Companion Article: Masic I, Miokovic M, Muhamedagic B. Evidence Based Medicine-New Approaches and Challenges. Challenges .
Presented by Marc Imhotep Cray Cray,1, M.D.
By the end of this presentation presentation the learner should: Understand the background, history, definition and importance of evidence-based medicine . Know how to formulate clinically relevant, answerable questions using the Patient Patient Intervention Comparison Outcome (PICO) framework. Be able to systematically perform a literature search to identify relevant evidence. Understand the importance of assessing the Understand quality and validity of evidence by critically appraising the literature. Know that different study designs provide varying types and levels of evidence .
Term "evidence-based medicine" has two main tributaries
First is insistence on explicit evaluation of evidence of effectiveness effectiveness when issuing clinical practice guidelines and other population-level policies
Second is introduction of epidemiological methods into medical education and individual patient-lev patient-level el decision-making o
This tributary had its foundations in clinical epidemiology a discipline that teaches medical students and physicians how to apply clinical and epidemiological research research studies to their practices
Background, history history and and definition
EBM methods were published to a broad physician audience in a series of 25 "Users’ Guides to the Medical Literature" published in JAMA between 1993 and 2000 by the Evidence-based Medicine Working Group at McMaster University.
What is Evidence-Based Medicine?
Evidence-based medicine (practice) is a systematic process primarily aimed at improving care of patients EBM Triad includes:
Clinical Judgement
EBM
Relevant Scientific Evidence
Patients’ Values and Pref Preferences erences 5
(2) Sackett and colleagues describe evidence-based medicine (a.k.a. evidence-based evidence-based practice[EBP]) as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients” Sackett DL, et al. BMJ. 1996; (7023): 71-72 .
(3) “Evidence-based medicine (EBM) is the process of systematically reviewing, appraising and using clinical research findings to aid the delivery of optimum clinical care to patients” Rosenberg W, Donald A. Evidence based medicine: an approach to clinical problem-solving. BMJ 1995; 310: 1122 –1126.
(4) Capsule EBM
is an approach to medical practice intended to optimize decision-making by eviden dence ce fr from om we wellllemphasizing use of evi designed and well-conducted resear research ch
Although all medicine based on science has some degree of empirical support EBM goes further classifying evidence by its scientific strength and requiring that only strongest types evidence (i.e., meta-analyses, systematic reviews, randomized controlled trials) trials) can yield strong recommendations o
weaker types of evidence (such as from case-control studies) can yield only weak recommendations
1940s-Formal assessment of medical interventions using controlled trials well established
1972-Prof. Archie Cochrane, director of Medical Research Research Council Epidemiology Research Unit in Cardiff expressed what later came to be known as evidence-based medicine (EBM) in his book Effectiveness Effectiveness and Efficiency: Efficiency: Random Reflections on Health Services
Late 1980s and early 1990s-EBM concepts were developed into a practical methodology by groups at Duke University University in North Nor th Carolina (David Eddy) and McMaster University in Toronto (Gordon Guyatt and David Sackett)
(2)
1992- UK governmen governmentt funded establish establishment ment of Cochrane Centre in Oxford objective was to facilitate preparation of systematic reviews of randomized controlled controlled trials of healthcare
1993-Cochrane Centre expanded into an international collaboration collaboration of centres, of which (as (as of 2009) 2009) there were thirteen, whose role is to co-ordinate co-ordinate activities of 11,500 researchers researchers
NB: Cochrane Collaboration considered as one of critical factors in spreading concept of EBM worldwide
EBM is part of multifaceted process of assuring clinical effectiveness effectiveness main elements are: Production of evidence through research and scientific review Production and dissemination of evidence-based clinical guidelines effective Implementation of evidence-based, cost effective practice through education and management of change Evaluation of compliance with agreed practice Evaluation guidance through clinical audit and outcomesfocused incentives
EBM involves a number of
key key principles discussed in turn during course of presentation:
Formulate a clinically relevant question Identify relevant evidence Systematically review and appraise evidence identified Extract most useful results and determine whether they are important in your clinical practice Synthesize evidence to draw conclusions Use clinical research findings to generate generate guideline recommendations which enable clinicians to deliver optimal clinical care to patients Evaluate implementation of EBM
