Introduction to Evidence Based Medicine

Introduction to Evidence Based Medicine Outline 1. Introduction: what is EBM 2. The steps in evidence based practice 3.An example 4. Reflection and further information Chaisiri Angkurawaranon Department of Family Medicine Question: Which is it? A or B A The doctor is there to give the patients all the information that the patient needs in order that the patient can make a decision, and the doctor should then implement that decision once the patient has made it B The patient is there to give the doctor all the information that the doctor needs in order that the doctor can make a decision, and the patient should then implement that decision once the doctor has made it We will come back at the end of class Why EBM A 21 st century clinical who cannot critically read a study is as unprepared as one who can not take a blood pressure or examine the cardiovascular system Evidence based medicine and the medical curriculum. BMJ 2008: 337: 704-705 Evidence Based Medicine EBM EBM is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research." (Sackett D, 1996) The basic skills of using (not doing) research searching, appraising and applying to individual patients 1

EBM EBM is the integration of clinical expertise, patient values, and the best evidence into the decision making process for patient care. Clinical expertise refers to the clinician's cumulated experience, education and clinical skills. The patient brings to the encounter his or her own personal and unique concerns, expectations, and values. The best evidence is usually found in clinically relevant research that has been conducted using sound methodology. (Sackett D, 2002) Example 1 A patient come to the clinic with fresh dog bite It looks clean It is necessary to give prophylactic antibiotics Yes No Example 1 A meta analysis indicated that the average infection rate for dog bites was 14% and that antibiotics halved the risk Would you give prophylactic antibiotic What skills are needed for a clinician to to apply such evidence? 2. Steps in EBM 2.1 Formulate an answerable question --ASK 2.2 Track down the best evidence of outcomes available-- ACQUIRE 2.3 critically appraise the evidence (how good and what it means) APPRAISE 2.4 apply the evidence-- APPLY Results + clinical expertise + patient values 2.5 Assess outcome- ASSESS Cummings P(1994) Antibiotics to prevent infection in patients with dog bite wounds: A meta-analysis of randomized control trials. Annals of Emergency Medicine 23: 533-40 Exercise In small groups: Write down some clinical questions or problems that you think a doctor may face Don t think too hard Can use your own experience or family experience Question Common Types of clinical Question What should I do about this condition or problem What is the cause of the problem Does this person have the condition or problem? Question type Intervention Aetiology and risk factors Diagnosis http://www.mathgoodies.com/calculators/random_no_custom.html Who will get the condition or problem How common is the problem What are the types of problems Prognostic and prediction Frequency and rate Phenomena or thoughts 2

Background questions Asked for general knowledge about a disorder Has two essentials components: a question root ( who, what, where, how, why) with a verb a disorder Background questions What are the symptoms and signs of someone presenting with MI? What are the diagnosis tests for MI? What are the causes of MI? What are the treatments for MI Textbooks answer background questions, they contain collected & synthesized wisdom for topics that do not change often. Clinical questions (Foreground questions) Step ins EBM 1.Formulate an answerable question - ASK Know your background Asked for specific knowledge about managing patients with a disorder It has 4 components (PICO analysis): P - Patient/ I - Intervention C - Comparison O - The relevent people in relation to the clinical problem Intervention, exposure or test that you want to find out about in relation to the clinical problem The alternative, control strategy, exposure or test for comparison with the one you are interested int What you or your patient is concerned about happening (or not happening) PICO Example PICO Example You ask your patient, a long term smoker, if he is interested in smoking He said he has tried unsuccessfully in the past His friend successfully quit with acupuncture, should he try? The interventions you are used to are nicotine replacement therapy and antidepressants Long term smoker Acupuncture Placebo or nicotine replacement or antidepressant Quit smoking (at 3-6 months? The clinical question: Does acupuncture, compared with other interventions, improve the chance of quitting smoking in long term smokers? Your friend wants to discuss with you the possibility of getting a vasectomy He heard that vasectomy can cause testicular cancer in later life Although you know that the risk is low, he wants to know the precise answer Adult males vasectomy No vasectomy Testicular cancer The clinical question: Does vasectomy increase the risk of getting testicular cancer in the future? 3

