Evidence Based Medicine

Clista Clanton, MSLS, AHIPJune 28 & 29, 2012

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

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.

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 isnt. BMJ, 312, 71-72.

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  lack of time  out-of-date textbooks, and  the disorganization of the up-to-date journals6Covell DG, Uman GC, Manning PR: Information needs in office practice: Are they being met? Ann Intern Med 1985;103:596-9.

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 continuingmedical education strategies. JAMA 1995;274:700-5.

Why is EBM important?  Knowledge translation – Table 1. Lind’s study on scurvy:1747 increasing the uptake of Additive to diet (n=2 Observed the best available evidence in each group effect into practice – has always Quart of cider Minor been a challenge improvement  Scurvy: use of citrus was Unspecified elixir No change proven to prevent and cure t.d.s scurvy in 1754, but it was Seawater No change almost 50 years after the data was published before lemon juice was added to Garlic, mustard and No change British ships horseradish Spoonfuls of vinegar No change Two oranges and a DramaticThe James Lind Library. Available from lemon recoveryhttp://www.jameslindlibrary.org/. Accessed 26 June 2008.

Puerperal fever mortality rates for the First and Second Clinic at the Vienna GeneralHospital 1841-1846. The top line is the First Clinic, bottom line Second Clinic.

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 Period Characteristics of period No. No. Maternal deliveries maternal deaths/1000 deaths deliveries 1784- No routine post-mortems 71,395 897 12.5 1822 1823- Routine post-mortems 65,035 3,745 57.6 1838 1839- Clinic arrangements changed 1847 First clinic: doctors and students 20,204 1,989 90.2 Second clinic: midwives 17,791 691 33.8 1848- Hand-washing introduced 1859 First clinic 47,938 1,712 35.7 Second clinic 40,770 1,248 30.6

EBM processes can help withdissemination and adoption

Complementary/Alternative Medicine and alternative medicine is a group of diverse Complementary 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/.

Are Complimentary and Alternative Medicine Interchangeable Terms?  Complementary medicine is used together with conventional medicine. Example: Using aromatherapy to help lessen a patients 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. Availableat: http://nccam.nih.gov/health/.

Family: Woman Died After Choosing HerbalMedicine 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.

$2.5 billion spent, no alternative cures foundBig, government-funded studies show most work no better than placebosThe Associated Pressupdated 11:15 a.m. CT, Wed., June 10, 2009BETHESDA, Md. - Ten years ago the government set out to test herbal andother alternative health remedies to find the ones that work. After spending$2.5 billion, the disappointing answer seems to be that almost none of themdo.Echinacea for colds. Ginkgo biloba for memory. Glucosamine and chondroitinfor arthritis. Black cohosh for menopausal hot flashes. Saw palmetto forprostate problems. Shark cartilage for cancer. All proved no better thandummy pills in big studies funded by the National Center for Complementaryand Alternative Medicine. The lone exception: ginger capsules may helpchemotherapy nausea.As for therapies, acupuncture has been shown to help certain conditions, andyoga, massage, meditation and other relaxation methods may relievesymptoms like pain, anxiety and fatigue.

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 minds 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. Availableat: http://nccam.nih.gov/health/.

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. Availableat: http://nccam.nih.gov/health/.

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. Availableat: http://nccam.nih.gov/health/.

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.

What is EBM? “Evidenced-based medicine is the concept of formalizing thescientific approach to the practice of medicine for identificationof “evidence” to support our clinical decisions. It requires anunderstanding of critical appraisal and the basic epidemiologicprinciples of study design, point estimates, relative risk, oddsratios, confidence intervals, bias, and confounding. By using thisinformation, clinicians can categorize evidence, assess causality,and make evidence-based recommendations. Evidence-basedmedicine allows analysis of complicated material so that we canmake the best possible clinical decisions for the populations weserve.”Williams JK. Understanding evidence-based medicine: a primer. Am J Obstet Gynecol 2001:185-275-278.

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

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.

