COMPARATIVE EFFECTIVENESS REVIEWS FOR CLINICIANS: Helping us Make Better Treatment Decisions. Research Focus: 14 Priority Conditions

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1 COMPARATIVE EFFECTIVENESS REVIEWS FOR CLINICIANS: Helping us Make Better Treatment Decisions Robert B. Baron MD MS Professor and Associate Dean UCSF School of Medicine Declaration of full disclosure: No conflict of interest Patient-Centered Outcomes Research: AHRQ s Effective Health Care Program Also known as comparative effectiveness research. Unbiased and practical, evidencebased information Compares drugs, devices, tests and surgeries, and approaches to health care Benefits and harms What is known and what isn t Descriptive, not prescriptive A Framework for Patient-Centered Outcomes Research Research Focus: 14 Priority Conditions Arthritis and nontraumatic joint disorders Functional limitations and disability Horizon Scanning Evidence Synthesis Evidence Need Identification Evidence Generation Strategies Interventions Conditions Populations Research Platform Infrastructure Methods Development Training Dissemination Translation Improvements in Health Care Cancer Cardiovascular disease, including stroke and hypertension Dementia, including Alzheimer s disease Depression and other mental health disorders Developmental delays, ADHD and autism Infectious diseases, including HIV/AIDS Obesity Peptic ulcer disease and dyspepsia Pregnancy including preterm birth Pulmonary disease/asthma Substance abuse 3 Diabetes mellitus 1

2 Effective Health Care Program Translation Products Confidence Scale Executive Summary Patient Decision Aid (available soon) Derived from systematic review of literature Web Site High Consistent results from good studies Clinician Guide Systematic Review Report Faculty Slides Medium Findings supported, but further research could change the conclusions Consumer Guide Policymaker Summary CE Modules Interactive Case Study Low Few studies, or existing studies are flawed Comparing Oral Medications for Adults with Type 2 Diabetes: 2007 Clinical issue: compare effectiveness and safety of oral hypoglycemics. Review of 216 studies Comparing Oral Medications for Adults with Type 2 Diabetes: Bottom Line As single agents all second generation sulfonlyureas, thiazolidinediones (TZDs), metformin, and repaglinide work well to reduce HbA1c by about 1 point on average (Confidence ) Combination therapies reduce HbA1c about 1 point more than monotherapies (Confidence ) People taking sulfonylureas, TZDs, and repaglinide gain about 2-10 lbs. Metformin does not cause weight gain (Confidence ) 2

3 Comparing Oral Medications for Adults with Type 2 Diabetes: Lipid Effects Little effect on HDL (Confidence ) Metformin best for lowering LDL, about 10mg/dl (Confidence ) TZDs increase LDL (rosiglitazone more than pioglitazone) (Confidence ) Medications To Reduce the Risk of Primary Breast Cancer in Women: 2010 Clinical issue: compare effectiveness and safety of two medications used to reduce primary breast cancer: tamoxifen and raloxifene Both drugs approved, but rarely used Review of 7 studies with 55,000 participants Medications To Reduce the Risk of Primary Breast Cancer in Women: Bottom Line Tamoxifen and raloxifene are both effective at reducing the risk of primary invasive breast cancer in women age (Confidence ) Raloxifene and tamoxifen reduce the likelihood of a woman developing breast cancer by a similar amount. (Confidence ) Medications To Reduce the Risk of Primary Breast Cancer in Women: Bottom Line Neither tamoxifen nor raloxifene reduce all-cause mortality. (Confidence ) Raloxifene and tamoxifen both increase the risk of thromboembolic events. (Confidence ) Tamoxifen increases the risk of endometrial cancer. (Confidence ) 3

4 Medications To Reduce the Risk of Primary Breast Cancer in Women: Patient Selection Overall, for every 1000 women taking either med will be 8 fewer cases of breast cancer (0.8%). Risk of serious adverse events (DVT, PE, or endometrial cancer) is also about 0.8% Use in highest risk women: age, FH, genetic mutations, mammographic breast density, and history of atypical hyperplasia. Core Needle Biopsy for Breast Abnormalities: 2010 Clinical issue: compare effectiveness of core needle biopsy with open surgical biopsy for diagnosing breast lesions Review of 107 research studies (Does not discuss fine needle aspiration) Core Needle Biopsy for Breast Abnormalities: Background Breast cancer is second most common cancer in women (250,000 new cases/year) Early detection improves survival Half of open biopsies are negative, and may lead to disfiguring More than half of biopsies use coreneedle procedures, thus important to determine accuracy and harms Core Needle Biopsy for Breast Abnormalities: Bottom Line Core-needle breast biopsies have a lower risk of any type of complication than open surgical biopsies. (Confidence ) The sensitivity of core-needle biopsies performed using either stereotactic or ultrasound guidance is percent. (Confidence ) 4

