september/october 2010, vol 3, no 5

EDITORIAL

U.S. Rebukes Health InsurersJanet Adamy

Resisting the Urge to Flatten HealthcareRobert E. Henry

REGULATORY

Assessment of Medicare Part D Communications to BeneficiariesMeghana Aruru, PhD, MBA, BSPharm; J. Warren Salmon, PhD

Stakeholder Perspective by Jack E. Fincham, PhD, RPh

BUSINESS

A Comparison of Drug Formularies and the Potential for Cost-SavingsAndrea L. Kjos, PharmD, PhD; Jon C. Schommer, PhD; Yingli Yuan, PhD

Stakeholder Perspective by Jeff Januska, PharmD

CLINICAL

Managing Dyslipidemia in Primary Care with Restricted Access to Lipid-Modifying TherapyJohn T. Lynch, MPH; Catherine E. Cooke, PharmD, BCPS, PAHM; Jonathan Rosen, MD; Sanjay Gandhi, PhD; Michael F. Bullano, PharmD

Stakeholder Perspective by Matthew Mitchell, PharmD, MBA

◆ Generic Drug Trends

◆ Industry Trends

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©2010 Engage Healthcare Communications, LLCwww.AHDBonline.com

SEPTEMBER/OCTOBER 2010 VOLUME 3, NUMBER 5

THE PEER-REVIEWED FORUM FOR EVIDENCE IN BENEFIT DESIGN™

FOR PAYERS, PURCHASERS, POLICYMAKERS, AND OTHER HEALTHCARE STAKEHOLDERS

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300 l American Health & Drug Benefits l www.AHDBonline.com September/October 2010 l Vol 3, No 5

EDITORIAL BOARD

CLINICAL EDITOR Thomas G. McCarter, MD, FACPChief Clinical OfficerExecutive Health Resources, PA

GOVERNMENT EDITORKevin B. “Kip” Piper, MA, FACHEPresident, Health Results GroupSr. Counselor, Fleishman-Hillard Washington, DC

ACTUARY David WilliamsMilliman Health ConsultantWindsor, CT

CANCER RESEARCHAl B. Benson, III, MD, FACPProfessor of MedicineAssociate Director for ClinicalInvestigationsRobert H. Lurie Comprehensive CancerCenter, Northwestern UniversityPresident, ACCCPast Chair, Board of Directors, NCCN

Samuel M. Silver, MD, PhD, FACPProfessor, Internal MedicineDirector, Cancer Center NetworkDivision of Hematology/OncologyAssistant Dean for ResearchUniversity of Michigan Health Systems

CARDIOLOGY RESEARCH Michael A. Weber, MDProfessor of MedicineDepartment of Medicine (Cardiology)State University of New York

ENDOCRINOLOGY RESEARCHJames V. Felicetta, MD Chairman, Dept. of Medicine Carl T. Hayden Veterans AffairsMedical Center, Phoenix, AZ

EMPLOYERSAlberto M. Colombi, MD, MPHCorporate Medical DirectorPPG Industries, Pittsburgh, PA

Wayne M. Lednar, MD, PhDGlobal Chief Medical OfficerDirector, Integrated Health ServicesDuPont, Wilmington, DE

Arthur F. Shinn, PharmD, FASCPPresident, Managed Pharmacy Consultants, Lake Worth, FL

F. Randy Vogenberg, RPh, PhDPrincipal, Institute of Integrated HealthcareSharon, MASenior Fellow, Jefferson School ofPopulation Health

EPIDEMIOLOGY RESEARCHJoshua N. Liberman, PhD Vice President, Strategic Research CVS Caremark, Hunt Valley, MD

Nirav R. Shah, MD, MPHAssistant Professor of MedicineNYU School of Medicine, NYCSenior Investigator, Geisinger HealthSystem, Danville, PA

HEALTH INFORMATION TECHNOLOGY J. B. Jones, PhD, MBAResearch Associate, Geisinger Health System, Danville, PA

Victor J. Strecher, PhD, MPHProfessor and Director, Center for HealthCommunications ResearchUniversity of Michigan Schools of PublicHealth and Medicine, Ann ArborFounder and Chief Visionary OfficerHealthMedia, Johnson & Johnson Co.

