February 2014 - JMCP

J MCP ■ Journal of Mana g ed Care Pharmac y ■ February 2014 ■ Vol. 20, No. 2 ■ Pa g es 101-218

volume twenty • number two February 2014 Peer-Reviewed Journal of the Academy of Managed Care Pharmacy

■■  ACO Pharmacy Series PCMHs, ACOs, and Medication Management: Lessons Learned from Early Research Partnerships ■■  BENEFIT Management Evaluation of Increased Adherence and Cost Savings of an Employer Value-Based Benefits Program Targeting Generic Antihyperlipidemic and Antidiabetic Medications Measuring Economic Impact of Applying Daily Average Consumption Limits Discrepancies Identified with the Use of Prescription Claims and Diagnostic Billing Data Following a Comprehensive Medication Review Incremental Health Care Resource Utilization and Economic Burden of Venous Thromboembolism Recurrence from a U.S. Payer Perspective ■■  CLINICAL Management Pharmacists’ Role in the Care of Patients with Heart Failure: Review and Future Evolution BE EMPOWERED, A Specialty Pharmacy Education Program for Hemophilia B Patients, Impacts Adult Joint Bleeds and Pediatric Use of RICE Analysis of Gastrointestinal Prophylaxis in Patients Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel Tolerability of Saxagliptin in Patients with Inadequately Controlled Type 2 Diabetes: Results from 6 Phase III Studies Adherence to National Recommendations for Safe Methotrexate Dispensing in Community Pharmacies Economic Burden of Urgency Urinary Incontinence in the United States: A Systematic Review

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JMCP Mission Statement and Editorial Policy

■■ Editorial Content and Peer Review All articles, editorials, and commentary in JMCP undergo peer review; articles undergo blinded peer review. Letters may be peer reviewed to ensure accuracy. The fundamental departments for manuscript submission are: • Research • Subject Reviews • Formulary Management • Contemporary Subjects • Brief Communications • Commentary/Editorials • Letters All manuscript submissions except Commentaries and Letters should include an abstract and 1-3 takeaway bullet points in each of 2 sections that immediately follow the abstract for “what is already known about this subject” and “what this study adds.” For manuscript preparation requirements, see “JMCP Author Guidelines” in this Journal or at www. amcp.org.

■■ Research

ed i to r i a l M i s si o n a n d p o l i ci e s JMCP publishes peer-reviewed original research manuscripts, subject reviews, and other content intended to advance the use of the scientific method, including the interpretation of research findings in managed care pharmacy. JMCP is dedicated to improving the quality of care delivered to patients served by managed care pharmacy by providing its readers with the results of scientific investigation and evaluation of clinical, health, service, and economic outcomes of pharmacy services and pharmaceutical interventions, including formulary management. JMCP strives to engage and serve professionals in pharmacy, medicine, nursing, and related fields to optimize the value of pharmaceutical products and pharmacy services delivered to patients. JMCP employs extensive bias-management procedures that include (a) full disclosure of all sources of potential bias and conflicts of interest, nonfinancial as well as financial; (b) full disclosure of potential conflicts of interest by reviewers as well as authors; and (c) accurate attribution of each author’s contribution to the article. Aggressive bias-management methods are necessary to ensure the integrity and reliability of published work. Editorial content is determined by the Editor-in-Chief with suggestions from the Editorial Advisory Board. The views and opinions expressed in JMCP do not necessarily reflect or represent official policy of the Academy of Managed Care Pharmacy or the authors’ institutions unless specifically stated.

These are well-referenced articles based on original research that has not been published elsewhere and reflects use of the scientific method. The research is ■■ Brief Communications guided by explicit hypotheses that are stated clearly The results of a small study or a descriptive analysis by the authors. that does not fit in other JMCP departments may be submitted as a Brief Communication. Brief ■■ Subject Reviews Communications may warrant an Abstract with These are well-referenced, comprehensive reviews the typical JMCP categories (Background, of subjects relevant to managed care pharmacy. The Objective, Methods, Results, Conclusion). Methods section in the abstract and in the body of the manuscript should make clear to the reader the ■■ Commentary source of the material used in the review, including These submissions should be relevant to managed the specific criteria used for inclusion and exclusion care pharmacy and address a topic of contempoof information and the number of articles included rary interest: they do not require an abstract but and excluded by each criterion. Narrative reviews, should include references to support statements. defined as noncomprehensive reviews that cover only a portion of the literature on a topic, are not considered for publication by JMCP. However, arti- ■■ Letters cles of this type may be considered as Commentary. If the letter addresses a previously published article, an author response may be appropriate. (See “Letter to the Editor” instructions at www.amcp.org.) ■■ Formulary Management These are well-referenced, comprehensive reviews of subjects relevant to formulary management methods or procedures in the conduct of pharmacy and therapeutics (P&T) committees and generally include description and interpretation of clinical evidence and comparative cost information.