At core of EBM is a care and respect for patients who will suffer if clinicians fall prey to muddled clinical reasoning and to neglect or misunderstanding of research findings
comprehensive Practitioners Practitioners of EBM strive for a clear & comprehensive understanding understanding of evidence underlying their clinical care and work w each pt. to ensure that chosen courses of action are in that pt’s best interest
Practicing EBM requires clinicians to understand how uncertainty about clinical research evidence intersects w an individual pt’s predicament, predicament, values & preferences preferences
To make EBM more acceptable to clinicians and to encourage its use best to turn a specified problem into answerable answerable questions by examining:
Person or population in question Intervention given Comparison (if appropriate) Outcomes considered
Next, it is necessary to refine problem into explicit questions then check to see whether evidence exists
But where can we find information to help us make better decisions? (answers to follow)
Framing questions ↓ Identifying relevant reviews ↓ Assessing quality of review and its evidence ↓ Summarizing the evidence ↓ Interpreting finding 15
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Common sources include:
Personal experience for example example,, a bad drug reaction Reasoning and intuition Colleagues
Published evidence
o
meta-analyses, systematic reviews and randomized randomized controlled controlled trials
NB: By becoming educated in strength of published evidence (and critical appraisal ), in contrast to more traditional--less rigorous--sources rigorous--sources of o f information use of ineffective, costly or potentially hazardous interventions can be reduced
In order to practice evidence-based medicine initial step = converting a clinical encounter into a clinical question
formatting a clinical c linical (or A useful approach to formatting research) question Patient Intervention Comparison Outcome (PICO) framework
(2) (PICO) Question is divided into four key components: 1. Patient/Population: Which pts. or popul. group of pts. are you interested in?
Is it necessary to consider any subgroups?
2. Intervention: Which intervention/treatment intervention/treatment is being evaluated? 3. Comparison/Control: What is/are main alternative/s alternative/s compared to intervention? 4. Outcome: What is most important outcome for patient?
Outcomes can include include short- or long-term long-term measures, measures, intervention intervention complications, social functioning or quality of life, morbidity, mortality or costs
Clinical Encounte E ncounterr Ali, 30 years old, was diagnosed with heart failure at 4 years old and prescribed a beta-blocker beta-blocker which dramatically dramatically improved his symptoms. Ali’s 5- year year-ol -old d daughter, daughter, Leda, has been recently diagnosed with chronic symptomatic CHF. Ali asks you, whether his daughter should also be prescribed a beta-blocker. Question: Is there a role for beta-blockers in the management of heart failure in children? Patient
Children with congestive heart failure
Interv erventi ention on Carv Carved ediilol lol (a β-blockers ) Comparison
No ca carvedilol
Outcome
Improvement of CHF symptoms
(4) Types of research questions Not all research questions ask whether an intervention
is better than existing interventions or no Tx at all From a clinical perspective EBM is relevant for three other key domains : 1. 2.
Etiology: Is exposure a risk factor for developing a certain condition? Diagnosis: How good is diagnostic test (history taking, physical examination, laboratory or pathological tests and imaging) in determining if a pt. has a particular condition?
3.
Questions usually asked about clinical value or diagnostic accuracy of test
there factors factors related related to pt. that predict a Prognosis: Are there particular outcome (disease progression, survival time after Dx of disease, etc.)?
Px is based on characteri characteristic sticss of pt. (“prognostic factors”)
(5) Important
that pt. experience is taken into account when formulating clinical question (p)atient experience may vary depending on which pt. population is being addressed determined: Following pt. views should be determined: o Acceptability of proposed (i)ntervention being evaluated
o o
Preferences for Tx options already available (c) What constitutes an appropriate, desired or acceptable (o)utcome
NB: Incorporating above pt. views will ensure clinical question is patient-centered & thus, clinically relevant relevant
Three Ways to Use the Medical Literature
Staying Alert to Important New N ew Evidence Problem Solving Asking Background & Foreground Foreground Questions
Analyzing information In using evidence it is necessary to : o o o o o o o
Search for and locate it Appraise it Interpret it in context Implement it Store and retrieve it Ensure it is updated Communicate it
Medical student, in early
training, training, seeing a patient with newly diagnosed type 2 diabetes mellitus She will ask questions questions such as:
What is type 2 diabetes mellitus? Why does this patient have polyuria? Why does this pt. have numbness & pain in his legs? What treatment options are available available?
