Evidence Based Medicine

1. Clista Clanton, MSLS, AHIPJune 22 & 23, 2010 Evidence Based Medicine

2. Today’s topics • What is EBM? • Why is it important? • Complementary/Alternative medicine • Developing the “well built” clinical question • Searching for evidence • Evaluating the evidence

3. What is evidence based medicine (EBM)? • “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” • The integration of individual clinical expertise with the best available external clinical evidence from systematic research. • Initially proposed by Dr. David Sackett and colleagues at McMasters University in Ontario, Canada. Sackett DL, et al. Evidence-Based Medicine: What it is and what it isn’t. BMJ 1996; 312:71-2.

4. Adapted from: Sackett D.L., Rosenberg M.C., Gray J.A., Haynes R.B., Richardson W.S. (1996). Evidence based medicine: what it is and what it isn't. BMJ, 312, 71-72.

5. Paradigm shift • Unsystematic observations from clinical experience are a valid way of building and maintaining one's knowledge about patient prognosis, the value of diagnostic tests, and the efficacy of treatment. • The study and understanding of basic mechanisms of disease and pathophysiologic principles is a sufficient guide for clinical practice. • A combination of thorough traditional medical training and common sense is sufficient to evaluate new tests and treatment. • Content expertise and clinical experience are a sufficient base from which to generate valid guidelines for clinical practice. • To sort out clinical problems, physicians can reflect on their own clinical experience, reflect on the underlying biology, go to a textbook, or ask a local expert. • The "Introduction" and "Discussion" sections of a paper could be considered an appropriate way of gaining the relevant information from a current journal. Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine. Available at http://www.cche.net/usersguides/ebm.asp#7

6. New Paradigm • Clinical experience, and the development of clinical instincts are crucial and necessary parts of becoming a competent physician. At the same time, systematic attempts to record observations in a reproducible and unbiased fashion markedly increase the confidence one can have in knowledge about patient prognosis, the value of diagnostic tests, and the efficacy of treatment. In the absence of systematic observation one must be cautious in the interpretation of information derived from clinical experience and intuition, for it may at times be misleading. Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine. Available at http://www.cche.net/usersguides/ebm.asp#7.

7. New Paradigm • The study and understanding of basic mechanisms of disease are necessary but insufficient guides for clinical practice. The rationales for diagnosis and treatment which follow from basic pathophysiologic principles may in fact be incorrect, leading to inaccurate predictions about the performance of diagnostic tests and the efficacy of treatments. • Understanding certain rules of evidence is necessary to correctly interpret literature on causation, prognosis, diagnostic tests, and treatment strategy. • Clinicians should regularly consult the original literature in solving clinical problems and providing optimal patient care. • Clinicians should be able to critically appraise the "Methods" and "Results" sections of journal articles. Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine. Available at http://www.cche.net/usersguides/ebm.asp#7.

8. What is EBM? • “Evidenced-based medicine is the concept of formalizing the scientific approach to the practice of medicine for identification of “evidence” to support our clinical decisions. It requires an understanding of critical appraisal and the basic epidemiologic principles of study design, point estimates, relative risk, odds ratios, confidence intervals, bias, and confounding. By using this information, clinicians can categorize evidence, assess causality, and make evidence-based recommendations. Evidence-based medicine allows analysis of complicated material so that we can make the best possible clinical decisions for the populations we serve.” Williams JK. Understanding evidence-based medicine: a primer. Am J Obstet Gynecol 2001:185-275-278.

9. Why is EBM important? • New types of evidence are being generated which can create changes in the way patients are treated • How much is actually being applied to patient care? • Although evidence is needed on a daily basis, usually physicians don’t get it. • lack of time • out-of-date textbooks, and • the disorganization of the up-to-date journals6 Covell DG, Uman GC, Manning PR: Information needs in office practice: Are they being met? Ann Intern Med 1985;103:596-9.

