Evidence Based Medicine

a brief overview about how and why to practice evidence based medicine, its clinical application, what it is and what it is not? benefits and challenges

1. E vidence B ased M edicine Dr. Mansij Biswas Dept . of Pharmacology & Therapeutics Seth GS Medical College & KEM Hospital

2. QUESTION : In patients with acute MI , does treatment with Aspirin/Streptokinase reduce mortality ? Evidence in 1988 : Results of ISIS- 2: ASA vs. placebo- significant 23% RR reduction in five-week cardiovascular mortality; ASA+STK vs. placebo - 42% RR reduction! Application in 1997: 463 patients in the ER with a definitive diagnosis of acute MI- Aspirin was NOT given to 55% ! September 03, 2015 2

3. What is EBM ? "A systematic approach to clinical problem solving by 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 , et al. Users' Guides to the Medical Literature, 2002 ) September 03, 2015 3

4. Historical Evolution Traces of EBM’s origin in ancient Greek & Chinese medicine Prof. Archie Cochrane, Scottish epidemiologist, through his book Effectiveness and Efficiency: Random Reflections on Health Services (1972), advocated concepts behind EBM. “Evidence based medicine” first appeared in the medical literature in 1992 in a paper by Guyatt et al. Methodologies used to determine “best evidence”, established by McMaster University Research Group led by David Sackett & Gordon Guyatt . September 03, 2015 4

5. EBM in practice Took an “evidence cart” on rounds - 1995 Looked up 2-3 questions per patient Took 15-90 seconds to find evidence Changed about 1/3 decisions, rounds took longer! September 03, 2015 5

6. When… There is evidence that something works, is good and benefits the patient- do it There is evidence that something does not work, is harmful or does not benefit the patient- do not do it There is insufficient evidence, rely on individual clinical expertise- be conservative September 03, 2015 6

7. Triad of EBM Sackett DL et al . Evidence based medicine: what it is and what it isn’t. BMJ  . 1996;312(7023):71 -2 . September 03, 2015 7

8. Misconceptions about EBM ×× It ignores clinical experience and clinical intuition. ×× Understanding of basic investigation and pathophysiology plays no part in it. ×× It ignores standard aspects of clinical training such as the history taking, physical examination etc . September 03, 2015 8

9. Why EBM ? Cost Delay of "bench-to-bedside" research Managing the literature Counter misleading marketing Dealing with conflicting results September 03, 2015 9

10. Cost Many companies often use cost-cutting measures (such as treatment algorithms) under the name of EBM. I ncreasing pressure to demonstrate effectiveness of interventions. When cost is a barrier for a patient, it is important for clinicians to know when treatments are wholly ineffective and make decisions to utilize the most cost effective measures. September 03, 2015 10

11. Delay of "bench-to-bedside" research September 03, 2015 11 Secondary Research Routine Clinical Practice Primary Literature “Lag period” ≈ years to decades!! Thrombolytics and Aspirin for acute MI : 6 years from the first Systematic Reviews of RCTs until most review articles, textbooks and expert opinions recommended their use. ( Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts . Treatments for myocardial infarction . JAMA 1992; 268(2): 240-8 . )

12. Managing the literature 60,000 articles/ year from 120 reputed journals worldwide. More than 3800 biomedical journals in MEDLINE, more than 7300 citations added weekly Just within their own fields, physicians would need to read 19 articles per day, 365 days per year, to keep up with research. Not all (~10%) of these articles are considered high quality and clinically relevant . Thus EBM helps us to find the most appropriate article for a specific clinical question CEBM ( Centre for Evidence-Based Medicine), Oxford University , PubMed data for RCTs[ Publication Type] September 03, 2015 12

13. Counter misleading marketing Pharmaceutical companies invest considerable resources to promote products based on skewed or selective evidence or through direct-to-consumer advertising. EBM provides tools to alert clinicians against potentially misleading marketing . One such tool to detect publication bias is clinical trial registries , w hich also guard against data mining by " post hoc" statistical analysis. Glasziou , Hayes. The paths from research to improved health outcomes, Evidenced Based Nursing, 2005; 8(2):36-8 . September 03, 2015 13

14. Dealing with conflicting results A counter-intuitive result, demonstrating the inability to make accurate predictions based on physiologic reasoning, theoretical knowledge or results of studies which are biased or having poor methodological flaws. Some examples: September 03, 2015 14

15. September 03, 2015 15 Beta-blockers were initially avoided after MI thinking that they would decrease compensatory sympathetic mechanisms. Later shown to decrease hospitalization & death .