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

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

PICO: Components of an answerable, searchable questionPatient population/disease The patient population or disease of interest - age - gender - ethnicity - with certain disorder (e.g., hepatitis)Intervention The intervention or range of interventions of interest - Exposure to disease - Prognostic factor A - Risk behavior (e.g., smoking)Comparison What you want to compare the intervention against - No disease - Placebo or no intervention/therapy - Prognostic factor B - Absence of risk factor (e.g., non-smoking)Outcome Outcome of interest - Risk of disease - Accuracy of diagnosis - Rate of occurrence of adverse outcome (e.g., death)Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia,PA: Lippincott Williams & Wilkins.

In patient with does or affect[Patient/ [Intervention] [Comparison, [Outcome]Problem] if any]In patients with chronic pain, does the use of progressivemuscle relaxation lead to a lessening of pain?In patients with significant anterior or posterior vaginalwall prolapse, do vaginal cones help?In patients with moderate depression, is St. John’s Wortvs. traditional SSRI’s effective in relieving symptomswith fewer adverse effects?

Types of Questions Diagnosis: How to select a diagnostic test or how to interpret the results of a particular test. Prognosis: What is the patients 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 patients risk factors be adjusted to help reduce the risk of disease? Cost: Looks at cost effectiveness, cost/benefit analysis.

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.

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

Case series/case reports Reports on treatment, etc. of individual patientsAnbar RD, Savedoff AD. Treatment of binge eating with automatic wordprocessing 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 thisreport, we describe a 16-year-old boy who utilized automatic word processing(AWP) and self-hypnosis techniques in treatment of his binge eating, andassociated anxiety, insomnia, migraine headaches, nausea, and stomachaches. Hewas able to reduce his anxiety by gaining an understanding that it originated as aresult of fear of failure. He developed a new cognitive strategy through AWP, afterwhich his binge eating resolved and his other symptoms improved with the aid ofself-hypnosis. Thus, AWP may have helped achieve resolution of his binge eatingby 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.

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

Hepatitis C; a retrospective study, literature review, and naturopathicprotocol. Milliman WB. Lamson DW. Brignall MS. Alternative MedicineReview. 5(4):355-71, 2000 Aug.The standard medical treatment of hepatitis C infection is only associated withsustained efficacy in a minority of patients. Therefore, the search for othertreatments is of utmost importance. Several natural products and theirderivatives have demonstrated benefit in the treatment of hepatitis C andother chronic liver conditions. Other herbal and nutritional supplements havemechanisms of action that make them likely to be of benefit. This articlepresents comprehensive protocol, including diet, lifestyle, and therapeuticinterventions. The authors performed a retrospective review of 41 consecutivehepatitis C patients. Of the 14 patients with baseline and follow-up data whohad not undergone interferon therapy, seven had a greater than 25-percentreduction in serum alanine aminotransferase (ALT) levels after at least onemonth on the protocol. For all patients reviewed, the average reduction in ALTwas 35 U/L (p=0.026). These data appear to suggest that a conservativeapproach using diet and lifestyle modification, along with safe and indicatedinterventions, can be effective in the treatment of hepatitis C. Controlled trialswith serial liver biopsy and viral load data are necessary to confirm thesepreliminary findings.

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

Kristal AR, Littman AJ, Benitez D, White E.Yoga practice is associated with attenuated weight gain in healthy, middle-aged menand women. Altern Ther Health Med. 2005 Jul-Aug;11(4):28-33.BACKGROUND: Yoga is promoted or weight maintenance, but there is little evidence ofits efficacy. OBJECTIVE: To examine whether yoga practice is associated with lower mean10-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 between2000 and 2002. MEASUREMENTS: Physical activity (including yoga) during the past 10years, diet, height, and weight at recruitment and at ages 30 and 45. All measures werebased on self-reporting, and past weight was retrospectively ascertained. METHODS:Multiple regression analyses were used to examined covariate-adjusted associationsbetween yoga practice and weight change from age 45 to recruitment, andpolychotomous logistic regression was used to examine associations of yoga practice withthe relative odds of weight maintenance (within 5%) and weight loss (> 5%) compared toweight gain. RESULTS: Yoga practice for four or more years was associated with a 3.1-lblower 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 wasassociated with a relative odds of 1.85 (95% confidence interval [CI] 0.63-5.42) for weightmaintenance (within 5%) and 3.88 (95% Cl 1.30-9.88) for weight loss (> 5%) compared toweight gain (P for trend .026 and .003, respectively). CONCLUSIONS: Regular yogapractice was associated with attenuated weight gain, most strongly among individualswho were overweight. Although causal inference from this observational study is notpossible, results are consistent with the hypothesis that regular yoga practice can benefit

Randomized controlledtrials 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

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.

