal
experimental design - Best design for TREATMENT
questions Must identify objective of treatment
(Ex cure, prevent complication, palliation,
reassurance) Still not always the right
intervention for individual patient at that
particular time and place
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What type of evidence best addresses the
question, problem or issue? CLINICAL
PRACTICE APPROPRIATE DESIGN FOR CLINICAL
RESEARCH Diagnosis, Dx testing Cross-sectional
study not randomized trial Prognosis Follow-u
p studies of patients evaluated at same early
point of illness Therapy, treatment RCT or
Systematic review of multiple RCTs must be used
Avoid non-experimental approaches to avoid
false conclusions about efficacy Exceptions
When treatment may be successful in an
otherwise fatal condition When no studies are
available (rare conditions, new treatments,
etc.) Harm RCT, Cohort, Case-control OTHER
INFORMATIONAL Explore hypothesis Qualitative
research History-taking Case control
study Individual trial error n of 1
trial Following clinical course Cohort
study Recordkeeping Systematic registry-based
(computer supported) research Quality of Care
research Individual peer review, Process
Evaluation MISCELLANEOUS Basic Science,
Genetics, Immunology, etc.
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WHAT FORM OF INFORMATION? Case
report Controlled Trial Systematic
review Meta-analysis Clinical guidelines etc.

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LITERARY SEARCH NEXT STEP IDENTIFY YOUR
RESOURCES Colleagues Consultation,
Discussion (Caution Response may be an outdated
This is what we do) Paper resources books,
reports, journals Electronic databases Health
Literature Services specialized librarians,
staff Review services, Abstract Services, etc.
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• SEARCH AND RETREIVE THE BEST EVIDENCE
• Learn and Practice various SEARCH STRATEGIES
• To find useful information quickly
• To eliminate irrelevant, inappropriate or weak
  information

SO MUCH INFORMATION, SO LITTLE TIME!
Try to develop the habit of learning as you go
Not just in lengthy formal sessions!
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• LITERARY SEARCH STRATEGY
• ASK FOR HELP!
• SPECIALIZED PERSONNEL
• track down information, textbooks, articles,
  guidelines
• may provide electronic search support or training
• EXAMPLES
• Medical Librarians
• Medical Informatics Specialists
• Specially trained staff member

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• LITERARY RESOURCES
• TEXTBOOKS (caution most obsolete!)
• Traditional
• Evidence Based
• JOURNALS (may be outdated)
• REVIEW ARTICLES (summaries, abstracts)
• SYSTEMATIC REVIEWS (prepared in systematic,
  rigorous manner) Ex Cochrane Collection
• META-ANALYSIS
• CLINICAL PRACTICE GUIDELINES
• Summarized and easily digestible information

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• ELECTRONIC RESOURCES, DATABASES, INTERNET
• Bibliographic Database
• Example Medline, PubMed
• Medical Information Services Medscape, HDCN
• Review Services
• Subjective
• Systematic Reviews
• Meta-analysis
• Examples
• Cochrane,
• Best Evidence,
• Up to Date

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MORE GREAT INTERNET RESOURCES Websites
cyberNephrology, National Kidney Foundation.
NIDDK, American Heart Association, American
Cancer Society. National Institutes of Health,
etc Listserve Discussion Groups CyberNephrology
, C-span, etc. Specialty Electronic
Databases Psyclit CancerLit CINAHL (allied
health and nursing journals) Etc
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OTHER RESOURCES Tapes Videos CD-ROMs Specialty
seminars Product information and comparisons
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A closer look at some Internet Resources
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MEDLINE WHAT IS IT? Searchable database of
medical information compiled by National Library
of Medicine in US 1966-present Catalogs articles
from approx 4000 world journals (of estimated
12-15k total) SEARCH METHODS Any word or words
(title, abstract, content, author name,
institution, etc.) Medical Subject Heading
(MeSH) terms A restricted thesaurus of medical
titles Articles categorized by most specific
possible MeSH heading
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• COST FREE!
• Or may subscribe to companies with specialized
  search strategies
• Ovid Technologies (ovid)
• Silver Platter Information (WinSPIRS)
• BENEFITS
• Free
• Vast database
• LIMITATIONS
• Not all articles are indexed on Medline (only 1/3
  of approx 10 million!)
• Much material listed and described on Medline can
  only be accessed through journal article

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• MEDLINE ELECTRONIC SEARCH STRATEGIES
• Search through Clinical Queries service of
  PubMed
• http//www.ncbi.nlm.nih.gov/clinical.html
• Medical Subject Headings (MeSH)
• Search filters
• Search by a text word can supplement a MeSH
  search
• Boolean search and, not, etc.
• To increase sensitivity
• use explode command
• avoid using subheadings
• Online Tutorial is available!

