Evidence Base Medicine A.A. Karimi MD.

EBM Sciences Clinic

“A 21st century clinician who cannot critically read a study is as unprepared as one who cannot take a blood pressure or examine the cardiovascular system.” BMJ 2008:337:704-705

Dr. Sackett defines EBM as: A BRIEF HISTORY 1990: McMasters University in Ontario, Canada Dr. David Sackett and colleagues proposed Evidence Based Medicine (EBM) as a new way of teaching, learning and practicing medicine. Dr. Sackett defines EBM as: “…The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.”

What is Evidence-Based Medicine? “Evidence-based medicine is the integration of best research evidence with clinical expertise and patient values

Evidence Based Medicine Patient Values Medical Decision Clinical Expertise Research Evidence

Values, Concerns Preferences, Expectations PATIENT Values, Concerns Preferences, Expectations Life predicament EBM INFORMATION Clinically relevant Proven by research Best up-to-date evidence PHYSICIAN Training & Experience Current Expertise Continued learning Demand for proof

THE FIVE BASIC STEPS OF EBM 1.Clinical Question Patient-focused, problem-oriented 2. Find Best Evidence Literary Search 3. Critical Appraisal Evaluate evidence for quality and usefulness 4. Apply the Evidence Implement useful findings in clinical practice 5. Evaluate The information, intervention, and EBM process

The MOST IMPORTANT step! The Clinical Question PICO ???????? The FIRST step The HARDEST step The MOST IMPORTANT step! RCT

Formulate your clinical question: Patient or Population Be specific Intervention Comparison Group i.e. standard therapy, “gold standard” Outcome of Interest i.e. efficacy of therapy, mortality, specificity of diagnostic test

EBM QUESTION: Should include multiple factors (Examples) P PATIENT type of patient or population Ex: 47 yr male w/DM2 and cellulitis toe, 25 yr female w/DVT and chest pain I INTERVENTION clinical intervention Ex: medication, procedure, test, surgery, radiation, drug, vaccine C COMPARISON compare alternative treatment Ex: other prior, new or existing therapy O OUTCOME clinical outcome of interest Ex: Reduced death rate in 5 yrs, decreased infections, fewer hospitalizations

In the following questions, identify the missing component: Is oral rehydration in the emergency room more cost-effective than IV rehydration? Patient/Population Not identified. Examples: infants, infants with vomiting. Intervention Oral rehydration. Comparison IV rehydration. Outcome Cost-effectiveness.

Will atrovent help prevent hospitalization of my 2 year old patient with an acute asthma exacerbation? Patient/Population Child w/ acute asthma Intervention Atrovent Comparison Not identified. Examples: standard therapy, albuterol alone. Outcome Prevent hospitalization.

Classify the Clinical Question into Domain Therapy Randomized controlled trials or meta analyses Diagnosis Sensitivity and specificity, predictive value, diagnostic errors Prognosis Cohort studies, survival analysis Harm or Casualty Case control studies, cohort studies

Research Study Design

Research Design Diagnostic tests Cross sectional study Prognosis Therapy Patients’ Preferences Cross sectional study Cohort study RCT Qualitative research Research design BMJ 1997;315:1636

What resources could be searched?

Why Should We Be Critical in Our Reading of the Literature?

Quality of the Medical Literature Journal High Quality Articles N Eng J Med 17% Ann Intern Med 13% JAMA 12% BMJ 9% Lancet 8%

What do we mean by Research Quality?

Quality of a Study The confidence that the study design, conduct and analysis has minimized biases in addressing the research question The better the quality, the higher is the likelihood that the results produced in the study are credible Self explanatory

Quality of a Study Validity Bias The degree to which the results of an observation are correct for the patients being studied. Bias A process that tends to produce results that depart systematically from the true values existing in the study population. Fletcher et al, 1988; Murphy, 1976 Important concepts when appraising papers.

Bias Conscious Unconscious Conflict of Interest

The Hawthorne Effect What is it?

Hawthorne Effect Outcomes changed By virtue of doing the study Irrespective of the intervention

Hierachy of Evidence Experimental studies Randomized controlled trials Controlled Observational studies Case-control studies Uncontrolled Observational studies Case series Case reports Sacks et al. Am J Med 1982;72:233-240; Cook et al. Chest 1992;102:305s-311s; Guyatt et al. JAMA 1993;270:2598-2601 Levels of quality. Why? BIAS - greater as we come down the hierachy.

EBM Basic Skills Critically appraise GATE Frame RAMMbo CASP CAT maker Formulate structured clinical question PICO(D) Search for evidence Systematic Select best evidence Critically appraise GATE Frame RAMMbo CASP CAT maker The tools under 'Critically appraise" are hyperlinked so that they can be demonstrated, if necessary - not essential. 29

AT-A-GLANCE Acronym Title Aim Groups Limbs – Intervention v Comparator Absolute Risk Reduction Number Needed to Treat (NNT) Clinical Conclusion Education for patients/carers

AT-A-GLANCE Acronym: is there a study name? as a mnemonic Title: Full title, authors, institute, journal, full reference Aim: specific aim of the study and why, what outcomes were used? Groups: who were the research subjects, inclusion criteria, exclusion criteria, who excluded by chance or bias Limbs – Intervention v Comparator, ? Versus placebo, ? Blinded, how randomised, Absolute Risk Reduction: What the main results?, what the main results on the outcomes studied, other main results, ? Side-effects, other harm events Number Needed to Treat (NNT): How many people do you need to treat to have one beneficial effect? Eg how many people to save a life? How many treated to have side-effects? Clinical Conclusion: What are the main clinical conclusions for you and the team? Can the results be implemented locally? ? Change in guideline needed? ? Clinical audit needed? Education for patients/carers: How can you explain the results to a patient/guardian prior to consent and explanation? State what you will actually say eg “Research has shown that………what do you think?”

Guidelines

Levels of evidence Level Type of evidence I Evidence obtained from at least one randomised controlled trial or from meta-analysis of randomised controlled trials II Evidence obtained from at least one well-designed controlled study without randomisation III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities This will be seen in guidelines. Remember- we still have to be critical about the primary studies - even RCTs and Systematic Reviews can be flawed!

Grading of recommendations Grade Recommendation A (Evidence level I) Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation B (Evidence levels II, III) Requires availability of well-conducted clinical studies but not randomised clinical trials on the topic of recommendation C (Evidence level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality Again - will be seen in guidelines.

To Summarise

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem This is a schematic exposition of the process.

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem Develop answerable questions This is a schematic exposition of the process.

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem Develop answerable questions Search and obtain relevant articles This is a schematic exposition of the process.

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem Develop answerable questions Search and obtain relevant articles This is a schematic exposition of the process. Critical appraisal of evidence

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem Develop answerable questions Decision making about diagnosis & treatment Search and obtain relevant articles This is a schematic exposition of the process. Critical appraisal of evidence

Experience & Pathophysiology Summary Expertise, Experience & Pathophysiology Clinical problem Develop answerable questions Decision making about diagnosis & treatment Search and obtain relevant articles This is a schematic exposition of the process. Critical appraisal of evidence

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