■■ Contemporary Subjects These are well-referenced submissions that are particularly timely or describe research conducted in pilot projects. Contemporary Subjects, like all articles in JMCP, must describe the hypothesis or hypotheses that guided the research, the principal methods, and results.

■■ Advertising and Disclosure Policies All aspects of the advertising sales and solicitation process are completely independent of the editorial process. Advertising is positioned either at the front or back of the Journal, and advertising is not accepted for placement opposite or near subject-related editorial content. The Academy of Managed Care Pharmacy endorses the Uniform Requirements for Manuscript Submissions to Biomedical Journals, available at: http://www.icmje.org/ including editorial freedom and management of conflicts of interest. Financial disclosure, conflict-of-interest statements, and

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February 2014

author attestations are required when manuscripts are submitted, and these disclosures accompany the article in abstracted form if the article is published. See JMCP Author Guidelines in this issue or online including complete description of disclosure policies and requirements for author attestations at www.amcp.org. See JMCP advertising opportunities at: www.amcp.org. Contact the Advertising Sales Office to receive a Media Kit.

Editorial Office Academy of Managed Care Pharmacy 100 North Pitt St., Suite 400 Alexandria, VA 22314 Tel.: 703.683.8416 Fax: 703.683.8417 E-mail: [email protected] Advertising Sales Office Mike Minakowski Scherago International 525 Washington Blvd, Ste. 3310 Jersey City, NJ 07310 Tel.: 215.860.0912 Fax: 201.653.5705 www.scherago.com

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Journal of Managed Care Pharmacy 101

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Volume 20, No. 2

Board of Directors

C ONTENTS ■ SUBJECT REVIEW 120 130

Tolerability of Saxagliptin in Patients with Inadequately Controlled Type 2 Diabetes: Results from 6 Phase III Studies Jaime A. Davidson, MD, FACP, MACE Economic Burden of Urgency Urinary Incontinence in the United States: A Systematic Review Karin S. Coyne, PhD, MPH; Alan Wein, MD, FACS, PhD; Sean Nicholson, PhD; Marion Kvasz, MD, MPH; Chieh-I Chen, MPH; and Ian Milsom, MD

■ RESEARCH

Evaluation of Increased Adherence and Cost Savings of an Employer Value-Based Benefits Program Targeting Generic Antihyperlipidemic and Antidiabetic Medications Bobby Clark, PhD, MSPharm, MHA, MS, MA; Janeen DuChane, PhD, MRP; John Hou, PhD; Elan Rubinstein, PharmD, MPH; Jennifer McMurray, PharmD; and Ian Duncan, FSA, FIA, FCIA, MAAA 151 BE EMPOWERED, A Specialty Pharmacy Education Program for Hemophilia B Patients, Impacts Adult Joint Bleeds and Pediatric Use of RICE Crystal S. Blankenship, PharmD; Bartholomew J. Tortella, MTS, MD, MBA, FACS, FCCM; and Marianna Bruno, PharmD, MPH 159 Measuring Economic Impact of Applying Daily Average Consumption Limits Bridget M. Flavin, PharmD; Lynn M. Nishida, RPh; Sean H. Karbowicz, PharmD; Mark E. Renner; and Ruth J. Leonard, PharmD 165 Discrepancies Identified with the Use of Prescription Claims and Diagnostic Billing Data Following a Comprehensive Medication Review Teresa E. Roane, PharmD, BCACP; Vinita Patel, PharmD; Heather Hardin, PharmD, BCACP; and Martha Knoblich, PharmD 174 Incremental Health Care Resource Utilization and Economic Burden of Venous Thromboembolism Recurrence from a U.S. Payer Perspective J. Lin, PhD; R. Preblick, PharmD, MPH; M. Lingohr-Smith, PhD; and W.J. Kwong, PharmD, PhD 187 Analysis of Gastrointestinal Prophylaxis in Patients Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel Kathleen M. Morneau, PharmD, BCPS; Anne B. Reaves, PharmD, BCACP; Julie B. Martin, PharmD; and Carrie S. Oliphant, PharmD, BCPS (AQ Cardiology) 194 Adherence to National Recommendations for Safe Methotrexate Dispensing in Community Pharmacies Ellen S. Koster, PhD; Joelle C.D. Walgers, BSc; Mariska C.J. van Grinsven, PharmD; Nina A. Winters, PharmD; and Marcel L. Bouvy, PhD, PharmD 141

■ COMMENTARY 201

206

PCMHs, ACOs, and Medication Management: Lessons Learned from Early Research Partnerships Evan S. Schnur, PharmD; Alex J. Adams, PharmD; Donald G. Klepser, PhD, MBA; William R. Doucette, PhD; and David M. Scott, MPH, PhD Pharmacists’ Role in the Care of Patients with Heart Failure: Review and Future Evolution Judy W.M. Cheng, BS, PharmD, MPH, FCCP, BCPS, and Hannah Cooke-Ariel, PharmD

