Critical Appraisal Articles About Therapy or Prevention A Bornstein, MD FACC March 26, 2017

Objectives After this session…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)

What’s Evidence Based Medicine?

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 on the basis of:Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients on the basis of: 1)Available evidence 2)Physician experiences 3)Patient values 4)System values DL Sackett BMJ 1996; 312: 71-2

Evidence Based Medicine 1)Generate the clinical question (PICO) –Harm, diagnosis, therapy, prognosis, prevention 2)Find answers –Unfiltered sources  Medline –Filtered sources  Up-to-date 3)Critically appraise the answers –Assess the results for validity, applicability 4)Apply the evidence –Patient, physician, system values

Hierarchy of Evidence: Therapy or Prevention N of 1 randomized controlled trialN of 1 randomized controlled trial Systematic reviews of RCTsSystematic reviews of RCTs Single RCTSingle RCT Systematic review of observational studiesSystematic review of observational studies Physiological studiesPhysiological studies Unsystematic clinical observationsUnsystematic clinical observations

Critical Appraisal

Background Diabetes is prevalentDiabetes is prevalent Diabetes is associated with complicationsDiabetes is associated with complications Rosiglitazone does good things with diabetesRosiglitazone does good things with diabetes  Can rosiglitazone prevent diabetes?

Methods DesignDesign –Multicenter (191 sites, 21 countries) –Randomized –Matching placebo controlled –Concealed

Methods Entry criteria:Entry criteria: –30 years old or older –Impaired glucose tolerance and/or –Impaired fasting glucose Exclusion criteria:Exclusion criteria: –Diabetes (except gestational) –CVD history –Intolerance to ACE or TZD

Methods InterventionIntervention –Rosiglitazone 4 mg QOD x 2 months; then 8 mg PO QOD –Placebo –Notes:  (Factorial design with ramipril 15 mg PO QOD)  All received lifestyle counseling

Outcomes PrimaryPrimary –Incident diabetes or all-cause death SecondarySecondary –Regression to normal fasting and 2 hr OGTT –Composite and individual: CV events –Composite individual: cardiorenal events OtherOther –ALT, ECG, waist & hip circumference, ECG Measurements: at 2 months, then Q 6 monthsMeasurements: at 2 months, then Q 6 months

Results

Control Versus Placebo Patient Populations

Secondary and Subgroups How much should we care?How much should we care?

Subgroup Analysis

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

Critical Appraisal