Transcript Why read papers: An Introduction to Evidence Based Medicine

Why read papers:
An Introduction to Evidence
Based Medicine
Arash Etemadi, MD PhD
Department of Epidemiology and Biostatistics,
School of Public Health, Tehran University of
Medical Sciences
[email protected]
Why do we read articles?
•
•
•
•
•
•
Browsing
For information
For research
For review
A paper from someone we know
For going to sleep!
Do We Read ?
• Self-reported reading time per week. (University
setting)
–
–
–
–
–
Medical students
Interns
Senior residents
Fellows
Attendings graduating
• Post 1975
• Pre 1975
60 min.
none
10 min.
45 min.
60 min.
30 min.
Do We Read?
• University of Virginia
• Mailing to primary care physicians
– 50% had not read a medical journal article in
the last year.
– The most commonly sited source of
information was pharmacutical representatives.
Why Don’t We Read ?
• We’re lazy?
– The fact of the matter is that none of us likes
feeling out of date. We like it so little in fact
that we are willing to work at night and on
weekends in an effort to stay current.
• Frustration.
– Conflicting information
– No one taught us HOW or WHAT to read.
What evidence-based medicine is:
the integration of best research evidence
with clinical expertise
and patient values.
Is EBM …
reading articles?
I. Best Research Evidence:
• clinically relevant research, often from the
basic sciences of medicine, but especially
from patient centered clinical research.
• Has a short doubling-time.
• Replaces currently accepted diagnostic tests
and treatments with new ones that are more
powerful, more accurate, more efficacious,
and safer.
II. Clinical Expertise:
• rapidly identify each patient's unique health
state and diagnosis,
• their individual risks and benefits of
potential interventions,
• and their personal values and expectations.
III. Patients’ Values &
Expectations
• the unique preferences, concerns and
expectations each patient brings to a clinical
encounter
• must be integrated into clinical decisions if
they are to serve the patient.
A model for evidence-based clinical decisions
Traditional medicine
experiences
Pathophysiology,
references,…
Patient value
Practice Based
On Theory
Retrolental Fibroplasia Lesson(1)
(Silverman, 1977, Scientific American)
• In early 1940’s, epidemic of retrolental fibroplasia began in premature
infants
Case reviews indicated “state of the art” care, including high
concentration of O2
• Suspicion arose that cause occurred after birth resulting in progressive
changes in retina blood vessels
• Early 1950’s, ACTH treatment proposed and RCT tested
Arm
ACTH
vs.
Results
1/3 Blind
Placebo
1/5 Blind
ACTH = adrenocorticotrophic
hormone
Retrolental Fibroplasia Lesson(2)
(Silverman, 1977, Scientific American)
• Search for a cause
– High dose O2 suspected based on anecdotal evidence of
147 infants
– Another observational series of 479 infants claimed
benefit
• One study attempted to lower O2 dose
– But nurses would turn O2 on at night and off in a.m.
– Felt no or low O2 unethical
Retrolental Fibroplasia Lesson(3)
(Silverman, 1977, Scientific American)
• 1953 NIH Conference - Two opinions
1. Need controlled study
2. No need, O2 already convicted
• 1953 RCT began on 800 infants
% Blinded
- standard O2 dose
23%
- 50% O2 dose only for clinical indications
7%
Also found a dose response
• 1954 Results published, high O2 practice stopped and
epidemic subsided
However, not before 10,000 infants had been blinded
Failure to Use Therapy
Based on Theory
Chronic Heart Failure
• Not many good therapies in 1980’s
• Beta blockers known to be effective in post
MI patient care
– Reduces mortality
– Lowers blood pressure
– Slows and regulates heart rate
• Proscribed for heart failure patients
Beta-Blocker HF
Trial Features
•
•
•
•
•
Class II-IV heart failure
Low ejection fraction
Beta-blocker vs. placebo
Randomized double blind
Several thousand patients
MERIT
Total Mortality
CIBIS-II
Lancet, 1999
COPERNICUS
NEJM, 2001
Long Standing Treatment
Based on Theory and
Observation/Association
Hormone Replacement Therapy
(HRT)
• Hypothesis that HRT reduced
coronary heart disease
• Supportive data
– Lipid lowering
– Non-human primate studies
– Observational studies
Observational Studies
•
Example – Refs:
1) Stampfer & Coldiz (Prev Med 1991)
Nurses Health Study
2) Grady (Ann Int Med 1992)
3) Cauley, Cummings, et al. (Am J OB/GYN, 1990)
4) Grodstein, Stempfer, Manson (NEJM 1996)
•
Suggest 40-50% reduction in CHD risk
HRT POPULAR
• 1/3 of post-menopausal women use HRT
• Second most prescribed drugs
• Year 2000, 46 million prescriptions for Premarin
(Estrogen)
• $1 billion in sales
• 22 million prescriptions for PremPro (E+P)
HORMONE REPLACEMENT
THERAPY FOR POSTMENOPAUSAL
WOMEN
• Secondary Prevention
HERS: Hully S, Grady D, Bush T, Furberg C, Herrington D, Riggs
B, Vittinghoff E; for the HERS Research Group: Randomized trial
of estrogen plus progestin for secondary prevention of coronary
heart disease in postmenopausal women. JAMA 28(7):605-13, 1998.