■ departments 112 Cover Impressions 109 Facts and Figures: Specialty Infographic 118 Facts and Figures: Part D Drug Utilization 214 Thanks to JMCP Peer Reviewers, 2013 www.amcp.org

Vol. 20, No. 2

February 2014

President: Kim A. Caldwell, RPh President-Elect: Dana Davis McCormick, RPh Past President: Douglas S. Burgoyne, PharmD Treasurer: H. Eric Cannon, PharmD, FAMCP Chief Executive Officer: Edith A. Rosato, RPh, IOM Director: David Calabrese, RPh, MHP Director: Stanley E. Ferrell, RPh, MBA Director: Kathleen Kaa, PhD, RPh Director: Lynn Nishida, RPh Director: Mitzi M. Wasik, PharmD Advertising

Advertising for the Journal of Managed Care Pharmacy is accepted in accordance with the advertising policy of the Academy of Managed Care Pharmacy. For advertising information, contact: Mike Minakowski Scherago International 525 Washington Blvd, Ste. 3310 Jersey City, NJ 07310 Tel.: 215.860.0912 Fax: 201.653.5705 www.scherago.com editorial

Questions related to editorial content should be directed to JMCP Managing Editor Jennifer Booker: [email protected]. Manuscripts should be submitted electronically at jmcp.msubmit.net. For questions about submission, contact Peer Review Administrator Jennifer A. Booker: [email protected]; 703.317.0725. subscriptions

Annual subscription rates: USA, individuals, institutions–$90; other countries–$120. Single copies cost $15. Missing issues are replaced free of charge up to 6 months after date of issue. Send requests to AMCP headquarters. reprints

Information about commercial reprints and permission to reuse material from JMCP may be found at www.jmcp.org. Authors may order reprints from the Sheridan Press; contact contact Tamara Smith, [email protected], 800.352.2210 All articles published represent the opinions of the authors and do not reflect the official policy or views of the Academy of Managed Care Pharmacy or the authors’ institutions unless so specified. Copyright © 2014, Academy of Managed Care Pharmacy. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without written permission from the Academy of Managed Care Pharmacy.

JMCP


Facts and Figures: SpecialtySpecialty Infographic provided by Accredo, Express Scripts Infographic

HEP C KILLS 15,000 AMERICANS EACH YEAR – MORE THAN HIV HEPATITIS C DRUG FORECAST INCREASE IN U.S. SPEND

By 2016, spending on medications for hepatitis C will exceed that of much more common conditions, including high blood pressure.

3.2M

16,000 2014 102.0%

2015 208.8%

AMERICANS LIVE WITH CHRONIC HEP C NEW CASES PER YEAR AND RISING

2016 205.0%

HISTORY OF TREATMENT OPTIONS Success Rate

Regimen

Doses Per Day

Side Effects

Past

Standard two drug treatments; Twice daily ribavirin and weekly interferon injections.

90%

8-12 weeks

1

Short-term Well-tolerated

DISEASE-SPECIFIC COUNSELING AND INDIVIDUALIZED CARE Hep C treatment is complex, and staying adherent to the prescribed medication can often be a major challenge. Specialty-trained pharmacists help identify potential safety concerns and provide disease-specific counseling to patients that can increase adherence and lower overall treatment costs. They prepare patients for treatment, provide guidance to mitigate side-effects and ensure appropriate use of medications – all of which boost adherence and improve health outcomes.

THE KEY TO SUCCESS IS

ADHERENCE & THE KEY TO ADHERENCE IS

SPECIALTY

Patients exclusively using a specialty pharmacy:

60% 15 MORE LIKELY TO ACHIEVE OPTIMUM ADHERENCE

FEWER THERAPY GAP DAYS (Days without any available medication)

PHARMACIES

FOR MORE INFORMATION, GO TO LAB.EXPRESS-SCRIPTS.COM

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20, No. 2 February 2014 January 2014 www.amcp.org Vol. 20, No. 1 Vol. www.amcp.org

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JMCP Author Guidelines JMCP accepts for consideration manuscripts prepared according to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals.1

including supplements, is indexed by MEDLINE/ PubMed, the International Pharmaceutical