These questions address normal physiology and pathophysiology assoc. w a medical condition
Traditional medical textbooks that describe underlying pathophysiology or epidemiology of a disorder provide an excellent resource for addressing these background questions
(2) …In
contrast, sorts of foreground questions questions that experienced clinicians usually ask require different resources, namely using current medical literature for pt.-related problem solving Formulating a question is first step and critical skill for this evidence-based practice (EBP)
Ways to use medical literature that follow provide an opportunity to start learning & practicing the skill
(3) “Clinicians do Problem Solving” Solving ” Experienced clinicians managing a pt. w T2DM will ask questions such as:
In pts w new onset T2DM, which clinical features features or test results predict development of diabetic complications? In pts with T2DM requiring drug therapy, does starting w metformin Tx yield improved diabetes control and reduce long-term complications better than other initial treatments?
NB: Here, clinicians are defining specific questions raised in caring for pts then consulting the medical literature to resolve these questions
(3) valuable single free access point is The Cochrane Library
Most
The Cochrane Library contains high-quality, independent evidence to inform all healthcare decision-making
An alternative to alerting systems are secondary evidence based journals
For example, example, in internal and general medicine, ACP medicine, ACP Journal Club (http://acpjc.acponline.org http://acpjc.acponline.org)) publishes synopses of articles that meet criteria of both high clinical relevance relevance and methodologic quality
See: Haynes RB, Cotoi C, Holland J, et al; McMaster Premium Literature Service (PLUS) Project . Second-order peer review of the medical literature for clinical practitioners. practitioners. JAMA. 2006;295(15):1801-1808
(4) Most efficient strategy for ensuring you are
aware of recent developments relevant to your practice is to subscribe to e-mail alerting systems, such as EvidenceAlerts
A free service w research staff screening approx. 45, 000 articles per year in more than 125 clinical journals for methodologic quality and a worldwide panel of practicing physicians physicians rating them for clinical relevance and newsworthiness newsworthiness
first set of questions, those of medical student , as background questions and of browsing and problem-solving sets as foreground questions In most situations you need to understand understand background thoroughly before it makes sense to address foreground issues
One can think of
Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed. New York: McGraw-Hill Education-JAMA Education-JAMA Network, 2015. 29
Five Types of Foreground Clinical Questions In addition to clarifying population, intervention or exposure, and outcome, it is productive to label nature of question that you are asking
Finding a Suitably Designed Study for Your Your Question Type You need to correctly identify category of study b/c to answer your question, you must find an appropriately designed study
o
For example, if you look for a randomized trial to inform properties of a diagnostic test, you will not find answer you seek
1. Therapy: determining effect effect of interventions on patient on patient important outcomes (symptoms, symptoms, function, morbidity, mortality, and costs) 2. Harm: ascertaining effects effects of potentially harmful agents (including therapies from first type of question) on patient-important outcomes 3. Differential diagnosis: in patients with a particular clinical presentation, presentation, establishing the frequency of the underlying disorders 4. Diagnosis: establishing power establishing power of a test to differentiate Betw. Betw. those with and without a target condition or disease 5. Prognosis: estimating a patient’ patient ’s future course
We will now review study designs associated with 5 major types of questions.
To answer questions about a therapeutic issue, we seek a randomized trial (group assignment analogous to flipping a coin) Once investigators allocate participants to treatment or control groups they follow them forward in time to determine whether they have, for instance, a stroke or myocardial infarction what we call outcome of interest
Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed. New York: McGraw-Hill Education-JAMA Network, 2015.
