Have you ever conducted a literature search? Odds are, you probably have when preparing a drug monograph for a Pharmacy and Therapeutics Committee meeting or answering a drug information question. If so, then you have practiced evidence-based medicine (EBM).
As defined by Sackett, "EBM is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients".1 In Evidence-Based Medicine: How to Practice and Teach EBM,2 Sackett describes the five steps of EBM:
- Step 1 - Convert the need for information (about prevention, diagnosis, prognosis, therapy, causation, etc.) into an answerable question.
- Step 2 - Track down the best evidence with which to answer that question.
- Step 3 - Critically appraise that evidence for its validity (closeness to the truth), impact (size of the effect), and applicability (usefulness in clinical practice).
- Step 4 - Integrate the critical appraisal with clinical expertise and with the patient's unique biology, values and circumstances.
- Step 5 - Evaluate your effectiveness and efficiency in executing Steps 1 through 4 and seek ways to improve both.
You know a topic has come of age when people begin to joke about it. Isaacs and Fitzgerald gave us their humorous take with the "Seven Alternatives to Evidence-Based Medicine":3
- Eminence-Based Medicine - Substitute advanced age and white hair for evidence.
- Vehemence-Based Medicine - Speak loudly to convince colleagues and relatives of your ability.
- Eloquence-Based Medicine - Substitute fancy attire and verbal eloquence for evidence.
- Providence-Based Medicine - Leave the outcome in the hands of the Almighty.
- Diffidence-Based Medicine - Do nothing from a sense of despair.
- Nervousness-Based Medicine - Overact, overinvestigate and overtreat due to a fear of litigation.
- Confidence-Based Medicine - Restricted to surgeons.
I'm sure we've all encountered a physician who has practiced one or more of the above alternatives to EBM. Hopefully, pharmacists won't fall into that same paradigm as we gain prescribing authority and patient-care responsibility.
Importance of EBM
McGlynn, et al, conducted a random sample of adults living in metropolitan areas in the United States, and found that only 54.9% of participants received recommended processes of care for various acute and chronic conditions or for preventative medicine.4 Developing and publishing practice recommendations is an extremely valuable first step in our collective efforts to realize the full public health benefits of clinical research.5
Clinical practice guidelines and critical pathways derived from EBM abound, ranging from guidelines for managing adult alcohol withdrawal syndrome,6 hypercholesterolemia,7 and cancer to supportive care,8 geriatric mental health care,9 and perhaps hundreds of other disease states. There's even a guideline on the pharmacist's role in the development, implementation and assessment of guidelines.10
A Recent Example
In 2005, clopidogrel (PLAVIX) ranked seventh among the top 200 brand-name drugs by retail dollars, enjoying $2.4 billion in retail sales-a 14.3% increase from the previous year.11 This level of success may be attributed in part to the 2002 joint statement issued by the American Heart Association and the American College of Cardiology endorsing the short-term use of clopidogrel as part of the treatment regimen for patients who had been evaluated in the emergency room with a mild heart attack or who were at high risk of having a heart attack.12 However, as presented by Bhatt, et al, dual antiplatelet therapy with clopidogrel plus low-dose aspirin had not been studied in a broad population of patients at high risk for atherothrombotic events.13 Therefore, Bhatt and colleagues randomly assigned 15,603 patients with either clinically evident cardiovascular disease (symptomatic) or multiple risk factors (asymptomatic) to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin, and followed them for a median of 28 months. The investigators concluded that the combination of clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes among patients with stable cardiovascular disease or multiple cardiovascular risk factors. Furthermore, the risk of moderate-to-severe bleeding was increased. Data on mortality rates suggest that dual antiplatelet therapy should not be used in patients without a history of established vascular disease.13
Whether the topic is clopidogrel, or the lack of efficacy of folic acid and B vitamins in reducing the risk of major cardiovascular events in patients with vascular disease,14 or aprotinin in cardiothoracic surgery,15 or nesiritide in heart failure,16 examples of significant findings abound in the clinical literature and are often reported in the lay press. How do you implement the changes required to effect appropriate, evidence-based patient care?
Yen conducted an extensive literature review of meta-analyses, systematic reviews and randomized controlled trials relating to strategies commonly used to influence physician behavior and developed an extensive list of strategies:17
- Printed educational materials - passive information transfer through the distribution of printed recommendations for clinical care (e.g., clinical practice guidelines, electronic publications, audio-visual materials).
- Formal continuing medical education - passive information transfer through participation in educational conferences, lectures, workshops, or meetings that occur outside the physician's office.