■■ Manuscript Preparation Recommended maximum manuscript length is 3,500 words. Manuscripts should include, in this order: title page, abstract, text, references, tables, and figures (see Manuscript Submission Checklist for details). JMCP abstracts should be carefully written narratives that contain all of the principal quantitative and qualitative findings, with the outcomes of statistical tests of comparisons where appropriate. Abstracts are required for all manuscript submissions except Commentaries and Letters. The format for the abstract is Background, Objective, Methods, Results, Conclusion. Reference numbering should begin in the text and should not be included in the abstract. For descriptions of editorial content, see “JMCP Editorial Policy” in this Journal or at www.amcp.org. Please note: • The JMCP Peer Review Checklist is the best guide for authors to improve the likelihood of success in the JMCP peer-review process. It is available at: www.amcp.org/JMCPhome.aspx. • A subsection in the Discussion labeled “Limitations” is required for all articles except Commentaries and Letters. • Most articles should incorporate or at least acknowledge the relevant work of others published previously in JMCP (see “Article Index by Subject Category” at www.amcp.org/JMCPhome.aspx). • Product trade names may be used only once for the purpose of providing clarity for readers, generally at the first citation of the generic name in the article but not in the abstract. • Many articles involve research that may pose a threat to either patient safety or privacy. It is the responsibility of the principal author to ensure that the manuscript is submitted with either the result of review by the appropriate institutional review board (IRB) or a statement of why the research is exempt from IRB review (see “Policy for Protecting Patient Safety and Privacy” at www.amcp.org/JMCPhome.aspx).

■■ Reference Style References should be prepared following modified AMA style. All reference numbers in the manuscript should be superscript (e.g., 1 ). Each unique reference should have only one reference number. If that reference is cited more than once in the manuscript, the same number should be used. Do not use ibid or op cit for JMCP references. Please provide Web (hyperlink) addresses for all free access references. An access date should be included for every URL except links to JMCP articles. See examples 2 and 3 in the second column. Here are examples of the style format for common types of references: 1. Journal article — (list up to 6 authors; if 7 or more, list only the first 3 and add et al.): Kastelein


The Journal of Managed Care Pharmacy,

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Abstracts (IPA), Science Citation Index Expanded (SCIE), Current Contents/Clinical Medicine (CC/CM), and Scopus.

JJ, Akdim F, Stroes ES, et al.; the ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431-43. Available at: http://content. nejm.org/cgi/reprint/358/14/1431.pdf. Accessed January 4, 2011. 2. No author given — Anonymous. More patients leaving Rxs at pharmacy counter. Manag Care. 2010;19(4):49. Available at: http://www.managedcaremag.com/archives/1004/1004.formfiles.html. Accessed January 4, 2011. 3. Journal or magazine paginated by issue — McKinney M. Alarm fatigue sets off bells. Mod Healthc. 2010;40(15):14. 4. Book or monograph — Tootelian DH, Gaedeke RM. Essentials of Pharmacy Management. St. Louis, MO: C.V. Mosby; 1993. 5. Book or monograph with editor, compiler, or chairperson as author — Chernow B, ed. Critical Care Pharmacotherapy. Baltimore, MD: Williams & Wilkins; 1995. 6. Chapter in a book — Kreter B, Michael KA, DiPiro JT. Antimicrobial prophylaxis in surgery. In: DiPiro JT, Talbert RL, Hayes PE, Yee GC, Matzke GR, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. Norwalk, CT: Appleton & Lange; 1992:1811-12. 7. Government agency publication — National Heart, Lung, and Blood Institute. Expert panel report 3: guidelines for the diagnosis and management of asthma. Full report 2007. August 28, 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed January 4, 2011. 8. Website - other online publication — Minnesota Department of Health. Essential Benefit Set Work Group. Background paper. September 4, 2009. Available at: http://www.health.state.mn.us/healthreform/essential/EBS_Background.pdf. Accessed January 4, 2011. 9. Newspaper article — Abelson R, Pollack A. Medicare widens drugs it accepts for cancer. NY Times. January 26, 2009. Available at: http://www. nytimes.com/2009/01/27/health/27cancer.html?_ r=2&ref=health. Accessed January 4, 2011. 10. Online news article — Marchione M. Study finds many patients shun free heart drugs. AP. November 14, 2011. Available at: http://articles. boston.com/2011-11-14/lifestyle/30398405_1_heartdrugs-medicines-patients. Accessed April 26, 2012. 11. Drug label – prescribing information — Xolair (omalizumab) for subcutaneous use. Genentech. July 2010. Available at: http://www.gene.com/gene/ products/information/pdf/xolair-prescribing.pdf.

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Accessed January 4, 2011. 12. Dissertation or thesis — Youssef NM. School adjustment of children with congenital heart disease [dissertation]. Pittsburgh, PA: University of Pittsburgh; 1988. 13. Paper or poster presented at a meeting — Gleason PP, Starner CI, Hyland-Marciniak B. Erythropoiesis-stimulating agent trends and utilization management opportunity. Poster presented at: 2010 AMCP Annual Meeting; April 9, 2010; San Diego, CA. Available at. http://www.amcp.org/data/ jmcp/141-168.pdf. 14. Letter or editorial — Barbuto JP. Categorizing patients from medical claims data – the influence of GIGO [letter]. J Manag Care Pharm. 2004;10(6):55960. Available at: http://www.amcp.org/data/jmcp/ Letters_559-566.pdf. 15. Journal supplement — Academy of Managed Care Pharmacy. AMCP guide to pharmaceutical payment methods, 2009 update (version 2.0). J Manag Care Pharm. 2009;15(6 Suppl A):S1-S61. Available at: http://www.amcp.org/data/jmcp/1002.pdf.