HEALTH OUTCOMES RESEARCH Gordon M. Cummins, MSDirector, IntegriChain

Kavita V. Nair, PhDAssociate Professor, School of PharmacyUniversity of Colorado at Denver

Gary M. Owens, MDPresident, Gary Owens AssociatesGlen Mills, PA

Timothy S. Regan, BPharm, RPhExecutive Director, XcendaPalm Harbor, FL

MANAGED CARE & GOVERNMENT AFFAIRSSharad Mansukani, MDChief Strategic Officer, Nations HealthSenior Advisor, Texas Pacific Group, FL

MANAGED MARKETS Jeffrey A. Bourret, MS, RPh, FASHPSenior Director, Customer Marketing & Innovation, US Specialty CustomersPfizer Specialty Business Unit, PA

Charles E. Collins, Jr, MS, MBAAssociate Director, Managed Markets Marketing, Boehringer-Ingelheim, CT

PATIENT ADVOCACY William E. Fassett, BSPharm, MBA, PhDProfessor of Pharmacy Law & EthicsVice Chair, Dept. of PharmacotherapyCollege of Pharmacy, Washington StateUniversity, Spokane, WA

PERSONALIZED MEDICINE Wayne A. Rosenkrans, Jr, PhDChairman and President, Personalized Medicine Coalition, Distinguished Fellow,MIT Center for Biomedical Innovation

PHARMACOECONOMICSJeff Jianfei Guo, BPharm, MS, PhDAssociate Professor of Pharmacoeconomics& Pharmacoepidemiology, College of Pharmacy, University of Cincinnati Medical Center, OH

PHARMACY BENEFIT DESIGN Joel V. Brill, MDChief Medical Officer, Predictive Health, Phoenix, AZ

William J. Cardarelli, PharmDDirector of PharmacyAtrius HealthHarvard Vanguard Medical Associates

Leslie S. Fish, PharmDSr. Director of Pharmacy ServicesFallon Community Health Plan, MA

Michael S. Jacobs, RPhNational Clinical Practice LeaderBuck Consultants, Atlanta

Matthew Mitchell, PharmD, MBAManager, Pharmacy ServicesSelectHealth, Salt Lake City, UT

Paul Anthony Polansky, BSPharm, MBAFormer Executive VP and Chief PharmacyOfficer, Sanovia Corp., Philadelphia, PA

Scott R. Taylor, RPh, MBAAssociate Director, Industry RelationsGeisinger Health System, Danville, PA

POLICY & PUBLIC HEALTH Joseph R. Antos, PhDWilson H. Taylor Scholar in Health CareRetirement PolicyAmerican Enterprise Institute

Jack E. Fincham, PhD, RPh Professor of Pharmacy, School of PharmacyUniversity of Missouri, Kansas City

Alex Hathaway, MD, MPH, FACPMPresident & Founder, J.D. BioEdgeHealth quality and biomedical research consultancy

J. Warren Salmon, PhDProfessor of Health Policy & AdministrationSchool of Public HealthUniversity of Illinois at Chicago

REIMBURSEMENT POLICYGrant D. Lawless, BSPharm, MD, FACPExecutive Director for Payor RelationsCorporate Account, Amgen, CA

RESEARCH & DEVELOPMENT Michael F. Murphy, MD, PhDChief Medical Officer and Scientific Officer Worldwide Clinical TrialsFaculty, Center for Experimental Pharmacology and Therapeutics, Harvard-MIT Division of Health Sciences andTechnology, Cambridge, MA