5 Core Needle Biopsy for Breast Abnormalities: Bottom Line Freehand core-needle breast biopsies have a lower sensitivity than biopsies performed using either stereotactic or ultrasound guidance. (Confidence ) More than 10 percent of core-needle breast biopsy specimens classified as atypical ductal hyperplasia or ductal carcinoma in situ are reclassified as invasive breast cancer on subsequent surgical biopsy. (Confidence ) Core Needle Biopsy for Breast Abnormalities: Patient Resources Having a Breast Biopsy: A Guide for Women and Their Families AHRQ Publications Clearinghouse (800) Core Needle Biopsy for Breast Abnormalities: Recent Study Florida data of 172,342 biopsies. 30% of breast biopsies are open. Goal less than 10%. Hospital fees for needle $5000-$6000; double for open MD fees for needle $750 -$1500; double for open Amer J Surgery, 2011 Adding ACEIs and/or ARBs to Standard Therapy for Stable Ischemic Heart Disease: 2010 Clinical issue: Should standard medical therapy in patients with stable ischemic heart disease be augmented with an ACEI (angiotensin-converting enzyme inhibitor) or an ARB (angiotensin II receptor blocker)? Review of 12 trials with 41,672 subjects 5

6 Standard Therapy for Chronic Stable Angina ASA Statins Beta-blockers Dual antiplatelet therapy For symptoms Nitrates Calcium channel blockers Revascularization Balloon angioplasty with or without stenting CABG Adding ACEIs and/or ARBs to Standard Therapy for Stable Ischemic Heart Disease: Bottom Line Adding an ACEI to standard treatment: Reduces total mortality, nonfatal MI, CHF hosptialization, and revascularizations (Confidence ) Increases syncope, cough, and hyperkalemia(confidence ) Adding ACEIs and/or ARBs to Standard Therapy for Stable Ischemic Heart Disease: Bottom Line Adding an ARB to standard treatment: For patients who are intolerant to ACEIs: Reduces combined end points of CV mortality, nonfatal, MI, and stroke, (Confidence ) Increases hyperkalemia (Confidence ) Adding ACEIs and/or ARBs to Standard Therapy for Stable Ischemic Heart Disease: Bottom Line Adding both an ACEI and an ARB to standard treatment: No additional benefit when compared to ACEI alone. (Confidence ) 6

7 Adding ACEIs and/or ARBs to Standard Therapy for Stable Ischemic Heart Disease: Bottom Line Adding an ACEI or an ARB close to a revascularization procedure: No additional benefit over standard therapy. (Confidence ) Radiofrequency Ablation for Atrial Fibrillation: 2009 Clinical issue: effectiveness and safety of catheter-based radiofrequency ablation (RFA) compared with antiarrhythmic drugs (AADs) for atrial fibrillation Radiofrequency Ablation for Atrial Fibrillation: Background Atrial fibrillation is most common arrhythmia AF can be paroxysmal, persistent (more than 7days), chronic (more than 1 year) Often causes symptoms Five fold increase in stroke, two fold increase in death Can treat to control rate alone, but for some symptoms not controlled Radiofrequency Ablation (RFA) for Atrial Fibrillation: 2009 RFA: An alternative method for restoring normal cardiac rhythm. A catheter is positioned in the area of an abnormal electrical circuit. The catheter tip heats the cardiac tissue using radiofrequency energy and prevents the abnormal electrical signals from being conducted. Several different ablation techniques are used for AF. With most techniques, the ablation targets are sites in the pulmonary veins and the left atrium. 7

8 Radiofrequency Ablation for Atrial Fibrillation: Bottom Line Evidence is insufficient to determine the effectiveness of RFA as first-line therapy compared with AADs. Among patients with AF who have failed at least one course of AADs, RFA is more effective than another trial of AADs for maintaining sinus rhythm at 1 year. (Confidence ) Serious complications are uncommon after RFA, but stroke and cardiac tamponade each occur in about 1 percent of cases. (Confidence ) Radiofrequency Ablation for Atrial Fibrillation: Bottom Line Outcome RFA vs. AADs Confidence Sinus at 1 year RFA better (74% vs. 20%) Off anticoagulants at 1 year More often with RFA (60% vs. 34%) Improved quality of life RFA better Avoiding stroke within 1 year No difference Avoiding CHF Unknown INSF Radiofrequency Ablation for Atrial Fibrillation: Treatment Selection Which patients with AF should be referred for RFA? 63 yo man with DM, HTN, lipid disorder. On max dose statin: LDL 83, HDL 37. Niacin (sustained release) results in pruritic macular papular rash. The next best step is: RFA appears to be superior to AADs in restoring sinus rhythm for patients with AF. For patients with AF who are persistently tachycardic or symptomatic despite having tried rate-control medications, electrical cardioversion, and AADs, RFA is a reasonable option. There has been little research on the use of RFA as first-line therapy. Thus far, no patient characteristics clearly predict which patients with AF will benefit from RFA and which will not. 1. Add bile acid sequestrant 2. Add ezetimibe 3. Add a fibrate 4. Add a short acting niacin 5. Add omega-3 fatty acids 6. Continue current regimen 32% 25% 18% 16% 9% 2%