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

Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. The Cochrane Database of SystematicReviews 2004, Issue 2.Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for theprevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness ofcranberries in preventing such infections.Objectives: To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptiblepopulations.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 ofreview 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 ofurinary 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 wascollected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic andasymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrativesynthesis 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 cranberryjuice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness ofcranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two goodquality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to0.91) compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave1:30 concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIsbetween 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 theoutcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trialswere high.Authors conclusions: There is some evidence from two good quality RCTs that cranberry juice may decrease the numberof symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly menand women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juicemay not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method ofadministration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.

Meta-analysis Examines a group of valid studies on a topic Combines results using accepted statistical methodology to reach a consensus on the overall results

Linde K, Berner M, Egger M, Mulrow C.St Johns wort for depression: meta-analysis of randomised controlled trials.Br J Psychiatry. 2005 Feb;186:99-107.BACKGROUND: Extracts of Hypericum perforatum (St Johns wort) are widelyused to treat depression. Evidence for its efficacy has been criticised onmethodological grounds. AIMS: To update evidence from randomised trialsregarding the effectiveness of Hypericum extracts.METHODS: We performed a systematic review and meta-analysis of 37 double-blind randomised controlled trials that compared clinical effects of Hypericummonopreparation with either placebo or a standard antidepressant in adultswith depressive disorders.RESULTS: Larger placebo-controlled trials restricted to patients with majordepression showed only minor effects over placebo, while older and smallertrials not restricted to patients with major depression showed marked effects.Compared with standard antidepressants Hypericum extracts had similareffects. CONCLUSIONS: Current evidence regarding Hypericum extracts isinconsistent and confusing. In patients who meet criteria for major depression,several recent placebo-controlled trials suggest that Hypericum has minimalbeneficial effects while other trials suggest that Hypericum and standardantidepressants have similar beneficial effects.

Levels of evidence Level I: obtained from at least one properly controlled randomized trial, considered the gold standard of evidence. Level II-1:derived from controlled trials without randomization. Level II-2: well-designed cohort or case-control studies. Level II-3: includes studies with external control groups or ecological studies. Level III evidence is derived from reports of expert committees, not because it is weaker than levels I or II, but because it is often difficult to ascertain the scientific origin of the committee opinion.

Evidence Pyramid Meta-analysis Systematic ReviewRandomized Controlled Trial Cohort Studies Case Control Studies Case Series/Case Reports Animal Research

Type of Question Suggested Best Type of StudyTherapy RCT > cohort > case control > case seriesDiagnosis Prospective, blind comparison to gold standardEtiology / Harm RCT > cohort > case control > case seriesPrognosis Cohort study > case control > case seriesPrevention RCT > cohort study > case control > case seriesClinical Exam Prospective, blind comparison to gold standardCost Economic analysisQuestions of therapy, etiology and prevention which can best beanswered by RCT can also be answered by a meta-analysis orsystematic review.

In patient with does or affect[Patient/ [Intervention] [Comparison, [Outcome]Problem] if any]Question:In adult with acute maxillary sinusitis, does a 3-daycourse of trimethoprim-sulfamethoxazole yield thesame cure rates as a 10-day course, with feweradverse effects and costs?Type of question: Type of study: RCT>cohort>case control> case Therapy series

A 42-year old woman presented at the emergency room of the hospitalcomplaining of muscle pain and tiredness. She was found to havehyperventilation and weakness of four limbs, with muscle power of grade 5( )/5. All her symptoms gradually subsided over the next few hours. Historyrevealed she was taking maqianzi, a herbal remedy, for neck pain. Couldthis herbal supplement have caused her problems?In patient with does or affect[Patient/ Problem] [Intervention] [Comparison, if [Outcome] any]Question:In an adult woman, does maqianzi cause muscle pain and tiredness? Type of question: Type of study: Etiology RCT>cohort>case control> case series

