E vidence

1. Sudigdo Sastroasmoro (s_sudigdo@yahoo.com) Medical School University of Indonesia E vidence B ased M edicine (”Bringing research evidence into practice”)

2. Dr. Benjamin Spock:Baby and Child Care “I think it is preferable to accustom a baby to sleeping on his stomach from the start of he is willing. He may change later when he learns to turn over”. Later evidence indicates that prone position is a an significant risk factor for SIDS (sudden infant death syndrome)

3. EBM & Clinical Epidemiology • Fletcher & Fletcher: CE = The application of epidemiologic principles in problems encountered in clinical medicine • Sackett et al: CE = The basic science for clinical medicine • Much resistance by experts • EBM: In principle – no one disagree • All major medical journals have adopted EBM • Centers for EBM all over the world

4. Previous practice: Problems with patients: Dx, Rx, Px 6 yrs medical education 40-50 yrs medical practice Consultants, colleagues Textbooks Handbooks Lecture notes Clinical guidelines CME, seminars, etc Journals Usu. see only Resultssection, or even worse, Abstract section

5. Trust me • In my experience …. • Logically • Textbook, handbook, capita selecta

6. What is Evidence-based Medicine? • “The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients” • “Pemanfaatan bukti mutakhir yang sahih dalam tata laksana pasien” • Integration of (1) physician’s competence (2) valid evidence from studies (3) patient’spreference

7. Pros : “New paradigm in medicine” • “Extraordinary innovations, only 2nd to Human Genome Project” • Cons : New version of an old song • ‘Fair’ : Nothing wrong with EBM, but: • Be careful in searching evidence • Meta-analyses, clinical trials, etc. should be critically appraised • Keyword for EBM: • Methodological skill to judge the validity • of study reports (Re. Andersen B: Methodological errors in medical research, 1989)

8. “Hierarchy of Lies” Statistics Damn lies..... Lies..... (Mark Twain)

9. WHY EBM? 1. Information overload • Keeping current with literature • Our clinical performance deteriorates with time (“the slippery slope”) 4. Traditional CME does not improve clinical performance 5. EBM encourages self directed learning process which should overcome the above shortages

10. The fact…….. • >25,000 periodical (journals) • 6,000,000 articles annually • 17,000 biomedical books annually • 3000 recognized diseases • 1500 therapeutic regimens (+250 annually)

11. Original Research Academic Reviews Decision/Cost Analysis Medical Cookbooks (Practice Guidelines) Translation Journals CME Clinical Experience Experts Newsletters and Survey Services Pharmaceutical Representatives Computer sources Audiotapes Qualitative Research The Flora and Fauna of the Medical Jungle

12. Our textbooks areout-of-date • Fail to recommend Rx up to ten years after it’s been shown to be efficacious. • Continue to recommend therapy up to ten years after it’s been shown to be useless.

13. The inevitable consequence: • On average, the clinically-important knowledge of physicians deteriorates rapidly after we complete our training.

14. 100% $ Relative % of remaining knowledge 2 4 6 8 10 12 Years after graduation THE SLIPPERY SLOPE

15. Steps in EBM practice • Formulate clinical problems in answerable questions • Searchthebestevidence: use internet or other on- • line database for current evidence 3. Critically appraise the evidence for • Validity (was the study valid?) • Importance (were the results clinically important?) • Applicability (could we apply to our patient?) • 4. Apply the evidence to patient • 5. Evaluate our performance VIA

16. Main area Diagnosis(Determination of disease or problem) Treatment(Intervention necessary to help the patient)Prognosis(Prediction of the outcome of the disease)

17. Others: Meta-analysisClinical guidelinesEconomic analysis Clinical decision makingCost-effectiveness analysisQualitative research

18. (I)Formulating clinical questions

19. A 2-month old infant with large VSD • Birth weight 3.1 kg • Weight 3.8 kg, HR=132, RR 68 • Retractions (+) • Systolic murmur, gallop rhythm • Hepatomegaly • Dx: Large VSD, Heart failure, Failure to thrive • Definite Rx: early surgery • Alternative Rx: Drugs first?

20. Medical students:(Background question) • What is VSD? • How to Dx? • What are symptoms & signs of CHF in infants with L-R shunt? • What is the treatment?

21. House officers(Foreground question) • In infants with large VSD and CHF, would administration of digoxin or other inotropic agent delay the need for surgery?

22. Foreground questions Background questions Experience with condition

23. Other example • In neonates born to mothers with history of herpes simplex infection, does the administration of IVIG (intravenous immunoglobulin) reduce the possibility of neonatal herpes?

24. In women with history of eclampsia, would administration of low-dose aspirin (compared with no aspirin) during pregnancy prevent eclampsia? Other example

25. Examples of clinical questions in practice

26. Example: Etiology P I C O …a risk factor for the developmnt HMD? “In premature infants … …is mode of delivery…

27. Example: Diagnosis P I C O “In patients with suspected malaria …effectively establish diagnosis? …comparedwith microscope exam …can rapid test

28. Example: Therapy P I C O will early IV Immuno-globulin (IVIG) “For px with Stevens Johnson syndrome …when compared with no IVIG …prevent severe complica- tions?

