Introduction to EBM

Introduction to EBM Rodney Smith, MD St. Joseph Mercy Hospital University of Michigan Objectives  What is EBM and Why do it?  Describe the EBM Process and its components      Patient Problem Clinical question Search for Evidence Critical Appraisal of the Evidence Apply the Results  The EBM Lecture Introduction  What is EBM?  "...the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients."  Integrated with clinical expertise  expertise in performing the history and physical examination  knowledge of the patient, the family, and the community which creates a context for therapeutic decision-making  a relationship with the patient informed by his or her beliefs and values  practical knowledge of the availability of resources in the community Introduction Introduction  "Without clinical expertise, practice risks becoming tyrannized by external evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient. Without current best external evidence, practice risks becoming rapidly out of date, to the detriment of patients." Introduction  Why do EBM     It is required by RRC/Residency Provide high quality care to patients Utilize high quality evidence in patient care Overcome limitations of current practice Introduction  Examples    Prevention of SIDS…”Back to Sleep” Patching corneal abrasion Arryhthmia suppression     Ecainide/flecainide Arrhythmia suppression RCT increased mortality Disease specific vs. patient specific outcomes Introduction  The failure of common sense    I shake a tree, an apple falls out, now I can eat I give antibiotics for sinusitis, the patient gets better, I’m doing a good job as a doctor I just saw a patient with tumor lysis syndrome, I will start looking for it more and maybe I’ll find it more Introduction  Variation in practice  Rate of prostatectomy for prostate CA Introduction Introduction  Source of Medical Information       Colleagues Conferences Drug Reps Textbooks Journals Internet/Patients Introduction The Clinical Question  Physician recall  1 question per 4 patients  Direct observation Covell DG, et al. Ann Intern Med 1985;103:596-9.     2 questions per 3 patients 15 questions per shift Information sources  Textbooks  PDR  Human sources 2/3 of questions go unanswered The Clinical Question  Unrecognized  Recognized  Pursued  Satisfied  Implemented The Clinical Question The Question  Background        Anatomy and Physiology Pathophysiology Pharmacology and Toxicology Differential diagnosis Diagnostic testing Treatment Textbooks, reviews, lectures, experts The Clinical Question  Foreground    Detailed information Patient focus Evidence-based process The Clinical Question  Patient or problem  Intervention  Comparison  Outcome The Question  Patient or Problem   Starts from the patient encounter Unrecognized vs. Recognized  Intervention  Be specific  Compared to what  Outcome  Disease-center vs. Patient-centered Example  68 yo WF, Hx CHF, S/P CABG, HTN, COPD  Meds: Digoxin, Lasix, Isosorbide, Albuterol  Mild increase in DOE past 4 days  Acutely SOB 1hr PTA  188/104 122 30 98.8 90% Non-rebreather  Crackles bases, Wheezes scattered  JVD, S3 gallop  Pretibial edema 2+ Example  BNP now available at St. Joe’s  Should I order a BNP on this patient? The Clinical Question  Patient or problem  Intervention  Comparison  Outcome The Question  ED patients with acute dyspnea  BNP  Standard evaluation  Diagnosis of CHF Finding the Evidence  Textbooks – NOT!   