16. Based on 16 cohort studies (and some physiologic reasoning) HRT used to be recommended for postmenopausal women to reduce the risk of CHD. WHI trial showed that it actually increased the risk of MI, stroke, and venous thromboembolism . September 03, 2015 16

17. Need of EBM for clinical pharmacologists? Expert opinion regarding drug therapy during clinical rounds Answering queries in drug information unit Formulating local guidelines Formulate h ospital medication policy As a regulatory authority In pharmaceutical industry- identifying unmet medical needs and developing the drug/device/diagnostic development program Generating more sound evidences September 03, 2015 17

18. Principles of EBM Construct a well-built clinical question and classify it into one category (therapy, diagnosis , etiology, prognosis, prevention or cost) Find the evidence in health care literature Critically appraise or formally evaluate for validity and usefulness Integrate the evidence with patient factors Evaluate the whole process September 03, 2015 18

19. 7 ‘A’s of EBM Ask question Acquire/Access information Appraise evidence Apply findings Analyze outcome Assess the patient Add knowledge September 03, 2015 19

20. Types of Questions: Background questions Asked for general knowledge about a disorder  Has two essentials components: A question root (who , what, where, how, why ) & a verb A particular disorder , test , treatment or other aspect of health care . Textbooks usually answer background questions, they contain collected & synthesized wisdom for topics that do not change much often. September 03, 2015 20

21. Foreground questions Asked for specific knowledge about managing patients with a particular disorder It has 4 components ( PICO analysis ): P - Patient /Population I - Intervention C - Comparison O - Outcome September 03, 2015 21

22. P atient / P opulation What is the primary problem, disease or co-existing conditions On what groups do you want information How would you describe a group of patients whether similar to the one in question or not? September 03, 2015 22

23. I ntervention What medical event do you want to study the effect of ? Which main intervention are you considering, prescribing a drug, ordering a test, ordering surgery. 23 September 03, 2015

24. C omparison Compared to what?   Better or worse than no intervention at all or than another intervention?   What is the main alternative to compare with the intervention, are you trying to decide between two drugs, a drug and a placebo, or two diagnostic tests . 24 September 03, 2015

25. O utcome What is the effect of the intervention ? What do you hope to accomplish, measure, improve, or affect with the intervention ? What are you trying to do for the patient, relieve or eliminate the symptoms, reduce side effects, reduce cost. 25 September 03, 2015

26. What is pancytopenia? What is the diagnostic test for meningitis? Should a 70 year old pancytopenic patient with suspected meningitis receive platelets before undergoing a lumbar puncture? September 03, 2015 26 BACKGROUND FOREGROUND Type of Question Clinical Experience

27. Simple Patient/ Population Patients with common warts Intervention Duct tape Comparison Cryotherapy Outcome Eliminating warts Answerable clinical question: In patients with common warts, is duct tape as effective as cryotherapy in eliminating warts? September 03, 2015 27

28. P atient/ Population In patients with acute MI In women w ith suspected c oronary artery disease does early treatment with a statin what is the accuracy of exercise ECHO compared to placebo compared to exercise ECG d ecrease c ardiovascular mortality ? for diagnosing significant CAD? Components of Clinical Questions I ntervention C omparison O utcome September 03, 2015 28

29. Category of Question Suggested best type of Study Therapy RCT > cohort > case control > case series Diagnosis Prospective , blind comparison to a gold standard Etiology RCT > cohort > case control > case series Prognosis Cohort > case control > case series Prevention RCT > cohort > case control > case series Cost Pharmaco -economic analysis September 03, 2015 29