You have heard that kidney yin deficiency is a valid tool to diagnose postmenopausal women with vasomotor symptoms. You need to find further information on this test.In patient with does or affect[Patient/ Problem] [Intervention] [Comparison, if [Outcome] any]Question:In a postmenopausal woman is kidney yin deficiency as effective asstandard tools in diagnosis of vasomotor symptoms? Type of question: Type of study: Diagnosis Prospective blind comparison to gold standard

Systems Computerized decision support Summaries Dynamed, UptoDate, PIER Clinical Evidence, EBM guidelines Adapted from Haynes (2001) Synopses TRIP ACP Journal Club Syntheses Cochrane Systematic Reviews, DARE Studies PubMed, CINAHL, ScopusHaynes RB. Of studies, summaries, synopses, and systems: the “5S" evolution of services for finding current best evidence. ACP JournalClub. 2001;134: A11–13.

If an original study is your best option…….Original Studies

IMRAD format Introduction: why the authors decided to conduct the research. Methods: how they conducted the research and analyzed their results. Results: what was found. And Discussion: what the authors think the results mean.

PP-ICONS  Problem  Patient or population  Intervention  Comparison  Outcome  Number of subjects  StatisticsFlaherty, Robert J. A simple method for evaluating the clinical literature. Fam Prac Mgt, May 2004;47-52. Available online athttp://www.aafp.org/fpm/20040500/47asim.html.

Scenario You just saw a nine-year old patient with common warts on her hands. She is an ideal candidate for cryotherapy. Her mother has heard about treating warts with duct tape and wants to know if you would recommend this treatment.

Clinical question What is your clinical question? PICO: Patient, Intervention/Comparison, Outcome “In children with warts, is duct tape as effective as cryotherapy in eliminating the wart?

Search After you have your clinical question, search the appropriate databases:  Dynamed, PIER, UpToDate, Cochrane, Clinical Evidence  PubMed Focht DR 3rd, Spicer C, Fairchok MP. The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart). Arch Pediatr Adolesc Med. 2002 Oct;156(10):971-4.

Abstract OBJECTIVE: To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts. DESIGN: A prospective, randomized controlled trial with 2 treatment arms for warts in children. SETTING: The general pediatric and adolescent clinics at a military medical center. PATIENTS: A total of 61 patients (age range, 3-22 years) were enrolled in the study from October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for analysis. INTERVENTION: Patients were randomized using computer-generated codes to receive either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a maximum of 2 months. Patients had their warts measured at baseline and with return visits. MAIN OUTCOME MEASURE: Complete resolution of the wart being studied. RESULTS: Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did so within the first month of treatment. CONCLUSION: Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.

Problem (PP-ICONS)  What is the clinical condition that was studied in the article? OBJECTIVE: To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts. The problem studied should be sufficiently similar to your clinical problem, or the results will not be relevant.

Patient or Population (PP-ICONS) Is the study group similar to your patient or practice? SETTING: The general pediatric and adolescent clinics at a military medical center. PATIENTS: A total of 61 patients (age range, 3-22 years) If the patients in the study are not similar to your patient (older, sicker, different gender or more clinically complicated), the results may not be relevant.

Intervention (PP-ICONS) Is the intervention the same as what you are looking for?  Could be a diagnostic test or a treatment The patient’s mother has heard about treating warts with duct tape and wants to know if you would recommend this treatment.

Comparison (PP-ICONS) The comparison is what the treatment is tested against.  Could be a different diagnostic test, another therapy, placebo, or no treatment at all.INTERVENTION: Patients were randomized usingcomputer-generated codes to receive eithercryotherapy (liquid nitrogen applied to each wart for10 seconds every 2-3 weeks) for a maximum of 6treatments or duct tape occlusion (applied directly tothe wart) for a maximum of 2 months.