- Audit and feedback - summary of clinical performance on patient care over a specified period based on medical records, computerized databases, patient surveys, or observation.
- Academic detailing - active information transfer through presentation by a trained person that occurs inside the physician's office.
- Local opinion leaders - health care providers who are nominated or considered by their colleagues to be "educationally influential".
- Reminders - manual or computerized prompts directed to physicians to perform a specific clinical action.
- Clinical decision support systems - information systems designed to improve clinical decision-making through the analysis of patient-specific clinical variables (e.g., diagnosis, preventive care, disease management, drug dosing and prescribing).
- Economic incentives - financial rewards or penalties for physicians or institutions for providing specific clinical activities.
Yen found that active information dissemination, such as involving physicians in care standardization, academic detailing (or counterdetailing), and automated decision support tools have convincingly been shown to improve clinical practice. Passive interventions that rely on physicians to seek out patient-specific information on their own are generally less effective.17 It is also a sobering, albeit important finding, that the most commonly used techniques to change physician behavior (i.e., printed education materials and formal continuing medical education) generally have the least benefit.17
It is the reader's challenge to determine which of the above-referenced steps are routinely employed within their own organization when a therapeutic interchange, clinical practice guideline or other strategic change in medication therapy is attempted. Do you rely on one or two trusted methodologies and wonder why they have lost effectiveness? Or do you rollout all eight strategies (or more) regularly? If you have limited time or resources, which methodologies should you focus upon? In this author's experience, a physician thought leader-one with the time and fortitude to bring EBM principles and their resultant guidelines, policies and/or therapeutic substitutions to the masses-is a very important variable in bringing about change in prescribing patterns.
EBM is not without its detractors. As Williams and Garner state, "Too great an emphasis on evidence-based medicine oversimplifies the complex and interpersonal nature of clinical care".18 Perhaps Browman summarized it best by stating "The single most important feature of the evidence-based approach (is) to be accountable for our decision through an explicit approach that documents how our decisions are made."19 So go forth, document your decision-making process, utilize your available tools, create new ones if needed, take a multifaceted approach and turn the evidence into medicine.
- Sackett DL, Rosenberg WMC et al. Evidence-based medicine: what it is and what it isn't. BMJ. 1996;312:71-72.
- Sackett DL, Straus SE, Richardson WS, Rosenberg W and Haynes RB. Evidence-based medicine: how to practice and teach EBM. 2nd Ed. Churchill Livingstone, Edinburgh, 2000.
- Isaacs D and Fitzgerald D. Seven alternatives to evidence-based medicine. BMJ. 1999;319:18-25.
- McGlynn EA, Asch SM et al. The quality of health care delivered to adults in the United States. N Engl J Med. 2003;348:2635-45.
- Lenfant C. Shattuck lecture: Clinical research to clinical practice-lost in translation? N Engl J Med. 2003;349:868-74.
- Stanley KM, Worrall CL, et al. Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients. Pharmacotherapy. 2005;25(8):1073-1083.
- Chobanian AV, Bakris Gl, et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (The JNC 7 Report). JAMA. 2003;289:2560-2572.
- National Comprehensive Cancer Network. Guidelines for the Treatment of Cancer by Site. www.nccn.org. Accessed March 13, 2006.
- Bartels SJ, Dums AR et al. Evidence-based practices in geriatric mental health care. Psychiatric Service. 2002;53:1419-1431.
- American Society of Health-System Pharmacists. ASHP guidelines on the pharmacist's role in the development, implementation, and assessment of critical pathways. Am J Health-Syst Pharm. 2004;61:939-45.
- Gebhart F. Lack of blockbuster launches makes for unevenful year; scripts still rise 3%. Drug Topics. 2006;150:26.
- Braunwald E, Antman EM, et al. ACC/AHA Guideline update for the management of patients with unstable/angina and non-ST-segment elevation myocardial infarction-2002: Summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation. 2002;106:1893-1900.
- Bhatt DL, Fox KAA, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354.
- The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354.
- Mangano DT, Tudor JC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006;354:353-65.
- Sackner-Bernstein JD, Skoicki HA et al. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 2005;111:1487-1491.
- Yen BM. Engaging physicians to change practice. JCOM. 2006;13:103-110.
- Williams DDR, Garner J. The case against "the evidence": a different perspective on evidence-based medicine. British Journal of Psychiatry. 2002;180:8-12.
- Browman GP. Essence of evidence-based medicine: a case report. J Clin Oncol. 1999;17:1969-1973.