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Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults with Type 2 Diabetes

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Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults with Type 2 Diabetes Comparative Effectiveness Review Number 14 Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes This report is based on research conducted by the Johns Hopkins Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0018). 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 report 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 14 Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes 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. 290-02-0018 Prepared by: The Johns Hopkins University Evidence-based Practice Center Investigators Rehan Qayyum, M.D. Lisa M. Wilson, Sc.M. Shari Bolen, M.D., M.P.H. Nisa Maruthur, M.D. Spyridon S. Marinopoulos, M.D., M.B.A. Leonard Feldman, M.D. Padmini Ranasinghe, M.D., M.P.H. Muhammad Amer, M.D. Eric B. Bass, M.D., M.P.H. AHRQ Publication No. 08-EHC017-EF September 2008 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: Qayyum R, Wilson LM, Bolen S, Maruthur N, Marinopoulos SS, Feldman L, Ranasinghe P, Amer M, Bass EB. Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults with Type 2 Diabetes. Comparative Effectiveness Review No. 14. (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-02-0018.) Rockville, MD: Agency for Healthcare Research and Quality. September 2008. 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 strengths 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 http://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. Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director Director, Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality iii Acknowledgments The Evidence-based Practice Center thanks Catherine Witkop and Bushra Abid for their assistance with article reviewing and Ritu Sharma for her assistance with final preparations of the report. Peer Reviewers Christopher H. Schmid, Ph.D. Tufts Medical Center Boston, MA Leonard Pogach, M.D. East Orange VAMC East Orange, NJ Arshag D. Mooradian, M.D. University of Florida College of Medicine Jacksonville, FL AHRQ Contacts Beth A. Collins Sharp, Ph.D. Barbara A. Bartman, M.D., M.P.H. Director Task Order Officer Evidence-based Practice Center Program Evidence-based Practice Center Program Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Rockville, MD Rockville, MD iv Contents Executive Summary ...................................................................................................................ES-1 Background and Key Questions...........................................................................................ES-1 Conclusions..........................................................................................................................ES-3 Key Questions 1 and 2: Comparative Effectiveness and Safety of Premixed Insulin Analogues ....................................................................................................ES-3 Key Question 3: Effect of Premixed Insulin Analogues in Certain Subpopulations .....ES-7 Key Question 4: Effect of Premixed Insulin Analogues Based on Patient Characteristics..........................................................................................................ES-7 Applicability ..................................................................................................................ES-8 Remaining Issues .................................................................................................................ES-8 Introduction......................................................................................................................................1 Background................................................................................................................................1 Conceptual Model......................................................................................................................3 Scope and Key Questions ..........................................................................................................5 Methods............................................................................................................................................7 Topic Development ....................................................................................................................7 Search Strategy ..........................................................................................................................7 Study Selection ..........................................................................................................................8 Data Abstraction ........................................................................................................................8 Quality Assessment ....................................................................................................................9 Applicability ............................................................................................................................10 Data Analysis and Synthesis....................................................................................................10 Data Synthesis for Intermediate Outcomes and Adverse Events .......................................11 Data Synthesis for Clinical Outcomes ...............................................................................12 Rationale for the Inclusion of Crossover Designs .............................................................12 Data Entry and Quality Control ...............................................................................................13 Rating the Body of
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