PICO Example Your Own Question A baby was born premature at 35 weeks. Her parents ask about her chances of developing deafness Premature baby deafness The clinical question: In infants born prematurely, what is the frequency (prev) of deafness? Step 2: tracking down the best evidence (ACQUIRE) Tracking the best evidence (intervention) Does this intervention help Step 1 (Level 1) Step 2 (Level 2) Step 3 (Level 3) Step4 (level 4) Step 5 (level 5) Systematic review of randomized trials or n-of-1 trials RCT or observational study with dramatic effect Non-randomized controlled cohort/follow up study Case-series, case control studies or historically controlled studies Mechanism-based reasoning A hierarchy of the LIKELY best evidence, OCEBM (Oxford centre for EBM) "The Oxford 2011 Levels of Evidence". Level of evidence Does not give a definitive judgment about the quality of evidence. Lower level evidence can still provide stronger evidence than a higher level study (example vegetable consumption and pancreatic cancer cohort vs systematic review) WILL NOT PROVIDE YOU WITH A RECOMMNATION, even if the treatment are supported by best evidence must consider Patient is similar to study Clinical benefit outweighs harms? Is another treatment better Are patient s values and circumstances compatible with treatment Levels can NOT tell you whether you are asking the right questions. If you interpret meningitis as the flu, finding best treatment for flu will not help 2. Choosing resources Pubmed or medline EMBASE/OVID Cochrane Library Web of science Subject advantages Disadvantages Biomedicine and clinical medicine. Veterinary medicine. Biomedicine and clinical medicine. Veterinary medicine. Clinical interventions only Gold standard systematic reviews Science, social sciences, arts & humanities General coverage of most academic disciplines. Free Good N. American coverage Links to some full-text Very good for pharmaceutical information Good European coverage Full text systematic reviews Free in many countries Can search reference lists and see who has cited articles of interest. Contains details of citation rates, H-index and other statistics Only covers journal articles North American bias Only covers journal articles European bias Information on interventions only Not as in-depth as the more subject specific resources. No subject headings/thesaurus searching available. Interface does not cope with very long, complex search strategies 4

Choosing Resources Google does not search every website in the world. This often includes the contents of bibliographic databases. When Google does a search, it does not search the live internet. It searches a copy that can be six months out of date, meaning you miss the most recent information. Google is a business. This means that the results on the first page are not always the best quality or the most relevant. Searching tips: Pubmed BOOLEANS in CAPITALS OR: example-- child OR adolescent AND: example child AND adolescent NEAR : words must be within 5 words of each other. Not available in pub med but in MEDLINE NOT: excludes studies containing words () : use parentheses to group words example * Truncation: example injur* = injury, injuries injured : search the phrase Combining your search strategy (concept 1 synonym OR concept 1 synonym OR concept 1 synonym) AND (concept 2 synonym OR concept 2 synonym OR concept 2 synonym) AND (concept 3 synonym OR concept 3 synonym OR concept 3 synonym) Combining your search strategy Can dengue fever outbreaks in south america be predicted by the weather (dengue OR aedes OR flavivirus) AND (weather OR climate* OR temperature* OR rain* OR season*) AND (South America OR Colombia OR Venezuela OR Guyana OR Suriname OR French Guiana OR Ecuador OR Peru OR Brazil OR Bolivia OR Paraguay OR Chile OR Argentina OR Uruguay) Clinical Queries using Research Methodology Filters (PUBMED) Clinical Queries rabies AND prophylaxis AND antibiotics http://www.ncbi.nlm.nih.gov/pubmed/clinical Summary so far 1. Introduction: what is EBM 2. The steps in evidence based practice Ask Acquire Appraise Apply Assess 3. Some examples 4. Reflection and further information 5

Break? Appraise How good they are for ANSWERING your clinical question Three overall questions What is the PICO of the study, and is it close enough to your PICO? How well was the study done? Internal validity (the quality of study, methods, prevention of bias and confounding) What do the results mean? RR?,ARR?, NNT? RRR? Clinical vs statistical significance, chance? Tools Worksheet CEBM provides critical appraisal worksheets for Systematic review Diagnostic research Prognosis Example worksheet RCT http://www.cebm.net/resources/cebmpresentations/medical-student-resources/ Step 4: Apply the evidence Ask Acquire Appraise Apply Assess Apply evidence Ask Is the treatment or test feasible in my setting Is it available Can you provide necessary monitoring and follow up Will patient be able to comply with the treatment or regimen What alternatives are available Is my patient so different that the results does not apply Potential benefits vs potential harms WHAT DOES MY PATIENT THINK ABOUT IT 6