• Primary Prevention
WHI: Writing Group for the Women’s Health Initiative
Investigators: Risks and benefits of estrogen plus progestin in
healthy postmenopausal women. Principal results from the
Women’s Health Initiative Randomized Controlled trial.
JAMA
288:321-333, 2002.
HERS
JAMA 28(7):605-13, 1998
• Postmenopausal women
• Secondary prevention, patients had
documented cardiovascular disease
• Estrogen-progestin vs. placebo
• Randomized double blind
• Outcomes
– CVD mortality
– Fractures
HERS
• Observed early clotting problems
– DVTs
– PEs
• Fracture trend for benefit
• Early negative trend in mortality that
reverses to neutrality (non-definitive)
HERS MORTALITY
JAMA, 1998
HERS IMPACT
• Many believed results only applied in
secondary prevention
• Many interpreted trend reversal as
suggesting benefit if longer follow-up
• No perceptible impact on HRT use since
HRT has other benefits
WOMEN’S HEALTH
INITIATIVE
JAMA 288(3):321-33, 2002
• A large factorial trial evaluating HRT, low fat
diet and calcium
• Multiple outcomes for each treatment
• For HRT
–
–
–
–
Coronary heart disease (MI & CHD death)
Invasive breast cancer
Global index
Fractures
WHI
373,092 Women Initiated Screening
18,845 Provided Consent &
Reported No Hysterectomy
16,608 Randomized
8506 Assigned to Receive
Estrogen + Progestin
8102 Assigned to
Receive Placebo
Status on April 30, 2002
Status on April 30, 2002
7968 Alive & Outcomes Data
Submitted in Last 18 Months
307 Unknown Vital Status
231 Deceased
7608 Alive & Outcomes Data
Submitted in Last 18 Months
276 Unknown Vital Status
218 Deceased
Cumulative Dropout and Drop-in Rates by
Randomization Assignment and Follow-up Duration
WHI
JAMA, 2002
Wisconsin State Journal
2002
WHI
Kaplan-Meier Estimates of Cumulative Hazards
for Selected Clinical Outcomes
JAMA, 2002
WHI
Kaplan-Meier Estimates of Cumulative Hazards
for Global Index and Death
JAMA, 2002
WHI
Kaplan-Meier Estimates of Cumulative Hazards
for Selected Clinical Outcomes
JAMA, 2002
WHI
Kaplan-Meier Estimates of Cumulative Hazards
for Selected Clinical Outcomes
JAMA, 2002
HRT: Low But Increased Risk
Outcome
CHD
Stroke
DVT
PE
Breast CA
Death
Rate %HR
HRT
PLBO
.37
.30
.29
.21
.26
.13
.16
.08
.38
.30
.52
.53
1.29
1.41
2.07
2.13
1.26
.98
Ann of Int Med
137(4), 2002
Evidence Based Medicine
• For important questions with serious
mortality/morbidity, need stronger evidence
such as RCTs
• If RCTs not possible, need to be cautious &
vigilant about Treatments only based on
observation/association or theory
The Hierarchy of Evidence
1. Systematic reviews & meta-analyses
2. Randomised controlled trials
3. Cohort studies
4. Case-control studies
5. Cross sectional surveys
6. Case reports
7. Expert opinion
8. Anecdotal
555 feet
Washington
Monument
A Year of MEDLINE
indexed journals
Medical Publishing
Annually:
• 20,000 journals
• 17,000 new books
MEDLINE:
• 4,000 journals
• 6 Million references
• 400,000 new entries yearly
Words used by 41 doctors to
describe their information supply
•
• Impossible Impossible
•
Impossible Impossible
•
Impossible Impossible
• Overwhelming Overwhelming •
