Statistical knowledge and
clinical knowledge
J. Nummenmaa
M.D. Ph.D.
Knowledge in Medicine -Questions in Medical Epistemology
Evidence-Based Medicine (EBM)
• Ensure availability of reliable research
results for clinicians
–
–
–
–
–
–
How effective treatment?
Research done on patients
Golden standard = Randomised trial
Critical evaluation on research & results
Quality improvement
Decreasing variation
• EBM Guidelines
– Bringing evidence to practice
What is good evidence?
Level A: Consistent Randomised Controlled Clinical Trial,
cohort study, all or none (see note below), clinical
decision rule validated in different populations.
Level B: Consistent Retrospective Cohort, Exploratory
Cohort, Ecological Study, Outcomes Research, casecontrol study; or extrapolations from level A studies.
Level C: Case-series study or extrapolations from level B
studies.
Level D: Expert opinion without explicit critical
appraisal, or based on physiology, bench research or
first principles.
Randomised trial
•
Dr. James Lind 1747
–
4
Scurvy prevention
Randomised trial
IS TREATMENT
X MORE EFFECTIVE THAN
•WHOSE
•PREVENTION
CHOICE?
TREATMENT?
DIAGNOSIS
ASOR
CLASSIFICATION
•REPRESENTATIVE
PATIENTS?
Y
IN
THE
TREATMENT
OF DISEASE Z?
•INDUSTRY?
•OBJECTIVES?
ONE
DIAGNOSIS
DOES
NOT EXCLUDE ANOTHER
•RANDOMISATION
ADHERENCE
•WHO
ELSE,
UNIVERSITY?
•DO
ALL
PATIENTS
SHARE
SAME
OBJECTIVES
DIFFERENT
DIAGNOSES
ARE
BASED
ON
•BLINDING
•WHY?
•COMPOSITE
DIFFERENTINDICATORS
CRITERIA
•CO-MORBIDITY
•FINANCIAL
INTERESTS?
N•APPLICABILITY
PATIENTS WITH
Z INDIVIDUAL PATIENTS?
DIAGNOSTIC
DIFFERENCES
ON
•OTHER
FACTORS,
LIFE-STYLE ETC
•SCIENTIFIC
INTERESTS?
IN
HOSPITALS
AND
PRIMARY
CARE
•SIDE-EFFECTS SELECTION
OF
•COMPARING
DIFFERENT
TREATMENTS
INTERNATIONAL
END-POINTS
•MEDICATION
PREVALENCE
AND INCIDENCE HALF TREATED
HALF
TREATED
WITH Y
WITH •SURGERY
XIN HOSPITALS AND PRIMARY CARE
•(PSYCHO)THERAPY
HOW TO CHOOSE
PROBLEMS
ON SOME
•CHOOSING ONE TREATMENT = NOT
CHOOSING
WHAT
PATIENT
OTHER
TREATMENT
TREATMENTS ARE
SELECTION
PROBLEMS
OF
COMPARED?
NUMBER
OF END –POINTS IN DIFFERENT GROUPS
DIAGNOSTIC
CRITERIA
Significance of the data
Statistical significance: p=0.036
•
Risk reduction 30.3%
Out of one hundred patients:
-> 97 remain healthy
-> will get sick whether treated or not
-> one incidence
can be preventedp-value
Statistical
significance:
-> ARR 1% -> NNT= 100
– Propability to get achieved results if null-hypothesis is true
Clinical significance:
Relative risk reduction :percentage
Absolute risk reduction (ARR%)
Number needed to treat (NNT)
Clinical importance
Treating individual patients
Clinically significant risk?
• Cholesterol-lowering medication should be
started if a person, even otherwise healthy,
has a propability of cardiac death higher than
5% / 10 years
– Finnish evidence based (Käypä hoito -)
guidelines for hyperlipidaemia
7
7
To treat or not to treat?
8
To treat or not to treat?
9
9
What to do with myself?
• At the age of 44
• Estimated life-span 88,48
• Intervention: regular exercise + 2-3 doses of
alcohol
• Benefits:
– 0,29 years= 1 600 hours awake
– January - March
– One hour / day= 16 235 hours
– Costs:
• Wine 32 500 €
• Exercise 500 € p.a. = 22 500 €
• Total 55 000 €
– One extra hour of life= 10 hours 34€
10
10
Evidence-Based or Value-Based?
• Comparison of hypertension control between
different countries: 17,5 - 86,4%
• Fahey & Peters: What constitutes controlled hypertension? Patient based
comparison of hypertension guidelines, BMJ, 1996, 313, 7049, 93-96
Recommendations based on same evidence: 50%
/ 50%
• Raine, R & al. Lancet, 2004, 364, 9432, 429-437
• Selection of literature
• Christiaens & al. Scand J Prim Health Care, 2004, 22, 141-145
Evidence-Based or Value-Based?
• 76% of Norwegian men in Trondelage
have higher risk for cardiac diseases
than guidelines recommend
– Cholesterol
– Blood pressure
• How to deal with risks?
– Getz & al 2004
12
Evidence-Based – really?
•
•
•
•
Is data really reliable?
Are the results applicable in practice?
Are the results politically acceptable?
How do the results relate to functioning of the working
group?
• Moreira T (2004): Diversity in clinical guidelines: The role of repertoires
of evaluation. Soc Sci Med 60:1975-1985.
• Value-Based recommendations:
–
–
–
–
13
Selection of literature?
Valuation of research methodology?
How effective treatment is effective?
What treatments are favored (Drugs, surgery, therapy)?
13
Hume and EBM Guidelines
• ”…when all of a sudden I am surprised to
find, that instead of the usual
copulations of propositions, is, and is
not, I meet with no proposition that is
not connected with an ought, or an
ought not. This change is imperceptible;
but is however, of the last
consequence.”
– David Hume: A treatise of human nature
(1739)
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General Practitioner
• Treating human beings not
diseases
• Contextuality.
• Networking
• Place of treatment: Clinic,
home
• Understanding meanings
• Resource control
•Continuity
•Openness
•Tolerance and ability to deal
with uncertainty
•Clinical encounter
•Social medicine
•Unselected population
•Patients present with
symptoms
EBM vs GP
• GP
• EBM
– Diagnosis
– Randomised trial
– Interpretation
statistical
– Patient, symptom
– Individual interpretation
– subjetive
– Uncertainty
– ”Objective”
• Limited data
– Uncertainty:
• Lack of knowledge
•
Statistical
significance
• Clinical significance
• Applying knowledge
• Ethics & values
• Limited time
Clinically relevant research?
• University?
• Evidence-Based Guidelines?
– Does not produce new data
– Valuation of research results favours
medical treatment
• Drug industry?
17
• GPs themselves?
How does a GP use EBM
Guidelines
• Source of information, as a textbook
• Searching answers for a specific question
• As an institutional quality improvement tool
– Grimshaw ja Eccles in Ridsdale L. (Ed.): Evidence-based practice in
primary care (Churchill Livingstone).