Ideally, we would also look to randomized trials to address issues of harm
For most potentially harmful exposures, exposures , however, randomly allocating patients is neither practical nor ethical o For example , one cannot suggest to potential study participants that an investigator will decide by the flip of a coin whether or not they smoke during next 20 years
For exposures such as smoking , best one can do is identify observational studies) provide less studies (subclassified as cohort or case-control studies) trustworthy evidence than randomized trials
Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed. New York: McGraw-Hill Education-JAMA Network, 2015.
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For sorting out differential diagnosis investigators collect a group of patients with a similar presentation presentation (eg, painless jaundice, syncope, or headache), conduct an extensive battery of tests, and if necessary follow patients forward in time
Ultimately, Ultimately, for each pt. investigato investigators rs hope to establish underlying cause of symptoms and signs with which pt. presented
Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed. New York: McGraw-Hill Education-JAMA Network, 2015.
In diagnostic test studies , investigators identify a group of patients among whom they suspect a disease or condition of interest interest exists (such as tuberculosis, lung cancer, cancer, or iron deficiency anemia) which we call the target condition
Pts. undergo new diagnostic test and a reference standard (also referred to as gold standard or criterion standard) Investigators evaluate diagnostic test by comparing its classification of pts. w that of reference standard
Guyatt G et al. (Eds). Users’ Guides to the M edical Literature: Essentials of Evidence-Based Clinical Practice
Final type of study examines examines a patient’s prognosis and may identify factors that modify that prognosis Here, investigators identify pts who belong to a particular group (such as pregnant women, pts. undergoing surgery, or pts w cancer) with or without factors that may modify their prognosis (such as age or comorbidity ) The exposure here is time investigators follow up pts to determine if they experience the target outcome such as an adverse obstetric or neonatal event at end of a pregnancy, a myocardial infarction after surgery, or survival in cancer
Guyatt G et al. (Eds). Users’ Guides to the M edical Literature: Essentials of Evidence-Based Clinical Practice
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Searching for Evidence is a Clinical Skill
Searching for current best evidence in medical literature literature has become a central skill in clinical practice On average, clinicians have 5 to 8 questions about individual patients per daily shift and regularly use online evidence-based medicine (EBM) resources to answer them
See: Chapter 4, Finding Current Best Evidence . In: Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed . New York: McGraw-HillMcGraw-HillJAMA Network, 2015.
Summaries and guidelines Nonpreappraised Nonpreappraised research
UpToDate DynaMed Clinical Evidence Best Practice US National Guidelines Clearinghouse
Preappraised research
ACP Journal Club McMaster PLUS DARE Cochrane Evidence Updates
PubMed (MEDLINE) CINAHL CENTRAL Filters: Clinical Queries in PubMed
Federated searches (engines)
ACCESSSS Trip SumSearch Epistimonikos
Abbreviations: ACCESSSS, ACCESSSS, ACCess to Evidence-based Summaries, Synopses, Systematic Systematic Reviews and Studies; CENTRAL, Cochrane Central Register of Controlled Trials; CINAHL, Cumulative Index to Nursing and Allied Health Literature; DARE, Database of Abstracts of Reviews of Effects.
http://www.cochranelibrary.com// http://www.cochranelibrary.com
Belsey J. What is evidence-based medicine? Hayward Medical Communications, 2009.
