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EVIDENCE BASED MEDICINE A new approach to clinical care and research

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EVIDENCE BASED MEDICINE A new approach to clinical care and research Developed and presented by Judy Tarselli, RN Dubai, UAE Karachi, Pakistan October 2003 – PowerPoint PPT presentation

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Title: EVIDENCE BASED MEDICINE A new approach to clinical care and research


1
EVIDENCE BASED MEDICINEA new approach to
clinical care and research
Developed and presented by Judy Tarselli,
RN Dubai, UAE Karachi, Pakistan October
2003 Organized by NKF cyberNephrology
University of Alberta, Canada www.cyberNephrology.
org
Special thanks to our sponsors Janssen-Cilag
2
PROGRAM OUTLINE
  1. Definition of EBM
  2. Basic Steps
  3. Trials, Studies and Reports
  4. Pros, Cons and Limitations
  5. EBM in Developing Countries
  6. EBM Library
  7. Advanced EBM

3
But first, a test
4
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

5
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

6
BUT Past knowledge and practice might be
outdated or inadequate
Up to date Knowledge
Clinical skills and Experience
Graduate Medical School
Practiced Physician
7
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

8
BUT This evidence may be biased, outdated,
incorrect, or not applicable to your patient
JOURNALS (1987 to present)
ARTICLES
ADVERTISEMENTS
9
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
10
The patient should be involved in all important
decisions But this is NOT always an easy task!
And conflicts WILL occur!
11
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!
12
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!
13
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!
14
An important rule in Evidence Based Medicine It
STARTS with the patient and ENDS with the patient.
The patients preferences MUST be considered!
15
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

16
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.
17
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!
18
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

19
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

20
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 in Developing Countries
  6. EBM Library
  7. Advanced EBM

21
What is Evidence Based Medicine?
And where did it come from?
22
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.
23
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)
24
THREE MAJOR COMPONENTS of EBM
PATIENT
Question or Problem
PHYSICIAN
INFORMATION
25
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
26
OPTIONAL COMPONENTS TO BE ADDED BY THE PHYSICIAN
PATIENT Values, Preferences Concerns,
Expectations Life predicament
CHARITY EBM is not a required practice (yet)
HUMILITY Non-authoritarian practice
EBM
PHYSICIAN Training Expertise Continued
Learning Demand for proof
INFORMATION Clinically relevant Proven by
research Current, up to date
ENTHUSIASM Challenge, Variety, Change
27
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?
28
The basic steps of EBM
29
  • 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

30
  • 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

31
  • 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

32
  • 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

33
  • 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

34
  • 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

35
The Clinical Question
The FIRST step The HARDEST step The MOST
IMPORTANT step!
36
FACT We all have informational needs!
That is not a problem!
37
  • 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

38
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!
39
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

40
WHEN PRACTICING EBM, a good question must also
ACTUAL CASE SCENARIO Large cauc male, age 40 2mo
ago Presented with classic nephrotic syndrome,
significant symptoms. Bx showed IgAN. Cr 1.4,
incr to 2 range, now 1.6 Tried prednisone 60mg qd
- tolerated poorly w/tremors and depression.
Needs new regimen, but others are aimed more at
nephritic IgA rather than nephrotic
syndrome. Suggestions?
  • 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.
41
THE EVIDENCE BASED RESPONSE Posted on Nephrol
4/13/03
Respondant recommends cyclophosphamide and
prednisolone (assuming secondary causes excluded)
- a combination that allows for lower dose
prednisolone
In the study below, proteinuria and renal
function improved on this combination Ballardie
FW, Roberts IS. Controlled prospective trial of
prednisolone and cytotoxics in progressive IgAN.
J Am Soc Nephrol 2002 Jan. I have patients on
this regime who have benefitted. Regards, Dr.
Paulose P. Thomas Nephrologist - Belhoul Apollo
Hospital, Dubai, UAE
42
BACKGROUND and FOREGROUND QUESTIONS (all part of
EBM)
FOREGROUND QUESTIONS
NEW POSSIBILITIES INDEFINITE ANSWERS Where do
we want to go, and how else might we get there?
Where are we now? And which way are we
headed? BASIC CONCRETE
BACKGROUND QUESTIONS
GRAD
STUDENT
EXPERT
43
BACKGROUND QUESTIONS BASIC CONCRETE
  • 1. QUESTION
  • Who, What, Where, When, Why, How
  • 2. VERB
  • is, causes, does, treats, reduces, cures,
    prevents, affects
  • 3. GENERAL KNOWLEDGE ABOUT DISORDER
  • clinical manifestations of disease, patient
    findings, differential diagnosis, etiology,
    patient experience, comorbid condition, screening
    and diagnostic tests, prognosis, therapy, risk
    factors, etc.