SPECIALTY PHARMACYAtheer A. Kaddis, PharmDVice President, Managed MarketsDiplomat Specialty PharmacySwartz Creek, MI

James T. Kenney, RPh, MBAPharmacy Operations Manager Harvard Pilgrim Health Care, Wellesley, MA

Copyright ©2010, Boehringer Ingelheim Pharmaceuticals, Inc. All rights reserved. (06/10) DI77201MHC-A

exploring DIABETES

inspired to make a

DIFFERENCE


PublisherNicholas [email protected]

Associate PublisherMaurice [email protected]

Editorial DirectorDalia [email protected]

Associate EditorLara J. [email protected]

Editorial AssistantJessica A. Smith

Senior Production ManagerLynn Hamilton

Business ManagerBlanche Marchitto

Editor-in-ChiefRobert E. [email protected]

American Health & Drug Benefits is foundedon the concept that health and drug benefitshave undergone a transformation: the econo -metric value of a drug is of equal importanceto clinical outcomes as it is to serving as thebasis for securing coverage in formularies andbenefit designs. Because benefit designs aregreatly affected by clinical, business, and pol-icy conditions, this journal offers a forum forstakeholder integration and collaborationtoward the improvement of healthcare.

This publication further provides benefitdesign de cision makers the integrated industryinformation they require to devise formulariesand benefit designs that stand up to today’sspecial healthcare delivery and business needs.

Contact Information:For reprints, subscription information, andeditorial queries, please contact:[email protected]

T: 732-992-1892F: 732-992-1881

Mission Statement

EDITORIAL

308 U.S. Rebukes Health Insurers (available in the print version only)Janet Adamy

308 Resisting the Urge to Flatten HealthcareRobert E. Henry

REGULATORY

310 Assessment of Medicare Part D Communications to BeneficiariesMeghana Aruru, PhD, MBA, BSPharm; J. Warren Salmon, PhD

317 Stakeholder Perspective by Jack E. Fincham, PhD, RPh

BUSINESS

321 A Comparison of Drug Formularies and the Potential for Cost-SavingsAndrea L. Kjos, PharmD, PhD; Jon C. Schommer, PhD; Yingli Yuan, PhD

330 Stakeholder Perspective by Jeff Januska, PharmD

TABLE OF CONTENTS

Continued on page 304

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American Health & Drug Benefits, ISSN 1942-2962 (print); ISSN 1942-2970 (online), ispublished 6 times a year by Engage HealthcareCommunications, LLC, 241 Forsgate Drive,Suite 205A, Monroe Township, NJ 08831.Copyright © 2010 by Engage Healthcare Communications, LLC. All rights reserved.American Health & Drug Benefits and The Peer-Reviewed Forum for Evidence in BenefitDesign are trademarks of Engage HealthcareCommunications, LLC. No part of this publication may be reproduced or transmittedin any form or by any means now or hereafterknown, electronic or mechanical, includingphotocopy, recording, or any informationalstorage and retrieval system, without writtenpermission from the Publisher. Printed in theUnited States of America.

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The ideas and opinions expressed in AmericanHealth & Drug Benefits do not necessarily reflect those of the Editorial Board, the Editors,or the Publisher. Publication of an advertise-ment or other product mentioned in American Health & Drug Benefits should not beconstrued as an endorsement of the product orthe manufacturer’s claims. Readers are encour-aged to contact the manufacturers about anyfeatures or limitations of products mentioned.Neither the Editors nor the Publisher assumeany responsibility for any injury and/or damageto persons or property arising out of or related to any use of the material mentionedin this publication.

