Evidence-based medicine and guidelines: development and implementation into practice

Transcription

1 Evidence-based medicine and guidelines: development and implementation into practice PD Dr D. Aujesky, MSc MER Médecin-adjoint Service de Médecine Interne CHUV 1 Goals To discuss the basics of evidence-based medicine (EBM) Definition Its utility in medical decision making Common misunderstandings around EBM To provide an overview of clinical practice guidelines (CPG) Definition Rationale for use Methodological standards Implementation 2 1

2 Traditional therapeutic decision-making Therapeutic medical decision-making is traditionally based on clinical judgment («experience») and pathophysiologic reasoning Pathophysiologic reasoning: identifies therapeutic interventions based on the pathophysiologic mechanism of a disease found in pathophysiologic studies («mechanistic approach») 3 Examples Pathophysiologic mechanism Lack of pancreatic insuline production Bacterial infection of the lungs Disease Type 1 diabetes Pneumonia Therapeutic intervention Insuline substitution Antibiotics Benefit in terms of efficacy and safety is so evident that a formal confirmation in clinical studies is not ethical However, if the benefit of an intervention is less clear or if several possible interventions co-exist, the pathophysiologic approach is often insufficient to find the best solution usefulness of EBM 4 2

3 Definition of EBM EBM is the conscientious and judicious use of current best scientific evidence from clinical research in the management of individual patients «Conscientious»: evidence should be applied consistently to all patients «Judicious»: physicians should integrate their clinical judgment (experience) Scientific evidence: usually (but not exclusively) from well conducted, patient-oriented studies with clinically relevant outcomes (mortality, morbidity, quality of life, costs) Sackett, BMJ Hierarchy of scientific evidence Systematic review of randomized trials (RCTs) Single RCT Systematic review of observational studies addressing relevant outcomes Single observational study addressing relevant outcomes Pathophysiologic studies Unsystematic clinical observations Guyatt, JAMA 2000 often large sample sizes randomized, double blind design: low risk of biases high internal validity often small sample size no control group: great risk of biases low internal validity often use of clinically less relevant, physiologic outcomes (surrogate markers) 6 3

4 Hierarchy of evidence matters Clinical question What is the impact of betablockers on mortality in heart failure patients? Low evidence level study Physiologic study enrolling 8 patients showed that propranolol reduced the ejection fraction in 4 patients. Authors concluded: «Betablockers may inhibit compensatory symphatic mechanisms» High evidence level study Systematic review of 18 RCTs enrolling 3023 patients showed a 32% mortality reduction among patients receiving betablockers compared to placebo Do encainide and flecainide decrease fatal ventricular arrhythmias after myocardial infarction? Does hormone replacement reduce the risk of cardiovascular events in postmenopausal women? Aujesky, Médecine & Hygiène 2004 Observational study enrolling 38 patients with refractory ventricular arrythmia found that encainide decreased the incidence of recurrent ventricular arrhythmias. Authors concluded: «Encainide is a safe and well tolerated antiarrhythmic» Multiple physiologic and observational studies showed that hormone replacement among postmenopausal women reduces the rate of cardiovascular events RCT enrolling 1498 patients with acute myocardial infarction found that encainide and flecainide increased the risk of cardiovascular death by a factor 2.6 compared to placebo RCT (WHI) enrolling postmenopausal women showed that hormone replacement significantly increased the risk of coronary heart disese (RR 1.29) and stroke (RR 1.41) 7 Practical skills of EBM Formulate a clinical question Find, with maximum efficiency, the best evidence with which to answer your clinical question (know how to do a literature search) Critically appraise that evidence for its internal validity (closeness to the truth) and external validity (clinical applicability to my patient) Apply the results of this appraisal in the management of your patient 8 4

5 Development of EBM Since the 1990s, interest in EBM grows exponentially 1 Medline citation in 1992 to > 13,000 citations in 2004 Discussion has moved from whether to teach EBM to how to teach it Explosion in the numbers of EBM courses, workshops, and seminars offered EBM terminology (e.g, number needed to treat or NNT) has extended in to the popular press 9 Misunderstandings around EBM (1) «Everyone is already doing it» So, why is the practice variation in patient care so great? «Can be conducted only from (university) ivory towers» Studies show that clinicians in internal medicine, surgery, and psychiatry have provided EBM-based care «Promotes a cookbook medicine» Not true, EBM explicitly requires the integration of clinical judgment (see slide no 5) 10 5

6 Misunderstandings around EBM (2) «Insurers may use EBM to cut costs» More frequent use of evidence-based interventions may actually increase costs! «EBM is restricted to randomized trials» Not true, EBM requires the use of the best available evidence for a given clinical question. This may be an pathophysiologic or observational study when randomized trials are not available or feasible (e.g., rapidly fatal conditions) 11 Example of a rapidly fatal condition: high-altitude free fall «Parachutes reduce the risk of injury after gravitational challenge, but their effectiveness has not been proved with randomised controlled trials» Remember the key statement on slide 4: the benefit of some interventions is so evident that further confirmation in clinical studies is not ethical Smith, BMJ

7 Absence of evidence is not evidence of absence (l absence de preuve d efficacité n est pas synonyme de preuve d absence d efficacité) An intervention that has not (yet) been evaluated in clinical studies may be effective A «negative» randomized trial does not necessarily mean that there is not treatment effect, especially, if it was underpowered to find such an effect 13 The 4 circles of good medical decision making PATHO- PHYSIOLOGY CLINICAL JUDGMENT EVIDENCE (EBM) PATIENT PREFERENCES Good medical decision making integrates all these components Cornuz, Rev Med Suisse

