Introduction to Evidenced Based Medicine

1. Introduction to Evidenced Based Medicine Presented By Dr.N.P.Singh

2. Intro to EBM • Objectives: • Define "Evidence Based Medicine" • Describe the need for EBM • List 3 components of Evidence-based decisions • Explain the concept of "hierarchy of evidence" • List reasons why the hierarchy of evidence is not absolute • Describe the 4 steps of the "EBM process" • Explain the rationale behind the 3 "broad questions" that can be used to evaluate any source of evidence.

3. What is EBM? • Definitions: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

4. What is EBM? • Key components: • "The integration of best research evidencewith clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

5. What is EBM? • Key components: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

6. What is EBM? • Key components: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

7. What is EBM?

8. What is EBM? • Key components: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

9. What is EBM? • Key components: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

10. What is EBM? • Philosophy ("conscientious, explicit, judicious..."): • "enlightened skepticism." Don't believe all you're told. • "Printed word bias. This occurs when a study is overrated because of undue confidence in published data." (Alejandro Jadad, Randomized Controlled Trials: A Users' Guide, 1998) • q.v. "prestigious journal bias," "non-prestigious journal bias," "prominent author bias," "famous institution bias" ... • Rigorous, intellectually exacting approach: "intuition, unsystematic clinical experience, and pathophysiologic rationale are [of themselves] insufficient grounds for clinical decision making." (Users' Guide p. 4) • "A formal set of rules must complement medical training and common sense..." (p. 4) • "EBM places a lower value on authority than the traditional medical paradigm does." (p. 4)

11. What is EBM? • Key components: • "The integration of best research evidence with clinical expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000) • "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

12. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results

13. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results • increasing pressure to • demonstrate effectiveness of interventions • utilize the most cost effective measures • How do you know what really works or is the most effective?

14. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results

15. Why EBM? Delay of "bench-to-bedside" research: Primary literature. Original research that generates new data. Secondary literature. Material published based on primary literature. • No new data is generated • Existing data is made more accessible • "Four "Ss": • pre-Selected studies: particularly relevant studies are culled from the body of primary literature. • Systematic Reviews: Particularly relevant studies are summarized (in a systematic way to avoid bias). • Synopses: Primary findings are re-organized and interpreted for pedagogical reasons (e.g., textbooks). • Systems: Primary findings are re-organized and interpreted to practical reasons (e.g. decision support, practice guidelines)

16. Why EBM? Delay of "bench-to-bedside" research: Primary Literature Secondary Research Years-to-Decades Routine Clinical Practice

17. Why EBM? Delay of "bench-to-bedside" research: Primary Literature Thrombolytic Drugs for acute MI: 6 years from the first Systematic Reviews of RCTs until most review articles and textbooks recommended their use. (Antman, Lau, et al. JAMA 1992) Secondary Research Routine Clinical Practice

18. Why EBM? Delay of "bench-to-bedside" research: Primary Literature Aspirin after acute MI: Not recommended by expert opinion until 6 years after the first systematic review. (Antman, Lau, et al. JAMA 1992) Secondary Research Routine Clinical Practice

19. Why EBM? Delay of "bench-to-bedside" research: Bed rest after back injury or surgery: Primary Literature • Studies in the 1940's showed no advantages for complete bed rest after surgery • Instead, DVT, bedsores. osteoporosis, and pneumonia identified as problems. • Ideas about bed rest remain entrenched... • e.g., 80% of neurological units in UK still insist on bed rest, despite 17 years of evidence showing no value Secondary Research Routine Clinical Practice (Allen C, Glasziou P, Del Mar C. Bed rest: a potentially harmful treatment needing more careful evaluation. Lancet 1999.)