Overwhelming Overwhelming •
Overwhelming Overwhelming •
• Difficult Difficult Difficult
•
Difficult
•
• Daunting Daunting Daunting
•
• Pissed off
•
• Choked
•
• Depressed
•
• Despairing
• Worrisome
•
• Saturation
•
Vast
Help
Exhausted
Frustrated
Time consuming
Dreadful
Awesome
Struggle
Mindboggling
Unrealistic
Stress
Challenging
Challenging Challenging
Excited
Vital importance
The information paradox
• “Doctors are overwhelmed with
information but cannot find
information when they need it”
• “Water water everywhere, nor
any drop to drink”
My students are dismayed when I say to them “Half
of what you are taught as medical students will in
10 years have been shown to be wrong. And the
trouble is, none of your teachers knows which
half.”
(Dr Sydney Burwell, Dean of Harvard Medical
School)
The Slippery Slope
r = -0.54
. ..
Knowledge
p<0.001
of best
. . .... ...
. ...
current
...
HTN
... ....
..
care
....
Years since Med School
graduation Shin,et al: CMAJ;1993: 969-976
Usefulness of
Relevance x Validity
=
Medical Information
Work
Adapted from Slawson et al,
J Fam Pract 1994; 38:505-513
A Paradigm Shift for Physicians
• From Memory Repositories
• To Information Managers
• From “How do I keep up with new
developments in medicine?”
• To “What developments in medicine
do I need to keep up with?”
1. Burn your (traditional) textbooks
• For a textbook to be dependable in the modern era:
· it should be revised frequently (at least once a year)
· it should be heavily referenced, at least for declarations
about diagnosis and management (so readers can get to
original sources for details and can also easily determine the
date of a given claim)
UpToDate
1965
1970
1980
1985
1990
1.0
Textbook/Review
Recommendations
2.0
2
65
3
149
4
316
7
1793
10
11
15
17
22
2544
2651
3311
3929
5452
23
5767
27
30
33
43
54
65
67
70
6125
6346
6571
21 059
22 051
47 185
47 531
48 154
Experimental
23
Rare/Never
1
Specific
Pts
Routine
Cumulative
Year
RCTs
0.5
Not Mentioned
Thrombolytic therapy in MI
Antman EM, et al. JAMA, 268:240-8, 1992
21
5
P<.01
1
10
1
2
2
8
7
8
1
P<.001
P<.00001
M
M
1
8
4
3
5
1
2
7
M
M
2
1
15
8
6
1
M
M
Odds Ratio (Log Scale)
Favours Treatment
Favours Control
12
1
Lag time from time of “knowing” to time
of implementation
• 13 yrs for thrombolytic therapy.
• 10 yrs for corticosteroids to speed fetal lung
maturity.
Our textbooks are out-of-date
• Fail to recommend Rx up to ten years after
it’s been shown to be efficacious.
• Continue to recommend therapy up to ten
years after it’s been shown to be useless.
2. Invest in evidence databases
•
ACP Journal Club
http://www.acponline.org/journals/acpjc/jcmenu.htm
•
•
•
•
•
•
•
Best Evidence www.acponline.org/
Cochrane Library
UpToDate
MEDLINE
Harrison’s Online
Medscape
www.medscape.com/Home/Topics/homepages.html
MD Consult www.mdconsult.com
Does CME Work?
• Davis D A, et al. Changing physician performance. A
systematic review of the effect of continuing medical
education strategies. JAMA 1995; 274: 700-1.
• Sibley J C, A randomized trial of continuing medical
education. N Engl J Med 1982; 306: 511-5.
