Evidence-Based Medicine in Clinical Practice. Title Page Dr. Harry Gee Dr. Chisale Mhango

"Every intervention is a two-edged sword." Iain Chalmers Quotation: interventions are meant to be beneficial but have side-effects. These can outweigh the benefits. The only way to know is be conducting properly controlled trials.

Practice Pradigms New paradigm Old paradigm Unsystematic clinical experience Pathophysiology Content expertise & authoritarianism New paradigm Systematic clinical experience Pathophysiology necessary but not sufficient Rules of evidence Pathophysiology is frequently implicated in clinical decision making. It often relies on intermediate outcomes, not key clinical outcomes that are of importance to patients. When unsupported by clinical studies, it may lead to erroneous decisions. For example, infection is a pathophysiological feature of SROM and antibiotics should help but in practice some antibiotics increased neonatal complications (NEC). This illustrates a recurrent theme in EBM - choice of patient centred outcome (mortality, morbidity, quality of life ect) rather than disease centre outcomes such as stopping of arrhythmias, or fall in serum rhubarb level, is a key feature.

Pre-Requisites Questioning Desire for Improvement The Knowledge Gap Honesty Humility Discerning What is merely custom and practice? Desire for Improvement These key steps will be repeated again and again throughout the day. 4

Our Aims Understand EBM What is it? Why do we need it? What are the benefits? Who benefits? Clear exposition of the purpose of Module 5

Our Objectives The key steps: Formulate a clinical question Search the literature Efficiently Confidently Appraise the evidence Apply the evidence What we want to achieve.

What is EBM?

Good Clinical Practice Knowledge from best external evidence based on clinical research Judgement from experience. Understanding of patient's beliefs & preferences. Definition: We need to contextualise this regarding the practice in Malawi. Thus, external evidence may not work, e.g. Ext Ceph Version is of proven value but only if pregnant women are being seen at a time when it can be performed (in the evidence to date - 36 weeks). If not, there is not the opportunity to employ it and this seems to be the current state of affairs in Malawi. We also need to refer back to Module 2 for values when adapting bullet point 3 - local patient beliefs and preferences. Sackett 1996

Who Benefits?

Evidence Based Medicine Conscientious, explicit and judicious use of current best evidence in making decisions about the care of an individual patient This takes evidence beyond studies and statistical analysis to applying evidence to the needs of the individual patient. This is the crux of practice. WHAT IS BEST FOR THIS PATIENT I HAVE TO TREAT? Sackett. BMJ 1996;312:311-2

EBM for the Clinician Knowledge & Skills Proficiency Application PRACTICE Confidence This Module will supply the skill but they need to be PRACTICED - only, then, will proficiency be achieved.

The 5 Steps Towards Evidence Based Practice 1. Ask the right clinical question: Formulate a searchable question 2. Collect the most relevant publications: Efficient Literature Searching Select the appropriate & relevant studies 3. Critically appraise and synthesize the evidence. 4. Integrate best evidence with personal clinical expertise, patient preferences and values: Applying the result to your clinical practice and patient. 5. Evaluate the practice decision or change: Evaluating the outcomes of the applied evidence in your practice or patient. 12

Asking the Right Questions This is all important.

Etiognostic Research Diagnostic Research Prognostic Research Clinical Process and knowledge requirements Research evidence sought from literature searches Etiology knowledge about causation Etiognostic Research Patient presentation knowledge about diagnosis Testing History Examination Investigations Diagnostic Research Diagnosis knowledge about prognosis This summarises practice and how research fits in. Prognostic Research Therapy Changes prognosis Therapy Research knowledge about therapeutic effectiveness Clinical outcome

The Question - Why is it so Important? A good answerable question will help us focus on evidence that is relevant to a patient’s clinical needs, (or your own knowledge needs). They can suggest high yield search strategies They can suggest the forms that useful answers might take (i.e. what is best research design to answer our question) Self- exaplanatory

Formulating Clinical Questions There is no right or wrong way to turn a scenario/knowledge need into a question. Just make sure it is concise, clinical and uses appropriate language (avoid colloquialism, in favour of technical language). Ask one question at a time. Simple guidance

PICO(D) Population Intervention Comparison Outcome (Design) They have seen this before. I want to develop the D part - awareness of appropriate DESIGN when evaluating papers. 17

Select best evidence Question Appropriate Study Type Up to Date Relevant Focussed Appropriate Study Type Up to Date Selecting he best papers available. 18

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? Brainstorm! Get participants to say what they think. Note it down on a flipchart. Do not make any comments whether positive or negative about their thoughts. Once you have collected reasonable number of thoughts over 2 minutes move to the next slide.

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% Why do WE need to have critical skills? Even in the best journals, only a minority are high quality publications. Nearly all research studies have faults - if not all. We have to be able to identify these and judge their impact on the result. Otherwise we cannot apply the results to our practice with any confidence.

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. 31

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

Performance Competence Proficiency Knowledge Skills Application PRACTICE Confidence Performane - Competency AND Proficiency. 44

Are We Together ???