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, case-control 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.

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Randomised trial• Dr. James Lind 1747

– Scurvy prevention

IS TREATMENT X MORE EFFECTIVE THAN Y IN THE TREATMENT OF DISEASE Z?

N PATIENTS WITH Z

HALF TREATED WITH X

HALF TREATED WITH Y

NUMBER OF END –POINTS IN DIFFERENT GROUPS

DIAGNOSIS AS CLASSIFICATIONONE DIAGNOSIS DOES NOT EXCLUDE ANOTHERDIFFERENT DIAGNOSES ARE BASED ON DIFFERENT CRITERIA

DIAGNOSTIC DIFFERENCESIN HOSPITALS AND PRIMARY CAREINTERNATIONAL

PREVALENCE AND INCIDENCEIN HOSPITALS AND PRIMARY CARE

Randomised trial

HOW TO CHOOSE WHAT

TREATMENTS ARE COMPARED?

•WHOSE CHOICE?•INDUSTRY?•WHO ELSE, UNIVERSITY?

•WHY?•FINANCIAL INTERESTS?•SCIENTIFIC INTERESTS?

•COMPARING DIFFERENT TREATMENTS•MEDICATION•SURGERY•(PSYCHO)THERAPY

•CHOOSING ONE TREATMENT = NOT CHOOSING SOME OTHER TREATMENT

PROBLEMS OF DIAGNOSTIC

CRITERIA

PROBLEMS ON PATIENT

SELECTION

•REPRESENTATIVE PATIENTS?•RANDOMISATION•BLINDING•CO-MORBIDITY•OTHER FACTORS, LIFE-STYLE ETC

ADHERENCE

SELECTION OF END-POINTS

•PREVENTION OR TREATMENT?•OBJECTIVES?

•DO ALL PATIENTS SHARE SAME OBJECTIVES•COMPOSITE INDICATORS

•APPLICABILITY ON INDIVIDUAL PATIENTS?•SIDE-EFFECTS

Clinical importanceTreating individual patients

Clinical significance:Relative risk reduction :percentageAbsolute risk reduction (ARR%)Number needed to treat (NNT)

Significance of the data

• Statistical significance: p-value

– Propability to get achieved results if null-hypothesis is true

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 prevented-> ARR 1% -> NNT= 100

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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

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To treat or not to treat?

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To treat or not to treat?

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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

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

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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

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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:– Selection of literature?– Valuation of research methodology?– How effective treatment is effective?– What treatments are favored (Drugs, surgery, therapy)?

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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)14

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

• EBM

– Diagnosis

– Randomised trial

– Interpretation

statistical

– ”Objective”

– Uncertainty:

• Statistical

significance

• Clinical

significance

• GP

– Patient, symptom

– Individual

interpretation

– subjetive

– Uncertainty

• Limited data

• Lack of knowledge

• Applying knowledge

• Ethics & values

• Limited time

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Clinically relevant research?

• University?

• Evidence-Based Guidelines?

– Does not produce new data

– Valuation of research results

favours medical treatment

• Drug industry?

• 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).