Incorporate Patient values Simple communication process Explain what would happen we did nothing Explain what the options are (feasibility, risk, benefit) Check the patient s expectations and ideas Steps in EBM 5. Assess Follow up the patient and assessment of outcomes after implication of treatment Outline 1. Introduction: what is EBM 2. The steps in evidence based practice (5 A s) 3. Some examples 4. Reflection and further information Example Mr. S has poorly manage Type II diabetes and ask if taking cinnamon would improve her fasting blood glucose Task 1: Asking-- Define PICO Task 2: Acquire--define simple search terms Searching The study Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database of Systematic Reviews 2012, Issue 9 This article systematically reviewed papers investigating whether cinnamon affected diabetic management, using fasting blood glucose as its primary outcome. The paper s recent publication suggests that the latest evidence collected will have been included in their review. The mean age range of participants in trials reviewed included that of Miss S. 7

Appraisal Appraisal The authors search: 14 search engines were used to find relevant papers, including: The Cochrane Library (issue 12, 2011). MEDLINE (until January 2012). EMBASE (until January 2012). Selection: 2 reporters independently scanned the abstract of every paper retrieved by the search to ensure inclusion criteria were met: Randomised controlled trials Orally administered monopreparations of cinnamon Placebo/ active medication/ no treatment. Type I or II diabetes Potential limitation only papers published in English were selected. Pertinent reports published in other languages may have been missed. RANDOMISATION 10 prospective, parallel-group design, randomised control trials, involving a total of 577 participants with either Type 1 or 2 diabetes were included. 1 of the 10 studies didn t use a placebo control. 6 studies were double-blinded, 2 single-blinded and 2 undefined with respect to blinding. However, the precise blinding protocol was not clearly described in many trials included in the review. ALLOCATION Gender was approximately distributed evenly in most trials. The mean age of participants ranged from 52-63 years. Bias was assessed independently by two reviewers using a pre-defined criteria (Higgins, 2008). Risk of bias was high or unclear in 8/10 trials, with the remaining 2 assessed as having a moderate risk. Leach MJ, Kumar S., 2012. Appraisal Results MAINTENANCE All studies used oral monopreparation of cinnamon in tablet or capsule form. 3 studies were excluded after careful evaluation of the full publication primarily due to failure to meet the diagnostic criteria for Type 1 or 2 diabetes. Where possible, any relevant missing information on the trial was sought from the original author(s) of the article e.g. reasons for drop-outs were inconsistently reported. MEASUREMENT Heterogeneity was assessed by visual inspection of the forest plots and by using a standard Chi 2 test: Cinnamon vs. Placebo; fasting blood glucose level (mmol/l) Chi 2 =0.97. If one of the primary outcome parameters showed significant differences between the intervention groups subgroup analysis was performed: Cinnamon species Cinnamon dosage Treatment duration Type of diabetes (I or II) The Results (interpretation of findings) There were 8 studies reporting data on fasting blood glucose for 388 participants. These showed significant heterogeneity (Chi 2 =0.82). Visual inspection of the funnel plot and subgroup analysis led the authors to exclude 2 out of these 8 studies as outliers. Analysis of the 6 remaining studies found no statistically significant difference in fasting blood glucose between cinnamon and placebo groups (P=0.55 ; 95%CI -0.34 to 0.18). Adverse effects were recorded in 4 trials. 3 events in intervention groups: Rash Hives Hypoglycaemic episode 4 events in control groups. Nausea Stomach ache Other frequent illness Overall, there was no significant difference between adverse effects in the intervention and control group. Implications Apply what would you say Outline 1. Introduction: what is EBM 2. The steps in evidence based practice (5 A s) 3. An example 4. Self Reflection and final thoughts 8

Self Reflection Next year ask Are you asking any questions at all? What is your success rate in asking answerable questions How is your searching going? --- still GOOGLE?/Wikepedia/Pantip? Are you critically appraising your search results Are you applying evidence in clinical practice EBM Help you make clinical decision Share decision with patients Provide better diagnostic reasoning Understand benefits versus harms Allow you to practice more safely Final Thoughts Wide variations in implementation of evidence based practice Crisis in EBM The evidence based quality mark has been misappropriated by vested interests (drug and medical device industries) Too much evidence (too many guidelines) Marginal gains and a shift from disease to risk Overemphasis on following algorithmic rules Poor fit for multimorbidity Real concept of EBM Makes the ethical care of the patient its top priority Demands individualized evidence in a format that clinicians and patients can understand Characterized by expert judgment rather than mechanical rule following Shares decisions with patients through meaningful conversation Builds on strong doctor-patient relationship and the human aspects of care Applies these principles at community level for evidence based public health Final Question: Which is it? A or B Questions A The doctor is there to give the patients all the information that the patient needs in order that the patient can make a decision, and the doctor should then implement that decision once the patient has made it B The patient is there to give the doctor all the information that the doctor needs in order that the doctor can make a decision, and the patient should then implement that decision once the doctor has made it 9