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• COCHRANE LIBRARY
• Cochrane Database of Systematic Reviews
• systematically compiled reviews of intervention
• Cochrane Controlled Trials Register
• citations of controlled trials identified
  anywhere in the world
• Cochrane Review Methodology Database
• methodological papers relating to systematic
  reviews
• Etc.

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• BEST EVIDENCE
• Electronic version of two publications
• Evidence Based Medicine
• American College of Physicians Journal Club
• Covers broad topics of information

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• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

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CRITICAL APPRAISAL

• Interpreting the evidence
• How to read a paper
• How to do the math

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CRITICAL APPRAISAL
IMPORTANT! You do NOT have to become a
researcher, epidemiologist, or statistician to
practice EBM.
Focus on how to USE research reports not on
how to generate them!
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CRITICAL APPRAISAL
HOWEVER You must have a solid understanding of
basic research principles and study designs in
order to understand and interpret the evidence!
83
TYPES OF STUDIES AND REPORTS Randomized
Controlled Trial - The Gold Standard Systematic
review Meta-analysis Retroactive vs
Prospective Incidence Prevalence Case
Control Cohort (Follow-up) Cross-sectional Ecologi
c Longitudinal Experimental Blinded vs
Open Qualitative Screening
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DETOUR
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BASIC RESEARCH PRINCIPLES
STUDY DESIGNS
86
THE TIME FACTOR
When was the study done?
What was its duration?
In what time direction is it headed?
RETROSPECTIVE
PROSPECTIVE
87
THE TIME FACTOR
When was the study done?
What year? What technology? (ie test, drug,
equipment, procedure) Any associated social
factor or historical event?
88
THE TIME FACTOR
What was the Study Duration?
Was it an appropriate length of time for the
intended goal? Limited time study or ongoing? Was
study completed? Stopped early?
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In what direction is it headed?
RETROSPECTIVE
PROSPECTIVE
LOOKING BACK Historical Review or Investigation
LOOKING FORWARD Future Results The Great Unknown
PRESENT
PAST
FUTURE
90
In what direction is it headed?
RETROSPECTIVE
PROSPECTIVE

• PRO
• Lower risk of bias
• CON
• May get faulty results based on incomplete data
  or insignificant subgroups
• (Example of Error Untreated hypertension
  unlikely to cause cardiac event in child, so
  treatment is unnecessary below age 18yrs)

• PRO
• May provide good direction for future study
• Hind Sight is 20/20
• CON
• Prone to Bias
• AFishing Expedition for positive results

PRESENT
91
CONTROLLED vs UNCONTROLLED STUDIES
Was there a similar comparison group?
92
UNCONTROLLED STUDY
No comparison group All subjects receive
Experimental Intervention
Experimental Intervention
93
UNCONTROLLED STUDIES
NO EVENT
Experimental Intervention
OUTCOME EVENT
Trial and Error? or Before After?
94
UNCONTROLLED STUDIES
Generally NOT accepted Potentially Dangerous
and Flawed Prone to BIAS!
Traditional Study Method May produce strong
results
Trial and Error
Before After

• BENEFITS
• Can answer some questions about
• likelihood of response
• adverse effect, etc.
• VERY PATIENT-SPECIFIC!
• MAY BE ONLY OPTION
• Rare conditions
• Previously unknown conditions

• PROBLEMS
• POSITIVE OUTCOME MAY BE DUE TO
• Other factors
• Natural course of disease (some get better, some
  dont!)
• Spontaneous change of health
• Placebo Effect
• Hawthorne Effect
• NEGATIVE OUTCOME
• May be due to study treatment.
• Could be disastrous!