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CLINICAL

340 Managing Dyslipidemia in Primary Care with Restricted Access to Lipid-Modifying TherapyJohn T. Lynch, MPH; Catherine E. Cooke, PharmD, BCPS, PAHM; Jonathan Rosen, MD;Sanjay Gandhi, PhD; Michael F. Bullano, PharmD

347 Stakeholder Perspective by Matthew Mitchell, PharmD, MBA

DEPARTMENTS

333 GENERIC DRUG TRENDSFDA’s Approval Process Borne Out by a Large Study: But CommunicatingGenerics’ Safety and Efficacy to the Public Leaves Much to Be DesiredDalia Buffery, MA, ABD

350 INDUSTRY TRENDS

Healthcare Reform: Quality Outcomes Measurement and Reporting

Cary Sennett, MD, PhD

CAPTION CONTEST

TABLE OF CONTENTS (Continued)



348

FORMERLYKAPIDEX™

(dexlansoprazole)

1200

1000

800

600

400

200

00 6 12 18 24

Time (h)

Mean plasma concentration (in healthy subjects; day 5; ng/mL)1

DEXILANT 60 mgDEXILANT 30 mgDEXILANT 60 mgDEXILANT 60 mgDEXILANT 30 mgDEXILANT 30 mgDEXILANT 30 mg

DEXILANT 30 mg provided full 24-hour heartburn relief in a majority of symptomatic non-erosive gastroesophageal reflux disease patients at week 41

Conclusions of comparative effi cacy cannot be drawn from this information.

IndicationsDEXILANT is indicated for healing all grades of erosive esophagitis (EE) for up to 8 weeks, maintaining healing of EE for up to 6 months, and treating heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for 4 weeks.

Important Safety Information DEXILANT is contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity and anaphylaxis have been reported with DEXILANT use. Symptomatic response with DEXILANT does not preclude the presence of gastric malignancy. Most commonly reported treatment-emergent adverse reactions: diarrhea (4.8%), abdominal pain (4.0%), nausea (2.9%), upper respiratory tract infection (1.9%), vomiting (1.6%), and flatulence (1.6%). Do not co-administer atazanavir with DEXILANT because atazanavir systemic concentrations may be substantially decreased. DEXILANT may interfere with absorption of drugs for which gastric pH is important for bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole). Patients taking concomitant warfarin may require monitoring for increases in international normalized ratio (INR) and prothrombin time. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Concomitant tacrolimus use may increase tacrolimus whole blood concentrations.

Please see adjacent brief summary of prescribing information for DEXILANT.

DEXILANT WORKS ASECOND SHIFT TO HELP SHUT DOWN ACID PUMPS

DEXILANT is the fi rst and only PPI with a Dual Delayed Release™ (DDR) formulation, which provides a second release of drug

11:00:12 AM

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATIONDEXILANT (dexlansoprazole) delayed release capsulesINDICATIONS AND USAGEDEXILANT is indicated for:

CONTRAINDICATIONS

[see Adverse Reactions].WARNINGS AND PRECAUTIONSGastric Malignancy

ADVERSE REACTIONS Clinical Trials Experience

Table 2: Incidence of Treatment-Emergent Adverse Reactionsin Controlled Studies

Adverse Reaction

Placebo

(N=896)%

DEXILANT30 mg

(N=455)%

DEXILANT60 mg

(N=2218)%

DEXILANTTotal

(N=2621)%

Lansoprazole30 mg

(N=1363)%

Tract Infection

Blood and Lymphatic System Disorders: Cardiac Disorders:

Ear and Labyrinth Disorders: Endocrine Disorders: Eye Disorders: Gastrointestinal Disorders:

General Disorders and Administration Site Conditions:

Hepatobiliary Disorders: Immune System Disorders: Infections and

Infestations: Injury, Poisoning

and Procedural Complications:

Laboratory Investigations:

Metabolism and Nutrition Disorders: Musculoskeletal and Connective

Tissue Disorders: Nervous System Disorders:

Psychiatric Disorders: Renal and Urinary

Disorders: Reproductive System and Breast Disorders: ; Respiratory, Thoracic and Mediastinal Disorders:

Skin and Subcutaneous Tissue Disorders: Vascular Disorders:

Postmarketing Experience

Eye Disorders: Gastrointestinal Disorders: General Disorders and Administration Site Conditions: Immune System Disorders:

Respiratory, Thoracic and Mediastinal Disorders:

Skin and Subcutaneous Tissue Disorders:

DRUG INTERACTIONSDrugs with pH-Dependent Absorption Pharmacokinetics

Warfarin

Tacrolimus

USE IN SPECIFIC POPULATIONSPregnancyTeratogenic Effects

6/10 Printed in U.S.A.

