The Five A’s of Evidence Based Practice for Internal Medicine

1. Rick Wallace, MA, MDiv, MAOM, MSLS, EdD, MPH (abd), AHIP February 11,2013 Internal Medicine Grand Rounds The Five A’s of Evidence Based Practice for Internal Medicine

2. What is EBM? • EBM is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient (population). It means integrating individual clinical expertise with the best available external clinical evidence from systematic research." [Sackett D, BMJ Jan 13 1996;312:71-73]

3. Why important? • Studies of information-seeking habits of physicians have shown that, when asked, physicians reported that their practice generated about 2 questions for every 3 patients. It has also been reported that only about 30% of physicians' information needs are met during the patient visit. Reasons for not pursuing answers to questions included office textbook collections too old, lack of knowledge of appropriate resources, and lack of time to find the needed information. • [Covell DG, Ann Intern Med. 1985 Oct;103(4):596-9] • When observed, investigators found that physicians actually had about 5 questions for each patient. 52% of these questions could be answered by the medical record or hospital information system. Information resources such as textbooks or MEDLINE could have answered another 25% of these questions. • [Osheroff JA, Ann Intern Med. 1991 Apr 1;114(7):576-81]

4. However, studies have also shown that when clinicians have access to information, it changes their patient care management decisions. In 1998, David Sackett, using an “evidence cart” on rounds, reported that of 71 information searches to answer clinical questions, 37 (52%) confirmed the management decision, but 18 (25%) lead to a new therapy or diagnostic test and 16 (23%) corrected a previous plan. • [Sackett, D, JAMA. 1998 Oct 21;280(15):1336-8] • Crowley et al reported similar results. The CAR study reported on 520 clinical questions for which residents sought answers in the medical literature. In 53% of the cases the literature confirmed the management decision, but in 47% of these cases the literature changed the resident’s orders for medication, diagnostic test, or prognostic information given to the patient. • [Crowley S, Acad Med. March 2003 78(3):270-4]

5. Anatomy of the Medical Literature

6. The 5S Pyramid From: http://guides.library.upenn.edu/content.php?pid=192036&sid=1610308

7. Types of Individual Studies • Systematic Reviews usually focus on a clinical topic and answer a specific question. An extensive literature search is conducted to identify studies with sound methodology. The studies are reviewed, assessed, and the results summarized according to the predetermined criteria of the review question. The Cochrane Collaboration has done a lot of work in the area of meta-analysis. • A Meta-analysis will thoroughly examine a number of valid studies on a topic and combine the results using accepted statistical methodology to report the results as if it were one large study. Some clinicians put Meta-analysis at the top of the pyramid because part of the methodology includes critical appraisal of the selected RCTs for analysis.

8. Difference in a Systematic Review & A Meta-Analysis • A systematic review focuses on a specific clinical question, conducts a systematic review of the evidence including published and unpublished studies, and then summarizes the results to present an answer to the question. • A meta-analysis follows the structure of a systematic review but takes the results one step further. It uses quantitative methods to combine the data from the individual studies and report the results as if it were one large study.

9. Types of Individual Studies • Randomized, controlled clinical trials are carefully planned projects that study the effect of a therapy on real patients. They include methodologies that reduce the potential for bias (randomization and blinding) and that allow for comparison between intervention groups and control groups (no intervention). • Cohort studies take a large population who are already taking a particular treatment or have an exposure, follow them forward over time, and compare them for outcomes with a similar group that has not been affected by the treatment or exposure being studied. Cohort studies are observational and not as reliable as randomized controlled studies, since the two groups may differ in ways other than in the variable under study.

10. Types of Individual Studies • Case control studies are studies in which patients who already have a specific condition are compared with people who do not have the condition. The researcher looks back to identify factors or exposures that might be associated with the illness. They often rely on medical records and patient recall for data collection. These types of studies are often less reliable than randomized controlled trials and cohort studies because showing a statistical relationship does not mean than one factor necessarily caused the other. • Case series and Case reports consist of collections of reports on the treatment of individual patients or a report on a single patient. Because they are reports of cases and use no control groups with which to compare outcomes, they have no statistical validity.

11. Other important study designs: • Studies that show the efficacy of a diagnostic test are called prospective, blind comparison to a gold standard study. This is a controlled trial that looks at patients with varying degrees of an illness and administers both diagnostic tests -- the test under investigation and the "gold standard" test -- to all of the patients in the study group. • Cross-sectional studies describe the relationship between diseases and other factors at one point in time (usually) in a defined population. Cross sectional studies lack any information on timing of exposure and outcome relationships and include only prevalent cases.