95
UNCONTROLLED TRIALS TRIAL AND ERROR
GOOD! Resistant to Cowpox and Smallpox
Example1
SMALLPOX VACCINATION
James Phipps, age 8 years
(NO DISEASE OUTCOME)

• SMALLPOX VACCINE
• 1. 1796 Edward Jenner inoculates 8yr-old James
  Phipps with cowpox virus from a milkmaids hands.
  
• Child develops illness, recovers.
• 2. Two weeks later, inoculates same child with
  smallpox virus.
• Child survives, no illness.
• (Centuries later, smallpox eradicated!)

n1
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n1
UNCONTROLLED TRIALS TRIAL AND ERROR
Example 2
NO OUTCOME
Drinks culture of H.pylori
SEVERE GASTRITIS
Dr. Marshall Microbiologist
HELICOBACTER PYLORI - GASTRIC ULCERS 1982
Australian microbiologist Barry J. Marshall
presents evidence showing a possible infectious
cause for gastric ulcers. Suggests they may be
treatable with antibiotics. Findings are met
with disinterest and disbelief by medical
community. Lacks support for further study. 5
years later Prepares a broth of live organisms
isolated from a gastric ulcer patient and drinks
it. Becomes violently ill, develops severe acute
gastritis. 1990s Antibiotics are used routinely
to cure some gastric ulcers!
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UNCONTROLLED TRIAL
RECOVERED
Experimental Intervention
DIED
May represent the ONLY treatment option for a new
or rare disease
Present
FUTURE
98
CONTROLLED STUDY
STRONGLY PREFERRED! Reduces BIAS. Provides
stronger results.
Experimental Intervention
Control Group
99
CONTROLLED STUDY
Only the TEST group receives the Experimental
Intervention
ExperimentalIntervention
Control group may receive
Nothing
IMPORTANT All other differences should be
minimized or eliminated to reduce potential BIAS
Placebo
Observation only
Other
Gold Standard Treatment
100
RANDOMIZED CONTROLLED TRIAL (RCT)
The Gold Standard
Experimental Intervention
Control Group
101
THE FIRST RANDOMIZED CONTROLLED TRIAL By Sir
Austin Bradford Hill
Streptomycin (n50)
(BLINDED)
Bedrest (n50)
1944 TUBERCULOSIS TREATMENT Streptomycin vs
Bedrest
102
OPEN vs BLINDED STUDIES
Experimental Intervention
OPEN
Control Group
103
OPEN vs BLINDED STUDIES
BLINDED TRIAL
BLINDED
BLINDED TRIAL
104
BLINDING
SINGLE BLINDED Pt unaware of what group s/he is
in
DOUBLE BLINDED Pt and MD unaware
OPEN LABEL Everyone is aware
105
RANDOMIZED vs NON-RANDOMIZED TRIALS
Experimental Intervention
How is this group divided?
Control Group
106
NON-RANDOMIZED
Experimental Intervention
Assigned to groups, usually by the researcher
Control Group
Potential for RESEARCHER BIAS!
107
RANDOMIZED
Experimental Intervention
Random method of assignment used
Control Group
Maximizes sameness, Eliminates BIAS!
108
RANDOMIZED CONTROLLED TRIAL (RCT) (EXPERIMENTAL
TRIAL)
Experimental Intervention
The Gold Standard
Control Group
Present
FUTURE
109
Other Common Studies
110
CROSSOVER TRIALS
ONE GROUP, MULTIPLE TESTS
(Best if participants are blinded)
Intervention A
Intervention A
Intervention B
Intervention B
ASSESS OUTCOMES 1
ASSESS OUTCOMES 2
COMPARE OUTCOMES
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PROS CONS
CROSSOVER TRIALS
Fewer participants needed than a RCT!
Intervention A
Intervention A
Intervention B
Intervention B
ASSESS OUTCOMES 1
ASSESS OUTCOMES 2
Lower costs
All are in experimental group
112
PROS CONS
CROSSOVER TRIALS
MUST HAVE SHORT CARRYOVER EFFECT MUST HAVE SHORT
WASHOUT EFFECT
Intervention A
Intervention A
Intervention B
Intervention B
ASSESS OUTCOMES 1
ASSESS OUTCOMES 2
(OR WAIT A SUITABLY LONG WASHOUT TIME!)
113
CASE CONTROL
(A LOOK BACK)
RISK FACTOR?
(PAST)
Present
114
CASE CONTROL
(A LOOK BACK)
HEALTHY
NEVER SMOKED
RISK FACTOR
LUNG CANCER
SMOKER
(PAST)
Present
115
CASE CONTROL
(A LOOK BACK)
NON-DIABETIC
NORMAL WEIGHT
RISK FACTOR
DM TYPE II
OBESITY
Present
116
COHORT
FOLLOWUP DESIGN
IS RISK FACTOR PRESENT?
(Exclude those with outcome already!)
Future Outcome
117
COHORT
TO INVESTIGATE ETIOLOGY OR HYPOTHETICAL CAUSE OF
DISEASE/OUTCOME
IS RISK FACTOR PRESENT?
FOLLOWUP DESIGN
Future Outcome
Present
118
COHORT
EXAMPLE
RISK FACTOR Hgb lt9
DIALYSIS PATIENTS
Measures future outcome for dialysis pts w/o
treatment of anemia
Present
119
CROSS SECTIONAL DESIGN
? Cause ? Risk factors
A look back
120
CROSS SECTIONAL DESIGN
OTHER CAUSES
RISK SLEEP PRONE
INFANT DEATHS
SIDS DEATHS
121
Problems of looking back
NON-SIMILAR CONDITIONS Social Personal Comorbid
conditions Other treatments Etc.
VARIATION IN TREATMENT OR METHOD
CURRENT GROUP OF PATIENTS
NO CONTROL OVER CONTROL GROUP
Not usually accepted by medical
journals (accepted in popular press, not
reviewed)
122
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
MAY BE BLINDED
Control Group
PROSPECTIVE
123
START WITH YOUR TARGET POPULATION
124
START WITH YOUR TARGET POPULATION