■■ Manuscript Submission A complete list of documents needed for submission to JMCP appears on the Manuscript Submission Checklist at www.amcp.org/JMCPhome.aspx and the Supplement Submission Checklist at www.amcp. org/JMCPhome.aspx. Prior to peer review, all manuscripts are reviewed by the editors and/or members of the Editorial Advisory Board for appropriateness of the topic for JMCP, methodological transparency, and compliance with submission requirements. See Author Guidelines for description of the “pre-review process.” Peer review generally requires 4-6 weeks but may extend as long as 12 weeks in unusual cases. Solicited manuscripts are subject to the same peerreview standards and editorial policy as unsolicited manuscripts. Disclosures and conflicts of interest: Manuscript submissions should (a) include a statement that identifies the nature and extent of any financial interest or affiliation that any author has with any company, product, or service discussed in the manuscript and clearly indicates the source(s) of funding and financial support and (b) be accompanied by completed and signed author attestation forms for the principal author and each coauthor.

■■ Manuscript Submission Checklist Before submitting your manuscript to JMCP, please review the JMCP Author Guidelines and please check to see that your package includes all items in the JMCP Manuscript Submission Checklist. Both are available at www.amcp.org/JMCPhome.aspx. Reference 1. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication. Updated April 2010. Available at: http://www. icmje.org/urm_full.pdf. Accessed August 25, 2011.

c o v e r i mp r e s s i o n s About the JMCP February Cover

S

teve Avey would be the first to say that he AMCP Format adopted nationally. He laughis a lucky man, although at first glance, it ingly attributes the recognition to “everyone might not seem so. being concerned I was about to die,” but his luck He did not feel so lucky 8 years ago when he held, and with great medical care, he not only was diagnosed with a rare form of cancer. But, survived the illness but has gone back to runhe did feel extremely fortunate when he beat ning half-marathons again. And, he recognizes it. A few years earlier, in 2000, Avey probably that the AMCP Format he helped create and wondered more than once if he was lucky to market stands as one of AMCP’s most critical be leading the effort to promote and educate accomplishments. P&T committees and manufacturers regardToday, as Vice President of Specialty ing the inaugural AMCP Format for Formulary Pharmacy Programs for MedImpact—the largSubmissions. As the work progressed, however, est privately held PBM in the country—Avey he realized how fortunate he was to be involved has found another professional mission. Avey in this great work. oversees his firm’s management of specialty Creating the AMCP Format involved “treSteven G. Avey pharmaceuticals for “rare chronic diseases that mendous effort on the part of a lot of people,” need considerable clinical management,” he Avey concedes, but it was for an important explains. These medications treat rare conditions from Crohn’s disprofessional cause. “In the late 1990s, formularies were becoming more sophisticated. But the only information we had, as pharmacists ease and cystic fibrosis to multiple sclerosis and rheumatoid arthritis. Specialty pharmacies tailor clinical pathways that achieve optimal in managed care trying to establish formularies, was the product outcomes within each patient population. In fact, optimal outcomes labeling that health care professionals receive. We needed a lot more information than that, including financials and a pharmacoeconomic often coincide with demonstrated financial savings for payers, model, to help us determine the value of a new medication and where patients, and physicians. Each program is designed to meet the needs of patients through education, reimbursement investigation, and it belonged on a formulary.” The Academy of Managed Care Pharmacy (AMCP) stepped up and ongoing clinical interaction and support. When Avey looks into the future, specialty pharmacy looms large asked the Format Executive Committee to create a tool that would provide consistent, standardized information for P&T committees to with promise and challenges. “Within 4 years, about half of this use when requesting information from pharmaceutical manufactur- nation’s drug spend will be from 1%-3% of the population who need ers. Those manufacturers initially balked at the use of such a tool, but specialty drugs,” he explains. “This could tip over the prescription through the efforts of Avey and others, they recognized that a stan- drug spend unless we find a way to appropriately manage these medidardized dossier could benefit them, as well, when they were called cations. We’ve got to get in front on this issue.” The expertise of managed care pharmacists will be more imporon to provide information to pharmacy benefit managers (PBMs) and health plans. Ultimately, the manufacturers responded positively tant than ever, Avey says. “First, we must ensure that it is appropriate when Avey requested funding to hold a series of 35 programs across for a patient to take one of these medications; sometimes, prescribers the country to educate stakeholders in how to appropriately use the will go right to a specialty medication, leaping over less expensive, first-line drugs. Second, we have to do everything we can to ensure AMCP Format. Today, the AMCP Format “is the standard for drug assessments,” adherence. Managed care organizations will have a big role to play Avey says. “PhRMA companies start preparing their dossiers well in and should offer programs to help pharmacists coach patients on the advance of approval so the information is available soon after the critical importance of adhering to their medication regimens.” He also sees a leading role for AMCP in this and other imporproduct launches.” It was also exciting for Avey to see the AMCP Format come into tant issues, such as government intervention in health care. “With use as a teaching tool. He explains that every year, pharmacy schools Medicaid expansion and the Affordable Care Act, we’ll have more across the country hold a student P&T committee competition. patients than ever with prescription benefits that are provided “Student chapters submit applications, and after local competitions, through managed care. And, government will definitely be very 8 schools are selected. Their teams are given AMCP Format dossiers involved in how this plays out. AMCP has been a tremendous voice on a medication, and then the teams review the clinical information, for us on Capitol Hill. They do this extremely well, and it will be assess the value proposition, and present their conclusions. This is critical, as these programs develop, for us to ensure that the right one of our biggest draws in bringing student chapters to our meetings, legislation is in place.” But most of all, Avey believes, “AMCP can never forget its roots. and it is extremely popular with the schools, students, and AMCP When I first got involved, it was because a respected colleague told me members.” Creating the AMCP Format “involved tremendous effort” from the Academy would provide me with everything I needed. That was everyone involved, Avey asserts, but “it is the most gratifying work I in 1992 when my company at the time was first setting up rudimenhave been involved in. The AMCP Format Committee and those who tary formularies, and although it was technically managed care, we helped in the education programs were highly committed, and we were not providing a lot of management. I needed AMCP to help me learn how to actually manage a client’s prescription benefit.” knew we were doing something very special for the profession.” According to Avey, AMCP still has a critical role in “nurturing In 2005, Avey was extremely honored when the AMCP Board chose to change the name of its Lifetime Achievement Award to the managed care pharmacists, providing continuing education, and Steven G. Avey Award in honor of his tireless work on getting the doing all the things it’s done so well over the past 25 years.”