Always out of date Recommendations often not referenced Finding the Evidence  Textbooks  Clinical Evidence        Published twice yearly Full version 1900 pages Concise version 400 pages CD ROM Online Access Cost $110 www.clinicalevidence.com Finding the Evidence  Textbooks  Scientific American Medicine   Online subscription $199 www.samed.com Online subscription $99 www.harrisonsonline.com  Harrison’s Textbook of Internal Medicine   Finding the Evidence  EBM Textbook     Evidence-Based On-Call Database of critically appraised topics (CATs) Bullet points with links to in-depth CAT www.eboncall.co.uk/content.jsp.htm Finding the Evidence  EBM Journals  ACP Journal Club     6 Issues per year Online access $78/yr Individual $55/yr Residents Finding the Evidence  EBM Journals  Bandolier    Summaries of secondary reviews Free online access www.jr2.ox.ac.uk/bandolier Finding the Evidence  EBM Journals  Evidence Based Medicine    Now combined with ACP Journal Club Articles from 1999 and prior available free online www.acponline.org/journals/ebm/ebmmenu.htm Finding the Evidence  EBM Databases  Evidence Based Medicine Reviews (EBMR)   Commercially available thru OVID Searches a variety of databases  Cochrane Database of Systematic Reviews  ACP Journal Club  Medline  Links databases together Finding the Evidence  EBM Databases  Cochrane Library   The Cochrane Database of Systematic Reviews The Cochrane Controlled Trials Register Finding the Evidence  EBM Databases  SUMSearch  Merck Manual.  MEDLINE for review articles and editorials from high quality, general journals that have full texts available.  National Guideline Clearinghouse from the Agency for Health Care Policy and Research (AHCPR)  Database of Abstract of Reviews of Effectiveness (DARE)  MEDLINE for original research  sumsearch.uthscsa.edu Finding the Evidence  EBM Databases  MEDLINE     Free online access thru PubMed www.ncbi.nlm.nih.gov/entrez/ Search by MESH terms or free text EBM Filters Finding the Evidence Finding the Evidence Finding the Evidence Finding the Evidence Finding the Evidence Finding the Evidence Finding the Evidence  Filters for Medline Search  Treatment   Randomized controlled trial Blind or Double Blind Sensitivity and Specificity  Diagnosis  Critical Appraisal  Is the evidence valid?  Is evidence important?  Does the evidence apply to our patient? Critical Appraisal  Users’ Guides to the Medical Literature  Book by Guyatt and Rennie   Available thru AMA/ Amazon.com $35/$60 CD-ROM version   www.usersguides.org www.cche.net/usersguides/main.asp/ Critical Appraisal  Diagnosis  Is the evidence valid?     Was there an independent, blinded comparison with a gold standard? Was the test evaluated in an appropriate spectrum of patients? Was the reference standard applied regardless of the test result? Was the test validated in a second, independent group of patients? Critical Appraisal  Diagnosis  Is this valid test important?    Distinguish between patients with and those without the disease Two by two tables Sensitivity and Specificity  SnNOut  SpPIn   ROC curves Likelihood Ratio 2 X 2 Table  Sensitivity = 90%  Specificity = 90%  Pos Predictive Value = Disease 90%  Neg Predictive Value = 90% Test Pos Present Absent 90 10 Test Neg 10 90 2 X 2 Table  Sensitivity = 90%  Specificity = 90%  Pos Predictive Value = Disease 8.3% (90/1090)  Neg Predictive Value = 99.9% (9000/9010)  Prevalence = 1% Test Pos Present Absent 90 1000 Test Neg 10 9000 2 by 2 Table  90% with disease have a positive test  15% without disease have a positive test  Someone with a Pos test is 6X more likely to have the disease as not (90%/15%)  Likelihood Ratio +  Disease Present Test Pos Test Neg 90 10 Absent 15 85 105 95 Sens /(1- Spec) 100 100 200 2 by 2 Table  10% with disease have a positive test  85% without disease have a positive test  Someone with a Neg test is less likely to have the disease by 1/8.5 X (10%/85%)  Likelihood Ratio  Disease Present Test Pos Test Neg 90 10 Absent 15 85 105 95 (1-sens)/spec 100 100 200 2 X 2 Table  Pre-test Odds X LR = Post-test Odds  Pre-test Odds = Pretest Prob/(1-Pretest Prob)  Post-test Probability = Posttest Odds/(1 + Posttest Odds) Probability to Odds Probability 1/2 Odds 1:1 Decimal 1.0 1/3 3/4 0.45 1:2 3:1 0.45:0.55 0.5 3.0 0.8 Odds to Probability Odds Probability 0.5 :1 0.25 :1 2.0 :1 10.0 :1 0.33 0.20 0.66 0.91 Critical Appraisal  Diagnosis  Can I apply this test to a specific patient     Is it available Is it affordable Is it accurate Is it precise Critical Appraisal  Diagnosis  Can I apply this test to a specific patient  Can I generate a sensible pre-test probability  Personal experience  Practice database  Assume prevalence in the study Critical Appraisal  Diagnosis  Can I apply this test to a specific patient  Will the post-test probability affect management  Movement above treatment threshold  Patient willing to undergo testing Critical Appraisal  Treatment  Are the results of this study Valid?       