10. Why is EBM important? • Up-to-date knowledge and clinical performance can deteriorate with time • There is a statistically and clinically significant negative correlation between a physician’s knowledge of up to date care and the years that have elapsed since graduation from medical school. • Traditional continuing medical education programs have not been shown to improve clinical performance • Systematic reviews of the relevant randomized trials have shown that traditional, instructional CME fails to modify clinical performance and is ineffective in improving the health outcomes of patients. Ramsey PG, Carline JD, Inui TS et al: Changes over time in the knowledge base of practicing internists. JAMA 1991;266:1103-7. Davis DA, Thompson MA, Oxman AD, Haynes RB: Changing physician performance. A systematic review of the effect of continuing medical education strategies. JAMA 1995;274:700-5.

11. Why is EBM important? • Knowledge translation – increasing the uptake of the best available evidence into practice – has always been a challenge • Scurvy: use of citrus was proven to prevent and cure scurvy in 1754, but it was almost 50 years after the data was published before lemon juice was added to British ships Table 1. Lind’s study on scurvy:1747 The James Lind Library. Available from http://www.jameslindlibrary.org/. Accessed 26 June 2008.

12. Why is EBM important? • Chloride of lime: In 1846 Ignatz Semmelweis attributed puerperal fever to an infection carried by obstetricians. Despite reducing maternal mortality from 18 to 1.2% by hand-washing in chloride of lime, his findings were rejected by the medical society of Vienna. It would take until the 1890’s before it was accepted that microorganisms can cause disease. Table 2. Mortality rates and characteristic of obstetrics clinics in Vienna 1784-1859

13. EBM processes can help with dissemination and adoption

14. Role of literature searching • Can improve the treatment of medical inpatients, even those already receiving evidence-based treatment. • Random sample of 146 inpatients cared for by 33 internal medicine attending physicians. • After physicians committed to a specific diagnosis and treatment plan, investigators performed standardized literature searches and provided the search results to the attending physicians. • Attending physicians changed treatment for 23 (18%) of the 130 eligible patients as a result of the literature searches. Lucas BP, Evans AT, et al. The impact of evidence on physician’s inpatient treatment decisions. J Gen Intern Med 2004;19:402-409.

15. Complementary/Alternative Medicine • Complementary and alternative medicine is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. • While some scientific evidence exists regarding some CAM therapies, for most there are key questions that are yet to be answered through well-designed scientific studies--such as: • Are these therapies safe? • Do these therapies work for the diseases or medical conditions for which they are used? National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at: http://nccam.nih.gov/health/.

16. Are Complimentary and Alternative Medicine Interchangeable Terms? • Complementary medicine is used together with conventional medicine. Example: Using aromatherapy to help lessen a patient's discomfort following surgery. • Alternative medicine is used in place of conventional medicine. Example: When Suzanne Somers rejected chemotherapy in favor of a drug called Iscador (uses extracts of Mistletoe) to treat her breast cancer. National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at: http://nccam.nih.gov/health/.

18. Family: Woman Died After Choosing Herbal Medicine Over Cancer Surgery Studies estimate that 60 percent of cancer patients try unconventional remedies and about 40 percent take vitamin or dietary supplements None has turned out to be a cure, although some show promise for easing symptoms. Touch therapies, mind-body approaches and acupuncture may reduce stress and relieve pain, nausea, dry mouth and possibly hot flashes, and are recommended by many top cancer experts. A recent study found that ginger capsules eased nausea if started days before chemotherapy. One quarter of supplements tested by an independent company over the last decade have had some sort of problem. Some contained contaminants. Others had contents that did not match label claims. Some had ingredients that exceeded safe limits. Some contained real drugs masquerading as natural supplements.

19. $2.5 billion spent, no alternative cures found Big, government-funded studies show most work no better than placebos The Associated Press updated 11:15 a.m. CT, Wed., June 10, 2009 BETHESDA, Md. - Ten years ago the government set out to test herbal and other alternative health remedies to find the ones that work. After spending $2.5 billion, the disappointing answer seems to be that almost none of them do. Echinacea for colds. Ginkgo biloba for memory. Glucosamine and chondroitin for arthritis. Black cohosh for menopausal hot flashes. Saw palmetto for prostate problems. Shark cartilage for cancer. All proved no better than dummy pills in big studies funded by the National Center for Complementary and Alternative Medicine. The lone exception: ginger capsules may help chemotherapy nausea. As for therapies, acupuncture has been shown to help certain conditions, and yoga, massage, meditation and other relaxation methods may relieve symptoms like pain, anxiety and fatigue.

