2. Evidence Based Medicine Workshop Diagnosis March 18, 2010

4. Objectives - Diagnosis At today’s end you’ll be able to… –consider rationale for diagnosis –define and calculate test characteristics –state the ideal research design for studying diagnostic tests –critically appraise articles about diagnostic testing

5. Seemingly Dumb Question… Why make a diagnosis?

6. Why Diagnose? Heart Failure Therapy / Prognosis

7. What are advantages and disadvantages of diagnostic testing?

8. Diagnostic Testing Advantages –can assess parameters beyond the 5 senses –can be more ‘objective’ than clinical data Disadvantages –test results can be incorrect –test results may lead you in the wrong direction –tests cost money –tests may confer risk –some diseases have no diagnostic test –tests may add little to what is already known

9. Issues in Diagnostic Testing Invasiveness –urine sample versus brain biopsy versus autopsy Cost –glucoscan strip ~ $1.00 versus MRI $900.00 Availability –hemogram versus Positive Emission Tomogram Patient Acceptability –urine sample versus 3 day fecal fat collection

10. Let’s Back Up…

11. What type of ‘testing’ is the cheapest, lowest risk, available anywhere, and needs no requisitions?

13. Clinical Scenario A 70 year old man –presents to the ED –1 hr x chest pain & shortness during 10 hr car trip PMH –prostate cancer Exam –distressed with splinting respiration (pleuritic cp) –HR 130 / min, RR 32 / min. What’s your working diagnosis?

15. Test for Pulmonary Embolism Gold Standard: pulmonary angiogram –invasive –costly –not readily available –risky Other tests: –D-dimer, V/Q scans, Spiral CT scan –? may be helpful in right setting with right results - complex

16. PE - diagnosis Pulmonary angiogram - gold standard

17. PE - diagnosis (spiral CT scan)

18. PE - diagnosis (V/Q scan) high probability V/Q scan (2 defects)

19. Pulmonary Thromboembolism

20. How well does the test perform? Welcome to the world of TEST CHARACTERISTICS

21. Take a deep breath...

22. Test Characteristics Sensitivity Specificity Positive predictive value Negative predictive value Accuracy Likelihood ratio

23. Individual A Cross-sectional survey: measure disease status & test status at same time point. Inidividual D Inidividual C Individual B D+ & T+ D+ & T- D- & T+ D- & T-

25. Hypothetical Test Results

26. Sensitivity Probability that test is positive given that disease is present. 80 / (80 + 10) = 88.9%

27. Specificity Probability that test is negative given that disease is absent. 90 / (90 + 20) = 81.8%

28. Sensitivity / Specificity Trade-off Sensitivity Decreases Specificity Increases

29. Test Characteristic Issues Highly Sensitive Tests: –tend to be less invasive, less risky, less costly –best for screening programs –best for ruling out disease: “SNOUT” Highly Specific Tests: –tend to be more invasive, more risky, more costly –best for confirming (ruling in) disease: “SPIN”

30. Positive Predictive Value Probability that disease is present given that the test was positive. 80 / (80 + 20) = 80.0%

31. Negative Predictive Value Probability that disease is absent given that the test was negative. 90 / (90 + 10) = 90.0%

32. Issue Sensitivity / Specificity versus Positive / Negative Predictive Values

33. Change Disease Prevalence from 90 to 110 per 200 prevalence = 110 / 200 = 0.55 = 55% (was 45%) sensitivity = 97.7 / 110 = 88.8% (unchanged) specificity = 73.6 / 90 = 81.7% (unchanged) positive predictive value = 86.5% (was 80%) negative predictive value = 85.8% (was 90%)

34. Accuracy (80+90) / (80+ 20 + 10 + 90) = 85.0%

35. Positive (test) Likelihood Ratio Ratio of: probability of positive test when disease is present -------------------------------------------------------------------- probability of positive test when disease is absent

36. Positive Likelihood Ratio (80 / 90) / (20 / 110) = 4.89

37. Utility of LR Pretest odds x Likelihood Ratio = Posttest odds Palpable 5.6 Screen 2.2

38. Critical Appraisal of an Article about Diagnosis Validity Results Applicability

39. Validity Primary Guides –Was there an independent, blind comparison with a reference standard? –Did the patient sample include an appropriate spectrum of patients to whom the diagnostic test will be applied in clinical practice? Secondary Guides –Did the results of the test being evaluated influence the decision to perform the reference standard? –Were the methods for performing the test described in sufficient detail to permit replication?

40. Results Are likelihood ratios for the test results presented or data necessary for their calculation provided? LRs >10  generate large changes from pre- to post-test probability; LRs 5-10  generate moderate changes in pre- to post-test probability; LRs 2-5  generate small (but sometimes important) changes in probability; LRs 1-2  alter probability to a small (and rarely important) degree.

41. Applicability Will the reproducibility of the test result and its interpretation be satisfactory in my setting? Are the results applicable to my patient? Will the results change my management? Will patients be better off as a result of the test?

44. Sensitivity:670 / 744 = 0.90 or 90% Specificity:640 / 842 = 0.76 or 76% PPV: 670 / 872 = 0.77 or 77% NPV: 640 / 714 = 0.90 or 90% Accuracy:(670 + 640) / 1586 = 0.83 or 83% Positive Likelihood Ratio (670 / 744) / (202 / 842) = 3.75

45. Let’s Design a Study…

46. End of the Line…