Were treatment assignments randomized and concealed? Was follow-up sufficiently long? Were patients evaluated in the group to which they were assigned? Was it double-blind? Were treatments equal apart from study treatment? Were the groups similar at the start of treatment? Critical Appraisal  Therapy  Are the valid results of this trial Important?   What is the magnitude of the treatment effect? How precise is this estimate of the treatment effect?  95% CI  Directly related to number of patients in a study Therapy  Are the valid results of this trial Important?  What is the magnitude of the treatment effect?  CER = control event rate  EER = experimental event rate  RRR = relative risk reduction = |CER – EER|/CER  ARR = absolute risk reduction = |CER – EER|  NNT = Number needed to treat = 1 / ARR Critical Appraisal CER EER RRR ARR NNT 50% 25% 50% 25% 4 5% 2.50% 50% 2.50% 40 0.05% 0.025% 50% 0.03% 4000 Critical Appraisal  Therapy  Are the valid, important results applicable to our patient?     How similar is our patient to the patients studied? Is the treatment feasible? What are our patient’s potential benfits and harms from the therapy? What are our patient’s values and expectations for both the outcome we are trying to prevent and the treatment we are offering? Critical Appraisal  Therapy CER Stroke or Death 5yr 50% - 69% EER RRR ARR NNT 43% 33% 23% 10% 10 Stroke or Death 5yr <50% 37% 36.20% 2% 1% 126 Stroke or Death 30 Days 2.40% 6.700% 179% 4% 24 Summary of Evidence  Critically Appraised Topic        Bottom line, bullet points PICO question Search Terms Summary of paper and results table Comments Expiration date References Using EBM in Emergency Medicine  EBM Lectures  Case conferences  Core lectures  Sign-out rounds  The “EBM Prescription”  Patient information  The Clinical Question (PICO)  Secondary sources Introduction to EBM Intermission The Question  ED patients with acute dyspnea  BNP  Standard evaluation  Diagnosis of CHF BNP Search BNP Search BNP Search BNP Search BNP Search Critical Appraisal Critical Appraisal  Was there an independent, blinded comparison with a gold standard?      Clinical diagnosis of CHF Two independent cardiologists Clinical evidence available in medical record and specific study data Blinded to results of BNP(ED MD blinded; ?others blinded?) ? What if they disagreed ? Critical Appraisal  Was the test evaluated in an appropriate spectrum of patients?   1586 patients from 7 sites (5 US) Inclusion  Shortness of breath as most prominent symptom  Exclusion  Under 18 years  “dyspnea was clearly not secondary to congestive heart failure (for example, those with trauma or cardiac tamponade)”  AMI or renal failure  USA unless they met the inclusion criterion Critical Appraisal  Was the reference standard applied regardless of the test result?  Yes  Was the test validated in a second, independent group of patients?  No BNP Results BNP 50 80 100 Sensitivity 97 93 90 Specificity 62 74 76 LR + 2.55 3.58 3.75 LR0.05 0.09 0.13 125 150 87 85 79 83 4.14 5.00 0.16 0.18 BNP ROC Curve LR + 10 BNP CAT Bottom Line  47% of 1586 patients presenting to 7 emergency departments with dyspnea had congestive heart failure  A BNP less than 80 rules out CHF (LR - = 0.09)  For BNP above 150, LR + = 5.0 ACE Inhibitors in Acute Pulmonary Edema Introduction to Evidence-Based Medicine Rodney Smith, MD Case Presentation         68 yo WF, Hx CHF, S/P CABG, HTN Meds: Digoxin, Lasix, Isosorbide Mild increase in DOE past 4 days Acutely SOB 1hr PTA 188/104 122 30 98.8 90% Non-rebreather Crackles to ½ bilat JVD, S3 gallop Pretibial edema 2+ Case Presentation  IV, O2, Monitor  Chest Xray, EKG, CCU labs, dig level  EKG sinus tach, old iwmi, ns