1. Vanderbilt Sports Medicine Evidence-Base Medicine How to Practice and Teach EBM Chapter 5 : Therapy

2. “4S” Organization of Evidence

3. Assessing Individual Studies Are the results VALID ? Are the results IMPORTANT ? Are the results APPLICABLE ?

4. Are The Results Valid? Was the assignment of patients to treatment randomized? - Randomization balances the treatment groups - Randomization balances the treatment groups for prognostic factors for prognostic factors - Mention of randomization usually made in title - Mention of randomization usually made in title or abstract or abstract - If study not randomized, move on to next study, - If study not randomized, move on to next study, unless… unless…

5. … no randomized trials found Then, options are: 1. Check search methods 1. Check search methods 2. Determine whether treatment effect is so large 2. Determine whether treatment effect is so large that false-positive results are unlikely (rare) that false-positive results are unlikely (rare) 3. Accept conclusion if study treatment determined 3. Accept conclusion if study treatment determined to be useless or harmful to be useless or harmful 4. Consider “n-of-1” trial 4. Consider “n-of-1” trial 5. Try to find evidence of another management 5. Try to find evidence of another management option option

6. Are The Results Valid? Was the assignment of patients to treatment randomized? Was the randomization concealed? Were the groups similar at the start of the trial? of the trial? - “Confounders” avoided or adjusted - “Confounders” avoided or adjusted for for

7. Are The Results Valid? Was the assignment of patients to treatment randomized? Was the randomization concealed? Were the groups similar at the start of the trial? Was the follow-up of patients sufficiently long and complete? sufficiently long and complete? - “Worst case” analysis – 20% - “Worst case” analysis – 20%

8. Are The Results Valid? Was the assignment of patients to treatment groups randomized? Was the randomization concealed? Were the groups similar at the start of the trial? Was the follow-up of patients sufficiently long and complete? Were all the patients analyzed in the groups to which they were randomized? - “Intention-to-treat” analysis - “Intention-to-treat” analysis

9. Are The Results Valid? Was the assignment of patients to treatment randomized? Was the randomization concealed? Were the groups similar at the start of the trial? Was the follow-up of patients sufficiently long and complete? Were all the patients analyzed in the groups to which they were randomized? Were patients, clinicians, and study personnel kept blind to treatment?

10. Are The Results Valid? Was the assignment of patients to treatment randomized? Was the randomization concealed? Were the groups similar at the start of the trial? Was the follow-up of patients sufficiently long and complete? Were all the patients analyzed in the groups to which they were randomized? Were patients, clinicians, and study personnel kept blind to treatment? Were groups treated equally, apart from the experimental therapy? - Prevents “co-interventions” in one group - Prevents “co-interventions” in one group

11. Are The Valid Results Of This Individual Study Important? What is the magnitude of the treatment effect? Event = Stroke 5 Years Control Rate Experimental Rate Relative Risk Absolute Risk Number Needed (CER) (EER) Reduction Reduction To Treat (CER) (EER) Reduction Reduction To Treat (RRR) (ARR) (NNT) (RRR) (ARR) (NNT) |CER-EER|/CER |CER-EER| 1/ARR |CER-EER|/CER |CER-EER| 1/ARR 5.7% 4.3% 25% 1.4% 72 5.7% 4.3% 25% 1.4% 72 (.014) (.014).000057%.000043% 25%.000014% 7,142,857.000057%.000043% 25%.000014% 7,142,857 (.00000014) (.00000014)

12. Are The Valid Results Of This Individual Study Important? What is the magnitude of the treatment effect? How precise is this estimate of the treatment effect? - NNTs are estimates of the truth - NNTs are estimates of the truth - Confidence Interval quantifies the - Confidence Interval quantifies the uncertainty in measurement; usually uncertainty in measurement; usually reported as “95% CI”, meaning the range reported as “95% CI”, meaning the range of values within which one can be 95% of values within which one can be 95% sure that the true value for the whole sure that the true value for the whole population lies population lies

13. EBM calculator www.cebm.utoronto.ca www.cebm.utoronto.cawww.cebm.utoronto.ca - “EBM TOOLBOX” - “EBM TOOLBOX”

14. Are The Valid, Important Results Of This Individual Study Applicable To Our Patient? Is our patient so different from those in the study that its results cannot apply? Is the treatment feasible in our setting? What are our patient’s potential benefits and harms from the therapy? (“decimal fraction”) What are our patient’s values and expectations for both the outcome we are trying to prevent and the treatment we are offering? - “likelihood of being helped and harmed” (LHH) - “likelihood of being helped and harmed” (LHH) LHH =(1/NNT) : (1/NNH) LHH =(1/NNT) : (1/NNH) = 1/72 : 1/5000 = 1/72 : 1/5000 = 70 times more likely to be helped than harmed = 70 times more likely to be helped than harmed - LHH may also take into account the decimal fraction - LHH may also take into account the decimal fraction - LHH may also account for patient’s individual, self-assessed - LHH may also account for patient’s individual, self-assessed “severity” rating “severity” rating

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