This report is based on research conducted by the Oregon Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0024). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services. This report is intended as a reference and not as a substitute for clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. Comparative Effectiveness Review Number 4 Comparative Effectiveness and Safety of Analgesics for Osteoarthritis Comparative Effectiveness Review Number 4 Comparative Effectiveness and Safety of Analgesics for Osteoarthritis Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-02-0024 Prepared by: Oregon Evidence-based Practice Center Investigators Roger Chou, M.D. Mark Helfand, M.D. Kim Peterson, M.S. Tracy Dana, M.L.S. Carol Roberts, B.S. AHRQ Publication No. 06-EHC009-EF September 2006 This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders. None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report. Suggested citation: Chou R, Helfand M, Peterson K, Dana T, Roberts C. Comparative Effectiveness and Safety of Analgesics for Osteoarthritis. Comparative Effectiveness Review No. 4. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-02-0024.) Rockville, MD: Agency for Healthcare Research and Quality. September 2006. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. ii Preface The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to organize knowledge and make it available to inform decisions about health care. As part of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Congress directed AHRQ to conduct and support research on the comparative outcomes, clinical effectiveness, and appropriateness of pharmaceuticals, devices, and health care services to meet the needs of Medicare, Medicaid, and the State Children’s Health Insurance Program (SCHIP). AHRQ has an established network of Evidence-based Practice Centers (EPCs) that produce Evidence Reports/Technology Assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care. The EPCs now lend their expertise to the Effective Health Care Program by conducting Comparative Effectiveness Reviews of medications, devices, and other relevant interventions, including strategies for how these items and services can best be organized, managed, and delivered. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm. AHRQ expects that Comparative Effectiveness Reviews will be helpful to health plans, providers, purchasers, government programs, and the health care system as a whole. In addition, AHRQ is committed to presenting information in different formats so that consumers who make decisions about their own and their family’s health can benefit from the evidence. Transparency and stakeholder input are essential to the Effective Health Care Program. Please visit the Web site (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an e-mail list to learn about new program products and opportunities for input. Comparative Effectiveness Reviews will be updated regularly. iii Acknowledgments We would like to acknowledge with appreciation the members of the Technical Expert Panel for their advice and consultation. In addition, we would also like to acknowledge Eric Johnson, Ph.D., for reviewing this manuscript. Technical Expert Panel Vibeke Strand, M.D. Adjunct Clinical Professor Division of Immunology, Stanford University Portola Valley, CA Expertise: Rheumatology Kenneth Saag, M.D., M.Sc. UAB Center for Education and Research on Therapeutics (CERTs) of Musculoskeletal Disorders Birmingham, AL Expertise: Rheumatology Leslie J. Crofford, M.D. UK Hospital, University of Kentucky Lexington, KY Expertise: Rheumatology Michel Boucher, B.Pharm., M.Sc. Canadian Coordinating Office for Health Technology Assessment Ottawa, Ontario Expertise: Pharmacology Lara Maxwell Coordinator, Cochrane Musculoskeletal Group Institute of Population Health University of Ottawa Ottawa, Ontario Expertise: Rheumatology AHRQ Contacts Beth A. Collins Sharp, Ph.D., R.N. Carmen Kelly, Pharm.D., R.Ph. Director Task Order Officer Evidence-based Practice Center Program Evidence-based Practice Center Program Center for Outcomes and Evidence Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Rockville, MD Rockville, MD iv Contents Executive Summary ................................................................................................................... 1 Chapter 1. Introduction............................................................................................................17 Scope and Key Questions .............................................................................................................19 Chapter 2. Methods....................................................................................................................23 Topic Development.......................................................................................................................23 Search Strategy .............................................................................................................................23 Study Selection .............................................................................................................................23 Data Extraction .............................................................................................................................24 Quality Assessment.......................................................................................................................24 Assessing Research Quality.............................................................................................24 Assessing Research Applicability....................................................................................24 Rating a Body of Evidence ..............................................................................................25 Data Synthesis...............................................................................................................................25 Effectiveness Versus Efficacy .........................................................................................25 Data Presentation .............................................................................................................25 Chapter 3. Results .....................................................................................................................27 Overview.......................................................................................................................................27 Key Question 1a. What are the Comparative Benefits and Harms of Treating Osteoarthritis with Oral Medications or Supplements?...................................................27 Benefits: Effectiveness and Efficacy ...............................................................................27 Safety: Serious Gastrointestinal and Cardiovascular Events...........................................30 Other Adverse Events Associated with Selective and Non-Selective NSAIDs ..............61 Key Question 1b. How Do these Benefits and Harms Change with Dosage and Duration of Treatment, and What is the Evidence that Alternative Dosage Strategies, such as Intermittent Dosing and Drug Holidays, Affect the Benefits and Harms of Oral Medication Use? .................................................................73 Key Question 2. Do the Comparative Benefits and Harms of Oral Treatments for Osteoarthritis Vary for Certain Demographic and Clinical Subgroups? .........................75 Demographic Subgroups Include Age,