st-t changes  CXR acute pulmonary edema  Treatment  Nitropaste  Lasix  MS Question—General Statement  What about using ACE inhibitors for acute pulmonary edema? Background  Describe pathophysiology of CHF and acute pulmonary edema  Discuss causes of decompensation of CHF  Discuss Diff Dx of acute pulmonary edema  Relate pathophysiology of CHF to treatment, especially role of ACE-I in CHF  Describe treatment goals  Describe standard treatment of CHF EBM Question  Patients: Acute Pulmonary Edema  Intervention: ACE Inhibitor  Comparison: Placebo  Outcome:  Mortality  Intubation  Hemodynamic parameters  ICU/CCU admission Critical Appraisal  Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. Circulation. 1996 Sep 15;94(6):1316-24  ICU patients with Swan Ganz catheters  Not intubated  Improved with 6hr standard treatment  Lasix  Nitrates  +/- Dopamine Annane, et al. Circulation. 1996;94(6):1316-24  Six-hour washout period  Randomized to IV enalapril or placebo  Hemodynamic parameters measured  Primary endpoints   Pulmonary capillary wedge pressure Renal blood flow Annane, et al. Circulation. 1996;94(6):1316-24  Statistically Significant Effects of ACE-I    Decreased diastolic and mean arterial BP Decreased PCWP Improved Renal and Brachial blood flow Annane, et al. Circulation. 1996;94(6):1316-24  Are the results Valid       Assignment randomized Follow-up for 8 hours Intention to treat analysis Double blind Patients treated equally Groups were similar at start of treatment Annane, et al. Circulation. 1996;94(6):1316-24  Are the valid results important?  What is magnitude of treatment effect?  PCWP T0 Enalaprilat Placebo 27 21 T2 22 21 T4 17 19 T8 20 22 Annane, et al. Circulation. 1996;94(6):1316-24  Are the valid results important?  What is magnitude of treatment effect?  Renal Blood Flow T0 Enalaprilat 617 T4 690 Placebo 570 577 Annane, et al. Circulation. 1996;94(6):1316-24  Are the valid, important results applicable to our patient?     Patients in ICU, Swan Ganz, 6 hour pretreatment (after ED treatment) Treatment is feasible ?Potential benefits. No particular harms Patient values likely in favor of treatment if it is of benefit Critical Appraisal  Rapid improvement of acute pulmonary edema with sublingual captopril. Acad Emerg Med. 1996 Mar;3(3):205-12  Emergency department patients  Randomized to sublingual captopril or placebo (standard treatment in both)  Outcomes   Clinical acute pulmonary edema distress score Intubation Hamilton RJ, et al. Acad Emerg Med. 1996;3:205-12  Improvement in APEX score  Improvement in number intubated  9% vs. 20% (NS, p = 0.1) Hamilton RJ, et al. Acad Emerg Med. 1996;3:205-12  Are the results valid       Randomized assignment  Non-consecutive (57 of 107 enrolled)  No data on 50 patients not enrolled  Too busy or research assistant not available  9 exclusions: 3 intubated, 5 incomplete records, 1 COPD Follow for 120 minutes Intention to treat analysis (see exclusions) Blinded to treatment (double blind) Equal treatment (“standard” therapy) Groups were similar at start of treatment Hamilton RJ, et al. Acad Emerg Med. 1996;3:205-12  What is magnitude of treatment effect?     25 to 40 min APEX reduction of 57% in treated APEX reduction of 75% in placebo Absolute improvement 18% Hamilton RJ, et al. Acad Emerg Med. 1996;3:205-12  What is magnitude of treatment effect?  Intubation  Absolute Risk Reduction: 20% - 9% = 11%  95% CI -8% to 31%; p = .10    Relative Risk Reduction: 11%/20% = 55% Number Needed to treat: 1/11% = 9 Treat Nine patients to avoid One intubation  With Confidence intervals  NNH = 1/8% = 12  NNT = 1/31% = 3 Hamilton RJ, et al. Acad Emerg Med. 1996;3:205-12  Are these valid, important results applicable to our patient?     Similar to our patient Treatment is feasible ?Potential benefit Patient Values likely in favor of treatment Conclusion  Patients with acute pulmonary edema treated with sublingual captopril had 18% more improvement at 30 minutes compared with placebo  Trend toward fewer intubations but study too small to tell