GRAD
STUDENT
EXPERT
44
FOREGROUND QUESTIONS NEW POSSIBILITIES INDEFINITE
ANSWERS
  • PT AND/OR PROBLEM Differential dx, Unusual
    presentation, uncertain etiology, pts prior
    experience, comorbid conditions
  • INTERVENTION Exposure, test. Prognostic factor,
  • treatment, pt perception, etc.
  • COMPARISON INTERVENTION
  • OUTCOMES

GRAD
STUDENT
EXPERT
45
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
46
  • 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?

47
  • CATEGORY OF QUESTION
  • MAJOR CATEGORIES
  • Diagnosis
  • Prognosis
  • Therapy/ Treatment PICO
  • Harm (iatrogenic, other) PEO
  • MISCELLANEOUS
  • Quality of care
  • Health economics
  • Office Management
  • Etc.

48
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.
49
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

50
QUALY QUALITY ADJUSTED LIFE YEAR
51
  • 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

52
Find the Best EvidenceThe Literary Search
HINT If your desk looks like this, its probably
the LAST place you should start looking!
53
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
54
  • 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

55
  • WHAT TYPE OF INFORMATION IS NEEDED?
  • WHAT CATEGORY IS THE QUESTION?
  • Diagnosis
  • Prognosis
  • Therapy
  • Harm

56
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.
57
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
58
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.
59
WHAT FORM OF INFORMATION? Case
report Controlled Trial Systematic
review Meta-analysis Clinical guidelines etc.

60
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.
61
  • 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!
62
  • 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

63
  • 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

64
  • 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

65
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
66
OTHER RESOURCES Tapes Videos CD-ROMs Specialty
seminars Product information and comparisons
67
A closer look at some Internet Resources
68
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
69
  • 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

70
  • 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!

71
  • 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.

72
  • BEST EVIDENCE
  • Electronic version of two publications
  • Evidence Based Medicine
  • American College of Physicians Journal Club
  • Covers broad topics of information

73
  • 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

74
CRITICAL APPRAISAL
  • Interpreting the evidence
  • How to read a paper
  • How to do the math

75
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!
76
CRITICAL APPRAISAL
HOWEVER You must have a solid understanding of
basic research principles and study designs in
order to understand and interpret the evidence!
77
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
78
DETOUR
79
BASIC RESEARCH PRINCIPLES
STUDY DESIGNS
80
THE TIME FACTOR
When was the study done?
What was its duration?
In what time direction is it headed?
RETROSPECTIVE
PROSPECTIVE
81
THE TIME FACTOR
When was the study done?
What year? What technology? (ie test, drug,
equipment, procedure) Any associated social
factor or historical event?
82
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?
83
In what direction is it headed?
RETROSPECTIVE
PROSPECTIVE
LOOKING BACK Historical Review or Investigation
LOOKING FORWARD Future Results The Great Unknown
PRESENT
PAST
FUTURE
84
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
85
CONTROLLED vs UNCONTROLLED STUDIES
Was there a similar comparison group?
86
UNCONTROLLED STUDY
No comparison group All subjects receive
Experimental Intervention
Experimental Intervention
87
UNCONTROLLED STUDIES
NO EVENT
Experimental Intervention
OUTCOME EVENT
Trial and Error? or Before After?
88
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!