20. Major Types of Complementary and Alternative Medicine • Alternative medicine systems: Built upon complete systems of theory and practice. Examples: homeopathic medicine, naturopathic medicine, traditional Chinese medicine, Ayurveda. • Mind-body interventions: Uses a variety of techniques designed to enhance the mind's capacity to affect bodily function and symptoms. Some techniques that were considered CAM in the past have become mainstream (patient support groups and cognitive-behavioral therapy). Other mind-body techniques are still considered CAM, including meditation, prayer, mental healing, and therapies that use creative outlets such as art, music, or dance. National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at: http://nccam.nih.gov/health/.

21. Major Types of Complementary and Alternative Medicine cont. • Biologically Based Therapies: Use substances found in nature (herbs, foods, and vitamins). Example: shark cartilage to treat cancer. • Examples of dietary supplements that have been incorporated into mainstream medicine: • Folic acid to prevent birth defects • Regimen of vitamins and zinc to slow the progression age-related macular degeneration (AMD). National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at: http://nccam.nih.gov/health/.

22. Major Types of Complementary and Alternative Medicine cont. • Manipulative or Body-Based Methods: Based on manipulation and/or movement of one or more parts of the body. Examples: chiropractic or osteopathic manipulation, massage. • Energy Therapies: Involve the use of energy fields. • Biofield therapies: intended to affect energy fields that purportedly surround and penetrate the human body (the existence of such fields has not yet been scientifically proven). Examples: qi gong, Reiki, Therapeutic Touch. • Bioelectromagnetic-based therapies: unconventional use of electromagnetic fields, such as pulsed fields, magnetic fields, or alternating-current or direct-current fields. National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at: http://nccam.nih.gov/health/.

23. NCCAM • National Center for Complementary and Alternative Medicine • Part of NIH, established in 1998 • Dedicated to exploring complementary and alternative healing practices in the context of rigorous science, training complementary and alternative medicine (CAM) researchers, and disseminating authoritative information to the public and professionals. • NCCAM Web site (nccam.nih.gov): publications, information for researchers, frequently asked questions, and links to other CAM-related resources.

27. Use of Alternative/Complementary Medicine in the U.S. • 36% of U.S. adults aged 18 years and over use some form of complementary and alternative medicine. • CAM use was greater among women; people with higher education; those who had been hospitalized within the past year; and former smokers, compared to current smokers or those who had never smoked. Barnes P, Powell-Griner E, McFann K, Nahin R. CDC Advance Data Report #343. Complementary and Alternative Medicine Use Among Adults: United States, 2002. May 27, 2004.

32. Developing clinical questions “To get the right answer, you must first ask the right question.”

33. Developing the clinical question • Step 1: Formulate the clinical issue into a searchable, answerable question. • Step 2: Distinguish what type of question you may have. Background Foreground Experience with Condition

34. Background questions • Background questions ask for general information about a condition or thing. • A question root (who, what, when, etc) combined with a verb. What microbial organisms can cause community-acquired pneumonia? Background questions are typically answered by textbooks.

35. Foreground questions • Foreground questions ask for specific knowledge about a specific patient with a specific condition. Is St. John’s Wort effective in relieving the symptoms of post-partum depression? Foreground questions are typically answered by databases that access the research literature

36. Developing the question • Foreground questions usually have four components. P = Patient population I = Intervention C = Comparison O = Outcome

37. PICO: Components of an answerable, searchable question Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia, PA: Lippincott Williams & Wilkins.

38. In patients with chronic pain, does the use of progressive muscle relaxationlead to a lessening of pain? In patients with significant anterior or posterior vaginal wall prolapse, do vaginal coneshelp? In patients with moderate depression, is St. John’s Wort vs. traditional SSRI’s effective in relieving symptoms with fewer adverse effects?