29. Example: Prognosis P I C O …worsen the prognosis? “For px with SLE …would history of heart failure …compared with no history of HF

30. Four elements of good clinical question:PICO The Patient or Problem The Intervention Comparative intervention The Outcome Domain Determinants Outcome

31. Four elements of a well constructed clinical question: PICO P I C O The main intervention considered The alternative to compare with the intervention Outcome expected from this intervention? Description of patient or problem B e b r i e f a n d s p e c i f i c

32. Remember (1) • Not all clinical questions contain 4 elements, depending on the nature of the condition being asked. • Examples: • In post-menopausal women on hormone replacement therapy, does addition of vitamin X reduce the likelihood of developing hip fracture? (PIO) • In patients with thalassemia HbE disease, what is the prevalence of single gene mutation? (PO)

33. Remember (2) • In the PICO context, Intervention does not necessarily mean TREATMENTor PREVENTION, but may be: • A diagnostic test (for diagnosis) • In a patient with solitary thyroid nodule, does ultrasound exam, compared with needle biopsy, differentiate malignant from benign tumor? • A risk factor (for etiology, prognosis) • Is poor fiber diet a risk factor for the development of colo-rectal cancer? • A condition in the patient himself (for prognosis) • In patient with SLE, would the history of cardiac failure, compared with no failure, worsen the long-term prognosis?

34. Relevance: Type of Evidence POE: Patient-oriented evidence mortality, morbidity, quality of life DOE: Disease-oriented evidence pathophysiology, pharmacology, etiology

35. Comparing DOEs and POEMs Example DOE POEM Comment DOE & POEM contradicts Drug A > mortality Antiarrhythmic Therapy Drug A  PVC On ECG Drug X  mortality POEM agrees With DOE Antihypertens. Therapy Drug X  BP PSA screening detects prostate Ca. early ? whether PSA screening  mortality Prostate screening DOE exists, but POEM unknown

36. IISearching the evidence

37. Examples of on-line Journals / Databases • http://bmj.com • http://adc/bmjjournals.com • MEDLINE/PubMed • EMBASE • MDConsult • AAP Journal Club • Cochrane Library

38. Use keywords for searching Note: • Spelling (American / British), terminology • Follow rigidly the instructions of each website Examples: • “Host vs graft reaction” AND management • hemosiderosis AND thalassemia OR thalassaemia • “breast cancer” OR “Ca mammae” AND immunoglobulin OR IVIG

39. IIIAppraising the evidence:VIA

40. VIA Validity:In Methods section: • design, sample, sample size, eligibility criteria (inclusion, exclusion), sampling method, randomization method, intervention, measurements, methods of analysis, etc Importance:In Results section • characteristics of subjects, drop out, analysis, p value, confidence intervals, etc Applicability:In Discussion section + our patient’s characteristics, local setting

41. Validity - other approach: RAMMbo • Recruitment: sampling methods, eligibility criteria, sample size • Allocation: randomization? concealment? • Maintenance: many drop outs? • Measurement • blinded – RCT, Dx test • objective – validity & reliability Can be applied for all designs with necessary Adjustment according to nature of the design

42. Example: Critical appraisal for therapy • Were the subjects randomized? • Were all subjects received similar treatment? • Were all relevant outcomes considered? • Were all subjects randomized included in the analysis? • Calculate CER, EER, RRR, ARR, and NNT • Were study subjects similar to our patients in terms of prognostic factors?

43. Rec Weight of Scientific Scrutiny A Level 1 Level 2 B Level 3 C Level 4 Hierarchy of evidence Meta-analysis of RCT Large RCT Small RCT Non-Randomized trials Observational studies Case series / reports Anecdotes, expert, consensus

44. Implementation of EBM practice:How to get started 1. Teaching EBM in medical schools / PPDS Easier than to change the already existing attitude Most important May be included in formal curricula or integrated in existing activities: ward rounds, on calls, case presentations, group discussions, journal clubs, etc 2. Workshop for teaching staff 3. Workshop for practitioners, incl. nurses

45. Resistance to EBM teaching & learning Rudimentary skill in critical appraisal / methodological skill Limited resources, esp. time factor Lack of high quality evidence Skepticism toward evidence-based practice ‘Happy’ with current practice

46. Development of EBM practice Passive diffusion model Active dissemination model Coordinated implementation model: Patients & community Health administrators Public policy makers Clinical policy makers

47. Summing up ....

49. Formulate In answerable question Apply The evidence Critically Appraise The evidence Search the evidence Patient With problem The EBM Cycle

50. Appropriate sampling technique Actual study subjects Subjects completed the study [Non-response, drop outs, withdrawals, loss to follow-up] Usu. Based on practical purposes Target population (Domain) Accessible population (time, place) (demographic, clinical) Your patient is here! Intended Sample [Subjects selected for study]