89
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
90
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!
91
UNCONTROLLED TRIAL
RECOVERED
Experimental Intervention
DIED
May represent the ONLY treatment option for a new
or rare disease
Present
FUTURE
92
CONTROLLED STUDY
STRONGLY PREFERRED! Reduces BIAS. Provides
stronger results.
Experimental Intervention
Control Group
93
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
94
RANDOMIZED CONTROLLED TRIAL (RCT)
The Gold Standard
Experimental Intervention
Control Group
95
THE FIRST RANDOMIZED CONTROLLED TRIAL By Sir
Austin Bradford Hill
Streptomycin (n50)
(BLINDED)
Bedrest (n50)
1944 TUBERCULOSIS TREATMENT Streptomycin vs
Bedrest
96
OPEN vs BLINDED STUDIES
Experimental Intervention
OPEN
Control Group
97
OPEN vs BLINDED STUDIES
BLINDED TRIAL
BLINDED
BLINDED TRIAL
98
BLINDING
SINGLE BLINDED Pt unaware of what group s/he is
in
DOUBLE BLINDED Pt and MD unaware
OPEN LABEL Everyone is aware
99
RANDOMIZED vs NON-RANDOMIZED TRIALS
Experimental Intervention
How is this group divided?
Control Group
100
NON-RANDOMIZED
Experimental Intervention
Assigned to groups, usually by the researcher
Control Group
Potential for RESEARCHER BIAS!
101
RANDOMIZED
Experimental Intervention
Random method of assignment used
Control Group
Maximizes sameness, Eliminates BIAS!
102
RANDOMIZED CONTROLLED TRIAL (RCT) (EXPERIMENTAL
TRIAL)
Experimental Intervention
The Gold Standard
Control Group
Present
FUTURE
103
Other Common Studies
104
n1
One patient, series of tests
TRIAL SERIES FOR INDIVIDUAL PATIENT
GOOD
GOOD
Experimental Intervention Trial of Medicine 1 Or
placebo
Experimental Intervention Trial of Medicine 2 Or
placebo
NO CHANGE OR BAD
NO CHANGE OR BAD
105
Why a TRIAL SERIES for one patient?
BENEFIT Produces data most applicable to the
individual patient
EXAMPLES Trial of different medications and/or
placebo for child reported to have ADHD symptoms
that are not clinically apparent Trial of
different analgesics for patient with chronic
pain from a combination of diseases not
previously studied
  • PATIENT
  • Must be blinded
  • Must keep diary or complete questionnaire
  • PHYSICIAN
  • May need to be blinded (enlist help of
    pharmacist!)
  • Must treat patient as usual in all other respects

106
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
107
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
108
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!)
109
CASE CONTROL
(A LOOK BACK)
RISK FACTOR?
(PAST)
Present
110
CASE CONTROL
(A LOOK BACK)
HEALTHY
NEVER SMOKED
RISK FACTOR
LUNG CANCER
SMOKER
(PAST)
Present
111
CASE CONTROL
(A LOOK BACK)
NON-DIABETIC
NORMAL WEIGHT
RISK FACTOR
DM TYPE II
OBESITY
Present
112
COHORT
FOLLOWUP DESIGN
IS RISK FACTOR PRESENT?
(Exclude those with outcome already!)
Future Outcome
113
COHORT
TO INVESTIGATE ETIOLOGY OR HYPOTHETICAL CAUSE OF
DISEASE/OUTCOME
IS RISK FACTOR PRESENT?
FOLLOWUP DESIGN
Future Outcome
Present
114
COHORT
EXAMPLE
RISK FACTOR Hgb lt9
DIALYSIS PATIENTS
Measures future outcome for dialysis pts w/o
treatment of anemia
Present
115
CROSS SECTIONAL DESIGN
? Cause ? Risk factors
A look back
116
CROSS SECTIONAL DESIGN
OTHER CAUSES
RISK SLEEP PRONE
INFANT DEATHS
SIDS DEATHS
117
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)
118
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
MAY BE BLINDED
Control Group
PROSPECTIVE
119
START WITH YOUR TARGET POPULATION
120
START WITH YOUR TARGET POPULATION
  • Set CRITERIA for
  • INCLUSION / EXCLUSION
  • This will determine
  • ELIGIBILITY at the start
  • VALIDITY at the end

121
START WITH YOUR TARGET POPULATION
122
ELIMINATE THOSE WHO DO NOT MEET THE CRITERIA
123
NEXT GATHER A SAMPLE GROUP
124
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
125
SAMPLE GROUP MAY BE SUBDIVIDED FURTHER
STRATIFICATION Divide into subgroups based on
important similar characteristics
RANDOMIZATION Divide into sub-groups based on
unknown confounders
126
  • STRATIFICATION
  • important similar characteristics
  • Examples
  • Male or Female
  • Age
  • Stage of illness
  • Prior illness or treatment
  • Hospital vs Office groups
  • Comorbid condition
  • Etc.

127
EXAMPLE OF STRATIFICATION
FEMALE
MALE
128
  • RANDOMIZATION
  • unknown confounders
  • Examples
  • Postal code
  • Month of birth
  • Random number
  • Etc.