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February 2014

Vol. 20, No. 2

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Facts and Figures: Part D Drug Utilization provided by MedImpact HealthCare Systems, Inc.

Top 10 Drugs by Rx Claim Volume for December 2013 (Nonspecialty)

Top 10 Drugs by Rx Claim Cost for December 2013 (Nonspecialty)

75%

25%

3.4%

Insulin Glargine

Levothyroxine Sodium 3.2% Lisinopril

3.1%

Fluticasone/Salmeterol 2.2%

Omeprazole

3.0%

Rosuvastatin Calcium 2.1%

Simvastatin

3.0%

Tiotropium Bromide

1.7%

Amlodipine Besylate

2.5%

Duloxetine HCL

1.7%

Atorvastatin Calcium

2.3%

Etanercept

1.5%

Metformin HCL

2.1%

Adalimumab

1.5%

Hydrocodone BIT/Acetaminophen

2.1%

Aripiprazole

1.5%

Furosemide

1.8%

Sitagliptin Phosphate 1.4%

Hydrochlorothiazide

1.6%

Glatiramer Acetate

82%

New Type 2 Drugs Q1 2014 (Pending FDA Approval)

18%

1.3%

State Distribution of Medicare Rx Lives January 2014

Drug

Manufacturer

FDA Deadline

Forxiga (dapagliflozin)

Bristol-Myers Squibb Company and AstraZeneca

PDUFA: January 11, 2014

Metreleptin

Bristol-Myers Squibb Company and AstraZeneca

PDUFA: February 27, 2014

Empagliflozin

Eli Lilly and Boehringer Ingelheim

PDUFA: March 25, 2014

Eperzan (albiglutide)

GlaxoSmithKline

Expected approval: April 15, 2014

Dulaglutide

Eli Lilly

Expected approval: Q4 2014

Medicare Rx Lives ■■ ■■ ■■ ■■ ■■

Quintile Highest fifth Fourth fifth Middle fifth Second fifth Lowest fifth

U.S. Total = 33.8 million Median = 425,060 (Colorado) States with the Most and Least Medicare Rx Lives Highest States California 3,943,697 Florida New York Texas Pennsylvania

Rank 1 2 3 4 5

Lowest States Alaska 27,466 District of Columbia Wyoming North Dakota Vermont

Source: BusinessOne Technologies’ Maestro. Medicare MA-PD and PDP lives as of January 6, 2014.