39. Types of Questions • Diagnosis: How to select a diagnostic test or how to interpret the results of a particular test. • Prognosis: What is the patient's likely course of disease, or how to screen for or reduce risk. • Therapy: Which treatment is the most effective, or what is an effective treatment for a particular condition. • Harm or Etiology: Are there harmful effects of a particular treatment, or how these harmful effects can be avoided. • Prevention: How can the patient's risk factors be adjusted to help reduce the risk of disease? • Cost: Looks at cost effectiveness, cost/benefit analysis.

40. Question Templates for Asking PICO QuestionsTherapyIn __________________, what is the effect of ____________________ on ______________________ compared with __________________?EtiologyAre ______________ who have _________________ at ________________ risk for/of ____________________ compared with _____________________ with/without ______________________?Diagnosis or Diagnostic TestAre (Is) _________________________ more accurate in diagnosing ________________ compared with ________________?PreventionFor _________________ does the use of _______________ reduce the future risk of ________________ compared with _________________?PrognosisDoes _______________ influence _________________ in patients who have __________________? Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia, PA: Lippincott Williams & Wilkins.

41. Medical literature • Primary – original research • Experimental (an intervention is made or variables are manipulated) • Randomized Control Trials • Controlled trials • Observational (no intervention or variables are manipulated) • Cohort studies • Case-control studies • Case reports • Secondary – reviews of original research • Meta-analysis • Systematic reviews • Practice guidelines • Reviews • Decision analysis • Consensus reports • Editorial, commentary

42. Case series/case reports • Reports on treatment, etc. of individual patients • Anbar RD, Savedoff AD. Treatment of binge eating with automatic word processing and self-hypnosis: a case report.Am J Clin Hypn. 2005 Oct-2006 Jan;48(2-3):191-8. • Binge eating frequently is related to emotional stress and mood problems. In this report, we describe a 16-year-old boy who utilized automatic word processing (AWP) and self-hypnosis techniques in treatment of his binge eating, and associated anxiety, insomnia, migraine headaches, nausea, and stomachaches. He was able to reduce his anxiety by gaining an understanding that it originated as a result of fear of failure. He developed a new cognitive strategy through AWP, after which his binge eating resolved and his other symptoms improved with the aid of self-hypnosis. Thus, AWP may have helped achieve resolution of his binge eating by uncovering the underlying psychological causes of his symptoms, and self-hypnosis may have given him a tool to implement a desired change in his behavior.

43. Case Control Studies • Studies in which patients who already have a specific condition are compared with people who do not • Rely on medical records and patient recall for data collection

44. Hepatitis C; a retrospective study, literature review, and naturopathic protocol. Milliman WB. Lamson DW. Brignall MS. Alternative Medicine Review. 5(4):355-71, 2000 Aug. The standard medical treatment of hepatitis C infection is only associated with sustained efficacy in a minority of patients. Therefore, the search for other treatments is of utmost importance. Several natural products and their derivatives have demonstrated benefit in the treatment of hepatitis C and other chronic liver conditions. Other herbal and nutritional supplements have mechanisms of action that make them likely to be of benefit. This article presents comprehensive protocol, including diet, lifestyle, and therapeutic interventions. The authors performed a retrospective review of 41 consecutive hepatitis C patients. Of the 14 patients with baseline and follow-up data who had not undergone interferon therapy, seven had a greater than 25-percent reduction in serum alanine aminotransferase (ALT) levels after at least one month on the protocol. For all patients reviewed, the average reduction in ALT was 35 U/L (p=0.026). These data appear to suggest that a conservative approach using diet and lifestyle modification, along with safe and indicated interventions, can be effective in the treatment of hepatitis C. Controlled trials with serial liver biopsy and viral load data are necessary to confirm these preliminary findings.

