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.

4 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 CLASSIFICATION  ONE DIAGNOSIS DOES NOT EXCLUDE ANOTHER  DIFFERENT DIAGNOSES ARE BASED ON DIFFERENT CRITERIA  DIAGNOSTIC DIFFERENCES  IN HOSPITALS AND PRIMARY CARE  INTERNATIONAL  PREVALENCE AND INCIDENCE  IN 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 importance Treating individual patients Clinical significance: Relative risk reduction :percentage Absolute 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

7 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

8 To treat or not to treat?

9 9

10 What to do with myself? At the age of 44 Estimated life-span 88,48 Intervention: regular exercise doses of alcohol Benefits: – 0,29 years= hours awake – January - March – One hour / day= hours – Costs: Wine € Exercise 500 € p.a. = € Total € – 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, Recommendations based on same evidence: 50% / 50% Raine, R & al. Lancet, 2004, 364, 9432, Selection of literature Christiaens & al. Scand J Prim Health Care, 2004, 22,

12 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

13 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: Value-Based recommendations: – Selection of literature? – Valuation of research methodology? – How effective treatment is effective? – What treatments are favored (Drugs, surgery, therapy)? 13

14 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

17 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).