https://plus.mcmaster.ca/EvidenceAlerts /
https://www.nlm.nih. gov/bsd/pmresources.html
http://www.medscape.com /
Once all possible studies
have been identified w literature search each study needs to be assessed for eligibility against objective criteria for inclusion or exclusion
identified those studies that meet inclusion criteria they are subsequently assessed for methodological quality using a critical appraisal framework
Having
Despite satisfying inclusion criteria, studies appraised as being poor in quality should also be excluded
(2) Critical appraisal
is process of systematically examining available evidence to judge its validity, and relevance in a particular context should make an objective assessment of study quality and potential for bias
Appraiser
Note: Methodological checklists for critically appraising study designs will be covered in a subsequent lecture
(3) Important to determine both
internal validity and external validity of study: External validity: extent to which study findings are generalizable generalizable beyond limits of study to study’s target population. Internal validity: Ensuring that study was run carefully carefully (research design, how variables were measured, etc.) and extent to which observed effect(s) effect(s) were produced solely by intervention being assessed (and not by another factor)
Three main threats to internal validity (confounding, bias and causality) for each of the key key study designs are discussed in subsequent lectures
Table shows study designs that answer treatment questions Further down list (or levels of evidence), greater risk of bias Randomizing participants in a study reduces bias, b/c confounding factors (such as age, gender, smoking status, etc.) are evenly distributed betw. intervention and control arms of study
Kulkarni K. et al. (Eds.). Oxford Handbook of Key Clinical Evidence,2nd Ed. New York: Oxford University Press, 2016.
A“Quality A“Qualityofevidence” ofevidence” framework Grading of Recommendations, Recommendations, Assessment, Development Development and a nd Evaluation (GRADE) Working Group is very useful in appraising medical research studies
Quality of evidence framework by
Although developed mainly to help guideline developers make evidence-based recommendations its approach to assessing quality of evidence is widely used and makes important distinction betw. evidence quality and strength of a recommendation Helps to point out importance of looking at “body of evidence” for a clinical question
Kulkarni K. et al. (Eds.). Oxford Handbook of Key Clinical Evidence,2nd Ed. New York: Oxford University Press, 2016.
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…reviewing medical literature poses a challenge to busy physicians. physicians. A willingness and ability to do so enhance quality of practice they bring to each of their patients. To save time, a brief primary survey of article of interest informs reader as to potential value of findings and to whether a more in-depth review is indicated. If so, this detailed analysis (secondary survey) allows reader to determine whether article's conclusion is supported by its results and whether these results are believable. Knowledge of standard anatomy anatomy of an article and idiosyncrasies idiosyncrasies of various types t ypes of studies will assist reader to intelligently review medical literature efficiently… Theodore J Gaeta et al. Evaluating the Literature. Available at http at http://emedicine.m ://emedicine.medscape.com/article/7 edscape.com/article/773527 73527 Accessed 07-08-17 07-08-17
Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of EvidenceBased Clinical Practice 3rd Ed. New York: McGraw-Hill Education-JAMA Network, 2015.
See next slide for links to tools and resources for further study.
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Textbooks Guyatt G et al. (Eds). Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3rd Ed . New York: York: McGraw-Hill Education-JAMA Network, 2015.
Kaura A. Evidence-Based Medicine: Reading and Writing Medical Papers (Crash Course Course Series). Philadelphia: Philadelphia: Mosby- Elsevier, Elsevier, 2012.
Kulkarni K. et al. (Eds.). Oxford Handbook of Key Clinical Evidence, 2nd Ed . New York: Oxford University Press, 2016. 2016.
Swiger KJ et al. (Eds). 50 studies every internist should know. New York: Oxford University Press, 2015.
Cloud Folders EBM (Evidence Based Medicine), Reading the Medical Literature and Medical Writing 54
Lefebvre, C., Manheimer, E., Glanville, J., 2011. Searching for studies. In: Higgins, Higgin s, J.P. J.P.T., Green, S. S . (Eds.), Cochrane Handbook Handb ook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011) . The Cochrane Collaboration. National Institute for Health and Clinical Excellence, March 2012. The Guidelines Manual. National Institute for Health and Clinical Excellence, London. Available from: http:// www.nice.org.uk Sackett, D.L., Rosenberg, W.M.C., 1995. The need for evidence based medicine.. J. R. Soc. Med. 88, 620 –624. medicine Sackett, D.L., Rosenberg, W.M.C., W.M.C., Gray, Gray, J.A.M., Haynes, R.B., R.B. , Richardson, W.S., W.S., 1996. Evidence based medicine: What it is and what it isn’t . BMJ 312, 71 –72.
Straus, S.E., McAlister, F.A., 2000. Evidence-based medicine: A commentary commentar y on common criticisms. CMAJ 163, 837 –841.
