Introduction to Evidence-Based Medicine Bill Cayley Jr MD MDiv UW Health Augusta Family Medicine

Objectives Describe the use of evidence in making medical decisions Demonstrate searching for an evidence-based answer to a medical question Learning Objectives: At the conclusion of this activity, participants will be able to: Describe the use of evidence in making medical decisions Demonstrate searching for an evidence-based answer to a medical question

What is “evidence-based medicine?” Introductory question for participants: “How would you define evidence-based medicine?”

Two fundamental questions… What is the purpose of medicine? How do I decide what to do? You have to know where you’re going before deciding how to get there… Two fundamental questions need to be addressed in medical practice: First, what is the purpose of medicine? Second, how do I decide what to do? Just as a person planning a cross-country trip maps out the journey based on decisions about the most desirable destination and the most desirable routing, so in medicine physicians must work with patients to decide on both overarching goals, and on the best way to reach those goals. In both travel and medicine, you have to know where you’re going before deciding how to get there.

What is the purpose of medicine? Patient care Public health Research Improving the quality of patients’ lives… While medicine has many facets, including direct patient care, public health, and research endeavors, the common goal of all medical ventures is improving the quality of patients’ lives. This common underlying goal can serve as the “destination” to guide all medical journeys and endeavors, regardless of which facet or field of medicine is the stage for the patient’s medical journey.

What is 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. Sackett, et al. BMJ 1996;312:71-72 In a much-quoted 1996 editorial, David Sackett, an early and prolific author on evidence-based medicine, defined evidence-based medicine (EBM) as the “conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.” (A) (italics added) This characterization highlights the three important parts of evidence-based medical practice: the patient, the evidence, and careful application of generalized evidence to the individual patient. (A) Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ. 1996 Jan 13;312(7023):71-2. PMID: 8555924 (http://www.bmj.com/cgi/content/full/312/7023/71)

What is “EBM” NOT? What we have always done “Cookbook medicine” Only a cost-cutting trick Only randomized trials Evidence based medicine IS… Tracking down the best external evidence with which to answer our clinical questions… Sackett goes on to argue that EBM is not old hat or just the same old medical practice, as evidenced by the wide variation that often occurs in clinical practice patterns. Neither is it intended to be “cookbook medicine” as EBM specifically advocates for individualized application of evidence to patient care, not forcing patient care to conform to generalized evidence. Further, EBM is not intended primarily as a savings tool – it is intended to guide practitioners to provide the best, not necessarily the cheapest, care. Lastly, EBM is not intended to be only concerned with randomized controlled trials, but with the best relevant evidence applicable to the situation in question. (A) Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ. 1996 Jan 13;312(7023):71-2. PMID: 8555924 (http://www.bmj.com/cgi/content/full/312/7023/71)

EBM – a short history… JAMA 1992 JAMA 1993 – 2000 1990s – 3 trends “EBM: a new approach…” JAMA 1993 – 2000 “Users' Guides to the Medical Literature” 1990s – 3 trends Systematic reviews Search engines Knowledge distillation and “push” services “Evidence-based medicine” was first introduced in the mainstream medical literature in a 1992 article, “Evidence-based medicine: A new approach to teaching the practice of medicine,” which presented EBM as “a fundamentally new approach” emphasizing “question formulation, search and retrieval of the best available evidence, and critical appraisal of the study methods to ascertain the validity of results”. (B) A subsequent series of “Users' Guides to the Medical Literature” presented skills for searching for, appraising, and applying various types of published evidence to medical practice. As EBM gained prominence in the late 1990s and beyond, three streams of evidence dissemination developed: 1) systematic reviews gained increasing prominence in the medical literature, 2) knowledge search engines (including internet engines such as Google, and medline interfaces such as Ovid) became standard tools for medical literature searching, and 3) knowledge distillation and “push” services developed as a way to compile and disseminate concise reviews of evidence on specific topics or questions (eg, ACP Journal Club, InfoPoems, etc). (B) (A) Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992 Nov 4;268(17):2420-5. PMID: 1404801 (http://jama.ama-assn.org/cgi/reprint/268/17/2420?ijkey=d3d27e0bf59a836b2ff7923ef06634c6304b1c75&keytype2=tf_ipsecsha) (B) Montori VM, Guyatt GH. Progress in evidence-based medicine. JAMA. 2008 Oct 15;300(15):1814-6. PMID: 18854545 (http://jama.ama-assn.org/cgi/content/full/300/15/1814)

Classification of evidence

How do I decide what to do? How do I make decisions? Dogma: “Natural is best” Tradition: “We’ve always done it that way” Convention: “Everyone does it this way” Evidence-Based: “Evidence supports this way” How do I decide what to do? Decisions can be guided by a number of different approaches to reasoning. Some decisions are guided by dogma, or an a-priori set of beliefs (eg, “natural is best.”). Some decisions are guided by tradition (eg, “we’ve always done it that way”), relying on the collective wisdom of the ages. Some decisions are guided by convention (eg, “everyone else does it that way”), relying on the collective wisdom of colleagues. An evidence-based approach makes decisions based on critical evaluation and reflection (eg, “the evidence supports doing it this way”).