• Conclusion
– Traditional CME in a nice place with
pleasant after lecture diversions is,
unfortunately, completely ineffective in
changing our behavior.
• Another reason to read!
What About Guidelines?
• Guidelines can be very useful
– Problems
• Surprise! They don’t all agree.
• Which ones do we use? (Determining validity)
• How do we implement? (How do we remember to
do what they say?)
– Once validity is established they can be an excellent resource
The Experts ?
• Remember, they’re in the same position we are
with information overload.
• They often look at a patient and a disease in a
fundamentally different way because they deal
with a selected patient population.
• Excellent resource once reliability has been
established.
Evidence
Based
Medicine
EBM process
1. Ask
2. Search
3. Appraise
4. Apply
5. Evaluate
Ask
• We need it twice for every 3 outpatients and
2 times for every inpatient
• Questions are most likely to be about
treatment
• Most of the questions generated in
consultations go unanswered.
EBM process
When caring for patients creates the need for
information:
1 Translation to an answerable question
(patient/maneuver/outcome).
4 Parts of ACQ (PICO)
• P – Patient and problem
• I – Intervention (treatment, test,
prognostic factor, etiology, etc.)
• C – Comparison (if necessary)
• O - Outcome
Treatment
• P – In a child with frequent febrile
seizures
• I – would anticonvulsant therapy
• C – compared to no treatment
• O – result in seizure reduction?
Diagnosis
• P – In an otherwise healthy 7-year-old boy
with sore throat,
• I - how does the clinical exam
• C – compare to throat culture
• O – in diagnosing GAS infection?
Prognosis
• P - In children with Down syndrome,
• I - is IQ an important prognostic factor
• C–
• O – in predicting Alzheimer’s later in life?
Etiology/Harm
• P – controlling for confounding factors, do
otherwise healthy children
• I - exposed in utero to cocaine,
• C – compared to children not exposed
• O – have increased incidence of learning
disabilities at age six years?
Good ACQ?
• Is Amoxicillin an effective treatment
for children with otitis media?
EBM process
1. Ask
2. Search
3. Appraise
4. Apply
5. Evaluate
EBM process
2 Efficient track-down of the best
evidence
–Secondary (pre-appraised)
sources e.g.,
– Cochrane (systematic reviews)
– E-B Journals
–primary literature
EBM process
1. Ask
2. Search
3. Appraise
4. Apply
5. Evaluate
EBM process
3-Critical appraisal of the
evidence for its validity and
clinical applicability
• Perhaps most published articles belong in
the bin, and should certainly not be used to
inform practice.
Why do I have to bother?
Can’t I trust the editors?
Percent of articles meeting quality criteria
NEJM
Ann Int Med
JAMA
Lancet
BMJ
Arch Int Med
12.6
7.6
7.2
6.2
4.4
2.4
The Hierarchy of Evidence
1. Systematic reviews & meta-analyses
2. Randomised controlled trials
3. Cohort studies
4. Case-control studies
5. Cross sectional surveys
6. Case reports
7. Expert opinion
8. Anecdotal
EBM process
1. Ask
2. Search
3. Appraise
4. Apply
5. Evaluate
EBM process
4 Integration of that critical appraisal
with clinical expertise and the
patient’s unique biology and
beliefs  action.
5 Evaluation of one’s performance.
"I know that most men (sic), including those at
ease with problems of the greatest complexity, can
seldom accept even the simplest and most obvious
truth if it be such as would oblige them to admit
the falsity of conclusions which they have
delighted in explaining to colleagues, which they
have proudly taught to others, and which they
have woven, thread by thread, into the fabric of
their lives.” Leo Tolstoy
Recommended Reading
• Gordon Guyatt, Drummond Rennie. Users’ Guides
To The Medical Literature, A Manual for EvidenceBased Clinical Practice. AMA.
• Sackett DL, Straus SE, Richardson WS, Rosenberg
W, Haynes RB. Evidence-based Medicine:
How to Practice and Teach EBM. Second Edition.
Churchill Livingstone: Edinburgh, 2000
• Trisha Greenhalgh : How to read a paper; the basis of
evidence based medicine. BMJ 2001.
Thank You!