1. November 5, 2014 Matthew Tuck, MD Hospitalist, Veterans Affairs Medical Center Assistant Professor of Medicine, George Washington University

2. http://www.npr.org/2014/04/18/304140932/born-with-hiv- building-a-future

3.  Take a minute to think about…  What this story made you feel?  What this story made you think?  What questions you have after listening to this story?

6. Ann Intern Med. 2002;136(12):888-895.

7.  Recognize the importance of practicing evidence-based medicine  Develop a systematic approach to practicing evidence- based medicine  Calculate absolute risk reduction, relative risk, relative risk reduction, and number needed to treat

9. Ask Assess Apply Appraise Acquire

10. 1. Ask: Convert the need for information into an answerable question. 2. Acquire: Track down the best evidence with which to answer that question. 3. Appraise: Critically appraise the evidence for its validity, impact, and applicability. 4. Apply: Integrate the evidence with our clinical expertise and our patient’s characteristics and values.

12. Background Question Foreground Question TYPE OF QUESTION CLINICAL EXPERIENCE

14.  Background  Foreground

15.  Cristina and Chris are sexually active. Chris is HIV negative. They are wondering what treatments are available to help Chris from contracting HIV while maintaining a sexual relationship. What do you tell them?

17.  Cristina and Chris are sexually active. Chris is HIV negative. They are wondering what treatments are available to help Chris from contracting HIV while maintaining a sexual relationship.  P = HIV serodiscordant couples  I = Antiretroviral prophylaxis  C = Standard medical care, placebo  O = HIV seroconversion

18. 1. Ask: Convert the need for information into an answerable question. 2. Acquire: Track down the best evidence with which to answer that question. 3. Appraise: Critically appraise the evidence for its validity, impact, and applicability. 4. Apply: Integrate the evidence with our clinical expertise and our patient’s characteristics and values.

20.  Not all evidence is created equal  A heirarchy of evidence guides clinical decision making  Evidence alone is never enough  Competent physicians balance risks and benefits of management strategies in the context of patient values and preferences

21. Experimental Observational

22.  P = HIV serodiscordant couples  I = Antiretroviral prophylaxis  C = Standard medical care, placebo  O = HIV seroconversion

24. 1. Ask: Convert the need for information into an answerable question. 2. Acquire: Track down the best evidence with which to answer that question. 3. Appraise: Critically appraise the evidence for its validity, impact, and applicability. 4. Apply: Integrate the evidence with our clinical expertise and our patient’s characteristics and values.

26.  Absolute Risk = Event Rate  The number of people experiencing an event as a proportion of the total number of people in a population  Key Words  Divide if you see  Relative  Ratio  Subtract if you see  Absolute  Difference  Reduction

27.  200 pre-schoolers  100 pre-schoolers were randomized to drug X vs. 1o0 pre-schoolers to placebo for prevention of nose picking  10 kids receiving drug X still picked their noses  15 kids receiving placebo still picked their noses

28.  Drug X event rate = 10%  Placebo event rate = 15%  There are only two things we can do to these numbers  Subtract, or  Divide

29.  15% - 10% = 5%  What does this number represent?  Absolute Risk Reduction (ARR) or Risk Difference  Arithmetic difference between 2 event rates  We refer to the risk of the adverse outcome in the control group as the baseline risk Baseline Risk Experimental Risk

30.  10% = 0.67 15%  What does this number represent?  Relative risk (RR)  Synonym = Risk Ratio  The proportion of the baseline risk that is still present when patients receive the experimental treatment Baseline Risk

31.  “What proportion of the baseline risk has been reduced by the experimental treatment?”  RRR = 1 – RR = 1 – 0.67 = 0.33 = 33% OR  RRR = ARR/baseline risk = 5%/15% = 0.33 = 33%

32. 50 25 10 5 2 1 ARR: RRR: 25% 50% 5%1% Control Exper.

33.  NNT = 1/ARRWhy?  If ARR = 5%...  Treating 100 people reduces outcome in 5; How many do I need to treat to help 1?  Answer = 20 100 ? 5 1

36. Outcome Yes Outcome No TDF-FTC Placebo

37. Outcome Yes Outcome No TDF-FTC13/1576 Placebo

38. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo

39. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo52/1578

40. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo52/15781526/1578

41. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo52/15781526/1578 ARR = 52/1578 – 13/1576 = 0.025

42. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo52/15781526/1578 RRR = 1 – 0.25 = 0.75

43. Outcome Yes Outcome No TDF-FTC13/15761563/1576 Placebo52/15781526/1578 NNT = 1/ARR = 1/0.025 = 40

44. 1. Ask: Convert the need for information into an answerable question. 2. Acquire: Track down the best evidence with which to answer that question. 3. Appraise: Critically appraise the evidence for its validity, impact, and applicability. 4. Apply: Integrate the evidence with our clinical expertise and our patient’s characteristics and values.

46. Matthew Tuck, MD Matthew.Tuck@va.gov 202-745-8000 x53994