How do I decide what to do? The answer from EBM… “…use of current best evidence…” Since EBM advocates that medical decisions should proceed from application of the “current best evidence,” an appreciation of how to evaluate, or grade, evidence is crucial to the application of “best evidence” in practice.

Evidence: systematic observation Meta-Analysis Randomized Controlled Trial Uncontrolled Trial Case Series Anecdote Conceptually, evidence starts simply with what is observed. Every individual observation is an isolated piece of evidence. To generate higher quality evidence, however, it is important to compile, organize, and evaluate those individual observations in a systematic way. Thus, while an anecdotal observation constitutes evidence regarding a single event, a more organized compilation of several observed events can constitute a case series, a higher level of evidence. An even more organized way to evaluate an event or an intervention is to use systematic observation, as in an uncontrolled or controlled trial. A meta-analysis provides even higher quality evidence by systematically grouping together and synthesizing the results of multiple trials. Thus, the more systematic an approach that is taken to gathering and organizing evidence, ranging from the individual anecdote up to the meta-analysis of controlled trials, the higher quality the evidence.

Randomized Controlled Trial Meta-Analysis Randomized Controlled Trial Uncontrolled Trial Case Series Anecdote More systematic observation ► better evidence While evidence-classification and rating may seem a daunting challenge, the basic premise is that the more systematic the observations that are available (eg, RCT instead of just a case series) the better the quality of evidence. And, since EBM seeks to apply the “current best evidence” it is important to see for the highest quality studies that are available to address a given clinical question.

Integrating evidence & practice

What type of outcome measures? Surrogate markers of disease: Hb A1c, cholesterol, blood pressure Stage or extent of disease: Diabetic ulcers, angiographic CAD, stroke Patient-oriented outcomes: Mobility, suffering, longevity Morbidity and mortality In order to decide what to do in practice, we also need to know how we’ll know when we are there – that is, what kind of outcomes do we seek? Medical outcomes can be broadly grouped into 3 categories. Some outcomes (eg, blood pressure or cholesterol levels) are merely surrogate markers of disease. We measure these surrogate markers because we think they tell us something prognostically about the expected course of a person’s disease process, but they do not directly impact how a patient feels from day to day. Others measure actual stage or extent of disease (eg, the stage of a diabetic ulcer, or the angiographic extent of disease). These may have a more direct bearing on a patient’s quality of life or extent of suffering, but still do not provide direct measures of long-term quality of life. The most important outcomes for guiding medical decisions are those that affect how patients feel and the quality of their lives – that is, patient-oriented outcomes such as mobilty, suffering, longevity, and other considerations that bear directly on how a patient experiences his or her quality of life. In short, patient oriented outcomes have primarily to do with long-term morbidity or mortality. (A) (A) Slawson DC, Shaughnessy AF, Ebell MH, Barry HC. Mastering medical information and the role of POEMs--Patient-Oriented Evidence that Matters. J Fam Pract. 1997 Sep;45(3):195-6. PMID: 9312554

Patient or disease oriented? Disease-Oriented Outcomes. Intermediate, histopathologic, physiologic, or surrogate results Examples: blood sugar, blood pressure, flow rate, coronary plaque thickness May or may not reflect improvement in patient outcomes. Patient-Oriented Outcomes. Outcomes that matter to patients and help them live longer or better lives Examples: including reduced morbidity, reduced mortality, symptom improvement, improved quality of life, or lower cost An even simpler way to break down the types of outcomes that may be considered is into “disease oriented” outcomes such as blood sugar, blood pressure, flow rate, coronary plaque thickness, or “patient oriented outcomes” such as reduced morbidity, reduced mortality, symptom improvement, improved quality of life, or lower cost. (A) (A) Ebell MH, Siwek J, Weiss BD, Woolf SH, Susman J, Ewigman B, Bowman M. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004 Feb 1;69(3):548-56. PMID: 14971837 (http://www.aafp.org/afp/20040201/548.html)

Which outcomes???? Topical antibiotics for bacterial conjunctivitis may improve early and late resolution rates, but nearly all cases ultimately have complete remission. Br J Gen Pract. 55: 962-4. Digoxin for symptomatic heart failure provides no significant difference in mortality but is associated with lower rates of hospitalization and of clinical deterioration. J Card Fail. 10:155-64. Long-acting beta-2 agonists for asthma are effective in reducing symptoms but may increase mortality or exacerbations. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006363. In applying evidence regarding patient-oriented outcomes, it is also important to work collaboratively with the patient to determine which outcomes are most important to the patient, as this will guide the decision as to which interventions to pursue. Three examples illustrate this point: 1) Topical antibiotics for bacterial conjunctivitis may improve early and late resolution rates, but nearly all cases ultimately have complete remission. (A) 2) Digoxin for symptomatic heart failure provides no significant difference in mortality but is associated with lower rates of hospitalization and of clinical deterioration. (B) 3) Long-acting beta-2 agonists for asthma are effective in reducing symptoms but may increase mortality or exacerbations. (C) Thus, it is vital to discuss the desired target outcome with a patient when deciding how to apply evidence to a specific patient’s situation. Sheikh A, Hurwitz B. Topical antibiotics for acute bacterial conjunctivitis: Cochrane systematic review and meta-analysis update. Br J Gen Pract. 2005 Dec;55(521):962-4. PMID: 16378567 Hood WB Jr, Dans AL, Guyatt GH, Jaeschke R, McMurray JJ. Digitalis for treatment of congestive heart failure in patients in sinus rhythm: a systematic review and meta-analysis. J Card Fail. 2004 Apr;10(2):155-64. PMID: 15101028 Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006363. DOI: 10.1002/14651858.CD006363.pub2.