8 EBM resources Books: Evidence-based pharmacy by P. Wiffen introduction to EBM for pharmacists Journals: ACP Journal Club, Evidence-Based Medicine, Clinical Evidence, various pharmacy reviews summarize results of relevant randomized trials and discuss their internal and external validity Cochrane Library high-quality systematic reviews of various medical fields National Institute of Clinical Excellence (NICE): high-quality cost-effectiveness analyses for drugs and other medical interventions 15 Clinical practice guidelines (CPG) Medical textbooks, journal reviews, and consensus conference reports have provided patient care recommendations based on scientific evidence for > 100 years What distinguishes «modern» CPGs from earlier documents is the use of a systematic method that explicitly describes the guideline s development 16 8

9 Definition of CPG CPG: systematically developed statement to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances Clinical Practice Guidelines, Institute of Medicine Rationale for CPG Wide variations in practice patterns Inappropriate use of medical services Out-of-control health care costs 18 9

10 Example: practice variation Jack Wennberg completed pioneering research in the 1970s (small area variations research) 4-fold difference in radical prostatectomy rates in adjacent US counties Variation in admission and length of hospital stay for common procedures in New England 19 Example: inappropriate use of services Retrospective study enrolling 227 inpatients from the CHUV s division of general internal medicine Only 22% of patients at risk of venous thromboembolism received adequate pharmacologic prophylaxis, whereas 38% of patients at low risk were given prophylaxis Authors conclusion: the high prevalence of over- and undertreatment is an indicator of less than optimal care Aujesky, Guignard, Pannatier, Cornuz, J Gen Intern Med

11 Major purposes of CPG Assist clinical decision making Educate individuals or groups Assess or improve quality of care Increase the value = Quality Costs 21 Methodological standards for scientifically good CPG Institute of Medicine (IOM) American Medical Association (AMA) Canadian Medical Association (CMA) Agency for Healthcare Research & Quality (AHRQ) Appraisal of Guidelines, REsearch and Evaluation (AGREE) Collaboration 22 11

12 Methodological standards for CPG: AGREE criteria Scope and purpose (objective and target population described) Stakeholder involvement (relevant professionals, patients) Rigor of development Methods for literature search and for selecting evidence described Link between recommendations and evidence External review by experts Procedure for updating described Clarity of presentation Applicability (barriers in applying recommendations discussed) Editorial independence (conflicts of interest reported) 23 The heart of CPG: grades of recommendations Users need to know if a recommendation is strong or week, and the methodologic quality of evidence underlying that recommendation Here EBM meets CPG! 24 12

13 GRADE: a method to grade recommendations in CPG Grades of recommendation Grade 1 =certainty that benefits do or do not outweigh harms/costs Grade 2 =less certainty that benefits do or do not outweigh harms/costs Levels of evidence A: RCT or observational studies with very large effects B: RCTs with limitations or observational studies with large effects C: RCTs with very serious limitations or observational studies Typical recommendations: 1A, 2C GRADE Working group, BMJ 2004; Guyatt, Chest Conceptual model of CPG effectiveness Clinically valid recommendations Persuade physicians (and patients) to change behavior Better value (improved outcomes at lower costs) 26 13

14 Effectiveness of guidelines (1) Objective: to assess the effectiveness of CPG meeting criteria for scientific rigor Design: structured literature review to identify articles on CPG for medical staff that evaluated processes of care and outcomes and had a rigorous design Types of studies: RCTs, controlled before-after studies Grimshaw, Lancet Effectiveness of guidelines (2) 59 CPG met criteria (24 clinical conditions, 27 prevention, 8 prescribing or x-ray services) 55/59 studies detected significant changes in processes of care 9/11 studies that evaluated outcomes detected some significant improvement Conclusion: explicit CPG do improve clinical practice Grimshaw, Lancet

15 Implementation of CPG Development of good CPG does not ensure their use in practice To maximize likelihood of CPG being used, coherent implementation strategies based on effective techniques of provider behavior change are needed Ultimate value of CPG will be determined by their impact on patient care (quality, costs) 29 Generally ineffective CPG implementation strategies Passive educational approaches Lectures, workshops Peer review publications Simple CPC dissemination through mailing or provision of CPG 30 15

16 Variably effective CPG implementation strategies Audit and feedback most effective for drug prescribing and test ordering Opinion leaders Patient education («direct to consumer») has a small positive effect Case-management 31 Generally effective CPC implementation strategies Reminders effective when used sparingly Most effective when real-time Computer reminders well proven Educational outreach (academic detailing, visite académique) One-on-one, face to face Effective for drug prescribing Multifaceted (=combined) interventions have a greater likelihood of success 32 16

17 CPG resources AHRQ guideline clearinghouse CMA guideline infobase - Scottish Intercollegiate Guidelines Network Cochrane Library and Cochrane Effective Practice and Organization of care (EPOC) Conclusion EBM is the use of current best scientific evidence from clinical research in the management of individual patients CPG are systematically developed statements to assist physician and patient decisions about appropriate health care for specific clinical circumstances EBM/CPG are intended to supplement and not replace clinical judgment Methodological standards for CPG exist To be effective (i.e., improve quality of care), GPG require implementation strategies of proven effectiveness 34 17

18 Thank you for your attention 35 18