129
EXAMPLE OF RANDOMIZATION
DX IN JANUARY-JUNE
DX IN JULY-DECEMBER
130
Next Divide your sample group(s) into STUDY
GROUPS
Experimental Intervention
Test Group
Control Group
Baseline Group
131
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
132
ASSIGN PATIENTS TO STUDY GROUPS
Experimental Intervention
Use caution against bias!
Control Group
Sample Group
Study Groups
133
  • 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

134
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Use random separation and assignment!
Control Group
135
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Control Group
136
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
Control Group
Present
Proceed with study
FUTURE
137
RANDOMIZED CONTROLLED TRIAL (RCT)
Experimental Intervention
EXPERIMENTAL EVENT RATE (EER)
Control Group
CONTROL EVENT RATE (CER)
138
RANDOMIZED CONTROLLED TRIAL (RCT)
The Gold Standard
Experimental Intervention
EXPERIMENTAL EVENT RATE (EER)
Control Group
CONTROL EVENT RATE (CER)
Present
FUTURE
139
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!)
140
RETURN FROM DETOUR
141
  • 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

142
CRITICAL APPRAISAL
  • Interpreting the evidence
  • How to read a paper
  • How to do the math

143
EVALUATE WRITTEN EVIDENCE FOR Quality Usefulnes
s
  • BY ASSESSING
  • Validity
  • Reliability
  • Relevance
  • Clinical importance

144
  • Critical Appraisal VALIDITY
  • What was the original purpose of the study?
  • When was it prepared?
  • By whom?
  • credentials?
  • affiliations?
  • Sample population
  • Did the subjects represent an appropriate test
    group?
  • How were they selected?
  • Were controls used?
  • Were groups similar for important prognostic
    characteristics?

145
  • VALIDITY
  • How was the information gathered and processed?
  • Were groups treated equally except for trial
    therapy?
  • Were appropriate criteria used to measure
    results?
  • Were criteria applied rigorously?
  • Was the study completed?
  • (Or ended early for a specified reason?)
  • Did the study account for all test subjects?
  • Including subjects lost to follow-up?
  • Were ALL pts analyzed in their allocated groups?
  • (ie INTENTION TO TREAT - not completed
    treatment analysis)

146
  • VALIDITY
  • Information
  • Does the paper support its claims?
  • Is the information accurately presented?
  • Does it represent the truth?
  • Results
  • Are the results believable?
  • To what degree of confidence?
  • Ex Disagreement is not uncommon on angiograms,
    EKGs, radiographs, pathology, PAP tests, etc.

147
  • VALIDITY
  • Comprehensiveness
  • Size Was it large enough to yield credible
    results?
  • Thoroughness Was it complete enough?
  • Duration Was it long enough?


148
  • CRITICAL APPRAISAL RELIABILITY
  • Do we trust the information and results?
  • APPROPRIATE TYPE OF STUDY
  • REPRODUCEABILITY
  • INTERPRETATION OF RESULTS
  • BIAS

149
RELIABILITY APPROPRIATE TYPE OF STUDY Was the
type of study design used proper for the
question? Example RCT would be choice for
questions on TREATMENT
150
  • RELIABILITY
  • Are the Measurements and Results reproducibile?
  • Different determinations may be caused by
  • Variation in measurement methods
  • Different interpretation of results
  • Lack of agreement
  • Example
  • BP checks on same patient may vary. Are
    differences result of pt factor, examiner factor,
    treatment factor, normal variance
  • Would the same results be obtained if patient is
    re-measured?
  • (with identical procedure)
  • at another time?
  • by another person?
  • Were any similar studies done?
  • Was the information comparable?
  • Did the results agree?

151
  • RELIABILITY
  • INTERPRETATION OF RESULTS
  • Is there consistency among researchers?
  • Different determinations may be caused by
  • Variation in measurement methods
  • Different interpretation of results
  • Lack of agreement
  • EXAMPLE
  • BANFF CONFERENCE - Setting standards in
    Transplant Pathology
  • established by Kim Solez, MD
  • Were any new questions or controversies raised by
    the study?