• Set CRITERIA for
• INCLUSION / EXCLUSION
• This will determine
• ELIGIBILITY at the start
• VALIDITY at the end

125
START WITH YOUR TARGET POPULATION
126
ELIMINATE THOSE WHO DO NOT MEET THE CRITERIA
127
NEXT GATHER A SAMPLE GROUP
128
THE SAMPLE GROUP WILL

• Represent the target population
• Meet the criteria for inclusion / exclusion

SIDE NOTES Study should be approved by an Ethics
Committee Informed consent should be obtained
from study participants
129
SAMPLE GROUP MAY BE SUBDIVIDED FURTHER
STRATIFICATION Divide into subgroups based on
important similar characteristics
RANDOMIZATION Divide into sub-groups based on
unknown confounders
130

• STRATIFICATION
• important similar characteristics
• Examples
• Male or Female
• Age
• Stage of illness
• Prior illness or treatment
• Hospital vs Office groups
• Comorbid condition
• Etc.

131
EXAMPLE OF STRATIFICATION
FEMALE
MALE
132

• RANDOMIZATION
• unknown confounders
• Examples
• Postal code
• Month of birth
• Random number
• Etc.

133
EXAMPLE OF RANDOMIZATION
DX IN JANUARY-JUNE
DX IN JULY-DECEMBER
134
Next Divide your sample group(s) into STUDY
GROUPS
Experimental Intervention
Test Group
Control Group
Baseline Group
135
Next Divide your sample group(s) into STUDY
GROUPS
Test Group
Experimental Intervention
Receives Experimental Intervention
Baseline Group

• Nothing
• Observation
• Same miscellaneous intervention
  (non-experimental)
• Placebo
• Gold Standard therapy - especially if unethical
  to do otherwise!

