1. Critical Appraisal Articles about Therapy or Prevention Jeffrey P Schaefer MSc MD FRCPC March 26, 2007

2. Objectives After this session… –know where Critical Appraisal fits within the Evidence Based Medicine Paradigm –know how to Critically Appraise Articles about Therapy or Prevention using the McMaster Protocol (JAMA)

3. What’s Evidence Based Medicine?

4. What’s EBM? Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. DL Sackett BMJ 1996; 312: 71-2 Best Available Evidence Physician Experiences Patient Values System Values

5. Evidence Based Medicine Generate the Clinical Question –harm, diagnosis, therapy, prognosis, prevention Find Answers –unfiltered sources –> Medline –filtered sources -> Uptodate Critically Appraise the Answers –assess Validity, Results, Applicability Apply the Evidence –patient, physician, system values

6. Hierarchy of Evidence: Therapy or Prevention N of 1 randomized controlled trial Systematic reviews of RCTs A single RCT Systematic review of observational studies Physiological studies Unsystematic clinical observations

7. Critical Appraisal

9. Background Diabetes is prevalent Diabetes is associated with complications Rosiglitazone does good things with diabetes Can rosiglitazone prevent diabetes?

10. Methods Design –multicentre (191 sites, 21 countries) –randomized –matching placebo controlled –concealed

11. Methods Entry –30 years or older –impaired glucose tolerance and/or –impaired fasting glucose –exclude: diabetes (except gest), h/o cv disease, intolerance to ACE or TZD

12. Methods Intervention –rosiglitazone 4 mg od x 2 mo then 8 mg od –placebo –Notes: (factorial design with ramipril 15 mg od) all received lifestyle couseling

13. Methods - Outcomes Primary –incident diabetes or all-cause death Secondary –regression to normal fasting and 2 hr OGTT –composite and indivudual: CV events –composite individual: cardiorenal events Other –ALT, ECG, waist & hip circumference, ECG Measurements: at 2 months, then q 6 months

14. Results

20. Secondary and Subgroups How much should we care?

21. Subgroup analysis

25. Author’s Conclusions Addition of rosiglitazone to lifestyle … reduces the risk of developing diabetes by two-thirds NNT 1000 people, 3 years  144 cases Rosiglitazone treats dysglycemia

26. Critical Appraisal