JMCP

February 2014

Vol. 20, No. 2

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Editorial Mission

JMCP publishes peer-reviewed original research manuscripts, subject reviews, and other content intended to advance the use of the scientific method, including the interpretation of research findings in managed care pharmacy. JMCP is dedicated to improving the quality of care delivered to patients served by managed care pharmacy by providing its readers with the results of scientific investigation and evaluation of clinical, health, service, and economic outcomes of pharmacy services and pharmaceutical interventions, including formulary management. JMCP strives to engage and serve professionals in pharmacy, medicine, nursing, and related fields to optimize the value of pharmaceutical products and pharmacy services delivered to patients. JMCP employs extensive bias-management procedures intended to ensure the integrity and reliability of published work.

Editorial staff Editor-in-Chief

John Mackowiak, PhD 919.942.9903, [email protected] Publisher

Edith A. Rosato, RPh, IOM Chief Executive Officer Academy of Managed Care Pharmacy

Assistant Editor

Managing Editor

Laura E. Happe, PharmD, MPH 864.938.3837, [email protected]

Jennifer A. Booker 703.317.0725, [email protected]

Assistant Editor

Copy Editor

Eleanor M. Perfetto, MS, PhD 410.706.6989, [email protected]

Carol Blumentritt 602.616.7249, [email protected]

Assistant Editor

Graphic Designer

Karen L. Rascati, PhD 512.471.1637, [email protected]

Margie C. Hunter 703.297.9319, [email protected]

Editorial advisory board

Committee Purpose: To advise and assist the editors and staff in the solicitation and development of JMCP content. For more information see: www.amcp.org/eab. To volunteer to be a committee member, watch for the call for AMCP volunteers every September. Patrick P. Gleason, PharmD, FCCP, BCPS, Prime Therapeutics, LLC, Eagan, MN (chair)

Bradley C. Martin, PhD, PharmD, Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, AR

J. Daniel Allen, PharmD, RegenceRx, Portland, OR

Robert P. Navarro, PharmD, College of Pharmacy, University of Florida, Gainesville, FL

Mitchell J. Barnett, PharmD, MS, Touro University College of Pharmacy, Vallejo, CA Christopher F. Bell, MS, Global Health Outcomes, Research & Development, GlaxoSmithKline, Research Triangle Park, NC Joshua Benner, PharmD, ScD, Crimson Health, McLean, VA Gary Besinque, PharmD, FCSHP, Kaiser Permanente, Downey, CA Scott A. Bull, PharmD, Johnson & Johnson Health Care Companies, Danville, CA H. Eric Cannon, PharmD, FAMCP, SelectHealth, Salt Lake City, UT Norman V. Carroll, PhD, School of Pharmacy, Virginia Commonwealth University, Richmond, VA Mark Conklin, MS, PharmD, PQA, Inc., Sewickley, PA Eric J. Culley, PharmD, MBA, Evolent Health, Pittsburgh PA Gregory W. Daniel, PhD, MPH, RPh, The Brookings Institution, Washington, DC Thomas Delate, PhD, Kaiser Permanente of Colorado, Aurora, CO Melissa S. Denno, PharmD, Xcenda, Tampa, FL Mark Jackson, BScPhm, BComm, RPh, Green Shield Canada, Windsor, Ontario Stephen J. Kogut, PhD, RPh, MBA, College of Pharmacy, University of Rhode Island, Kingston, RI Charnelda Gray Lewis, PharmD, BCPS, Kaiser Permanente, Stone Mountain, GA

Robert L. Ohsfeldt, PhD, Department of Health Policy & Management, Texas A&M Health Science Center, College Station, TX Brian J. Quilliam, PhD, RPh, College of Pharmacy, University of Rhode Island, Kingston, RI M. Christopher Roebuck, MBA, RxEconomics LLC, Sparks, MD Elan Rubinstein, PharmD, MPH, EB Rubinstein Associates, Oak Park, CA Jeremy A. Schafer, PharmD, MBA, Prime Therapeutics, LLC, Eagan, MN Jordana Schmier, MA, Exponent, Alexandria, VA Marvin D. Shepherd, PhD, Center for Pharmacoeconomic Studies, University of Texas at Austin, Austin, TX Joshua J. Spooner, PharmD, MS, School of Pharmacy, Western New England University, Springfield, MA Linda M. Spooner, PharmD, BCPS, Massachusetts College of Pharmacy, Worcester, MA Connie A. Valdez, PharmD, MSEd, BCPS, School of Pharmacy, University of Colorado, Aurora, CO Vincent Willey, PharmD, University of the Sciences in Philadelphia, Philadelphia, PA Karen Worley, PhD, Humana Inc., Cincinnati, OH

Journal of Managed Care Pharmacy (ISSN 1083–4087) is published 12 times per year and is the official publication of the Academy of Managed Care Pharmacy (AMCP), 100 North Pitt St., Suite 400, Alexandria, VA 22314; 703.683.8416; 800.TAP.AMCP; 703.683.8417 (fax). The paper used by the Journal of Managed Care Pharmacy meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper) effective with Volume 7, Issue 5, 2001; prior to that issue, all paper was acid-free. Annual membership dues for AMCP include $90 allocated for the Journal of Managed Care Pharmacy. Send address changes to JMCP, 100 North Pitt St., Suite 400, Alexandria, VA 22314.