45. Cohort studies • From a large population, follows patients who have a specific condition or receive a particular treatment over time and compared with another group that has not been affected by the condition or treatment studies

46. Kristal AR, Littman AJ, Benitez D, White E.Yoga practice is associated with attenuated weight gain in healthy, middle-aged men and women. Altern Ther Health Med. 2005 Jul-Aug;11(4):28-33.BACKGROUND: Yoga is promoted or weight maintenance, but there is little evidence of its efficacy. OBJECTIVE: To examine whether yoga practice is associated with lower mean 10-year weight gain after age 45. PARTICIPANTS: Participants included 15,550 adults, aged 53 to 57 years, recruited to the Vitamin and Lifestyle (VITAL) cohort study between 2000 and 2002. MEASUREMENTS: Physical activity (including yoga) during the past 10 years, diet, height, and weight at recruitment and at ages 30 and 45. All measures were based on self-reporting, and past weight was retrospectively ascertained. METHODS: Multiple regression analyses were used to examined covariate-adjusted associations between yoga practice and weight change from age 45 to recruitment, and polychotomous logistic regression was used to examine associations of yoga practice with the relative odds of weight maintenance (within 5%) and weight loss (> 5%) compared to weight gain. RESULTS: Yoga practice for four or more years was associated with a 3.1-lb lower weight gain among normal weight (BMI < 25) participants [9.5 lbs versus 12.6 Ibs] and an 18.5-lb lower weight gain among overweight participants [-5.0 lbs versus 13.5 Ibs] (both P for trend <.001). Among overweight individuals, 4+ years of yoga practice was associated with a relative odds of 1.85 (95% confidence interval [CI] 0.63-5.42) for weight maintenance (within 5%) and 3.88 (95% Cl 1.30-9.88) for weight loss (> 5%) compared to weight gain (P for trend .026 and .003, respectively). CONCLUSIONS: Regular yoga practice was associated with attenuated weight gain, most strongly among individuals who were overweight. Although causal inference from this observational study is not possible, results are consistent with the hypothesis that regular yoga practice can benefit individuals who wish to maintain or lose weight.

47. Randomized controlled trials • Study effect of therapy on real patients • Include methodologies that reduce the potential for bias • Intervention group vs control group • Patients assigned in randomized fashion • Blinded or non-blinded studies

48. Harikumar R, Raj M, Paul A, Harish K, Kumar SK, Sandesh K, Asharaf S, Thomas V. Listening to music decreases need for sedative medication during colonoscopy: a randomized, controlled trial. Indian J Gastroenterol. 2006 Jan-Feb;25(1):3-5. • BACKGROUND: Music played during endoscopic procedures may alleviate anxiety and improve patient acceptance of the procedure. A prospective randomized, controlled trial was undertaken to determine whether music decreases the requirement for midazolam during colonoscopy and makes the procedure more comfortable and acceptable. METHODS: Patients undergoing elective colonoscopy between October 2003 and February 2004 were randomized to either not listen to music (Group 1; n=40) or listen to music of their choice (Group 2; n=38) during the procedure. All patients received intravenous midazolam on demand in aliquots of 2 mg each. The dose of midazolam, duration of procedure, recovery time, pain and discomfort scores and willingness to undergo a repeat procedure using the same sedation protocol were compared. RESULTS: Patients in Group 2 received significantly less midazolam than those in Group 1 (p=0.007). The pain score was similar in the two groups, whereas discomfort score was lower in Group 2 (p=0.001). Patients in the two groups were equally likely to be willing for a repeat procedure. CONCLUSION: Listening to music during colonoscopy helps reduce the dose of sedative medications and decreases discomfort experienced during the procedure.

49. Systematic review • Extensive literature search is conducted in systematic fashion • Only uses studies with sound methodology • Studies are collected, reviewed, assessed and the results summarized according to predetermined criteria of the review question

50. Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. The Cochrane Database of Systematic Reviews 2004, Issue 2. Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in preventing such infections.Objectives: To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptible populations.Search strategy: Electronic databases and the Internet were searched using English and non English language terms; companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of review articles and relevant trials were searched…searched in February 2003.Selection criteria: All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of urinary tract infections in susceptible populations. Trials of men, women or children were included.Data collection and analysis: Two reviewers independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic and asymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria.Main results: Seven trials met the inclusion criteria (four cross-over, three parallel group). The effectiveness of cranberry juice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness of cranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two good quality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91) compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave 1:30 concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIs between cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five trials were not included in the meta-analyses due to methodological flaws or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trials were high.Authors' conclusions: There is some evidence from two good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly men and women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juice may not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method of administration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.