152
  • RELIABILITY
  • IS THERE ANY EVIDENCE OF BIAS?
  • A dangerous pitfall!
  • PATIENTS
  • RESEARCHERS

153
PATIENT BIAS Social Desirability Bias
  • Patient responds in the way they perceive as
    correct
  • to support MD
  • to support a preconceived notion (ie foods vs
    ADD)

Patient denies unhealthy behavior, gets
misclassified Ex Smoker vs Non-smoker
154
PATIENT BIAS
Hawthorne Effect
People act differently when they know they are
being watched. Ex Follow more careful diet when
regular weigh-ins are scheduled
Authors must take steps to reduce this bias by
treating all equally! Ex Weigh all patients
with same frequency, even for group not on
special diet
155
RESEARCHER BIAS
  • Who sponsored or funded the study?
  • Personal gain or loss from results?
  • Affiliates
  • Special interests
  • Conflict of interest
  • Biased goal?
  • To satisfy editors and reviewers rather than
    solve real life clinical problems

156
RESEARCHER BIAS
Criteria bias? Risk-avoidance by researchers
(will focus energy on topics that produce
positive results) Bias toward patients? Sample
selection criteria used (inclusive,
exclusive) Assignment to test group or control -
Random? Blind?
157
RESEARCHER BIAS
  • Data collection methods used
  • applied similarly to all subjects, including
    controls?
  • starting point prospective/retrospective, stage
    of patient?
  • Was assessment blind?
  • Data analysis
  • Were all potential subjects included in
    denominator or otherwise accounted?
  • Were they evaluated in originally designated
    group?
  • (INTENTION TO TREAT)

158
  • REDUCING OR ELIMINATING BIAS AND ERROR
  • CONDUCT BLIND STUDIES
  • Single
  • Double-blinded
  • USE INDEPENDENT OBSERVERS
  • When doctor and/or patient can not be blinded,
    blinded IO measures outcome
  • IO may even be unaware of study hypothesis
  • USE MULTIPLE OBSERVERS
  • Ex Send subject slides to multiple pathologists
    for interpretation
  • ESTABLISH CLEAR STANDARDS
  • Exact methods to use to reduce variation in
    technique among researchers
  • Clear wording on surveys, etc
  • VALIDATING INSTRUMENTS
  • Repeat screening to check for correct answers on
    surveys

159
NEXT STEP IN CRITICAL APPRAISAL RELEVANCE QUEST
ION Is the report applicable to
our Problem? Does it address the questions
raised? Patient(s)? Will my patient respond
like those in the study? Practice? Can it be
done within my practice or circle?
160
  • ARE THE STUDY PATIENTS
  • Comparable within the study? (similar traits,
    age, socioeconomic group, stage of illness,
    treatment, etc.)
  • Comparable to your patient?
  • ARE THE STUDY PROFESSIONALS
  • Comparable to you?
  • (general/specialist, primary care/teaching
    hospital, etc.)

161
  • NEXT STEP in CRITICAL APPRAISAL
  • CLINICAL IMPORTANCE
  • Information can be true and interesting in
    theory,
  • yet useless in clinical practice!
  • Is the information clinically important?
  • If yes, how important is it?
  • study design - See Hierarchy of Evidence
  • weight of results

162
  • 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

163
RANDOMIZED CONTROLLED TRIAL (RCT)
Evaluation of RCT Were all clinically appropriate
outcomes measured? Did an ethics committee
approve the study? Any statistically significant
results also clinically significant? Any
significant adverse reactions? Was follow-up
procedural analysis identical? Was continuous
data analysis vs end of trial data used?
164
  • Interpreting the evidence
  • How to read a paper
  • How to do the math

165
HOW TO DO THE MATH Incidence Prevalence Statistic
al Formulas /- Predictive Values - Probability -
The p value Relative Risk Risk Reduction Odds
Ratios NNT (Number Needed to Treat) Risk
Reduction Confidence Intervals Sensitivity and
Specificity Regression Analysis Subgroup
Analysis Health Status Evaluation Health Economics
166
OUTCOMES NOT STUDY FAILURES
  • ACCOUNT FOR ALL even if
  • Non-compliant
  • Lost to follow-up
  • OUTCOMES RELATE TO EVERYDAY CLINICAL PRACTICE,
    including
  • Deaths
  • Poor compliance
  • Wrong treatment received
  • Lost to follow-up
  • Etc.
  • Analyze as a member of the originally assigned
    group!
  • Analysis SHOULD BE BASED ON
  • INTENTION TO TREAT
  • NOT on completed treatment analysis

167
INCIDENCE PREVALENCE
NEPHROL, a service of NKF cyberNephrology
7/10/03 101712AM Dear Nephrolers, I would
like to know how to calculate incidence and
prevalence of B and C virus in HD. Thank you in
advance. Mario Cuba, MD Servicio de
Nefrologia Hospital Lucia Iniguez Landin Holguin,
Cuba
168
INCIDENCE PREVALENCE
Response from Michel Jadoul, MD NEPHROL, a
service of NKF cyberNephrology Preval
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