Clinical Problem Solving an introduction to Evidence-Based Medicine basics

1. Clinical Problem Solving an introduction to Evidence-Based Medicine basics

2. Lecture overview • Objectives • EBM skills for practicing medicine • Asking • Acquiring • Assessing • Applying

3. Objectives • Define evidence-based medicine (EBM) • Explain why we use EBM • Compare with expert-based medicine • How are we misled by: • Surrogate outcomes • Personal observation • Pathophysiologic reasoning • Describe the tools of EBP • Construct a well-built clinical question

4. What is Evidence-Based Medicine (EBM)? “Using the best available evidence for making decisions about health care”

5. What is important to read in the medical literature Things that • Have patient oriented outcomes • Answer a patient-care question • Might change your practice • Are on a topic you have been following • People are talking about and you want to know more • You find interesting POEM or DOE • Patient-oriented evidence that matters vs disease-oriented evidence

6. “Intro”: EBM (I) “Evidence-based medicine (EBM) requires the integration of the best research evidence with our clinical expertise and our patient’s unique values and circumstances” EBM, 2006, Straus et al

7. Why learn EBM / EBP?

8. “Good education teaches us to become both producers of knowledge & discerning consumers of what other people claim to know.”

9. Helps you find the truth in face of pharmaceutical marketing Cal Ripkin, Jr. is not hypertensive and is not taking PRINIVIL Its always in the fine print.

10. Value of Learning EBM: Short-Term Trial • A controlled trial of teaching critical appraisal of clinical literature conducted among medical students • Experimental group of students worked with clinical tutors who had • Taken course in clinical appraisal • Evaluated specialty-specific articles on diagnostic tests and treatments • Control group of students worked with usual clinical tutors Bennett et al. JAMA. 1987;257:2451-2454.

11. Value of Learning EBM: Short-Term Trial (cont) • Students in experimental group made greater number of correct diagnostic and treatment decisions and were better able to justify their decisions • Students in control group were more likely to make incorrect decisions after their tutorial than before it • Students in the control group had become more accepting of recommendations from authority figures Bennett et al. JAMA. 1987;257:2451-2454.

12. The Patient • Patient is a 27-year-old woman with severe right lower quadrant pain. • initial peri-umbilical pain x 2 days migrating yesterday to current site. • Loss of appetite. No vomiting, diarrhea; no bowel movement • no known infectious exposure/ suspicious ingestions, or recent travel

13. Standard medical practice for hot, moist diseases

14. Louis’ Study of Bloodletting Day of 1st bleeding Averages Duration of illness Number of bleedings

15. Pierre Louis (1787-1872)Inventor of the “numeric method” and the “method of bservation” Discovered in 1828 that patients who were bled did worse than those who weren’t

16. Many advances in medicine with uncontrolled use • PCN for life-threatening disease • Insulin for type I diabetes • Treatment of malignant hypertension

17. Traditional Guides to Medical Practice • Pathophysiology and pharmacology • Foundation of medical practice • Do what “makes sense” • Expert opinion • In training: learning at the bedside from the master clinician • In practice: lectures and seminars with thought leaders • Clinical experience • Successes, outcomes, and adverse events in our own practice

18. Cardiac ArrhythmiaSuppression Study 1498 subjects with suppressible arrhythmias post-MI RANDOMIZED Placebo Treatment 7.7% Mortality 3.0%

19. Problems With the Traditional Approach • Physiology may not predict clinical response • Beta-adrenergic blockade in heart failure • Encainide for post-MI arrhythmia • Estrogen replacement for cardioprotection • Expert opinion • Only as good as the expert • May be affected by biases and conflicts of interest • Clinical experience • Dramatic clinical experiences may unduly influence our practice patterns • May not take account of recent medical literature Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-BasedClinical Practice. Chicago, IL: American Medical Association; 2001.

20. Paradigms of Medicine

21. Seven alternatives to EBMHumorous approach from BMJ BMJ 1999;319:1618-1618

22. Integrates Evidence With • Clinical expertise • Experience • Judgment • Patient values and preferences • Quality of life • Costs • Other important factors

23. Clinical Expertise Patient Values and Preferences Best Available Evidence Quality of Life Costs

24. Focus: Treatment & Diagnosis

25. The Patient • Patient is a 27-year-old woman with severe right lower quadrant pain. • initial peri-umbilical pain x 2 days migrating yesterday to current site. • Loss of appetite. • No vomiting, diarrhea; no bowel movement • no known infectious exposure/ suspicious ingestions, or recent travel

26. Patient exam VS BP 120/78 P 16 RR 12 T 98.8 Chest CTA. CV RRR s M/R/G ABD: NML exam x decreased bowel tones and definite right lower quadrant pain, specifically at McBurney’s point. no heptomegaly nor splenomegaly (enlarged liver or spleen). She has no rebound pain or involuntary

27. The Five “A’s” • Ask the right question • Acquire the evidence • Appraise the evidence • Apply the evidence • Assess its impact

28. Concern: • Case discussion: 27 year old woman with right lower quadrant (RLQ) abdominal pain • Background information available from textbooks- • What typically presents as RLQ pain • What is the clinical course of the different diagnoses • Specifically, what is typical presentation of appendicitis • Foreground information • How good is a CT scan for appendicitis?

