Evidence Based Medicine

October 21, 2008 Mount Royal College Jeffrey P Schaefer, MD

Objectives • After this session – describe EBM process – understand the role of Critical Appraisal dr.schaeferville.com

What’s Evidence Based Medicine?

“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 Patient, Provider, and System Values

Evidence Based Medicine Process 1. Formulate a Clinical Question 2. Search for Evidence 3. Critically Appraise the Evidence 4. Apply the Evidence • Store what was learned • Assess the effects of decisions

Clinical Process • patient presents a problem (chief complaint) • history – describe the problem – risk factors for diseases are considered – test diagnostic hypotheses • physical examination • investigations • diagnosis • therapy / prevention • prognosis • harm

Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

Five Clinical Questions • harm?

• prevention?

• diagnosis?

• therapy?

• prognosis?

hypertension

Question ID: CC: 75 year old male ‘get my blood pressure checked out’ HPI: was at the mall, BP was 195 / 80 mmHg no symptoms PMH:negative FH: negative PSH: non-smoker, non-drinker Med: none (including over the counter medication) Allergy: negative ROS: negative

Question Physical Examination general: VS: well 180 / 75 mmHg, 82 /min derm: normal HNEENT: normal Chest: CVS: normal normal Abdo: GU: Neuro: MSK normal normal normal normal

Question Diagnosis: primary isolated systolic hypertension Patient asks, “should I be on something?”

Five Clinical Questions • harm?

• prevention?

• diagnosis?

• therapy?

• prognosis?

(hypertension is the disease in this case)

Question “should he be on something?”

Question • Making a good question better… • Include – patient – intervention (exposure) – outcome – alternative

Formulating the Clinical Question: case 1 • patient / problem: – elderly person with isolated systolic hypertension • intervention / exposure – anti-hypertensive therapy • alternative – no therapy (or placebo in clinical trials) • outcomes (desired / undesirable) – cardiovascular outcomes / adverse effects / cost

Formulating the Clinical Question: case 1 “What is the effect of anti-hypertensive therapy on cardiovascular outcomes among elderly patients with isolated systolic hypertension when compared to no treatment?”

Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

Gathering Evidence What’s your 411?

Gathering Evidence

Gathering Evidence • Browsing • Problem Solving

Gathering Evidence • Filtered • Unfiltered

Diagnosis --> Cross Sectional Design Harm --> Cohort or Case Control Prognosis --> Cohort Therapy - Prevention --> RCT or Systematic Review

Therapy / Prevention Heirarchy • N of 1 randomized controlled trial • Systematic reviews of RCTs •

A single RCT

• Systematic review of observational studies • Physiological studies • Unsystematic clinical observations

Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

Critical Appraisal www.cche.net

validity results applicability

Critical Appraisal: Therapy / Prevention • Validity: – random allocation? – subject accounting?

– follow-up complete? – intention to treat analysis? – concealment?

– group similarity?

– similar treatment except for intervention?

Experimental baseline time Experimental post intervention

Population with Condition

Eligible

(entry and exclusion criteria)

allocation Control baseline time Control post intervention

• Typical Controlled Clinical Trial Design

stroke rate What if… % smoker % smoker % smoker Bias New 5% Current 10% 30 50 30 30 30 50

Heart Outcomes Prevention Evaluation Trial Lancet 2000

Critical Appraisal: therapy / prevention • Were patients analyzed in the group to which they were randomized? • Intention to treat • Explanatory analysis

intention to treat analysis explanatory analysis Consider: adjuvant therapy for breast cancer 200 patients --> 100 adjuvant ----> only 80 receive 100 control-------> all 100 receive ITT: outcome/100 (adjuvant) VERSUS outcome/100 (control) Exp: outcome/80 (adjuvant) VERSUS outcome/120 (control) ITT preferred:

not receiving adjuvant is a risk of adjuvant tx

Critical Appraisal: therapy / prevention

• Results

–Magnitude of effect?

• how large is the effect –Precision of measurement?

• confidence interval

Critical Appraisal: therapy / prevention • Applicability – apply to my patient(s)?

– were all important outcomes considered?

– treatment worth the risk / cost?

What Critical Appraisal is Not...

• It’s not about trashing an article – something can be learned from every article, even if it’s how to design a better trial!

• It’s not about black and white answers – most studies have strengths and weaknesses – some articles are highly edited • It’s not the only reason to embark on a course of action – other factors to consider (harm, cost, patient values)

Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

Applying the Evidence • EBM does not replace patient values • EBM enhances patient decision making

Applying the Evidence • Antibiotics in pneumonia – good evidence to support antibiotics – antibiotics for a palliative care patient may not be appropriate depending on the patient (or surrogate decision maker’s) preferences • Numerous difficult questions – feeding tube in the setting of stroke – palliative chemotherapy, radiation, surgery – treating serious disease in children

Why EBM?

• Good Ole Days… – clinical trials were sparse – treatment based on ‘common sense’ – risks / benefits unknown

Volume 292 January 2, 1975

Number 1

• • • • • •

Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease Immunoblastic lymphadenopathy with mixed cryoglobulinemia. A detailed case study Vinyl-chloride-induced liver disease. From idiopathic portal hypertension (Banti's syndrome) to Angiosarcomas Hodgkin's Disease, tonsillectomy and family size Reduction of ischemic injury by nitroglycerin during acute myocardial infarction (no abstract available) Frederick Stohlman, Jr., M.D

Risk / Benefit • Trephination • Vaccination

Previous Paradigm...

• Example – Premature Ventricular Complexes (PVCs) are a risk factor for Ventricular Fibrillation (V fib), – Suppressing PVC  Reduce V-fib

PVC’s (R on T) ---> V Tach --> V Fib

Previous Paradigm • CAST (cardiac arrhythmia suppression trial) found that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. N Engl J Med 1989; 321: 406-412.

Examples of Disparity...

• Atrial Fibrillation (AF) – Atrial fibrillation is a risk factor for stroke – Warfarin anticoagulation significantly reduces risk of stroke among those with atrial fibrillation • Q: Is warfarin prescribed for those with AF?

• A: Lancet 1998;352:1167-1171 • Among 26 practices in the UK, 49% of those with AF missed out on therapy.

EBM Criticisms • EBM is cookbook medicine • EBM is the knife of the cost cutter • EBM is impractical for the front line • EBM cannot substitute for experience

Therapy

Had enough?