20. Why EBM? Delay of "bench-to-bedside" research: Primary Literature Use of albumin in fluid resuscitation: • Based on physiologic reasoning. Used for >50 years for hypovolemia, shock, burns... • Later RCTs suggested increased mortality in some conditions • Modern, large Systematic Reviews showed possible biphasic effect based on dose. (Wilkes, Navickis. Ann Int Med 2001) Secondary Research Routine Clinical Practice

21. Why EBM? Delay of "bench-to-bedside" research: "Life Cycle of Translational Research" Primary Literature Median time from "initial discovery of a medical intervention" to a "highly cited article" was 24 years. (Contopoulos-loannidis, Alexiou, et al. Science 2008) Secondary Research Routine Clinical Practice

22. Folate for prevention of neural tube defects (ca. 1963-1991) AZT for prevention of perinatal HIV infection (ca. 1989-1994) Why EBM? Median time from "initial discovery" to a "highly cited article" was 24 years. (Contopoulos-loannidis, Alexiou, et al. Life-cycle of translational research for medical interventions, Science 2008)

23. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results • Early, judicious use of the primary literature may help save lives. • How to decide what constitutes "Judicious" will to be explained more as the course progresses.

24. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results

25. Why EBM? Managing the primary literature

26. Why EBM? Managing the primary literature 100 K 35 K 15 K

27. Why EBM? Managing the primary literature • MEDLINE adds 4500 records daily. • Just within their own fields, physicians would need to read 19 articles per day, 365 days per year, to keep up with research. (Oxford Center for EBM) • Not all (~10%) of these articles are considered high quality and clinically relevant. (Oxford) EBM helps you find the most appropriate article for a specific clinical question.

28. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results Pharmaceutical companies invest considerable resources to promote products based on skewed or selective evidence (or emotion appeals through direct-to-consumer advertising). EBM provides tools to help alert clinicians to potentially misleading marketing. (Glasziou, Hayes. The paths from research to improved health outcomes, Evidenced Based Nursing, 2005; 8(2):36-8.)

29. Why EBM? • What is the need? • Cost • Delay of "bench-to-bedside" research • Managing the primary literature • Counter misleading marketing • Dealing with conflicting results

30. Vitamin E for CAD prevention Vitamin E for CAD prevention Why EBM? Dealing with conflicting results? "My students are dismayed when I say to them "Half of what you are taught as medical students will in ten years have been shown to be wrong. And the trouble is, none of your teachers know which half." -Sydney Burwell, M.D., Dean, Harvard Medical School (1956) Postmenopausal HRT (Contopoulos-loannidis, Alexiou, et al. Science 2008)

31. Why EBM? Dealing with conflicting results • Back-to-Sleep: Based on physiologic reasoning, Dr. Benjamin Spock recommended that babies sleep on their stomach to prevent risk of vomiting and choking. • Later shown to increase the risk of SIDS:

32. Why EBM? Dealing with conflicting results • Beta-blockers initially avoided after MI due to pathophysiologic reasoning that they would decrease compensatory sympathetic mechanisms • Later shown to decrease hospitalization & death:

33. Why EBM? Dealing with conflicting results • Based on 16 cohort studies (and some physiologic reasoning) HRT used to be recommended for postmenopausal women to reduce the risk of CHD. • Womens' Health Initiative show it actually increased the risk of MI, stroke, and venous thromboembolism:

34. Why EBM? Dealing with conflicting results • Since the 1960s, lidocaine was used for V-fib & V-tach prophylaxis in patients with acute MI. • A meta-analysis showed some reduction in V-fib & V-tach, but a probably increase in actual mortality:

35. Why EBM? Dealing with conflicting results Damned if you do... ...Damned if you don't

36. Why EBM? Dealing with conflicting results: Hierarchy of Evidence: The notion that some study designs are less susceptible to bias than others, with the effect that some study results are more likely to be valid than others. "Study design," "bias," and "validity" will be more rigorously explained later. Casual understanding is sufficient for now.