Control Group
136
ASSIGN PATIENTS TO STUDY GROUPS
Experimental Intervention
Use caution against bias!
Control Group
Sample Group
Study Groups
137

• STUDY INVESTIGATOR
• usually assigns patients to study groups.
• usually has a personal preference for the
  treatment or patient
• might unconsciously work harder to make the
  study work with non-preferred candidates

Experimental Intervention
Control Group

• POTENTIAL FOR BIAS

138
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Use random separation and assignment!
Control Group
139
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Control Group
140
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Control Group
Present
Proceed with study
FUTURE
141
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
EXPERIMENTAL EVENT RATE (EER)
Control Group
CONTROL EVENT RATE (CER)
142
RANDOMIZED CONTROLLED TRIAL (RCT)
The Gold Standard
Experimental Intervention
EXPERIMENTAL EVENT RATE (EER)
Control Group
CONTROL EVENT RATE (CER)
Present
FUTURE
143
Disadvantages of RCT Expensive large pts
needed Prolonged recruitment and follow-up time
needed Funding difficult to obtain except
w/support of pharmaceutical companies
(problematic!)
144
RETURN FROM DETOUR
145

• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

146

• HEIERARCHY OF EVIDENCE
• (value of study design to maximize wt, minimize
  bias)
• Systematic Review of all relevant RCTs
• At least one properly designed RCT
• Trials and case studies
• Well-designed Controlled Trial without
  Randomization
• Well designed Cohort or Case Control Studies,
  preferably from gt1 centre or group
• Multiple Time series with or without intervention
• (Exception Dramatic results in uncontrolled
  trials, such as introduction of PCN in the 1940s)
• Opinions of respected authorities, based on
• Clinical expertise
• Descriptive studies
• Reports of Expert Committees

147

• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

148

• THE FIVE BASIC STEPS OF EBM
• Clinical Question
• Patient-focused, problem-oriented
• 2. Find Best Evidence
• Literary Search
• 3. Critical Appraisal
• Evaluate evidence for quality and usefulness
• 4. Apply the Evidence
• Implement useful findings in clinical practice
• 5. Evaluate
• The information, intervention, and EBM process

149
Evaluate
INFORMATION Adequate resources? Ease or
Difficulty of finding and getting desired
information? Costs? INTERVENTION Patient
response or acceptance? Ease or Difficulty of
Application? Clinical outcomes? EBM
PROCESS EFFECT ON PRACTICE Will this particular
experience change our thinking or practice? SELF
EVALUATION How did we do? (Question, Search,
Appraise, Apply) How could we improve our own EBM
performance?
150
EBM PROS, CONS and LIMITATIONS
151
PROS Clinicians update knowledge base
routinely Improved understanding of research
methods Physician becomes more critical in use
of data Increased confidence in management
decisions Increased computer literacy, data
search technology Better reading
habits Provides framework for group problem
solving, team generated practice
152
Transforms weakness or paucity of knowledge into
positive change OK to be uncertain OK to be
skeptical OK to be flexible Integrates medical
education, research and clinical expertise Can
be learned by non-clinicians other HCWs,
patient groups, purchasers, etc. Allows us to
keep up with our better-educated patients!
153
Increased contribution of junior MDs Increased
patient benefit Better communication with
patients re rationale of management
decisions Promotes better and more appropriate
use of limited resources May reduce costs or
medical care or practice by eliminating outdated
or unnecessary factors Can be learned at any
stage of physicians career
154
CONS Time consuming Information overload Time
to learn and practice Time may be needed for
team conferencing, planning and review Takes
to establish resource infrastructure library,
office, etc. computers, peripherals
155
Internet costs Programs, software information,
CD-ROMS Subscription costs online and paper
resources May increase cost of care (but
hopefully offset by elimination of unnecessary
medical interventions, tests, journals, etc.
plus save time in getting proper
intervention) Online references made to
unavailable journals or references Exposes gaps
in the evidence (but provides ideas for
researchers!)
156
Requires computer skills (but can be done with
minimal computer literacy and skill) May expose
your current practice as obsolete or dangerous
(loss of authority and respect)
157
LIMITATIONS Lack of evidence (shortage of
studies) Difficulty applying evidence to care of
a particular patient Barriers to the practice
of high quality medicine Lack of skills (search,
appraise, etc.) (foster development of new
skills!) Lack of time to learn and practice
EBM (promotes lifelong learning thru better
focus) Lack of physician resources for instant
access to evidence (EBM has worldwide
applicability)
158
RESTRICTED AVAILABILITY OF LAB TESTS NON-TEXTBOOK
CASE co morbidity, additional risk
factors AFFORDABILITY (MD PT)I cant afford
to practice EBM. Language barriers available
evidence may be unreadable, should be included
159
Physician attitude Can be the greatest
limitation! It decreases the importance of my
clinical expertise (thats a necessary
component!) It only applies to those involved
in research. (promotes cooperation among
multiple physicians) It ignores patient values
and preferences. Its just another cookbook
approach to medicine. Its a poorly disguised
way to cut medical costs. (cost of care may
actually increase) Its a way to ration care
and resources. (Provides better utilization of
avail resources)
160
DISAGREEMENT Pts comfort, choice, acceptance,
values preferences Vs MDs recommendations DOES
RISK OR SIDE EFFECTS OF TREATMENT OUTWEIGHT THE
BENEFITS?
161
The unanswered question DOES EBM REALLY MAKE A
DIFFERENCE? Effect of practicing EBM on patient
outcome is actually unknown no studies
done EBM good based on population studies (ie
Pts who recd ___ generally fare better than
those who dont)
162
EBM IN DEVELOPING COUNTRIES
LIMITED RESOURCES May help to eliminate
unnecessary or poor quality screening tests (ie
resting EKG to screen for CAD high false
negative and false positive rates) LIMITED DRUG
REGULATION Approval for drug marketing easy -
promotes insurgence of new drugs for questionable
indications, limited effectiveness, false claims,
inflated prices based on ad response (include
more expensive is better)
163
EBM IN DEVELOPING COUNTRIES LIMITED CAPACITY FOR
CME Drug companies - may sponsor meetings that
are little more than captive marketing sessions
or biased education sessions (drug education vs
promo) Result may be push for more expensive,
less effective treatments (ie push for CCBs over
BBs) - calc channel blockers over Beta Blockers
164
EBM IN DEVELOPING COUNTRIES LIMITED ACCESS TO
LITERATURE DATABASES Desktop computer with CD
ROM reader and modem (900) Electricity 1 yr
subscription to MedLine on CD ROM (?500) Internet
connection 25/mt Convince administrators of
expense Publicly cite how searches help with
lectures, research and patient care management
decisions Get equipment from drug companies
(usually strings attached)
165