www.amcp.org

Vol. 20, No. 2

February 2014

JMCP


SUBJECT REVIEW

Tolerability of Saxagliptin in Patients with Inadequately Controlled Type 2 Diabetes: Results from 6 Phase III Studies Jaime A. Davidson, MD, FACP, MACE

ABSTRACT BACKGROUND: Oral antihyperglycemic drugs used to treat type 2 diabetes mellitus (T2DM) vary in safety and tolerability. Treatment-related hypoglycemia and weight gain can exacerbate underlying disease. OBJECTIVE: To evaluate the tolerability of saxagliptin using data from phase III clinical trials. METHODS: Six 24-week randomized studies in 4,214 patients with T2DM were assessed. Saxagliptin 2.5 mg or 5 mg was compared with placebo in 2 trials of monotherapy in treatment-naïve patients and in 3 trials of add-on therapy to metformin, glyburide, or a thiazolidinedione; initial combination therapy with saxagliptin 5 mg plus metformin was compared with metformin monotherapy in treatment-naïve patients. Data from the monotherapy and add-on studies were pooled; data from the initial combination study were analyzed separately. No statistical analyses of between-group comparisons across studies were conducted for these safety analyses because of multiplicity of end points and relative lack of statistical power and because small differences not reaching statistical significance have the potential to be clinically relevant. RESULTS: In the pooled analysis, incidence rates for adverse events (AEs) with saxagliptin 2.5 mg, 5 mg, and placebo were 72.0% (635/882), 72.2% (637/882), and 70.6% (564/799), respectively; rates for serious AEs (SAEs) were 3.5% (31/882), 3.4% (30/882), and 3.4% (27/799); rates of discontinuation due to AEs were 2.2% (19/882), 3.3% (29/882), and 1.8% (14/799). AEs reported in ≥ 2% of patients receiving saxagliptin and occurring ≥ 1% more frequently with saxagliptin than with placebo were sinusitis, gastroenteritis, abdominal pain, and vomiting. In the initial combination study, AE incidence rates with saxagliptin 5 mg plus metformin and metformin monotherapy were 55.3% (177/320) and 58.5% (192/328), respectively; incidence rates for SAEs were 2.5% (8/320) and 2.4% (8/328); and rates of discontinuation due to AEs were 2.5% (8/320) and 3.4% (11/328). CONCLUSION: Saxagliptin 2.5 mg or 5 mg was generally well tolerated as monotherapy, add-on combination therapy with other oral antihyperglycemic drugs, and initial combination with metformin. J Manag Care Pharm. 2014;20(2):120-29 Copyright © 2014, Academy of Managed Care Pharmacy. All rights reserved.

What is already known about this subject • Oral antidiabetic drugs (OADs) differ in their safety and tolerability profiles. For example, the sulfonylureas are associated with weight gain and risk of hypoglycemia, whereas metformin is associated with gastrointestinal intolerance, and its use is limited by renal impairment. Thiazolidinediones (TZDs) are associated with increased risk of bone fracture (mainly in women), edema, weight gain, congestive heart failure, and possibly myocardial infarction (rosiglitazone).


JMCP

February 2014

Vol. 20, No. 2

• Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of OADs. The DPP-4 inhibitor saxagliptin is approved as an adjunct to diet and exercise for improving glycemic control in patients with type 2 diabetes mellitus (T2DM) and has also been shown to be efficacious as add-on therapy to metformin, a sulfonylurea (glyburide), and a TZD, as well as in initial combination therapy with metformin. The current evaluation of saxagliptin tolerability is based on an analysis of the phase III clinical trial program, consisting of 6 phase III studies, all of which were 24-week randomized, double-blind, placebo- or active-controlled studies.

What this study adds • The purpose of the pooled analysis of placebo-controlled monotherapy and add-on therapy trials was to identify any safety signals for saxagliptin that might not have been identified in the smaller populations of the individual trials. The initial combination study was reported separately because patients in that study had new-onset T2DM, and the comparison was of initial add-on rather than sequential add-on therapies. • Across 6 double-blind phase III clinical trials, saxagliptin was generally well tolerated as monotherapy; as add-on combination therapy with metformin, glyburide, or a TZD; and as initial combination therapy with metformin in patients with T2DM. Incidence rates of adverse events were comparable with saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo (pooled analysis) and with saxagliptin 5 mg plus metformin and metformin monotherapy (initial combination study).

D

espite many available therapies, only 57% of patients with type 2 diabetes mellitus (T2DM) in the United States reach the American Diabetes Association (ADA) recommended glycated hemoglobin (HbA1c) goal of