29. Formulating the Question

30. Formulating the Question • An ideal question: • Focused enough to be answerable • Pertinent to clinical scenario • Framed as Population receiving an Intervention (test or treatment) [as Compared to other test/treatment or placebo] associated with Outcome (disease or improvement)

31. PICOS P roblem/population I ntervention C omparison O utcome S tudy design

32. Examples of tough questions • Should I screen men for prostate cancer? • Who is a good candidate for hormone replacement therapy? • Are angiotensin receptor blockers now first-line for hypertension?

33. Examples of better questions • Would a PSA test reduce mortality in a 65 year-old asymptomatic man? • What is the reduction in fracture risk associated with hormone replacement therapy? • Is losartan more effective than atenolol at preventing cardiovascular events in middle-aged hypertensive diabetic women?

34. PICOS PICOS for confirmatory diagnosis of appendicitis P: 27 year old woman with symptoms suggestive of appendicitis I: CT Scan C: Ultrasound O: Accurate diagnosis without undue delay S: ??

35. Important Outcomes • Patient Oriented Outcomes: outcomes patients actually care about • Death (overall or disease-specific) • Heart attacks, strokes, amputations, bed sores, broken hips, renal failure, etc. • Ability to perform activities of daily living Versus • Disease oriented outcomes: • Biochemical, physiologic, pharmacologic, or laboratory measures

36. Comparing DOE and POE Shaughnessy AF, Slawson DC. Getting the Most from Review Articles: A Guide for Readers and Writers. American Family Physician 1997 (May 1);55:2155-60.

37. Background versus foreground information • Case discussion: 27 year old woman with right lower quadrant (RLQ) abdominal pain • Background information available from textbooks- • What typically presents as RLQ pain • What is the clinical course of the different diagnoses • Specifically, what is typical presentation of appendicitis • Foreground information • How good is a CT scan for appendicitis?

38. Steps of EBM-5 A’s • Ask • Acquire • Appraise • Apply • Assess

39. “Finding Evidence”: Sources (I) • Primary research database (articles) • PubMed (aka MEDLINE), Pyschlit, CCTR • Secondary research databases (synthesis) • Cochrane Library, Clinical Evidence, InfoPOEMS, UpToDate • Tertiary resources (meta search engines, databases of databases) • TRIP+ (Translating Research Into Practice), PrimeEvidence

40. “Finding Evidence”: Sources • PubMed • 16 million peer reviewed biomedical articles indexed (note can use PubMed limits to search on particular populations, study types, etc.) • Cochrane Library • ~3000 clinical systematic reviews (gold standard database) • Clinical Evidence • ~2500 tsystematic reviews of treatment classified by likelihood of benefit • InfoPOEMS (www.infopoems.com) • ~3000 regularly updated entries, Patient Oriented Evidence the Matters (POEM), 100+ journals monitored • UpToDate • 70,000 pages, evidence based clinical information resource, ~3000 authors, 350+ journals monitored, peer reviewed • TRIP+ • Meta-search of 55 sites of evidence based information

41. “Finding Evidence”: Searching • Convert clinical question to searchable question (e.g. PICOS) • Choose the database you want to search (e.g. PubMed) • Apply filters to restrict your search (e.g. PubMed limits linked to PICOS such as gender, age, study type limits) • Assess result (e.g. using systematic review worksheet) • Decide if you have enough information to make a decision • If not then refine steps 1-3 until you either have an answer or decide there isn’t enough evidence to make an evidence based decision

42. Appraising the Evidence

43. Assess the Evidence • Is the study valid? • Validity is defined as relative freedom from bias and confounding factors • What are the results? • What is the outcome and how was it measured? • What is the magnitude of the effect? • Are the results statistically significant? • Do the results apply to my patient? • Does my patient resemble those in the study? • Were all outcomes relevant to my patient evaluated? • Are there other factors (eg, cost, availability) that limit applicability to my patient? Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001

44. Objectives • Understand difference between observational and experimental studies • For 2 major study designs (randomized controlled trial and cohort study) describe • How the study is designed • Advantages and disadvantages of design • How to assess validity • How to assess results • How to assess applicability

45. Experimental vs Observational Studies • In experimental studies, the investigator controls subjects’ exposure to intervention • Example: randomized controlled trial (RCT) • In observational studies, investigator does not control the exposure; it occurs naturally or is initiated by patients or their physicians • Examples: cohort study, case-control study Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

46. RCTs Generally held to be the optimal methodology for determining benefit or harm Treatment Outcome Eligible Patients Randomization Outcome Control Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

47. RCTs: Advantages • Treatment and control groups are likely to have similar distribution of known and unknown prognostic factors (potential confounders) • Outcomes are determined prospectively in a standardized, systematic fashion Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

48. RCTs: Disadvantages • Costly to perform • Size limitations make detection of rare events difficult (eg, adverse medication effects) • Eligibility restrictions may reduce applicability to real patients • Cannot be ethically performed if exposure is expected to cause harm (eg, smoking) Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

49. RCTs: Disadvantages • Costly to perform • Size limitations make detection of rare events difficult (eg, adverse medication effects) • Eligibility restrictions may reduce applicability to real patients • Cannot be ethically performed if exposure is expected to cause harm (eg, smoking) Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

50. Assessing the Validity of RCTs • Was randomization concealed? • Were patients analyzed in groups to which they were randomized? • Were patients in treatment & control groups similar with respect to prognostic factors? • Were patients, clinicians, outcome assessors, and data analysts aware of allocation? • Were groups treated equally? • Was follow-up complete? Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.