Transcript Teaching Family Physicians To Be Information Masters

Information Mastery:
A Practical Approach to Evidence-Based Care
Course Directors:
Allen Shaughnessy, PharmD, MMedEd
David Slawson, MD
Tufts Health Care Institute
Tufts University School of Medicine
November 10-12, 2011
Boston, Massachusetts
Information Mastery:
A Practical Approach to Evidence-Based Care
Is It True? Evaluating Research about a
Therapy
The new paradigm: probabilistic
thinking
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Current paradigm: the biomedical model
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The body can be approached as an engineering problem
• External fetal monitoring
Nelson KB, Dambrosia JM, Ting TY, Grether JK. Uncertain value of electronic
fetal monitoring in predicting cerebral palsy. N Engl J Med 1996;334:613-8.
• Right heart catheterization
Shah MR, et al. Impact of the pulmonary artery catheter in critically ill patients:
meta-analysis of randomized clinical trials. JAMA. 2005 Oct 5;294(13):1693-4.
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The new paradigm: Probabilities
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What can we do for people that, on average, will help most of
them most of the time?
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What is Evidence-Based Medicine?
“The judicious use of the best current evidence in making
decisions about the care of the individual patient.”
--EBM working group
“An acknowledgment that there is a hierarchy of evidence and
that conclusions related to evidence from controlled
experiments are accorded greater credibility than conclusion
grounded in other sorts of evidence.”
-- Brian Hurwitz. BMJ 2004;329:1024-8.
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The Hierarchy of Evidence
Credibility
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Results from controlled trials
Results from case-control studies
Results from case series
Expert consensus or opinion
Pathophysiologic reasoning
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The Place of EBM in Medicine
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Goals of medicine: Relieve/prevent suffering;
maintain/provide hope; prevent, treat, or cure disease
The science of medicine: knowing the best way to
prevent, treat, or cure disease (EBM can address this
aspect)
The art of medicine: Determining, using intuition,
experience, and judgment, what patients need the
most
Combining the art and science  Clinical Jazz
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Study Methods
to Answer This Question
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Epidemiology: Patients taking a vitamin are less likely to
have migraines
Pharmacology: Drug x affects cerebral vasculature in rat
brain isolates
Case report: “It worked on one patient”
Case-series: “It worked on a bunch of patients”
Randomized controlled trial: 1/2 get drug, 1/2 placebo.
No one knows who ‘til the end who took what
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Validity
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Internal validity: How well was the study
done? Do the results reflect the truth?
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External validity: can I apply these results to
MY patients?
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Was it a
randomized controlled trial?
Randomization is the
best protection against
being mislead
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The value of randomization
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32 controlled trials of anticoagulation in acute MI
Results by type of study:
Historical
control
Controlled
trial
Randomized
controlled trial
Concealed
Allocation
Relative Risk
Reduction
Case fatality
rate
42%
38.3%
33%
29.2%
31%
19.6%
18%
12.1%
Chalmers TC, et al. N Engl J Med 1977;297:1091-6.
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Was allocation assignment
“concealed”?
Did investigators know to
which group the potential
subject would be
assigned before enrolling
them?
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Importance of concealed allocation
Trials with unconcealed allocation consistently
overestimate benefit by ~40%
Schulz KF, Chalmers I, Hayes RJ, et al. JAMA 1995;273:408-12
Schulz KF, Grimes DA. Lancet 2002;359:614-18.
Pildal J, et al. Int J Epidemiol 2007;36:847-857
Moher D, et al. Lancet 1998;352:609-13.
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Was allocation assignment
“concealed”?
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Concealed allocation  blinding
• Blinding can occur without concealed allocation
• Surfactant in the NICU
• Allocation can be concealed in an unblinded study
• PT vs surgery for knee DJD
Moseley JB, O'Malley K, Petersen NJ, et al. N Engl J Med 2002; 347:81-8.
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Conducting a Study
Potential Subjects
Concealed
Allocation
Trial starts
Actual
Subjects
A
Randomization
Blinding, etc
B
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Importance of concealed
assignment
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Meta-analysis of trials evaluating screening
mammography
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In studies in which allocation wasn’t concealed
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Trials with concealed allocation = screening harmful!
• Higher SE status, education level in screened group
• Age disparity (average 6 mo older in the unscreened group)
• Richer, smarter, younger
• No effect or increased mortality
• 20% more mastectomies
Lancet Jan 8, 2000; Oct 20, 2001
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Mammography Study Sign-up
Conducting
a Study
Number Group
Patient name
1
2
3
4
5
6
7
8
9
10
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12
13
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Trial starts
A
Mamm.
Sara Smith
No Mamm
Jill Jones
Wendy Walsh
Mamm
Potential
Subjects
No Mamm
Linda Lucky
No Mamm
Mamm
Linda Lucky
Mamm
No Mamm
Mamm
No Mamm
Mamm
Actual
Mamm
No mammSubjects
No mamm
Mamm
Randomization
Blinding, etc
Concealed
Allocation
B
Technical Nitpicking? Could this
really make a difference?
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Cumulative database: ~500,000 women
Current policy is based on very small differences:
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Deaths in unscreened women 902
Deaths in screened women
837
Death difference (of 456,349) 65!
Systematic bias is not “random error” for which metaanalysis can compensate
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Mundus Vult Decipi
“The world wishes to be
deceived”
People would rather be deceived than
have the truth cause anxiety
Caleb Carr, Killing Time
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“YOU WANT ANSWERS??!!!
“I WANT THE TRUTH!!”
“YOU CAN’T HANDLE THE TRUTH!!”
Jack Nicholson and
Tom Cruise
“A Few Good Men”
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Nonfebrile Seizure Incidence
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Were all the patients properly accounted for
at its conclusion?
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Complete follow-up?
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“Intention to treat” analysis?
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Patients are analyzed in the groups to which they are assigned
Attempts to reflect “real world” clinical situations in which not all
patients follow treatment recommendations
Watch when they compare only compliers with compliers and noncompliers
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Compliant subjects always do better overall
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Was study “double-blinded”?
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Did the patients know to which group they were
assigned?
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Did the treating physician know?
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Did investigators assessing outcomes know (“tripleblinding” – up to 7 levels!)?
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Judicial assessor blind + allocation concealment = surgery
RCTs
Schulz KF. Ann Int Med 2002;136:254-9.
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Were intervention and control groups
similar?
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See Table 1 of most studies
Randomization is best way to avoid bias, though
imbalances still can occur (especially if allocation
was not concealed)
Small differences sometimes are important
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