12. Most common types of questions are related to clinical tasks: 1.Therapy -- how to select treatments to offer patients that do more good than harm and that are worth the efforts and costs of using them. 2. Diagnosis • Differential Diagnosis -- when considering the possible causes of a patient's clinical problem, how to rank them by likelihood, seriousness and treatability • Diagnostic Testing -- how to select and interpret diagnostic tests, in order to confirm or exclude a diagnosis, based on considering their precision, accuracy, acceptability, expense, safety, etc. 3. Prognosis -- how to estimate the patient's likely clinical course over time and anticipate likely complications of disease 4. Harm/Etiology -- how to identify causes for disease (including iatrogenic forms)

13. Other types of questions related to clinical tasks: • Clinical examination -- how to properly gather and interpret findings from the history and physical examination • Prevention -- how to reduce the chance of disease by identifying and modifying risk factors and how to diagnose early by screening • Cost-Analysis -- how to compare the cost and consequences of different treatments and tests

14. Best Type of Study

15. 5 steps

16. Step 1- Assess • Start with the population -- a clinical problem /question arises out of the care of a patient

17. Example: Clinical Case Scenario: Your patient is a 68 year old woman with a history of known CAD, s/p Inferior MI 7 years ago. Following her MI, she did extremely well. She has been on aspirin and b-blocker therapy. For the past 2 years she had been walking 2 miles four times each week without pain until 3 weeks ago when she noted exertional pain when she goes for her walk. She presented to the ER this evening when she had 4/10 substernal pain while sitting down at dinner. She denied SOB, N/V or diaphoresis. In the ER she was treated with aspirin, oxygen and sublingual nitroglycerine with complete resolution of her pain. Her initial physical examination was significant for HR 100 bpm, BP 105/70, clear lungs and heart exam without murmurs or gallops. She had no signs of CHF. Her presenting EKG showed anterior ST depression which resolved post nitroglycerine. She is admitted to the hospital.

18. Question #1: The intern is writing the admission orders and asks you whether to treat this patient with Heparin at this time. Do you want to treat this patient with heparin? Question #2: The medical student adds that the patient was told at the time of her previous MI that she had some blood in her stools. She doesn’t recall receiving any transfusions for this and doesn’t recall what work up was done because “she had so many tests at that time”. You don’t have access to these medical records. At this time, she is guaiac negative. The patient is concerned about bleeding and would like to know more about her risk of bleeding. Because you care so much about the learning experience of your medical student

19. Step 2- Ask • Construct a relevant, answerable question derived from the case

20. PICO • Background questions: • What’s the latest on treating otitis media? • Foreground questions: • (P) patient and/or problem • (I) intervention • (C) comparison intervention (if relevant) • (O) clinical outcomes.

21. P patients with unstable Angina • I heparin plus aspirin • C aspirin alone • O prevent MI and death • P patients with unstable Angina • I heparin plus aspirin • C aspirin alone • O cause bleeding

22. More on PICO • Formulating the clinical question is done to focus the information need and to facilitate searching the literature. So when you define your PICO think about it in terms of searching the literature. You want to end up with a question that makes sense and can be effectively searched.

23. More on PICO • You might not need to use all the terms in the PICO for the search strategy, but they can help you decide which specific articles are most appropriate for your case.

24. Example • In patients with Unstable Angina, is heparin plus aspirin more effective than aspirin alone in preventing MI and death? • In patients with Unstable Angina, is heparin plus aspirin more likely than aspirin alone to cause bleeding?

25. Step 3- Acquire • Select the appropriate resources and conduct a search

26. JAMA. 1996 Sep 11;276(10):811-5. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. OBJECTIVE: To estimate the risk of myocardial infarction (MI) and death in patients with unstable angina who are treated with aspirin plus heparin compared with patients treated with aspirin alone. CONCLUSIONS: Our findings are consistent with a 33% reduction in risk of MI or death in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The bulk of evidence suggests that most patients with unstable angina should be treated with both heparin and aspirin.