Outcome (PP-ICONS) Disease-oriented outcomes (DOEs): usually reflect changes in physiologic parameters.  It has long been assumed that improving the physiologic parameters of a disease will result in a better outcome, but this is not always true. Patient-oriented evidence that matters (POEMs): look at outcomes such as morbidity, mortality and cost. Therefore, DOEs are interesting but of questionable relevance, whereas POEMs are very interesting and very relevant. MAIN OUTCOME MEASURE: Complete resolution of the wart being studied.

Number (PP-ICONS)  Number of subjects in the study is crucial in whether accurate statistics can be generated from the data.  Too few patients may not be enough to show that a difference really exists between intervention and comparison groups (power of a study).  Many studies contain <100 subjects, which is usually inadequate to provide reliable statistics.  Good rule of thumb – 400 subjects needed. 51 patients completed the studyKrejcie RV, Morgan DW. Determining sample size for research activities. Educational and Psychological Measurements. 1970;30:607-610.

Statistics (PP-ICONS) Relative risk reduction (RRR): the percent reduction in events in the treated group compared to the control group event rate.  Not a good way to compare outcomes  Amplifies small differences and makes insignificant findings appear significant  Doesn’t reflect the baseline risk of the outcome event  Can make weak results look good, therefore  Popular and will be reported in almost every journal article  Ignore – it can mislead you RRR would be (85 percent – 60 percent/60 percent x 100 = 42 percent I.e. 42 percent more effective than cryotherapy in treating warts

Statistics (PP-ICONS) Absolute risk reduction (ARR): the difference in the outcome event rate between the control group and the experimental group. ARR for the wart study is the outcome event rate (complete resolution of warts) for duct tape (85 percent) minus the outcome event rate for cryotherapy (60 percent) = 25 percent  A better statistic to evaluate outcome, as it does not amplify small differences, but shows the true difference between the experimental and control interventions.

Statistics (PP-ICONS) Number needed to treat (NNT): number of patients who must be treated to prevent one adverse outcome OR the number of patients who must be treated for one patient to benefit  Single most clinically useful statistic  Easy to calculate, simply the inverse of the ARR. For the wart study, the NNT is 1/25 percent = 1/0.25 = 4 4 patients need to be treated with duct tape for one to benefit more than if treated by cryotherapy  The lower the NNT, the better. For primary therapies, an NNT of 10 or less is good, with less than 5 being very good.  For preventive interventions, the NNT will be higher. A NNT for prevention of less than 20 might be particularly good.

Intention to Treat Analysis  Attrition: Were patients lost to follow-up, and if so, why? Intention to treat: subjects are analyzed according to the categories into which they were originally randomized. – Benefits of a treatment are more difficult to demonstrate with intention-to-treat analysis. – Helps to mitigate differences by including subjects who are unlikely to have experienced benefit from the intervention. Six patients from cryotherapy group and 4 patients from the duct tape group were lost to follow-up (16% of patients). Worst case scenario: 6 cryotherapy patients had wart resolution and the 4 duct tape patients had residual wart. Wart resolution would then be: duct tape 78% and cryotherapy 68% (95% CI, -17 to 28) – therefore not a statistically significant difference between the two treatments.Christakis DA, Lehmann HP. Is duct tape occlusion therapy as effective as cryotherapy for the treatment of the common wart? Arch Pediatr Adolesc Med, Oct 2002; vol.156; 975-977.

Best Type of Study for Your Question Type of Question Suggested Best Type of StudyTherapy RCT > cohort > case control > case seriesDiagnosis Prospective, blind comparison to gold standardEtiology / Harm RCT > cohort > case control > case seriesPrognosis Cohort study > case control > case seriesPrevention RCT > cohort study > case control > case seriesClinical Exam Prospective, blind comparison to gold standardCost Economic analysisQuestions of therapy, etiology and prevention which can best be answeredby RCT can also be answered by a meta-analysis or systematic review.

Assignment Identify a clinical problem with a patient Formulate a clinical question using PICO Search the literature for appropriate article(s) Evaluate the article(s) Complete the online assignment within two weeks after date of lecture. http://biomedicallibrary.southalabama.edu/library/?q=ebmrotationsassignment

Evidence Based Medicine

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