9 Treating Cholesterol With Combination Therapy: 2009 Clinical issue: Aggressive Rx of LDL reduces risk of CAD and stroke. Statin is first line medication. If goal LDL not achieved, what is role of adding a second lipid-lowering medication? Review of over 100 studies Treating Cholesterol With Combination Therapy: 2009 Insufficient evidence to conclude that combination therapy leads to lower rates of events and death. Insufficient evidence to assess whether combination regimens provide greater LDL reduction, increased HDL, or coronary or carotid intima thickening. 63 yo man with DM, HTN, lipid disorder. On max dose statin: LDL 83, HDL 37. Niacin (sustained release) results in pruritic macular papular rash. The next best step is: 1. Add a bile acid sequestrant 2. Add ezetimibe 3. Add a fibrate 4. Add a short acting niacin 5. Add omega-3 fatty acids 6. Continue current regimen 68 yo woman with painful osteoarthritis of knees, hips, and back. History of stable CAD, creatinine 1.4. Currently on acetaminophen 3000 mg per day. The next best step for her pain is: 1. Add more acetaminophen 2. Add NSAID (plus PPI) 3. Add topical cream with NSAID 4. Add capsaicin 5. Add glucosamine and chondroitin 6. Add low dose opioid 2% 15% 10% 19% 21% 33%

10 Choosing Non-Opioid Analgesics for Osteoarthritis: 2009 Clinical issue: 21 million Americans have osteoarthritis. Managing pain can assist in mobility and improved quality of life. Non-opioid drug treatments: Acetaminophen NSAIDS Glucosamine and chondroitin Topical medications Review of over 351 studies Choosing Non-Opioid Analgesics for Osteoarthritis: Bottom Line Acetaminophen relieves mild pain but is inferior to NSAIDs for moderate or severe pain. Acetaminophen has fewer side effects than NSAIDs. (Confidence ) All non-aspirin NSAIDs work equally well for pain reduction. (Confidence ) NSAIDs increase the risk of GI bleeding. The risk increases with higher doses and with age. People older than 75 have the highest risk. (Confidence ). Choosing Non-Opioid Analgesics for Osteoarthritis: Bottom Line Celecoxib, high dose ibuprofen, and high dose diclofenac increase the risk of MI. Naproxen does not increase the risk of MI. (Confidence ) Capsaicin cream relieves chronic OA pain, but about half will experience local burning sensations (which diminishes over time). (Confidence ) OTC topical creams containing salicylates do not reduce osteoarthritic pain. (Confidence ) Choosing Non-Opioid Analgesics for Osteoarthritis: Bottom Line Topical creams with NSAIDS work as well as oral NSAIDS. (Confidence ) Glucosamine and chondroitin alone or together do not improve pain or function. (Confidence ) Glucosamine and chondroitin are not regulated and purity may vary. (Confidence ) 10

11 68 yo woman with painful osteoarthritis of knees, hips, and back. History of stable CAD, creatinine 1.4. Currently on acetaminophen 3000mg per day. The next best step for her pain is: 1. Add more acetaminophen 2. Add NSAID (plus PPI) 3. Add topical cream with NSAID 4. Add capsaicin 5. Add glucosamine and chondroitin 6. Add low dose opioid 68 yo woman with painful osteoarthritis of knees, hips, and back. Self-referred to ortho. Ortho suggests injection (viscosupplementation), and consideration of arthroscopic lavage. 1. OK to proceed with either 2. OK to perform viscosupplementation but not lavage 3. OK to perform lavage but not viscosupplementation 4. Neither is evidence-based 2% 26% 2% 70% Treatments for Osteoarthritis of the Knee: 2009 Review of over 86 studies Treatments for Osteoarthritis of the Knee: Bottom Line For people with osteoarthritis of the knee, the following do not lead to clinically meaningful improvement: Glucosamine and chondroitin (Confidence ) Viscosupplementation (intra-articular injection of hyaluronan products (Confidence ) Arthroscopic lavage with or without debridement (Confidence ) 11

12 68 yo woman with painful osteoarthritis of knees, hips, and back. Self-referred to ortho. Ortho suggests injection (viscosupplementation), and consideration of arthroscopic lavage. 1. OK to proceed with either 2. OK to perform viscosupplementation but not lavage 3. OK to perform lavage but not viscosupplementation 4. Neither is evidence-based Interventions for Rotator Cuff Tears in Adults: 2010 Partial or full tears of the rotator cuff result from injury or degeneration, and the incidence increases with age. Patients may experience significant disability. Non-operative treatment: 6 to 12 weeks of pain management, rest, passive and active exercise, among others. Interventions for Rotator Cuff Tears in Adults: 2010 Surgical interventions: when nonoperative therapy fails and for selected patients with traumatic tears. Question: early surgical intervention or if and when to forgo nonoperative treatment for operative intervention. Interventions for Rotator Cuff Tears in Adults: Bottom Line Evidence too limited to favor early surgical repair. Significant improvement in all study groups Review of 137 studies. 12

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