Statistical knowledge and clinical knowledge

1. Statistical knowledge and clinical knowledge J. Nummenmaa M.D. Ph.D. Knowledge in Medicine -Questions in Medical Epistemology

2. 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

3. 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

5. IS TREATMENT X MORE EFFECTIVE THAN Y IN THE TREATMENT OF DISEASE Z? N PATIENTS WITH Z Randomised trial HALF TREATED WITH Y HALF TREATED WITH X • 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 • PREVENTION OR TREATMENT? • OBJECTIVES? • DO ALL PATIENTS SHARE SAME OBJECTIVES • COMPOSITE INDICATORS • APPLICABILITY ON INDIVIDUAL PATIENTS? • SIDE-EFFECTS • 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 • REPRESENTATIVE PATIENTS? • RANDOMISATION • BLINDING • CO-MORBIDITY • OTHER FACTORS, LIFE-STYLE ETC ADHERENCE NUMBER OF END –POINTS IN DIFFERENT GROUPS SELECTION OF END-POINTS HOW TO CHOOSE WHAT TREATMENTS ARE COMPARED? PROBLEMS ON PATIENT SELECTION PROBLEMS OF DIAGNOSTIC CRITERIA

6. Significance of the data Statistical significance: p=0.036 Riskreduction 30.3% Out of onehundredpatients: -> 97 remainhealthy -> willgetsickwhethertreatedornot -> oneincidencecanbeprevented -> ARR 1% -> NNT= 100 • Statistical significance: p-value • Propability to get achieved results if null-hypothesis is true • Clinicalsignificance: • Relativeriskreduction :percentage • Absoluteriskreduction (ARR%) • Numberneeded to treat (NNT) • Clinicalimportance • Treatingindividualpatients

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. To treat or not to treat? 9

10. 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

11. 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

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 60:1975-1985. • 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

15. 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 • Clinicalencounter • Social medicine • Unselectedpopulation • Patientspresent with symptoms

16. 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 EBM vs GP

17. Clinically relevant research? • University? • Evidence-Based Guidelines? • Does not produce new data • Valuation of research results favours medical treatment • Drug industry? • GPs themselves?

18. 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).