37. Hierarchy of Evidence A Hierarchy of Evidence (strongest type of evidence on top): Meta-Analysis Randomized Controlled Trial Cohort Study Case-Control Study Case Series Single Case Reports Anecdotal Reports Pathophysiologic Reasoning Ideas, opinions, etc. (Petrie A. Statistics in orthopaedic papers. The Journal of Bone and Joint Surgery 2006; 88-B(9):1121-36)

38. (I-1) a well done systematic review of 2 or more RCTs (I-2) a RCT (II-1) a cohort study (II-2) a case-control study (II-3) a dramatic uncontrolled experiment (III) respected authorities, expert committees, etc.. (IV) ...someone once told me.... http://www.phru.org/casp/ See also AAFP Levels of Evidences

39. The EBM Process • An approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise. • A four-step process: • Ask a "well-built" clinical question • Search for the best evidence to answer the question. • Critically appraise the evidence • Apply the evidence to a particular patient

40. The EBM Process • An approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise. • A four-step process: • Ask a "well-built" clinical question • Search for the best evidence to answer the question. • Critically appraise the evidence • Apply the evidence to a particular patient

41. The EBM Process • Step 1: Ask a well-built clinical question • Use the Mnemonic PICO: • P = Patient characteristics • age (adult, pediatric) • sex • diagnosis or condition • social situation, resources, values • setting: inpatient, outpatient, rural, tertiary care, etc. • public health issue or individual patient issue?

42. The EBM Process • Step 1: Ask a well-built clinical question • I = Intervention • What it is you are considering trying • Could be a medication, a diagnostic test, or some other type of treatment • Most useful when you need to choose between treatment options

43. The EBM Process • Step 1: Ask a well-built clinical question • C = Comparison • One of the options you are choosing between • Sometimes the labeling of one treatment as "Intervention" and the other as "Comparison" is arbitrary. • A treatment (or test) can really only be assessed in comparison to something else... • ...Even if the "something else" is "standard treatment," "watch-and-wait," or "no treatment."

44. The EBM Process • Step 1: Ask a well-built clinical question • O = Outcome • The effect you want to achieve (or avoid) • Can include treatment effects as well as side effects • Usually, you are interested in one primary outcome (even if the primary outcome is fairly global such as "quality of life," "functionality," or "hospitalizations." • Surrogate outcomes: Measurements that are not of themselves important to patients (e.g., blood pressure, bone density, cholesterol level) but that are associated with outcomes that are important to patients (e.g., stroke, fracture, MI). • Use caution with surrogate outcomes (e.g., Lidocaine use after AMI: decreased V-fib but increased death.)

45. The EBM Process • Outcomes • Efficacy: The effects of an intervention under ideal conditions (e.g., a laboratory experiment) • Most RCT's measure efficacy. • Effectiveness: The effects of an intervention under the usual conditions (e.g., in the field) • RCT's may overestimate effectiveness • Observational studies may give a better estimate of actual effectiveness. • Efficiency: The relative ease (or lack of waste) in producing an effect. • Related to the idea of potency • Not really an EBM concept, but included here since it is another "eff-" word that is commonly confused with efficacy and effectiveness.

46. Questions: PICO Centre for EBM: http://163.1.212.5/docs/focusquest.html

47. The EBM Process • An approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise. • A four-step process: • Ask a "well-built" clinical question • Search for the best evidence to answer the question. • Critically appraise the evidence • Apply the evidence to a particular patient

48. The EBM Process Step 2: Search for the Evidence Searching techniques can be involved and take a lot of experience and trial & error to discover what works well. These will be covered in more detail in a later module. • In searching, you should consider: • What databases are available & relevant to my question? • How does each database work? How do you enter searches? How can you refine or narrow searches? • Use your PICO question to choose key words • What type of article (treatment, harm, diagnosis, prognosis, etc.) is most relevant to my question? • Which articles are of the highest level of evidence?

49. The EBM Process • Step 2: Search for the Evidence • In general, the highest level of evidence is preferred. Emphasize additional criteria when: • You find >1 article at the highest available level of evidence • Results are inconsistent from article to article • The patients studied, the clinical setting, or the outcome measured are significantly different from your PICO question • In these cases you should especially consider: • Which articles have a clinical setting, patient population, or outcome most similar to my PICO question? • Which studies are the most recent? • How large are the sample sizes? • How well done are the studies? (Step 3 of the EBM process)

50. The EBM Process • An approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise. • A four-step process: • Ask a "well-built" clinical question • Search for the best evidence to answer the question. • Critically appraise the evidence • Apply the evidence to a particular patient