SORT The “Strength of Recommendation Taxonomy” is one system of evidence grading, developed by a collaboration among family medicine editors, that seeks to provide a user-friendly approach to classifying evidence in terms of both evidence quality, and the degree to which it bears on patient-oriented outcomes. (A) (A) Ebell MH, Siwek J, Weiss BD, Woolf SH, Susman J, Ewigman B, Bowman M. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004 Feb 1;69(3):548-56. PMID: 14971837 (http://www.aafp.org/afp/20040201/548.html)

When guidelines conflict… Questions of evidence Questions of outcomes Were the clinical questions different? Were different studies considered? Were the results analyzed differently? Was the quality of evidence assessed differently? Did the effect estimates for important outcomes differ? Did judgments about evidence quality differ? Were health consequences weighed differently? Were economic consequences considered differently? Clinicians striving to practice EBM, applying the best current evidence to patient care, will still be faced (sometimes frequently) with the task of reconciling competing or conflicting recommendations. Oxman, Glasziou and Williams provide some helpful suggestions for issues to consider when trying to make clinical sense out of seemingly conflicting evidence or recommenations. Questions to consider regarding the evidence presented include: Were the clinical questions different? Were different studies considered? Were the results analyzed differently? Was the quality of evidence assessed differently? Questions of outcome or consequences that need to be considered include: Did the effect estimates for important outcomes differ? Did judgments about evidence quality differ? Were health consequences weighed differently? Were economic consequences considered differently? (A) Oxman AD, Glasziou P, Williams JW Jr. What should clinicians do when faced with conflicting recommendations? BMJ. 2008 Nov 28;337:a2530. doi: 10.1136/bmj.a2530. PMID: 19042938

Systems applications

Clinical Questions Background - “What is it?” General information on a condition or disease Foreground – “What do I do for this patient?” Patient Intervention/Investigation Comparison Intervention/Investigation Outcome (Patient-Oriented) Clinical questions generally fall into two categories: Background questions have to do with general information, the “lay of the land” of a certain medical topic, or just building one’s general fund of knowledge regarding a specific topic or condition or treatment. Foreground questions have to do with addressing a specific problem for a specific patient. It can be helpful to formulate “foreground” questions into the “PICO” format. Source: Huang X, Lin J, Demner-Fushman D. Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annu Symp Proc. 2006:359-63. PMID: 17238363

Clinical Questions - “PICO” Example: In a 5 year old child with conjunctivitis (patient) will topical antibiotics (intervention) compared to no treatment (comparison) lead to quicker symptom relief (outcome)? In a 5 year old child with conjunctivitis (patient) will topical antibiotics (intervention) compared to no treatment (comparison) lead to improved cure rates (outcome)?

Finding Evidence-based Answers Trip Database (http://www.tripdatabase.com/) Database of Abstracts of Reviews of Effectiveness (http://www.crd.york.ac.uk/crdweb/) DynaMed (http://www.dynamicmedical.com/) *Subscription required. Essential Evidence Plus (http://www.essentialevidenceplus.com/) Cochrane Library (http://www.cochrane.org/) *Subscription for full access, abstracts free. FPIN (http://www.fpin.org/) Clinical Evidence (www.clinicalevidence.com/)

For further reading… Woolever DR. The art and science of clinical decision making. Fam Pract Manag. 2008 May;15(5):31-6. PMID: 18546805 (http://www.aafp.org/fpm/20080500/31thea.html) Krumholz H, Lee T. Redefining Quality -- Implications of Recent Clinical Trials. N Engl J Med 2008 358: 2537-2539 (http://content.nejm.org/cgi/content/full/358/24/2537) Ebell MH. How to find answers to clinical questions. Am Fam Physician. 2009 Feb 15;79(4):293-6. PubMed PMID: 19235495. (http://www.aafp.org/afp/2009/0215/p293.html)

In short… EBM is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. Evidence Systematic observation = high-quality evidence Patient-oriented evidence preferable to Stage of disease Surrogate markers In summary: Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. Evidence is essentially about observation, but high-quality evidence requires systematic observation Evidence is best applied in the pursuit of patient-oriented outcomes