• EBM IN DEVELOPING COUNTRIES
• LIMITED ACCESS TO ADEQUATE LIBRARY FACIILITIES
• ALMOST INEVITABLE IN DEVELOPING COUNTRIES
• Identify resources via search, but then unable to
  retrieve articles!
• A top EBM practitioner (Philippines) recommends
• Top 3 medical libraries in your country
• Multinational drug company libraries
• Friends and colleagues - including in other
  countries

166

• EBM IN DEVELOPING COUNTRIES
• QUESTIONABLE APPLICABILITY OF ARTICLES RETRIEVED
• Article describes a treatment that worked in one
  country, but seems impossible in yours
• Check
• Are there pathophysiologic differences?
• Will patient differences diminish the treatment
  response?
• Patient compliance issues?
• Provider compliance issues?
• Co-morbid conditions which will alter the
  benefits or risks?

167
EBM IN DEVELOPING COUNTRIES OBSTACLES TO
TEACHING OR LEARNING EBM Your Hospital or
Institution does not reimburse for time spent on
Continuing Medical Education programs The
standard 5-day workshop would be far too costly
to provide or attend! Need to learn the basics -
computer skills, etc. TRY THESE! Combine efforts
to learn more and practice EBM with handful of
colleagues (small group learning) Ask about
basis for information provided by drug reps,
medical supply companies, etc. It will prompt
them to provide you with on the spot teaching and
better information, too!
168

• EBM LIBRARY
• BASIC REQUIREMENTS
• Convenient easy access at point of contact with
  patient if possible
• Current Up to date information
• Electronic Database Should be included
• Online
• CD-ROM

169
ELECTRONIC DATABASES Evidence-Based Medicine
Reviews (EBMR) from Ovid (ovid.com) - combines
Cochrane, Best evidence, Evidence Based Mental
health, EB Nursing, Cancerlit, healthstar,
AIDSline, Medline, and journal links (Described
by one EBM specialist as the best) Cochrane
Library Gold Standard for systematic reviews
Best Evidence Medline worlds largest, free
resource over 10 million references
170
PERSONNEL Medical Librarian Informatics
Specialist We can learn a great deal about
current best information sources from librarians
and other experts in medical informatics, and
should seek hands-on training from them as an
essential part of our clin