27. Ideal Resource • What is the ideal resource? • Easy to use • Fast, reliable connection • Comprehensive /Full Text • Allows the separation of ‘junk” from “gold” (quality of the search interface) • Provides or reviews the primary data

29. Step 4- Appraise • Appraise that evidence for its validity (closeness to the truth) and applicability (usefulness in clinical practice)

31. Therapy Appraisal • Key issues for evaluating therapy studies: • F-R-I-S-B-E • Follow-up (80% or better) • Randomization and concealed allocation • Intention to Treat • Same at Baseline (established at the start of the trial) • Blinding (the more blinding the better) • Equal Treatment

32. Diagnosis Appraisal • Key issues for diagnostic studies: • Independent blind comparison with gold standard • Appropriate spectrum of patients • All patients receive both tests

33. Prognosis Appraisal • Key issues for prognosis studies: • Well-defined sample of patients • Similar prognostic factors • Follow-up • Objective outcome criteria

34. Harm Articles • Key issues for etiology/harm studies: • Similarity of comparison groups • Outcomes and exposure measured the same for both groups • Follow-up of sufficient length

35. Systematic Review/Meta-Analysis Appraisal • Key issues for Systematic Review/Meta Analysis: • Focused question • Thorough review of the literature • Clear validity criteria • Reproducible assessments of studies

36. Statistical Measures to Know

37. Absolute Risk Reduction • Absolute Risk Reduction is the arithmetic difference between the rates of events in the experimental and control group. An Absolute Risk Reduction (ARR) refers to the decrease of a bad event as a result of the intervention. An Absolute Benefit Increase (ABI) refers to the increase of a good event as the result of the intervention.

38. Relative Risk or Risk Ratio • Relative Risk (RR) or Risk Ratio (RR) is the ratio of risk in the exposed group to the risk in the unexposed group. In other words, it's the probability of an event in the treated group divided by the probability of an event in the control group. If the RR is greater than 1 there is a higher risk of the event occurring; if the RR is 1 the risk is equal; if the RR is less than 1 there is a lower risk of the event happening.

39. Relative Risk Reduction • Relative Risk Reduction (RRR) is the proportional reduction in risk between the rates of events in the control group and the experimental group. Relative Risk Reduction is often a larger number than the ARD and therefore may tend to exaggerate the difference.

40. Number Needed to Treat • Numbers Needed to Treat (NNT) is the number of patients who need to be treated to prevent one bad outcome or produce one good outcome. In other words, it is the number of patients that a clinician would have to treat with the experimental treatment to achieve one additional patient with a favorable outcome. The smaller the NNT, the more effective the treatment.

41. Confidence Intervals • Confidence Intervals are a measure of the precision of the results of a study. For example, "36 [95% CI 27-51]", a 95%CI range means that if you were to repeat the same clinical trial a hundred times you can be sure that 95% of the time the results would fall within the calculated range of 27-51. Wider intervals indicate lower precision; narrow intervals show greater precision.

42. P Value • P value refers to the probability that any particular outcome would have arisen by chance. (The smaller the P value the less likely the data was by chance and more likely due to the intervention.) Standard scientific practice, usually deems a P value of less than 1 in 20 (expressed as P=.05) as "statistically significant". The smaller the P value the higher the significance.

43. Sensitivity & Specificity • Sensitivity: measures the proportion of patients with the disease who also test positive for the disease in this study. • Specificity: measures the proportion of patients without the disease who also test negative for the disease in this study. • Sensitivity and specificity are characteristics of the test but do not provide enough information for the clinician to act on the test results.

44. Likelihood Ratio • Likelihood ratios: expresses the relative likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that the same result would be expected in a patient without that disorder

45. Prognostic Factor • Prognostic Factor is a patient characteristic that can predict that patient's eventual outcome: • demographic: e.g. age, sex, weight • disease-specific: e.g. tumor stage • comorbid: other co-existing conditions

46. Relative Risk • Relative Risk is the risk of the adverse outcome in the exposed group divided by the risk of the adverse outcome in the unexposed group.

47. Odds Ratio • Odds Ratio is the odds of exposure in patients who have the adverse outcome or bad event compared to the patients who do not have the adverse outcome or bad event. (An OR of 3.0 means that patients with the adverse outcome were 3 times more likely to have been exposed than were patients without the adverse outcome.)

48. Step 5- Application • Return to the patient (population) -- integrate that evidence with clinical expertise, patient preferences and apply it to practice

49. Evaluate Performance with Patient/Population • Did I ask the right question? • Were the necessary EBM resources readily available? • Did I know how to access and use them? • Was I able to obtain full text information? • Did I find a useful answer? • Did I actually use the findings in your clinical practice? • What could I have done better?

50. Conclusion • We will work with you one-on-one or in small groups at any time, any place • We will load clinical databases on your smartphone • We will sign you up for the DailyPoems • We stay open 24/7. Residents should have access to the basement with an ETSU idea card during the hours the library is closed