30. Searching evidence “My students are dismayed when I say to them, h alf of what you are taught as medical students today, will have been shown to be wrong in 10 years, and the trouble is, none of us knows which half!” ≈ Dr. Sydney Burwell September 03, 2015 30

31. Primary Literature : articles and studies presented in peer-reviewed journals. Secondary Literature : compiled by indexing and abstracting services that can be used to systematically locate various types of published literature through various databases like Medline ( PubMed), Cochrane Library, Ovid, Embase etc. Tertiary Literature: core knowledge established via primary literature or accepted as standard of practice within the medical community. The tertiary reference may consist of textbooks/handbooks/manuals on various drugs or disease topics ( Harrison's Principles of Internal Medicine ), compendia ( Physician's Desk Reference ) etc. September 03, 2015 31

32. Unfiltered Expert Opinion Filtered More time More work More evidence Less time Less work Less evidence September 03, 2015 32

33. September 03, 2015 Systematic Review Cochrane reviews Evidence based journals EBM, EBN, EBMH, ACP J club Computerized Decision Support System (CDSS) 5’S’ Information Resources: Information in top 4 are used Original articles: BMJUpdates , PubMed, Clinical Queries Evidence based textbooks: UpTo Date, DynaMed , ACP PIER, BMJ Clinical Evidence Studies Syntheses Synopses Summaries Systems Haynes, R. (2006, November). Of studies, syntheses, synopses, summaries, and systems: the 5S evolution of information services for evidence-based health care decisions. ACP Journal Club, 145(3), A8-A9. POCRaTs 33

34. September 03, 2015 34 The Evidence Pyramid *Meta - Analysis ( Ia ) Bias Bias

35. Critically Appraise the Evidence Determine the appropriateness of some evidence for a particular clinical situation . Three main aspects to be appraised: V - I - A 1. Validity: (closeness to the truth)  in the methodology section. Internal validity: Refers to the soundness of the research methodology. External validity: Refers to generalizability of the results. September 03, 2015 35

36. 2. Importance: (usefulness)  in the results section. 3. Applicability: (whether can be applied in clinical practice)  in the discussion section. September 03, 2015 36

37. Apply the evidence to a particular patient Compare the patient with those in the study from which evidence has been generated ( similar disease state, similar baseline characteristics etc ). Consider the patient’s baseline risk for the outcome of interest and other risks associated with therapy. Consider the patient’s values, beliefs, concerns, affordability, compliance and readiness for the intervention . September 03, 2015 37

38. Evaluate the whole process Once the therapy is administered, evaluate the following: Did I formulate a focused question? Did I use the most appropriate resource ? Did the evidence work in my patient? Reassess the strategy. Collaborate with your colleagues and professional bodies in developing practice guidelines. September 03, 2015 38

39. Benefits of adopting EBM Minimizes the error and optimizes the quality in patient care Reduces the cost of treatment Helps in advancement of knowledge and keeping pace with scientific progress September 03, 2015 39

40. Challenges in a dopting EBM Technology and online information resources must be available to the clinicians . Understanding of the epidemiological study designs and concepts of biostatistics should be clear. Attitude of the clinician - one must realize that clinical performance depends upon regularly updating knowledge and not merely on practical clinical experience. September 03, 2015 40

41. Conclusion: What EBM is NOT But it is "Cookbook" medicine Rigid adherence to clinical guidelines Managed care Cost-cutting measures A rigorously systematic way to evaluate the strength and appropriateness of available evidences for a particular clinical situation A way to avoid waste by considering both the efficacy and effectiveness and cost of a particular intervention in a particular clinical setting. September 03, 2015 41

42. Conclusion: What EBM is NOT But it is The same thing as clinical epidemiology or biostatistics Limited to RCTs Build on concepts so we can better understand the strength of inferences from available evidence. A recognition that some study designs (esp. RCTs) are less susceptible to bias than others, and therefore less likely to mislead, but other evidences should also be used in clinical decision making as long as we understand their limitations. September 03, 2015 42

43. A lighter way to summarize September 03, 2015 43 https ://www.youtube.com/watch?v= Ij8bPX8IINg (“Some Studies T hat I Like T o Quote”)

44. September 03, 2015 44