A reproduction study conducted in rabbits at oral dexlansoprazole doses up to 30 mg per kg per day (approximately 9-fold the maximum recommended human dexlansoprazole dose (60 mg) revealed no evidence of harm to the fetus due to dexlansoprazole. In addition, reproduction studies performed in pregnant rats with oral lansoprazole at doses up to 40 times the recommended human dose and in pregnant rabbits at oral lansoprazole doses up to 16 times the recommended human dose revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole.Nursing MothersIt is not known whether dexlansoprazole is excreted in human milk. However, lansoprazole and its metabolites are present in rat milk following the administration of lansoprazole. As many drugs are excreted in human milk,and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies [see Carcinogenesis, Mutagenesis, Impairment of Fertility],a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.Pediatric Use Safety and effectiveness of DEXILANT in pediatric patients (less than 18 years of age) have not been established.Geriatric UseIn clinical studies of DEXILANT, 11% of patients were aged 65 years and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.Renal ImpairmentNo dosage adjustment of DEXILANT is necessary in patients with renal impairment. The pharmacokinetics of dexlansoprazole in patients with renal impairment are not expected to be altered since dexlansoprazole is extensively metabolized in the liver to inactive metabolites, and no parent drug is recovered in the urine following an oral dose of dexlansoprazole.

Hepatic ImpairmentNo dosage adjustment for DEXILANT is necessary for patients with mild hepatic impairment (Child-Pugh Class A). DEXILANT 30 mg should be considered for patients with moderate hepatic impairment (Child-Pugh Class B). No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C).OVERDOSAGEThere have been no reports of significant overdose of DEXILANT. Multiple doses of DEXILANT 120 mg and a single dose of DEXILANT 300 mg did not result in death or other severe adverse events. Dexlansoprazole is not expected to be removed from the circulation by hemodialysis. If an overdose occurs, treatment should be symptomatic and supportive.CLINICAL PHARMACOLOGYPharmacodynamicsAntisecretory ActivityThe effects of DEXILANT 60 mg (n=20) or lansoprazole 30 mg (n=23) once daily for five days on 24-hour intragastric pH were assessed in healthy subjects in a multiple-dose crossover study. Serum Gastrin EffectsThe effect of DEXILANT on serum gastrin concentrations was evaluated in approximately 3460 patients in clinical trials up to 8 weeks and in 1023 patients for up to 6 to 12 months. The mean fasting gastrin concentrations increased from baseline during treatment with DEXILANT 30 mg and 60 mg doses. In patients treated for more than 6 months, mean serum gastrin levels increased during approximately the first 3 months of treatment and were stable for the remainder of treatment. Mean serum gastrin levels returned to pre-treatment levels within one month of discontinuation of treatment.Enterochromaffin-Like Cell (ECL) EffectsThere were no reports of ECL cell hyperplasia in gastric biopsy specimens obtained from 653 patients treated with DEXILANT 30 mg, 60 mg or 90 mg for up to 12 months. During lifetime exposure of rats dosed daily with up to 150 mg per kg per day of lansoprazole, marked hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors, especially in female rats [see Nonclinical Toxicology].Effect on Cardiac RepolarizationA study was conducted to assess the potential of DEXILANT to prolong the QT/QTc interval in healthy adult subjects. DEXILANT doses of 90 mg or 300 mg did not delay cardiac repolarization compared to placebo. The positive control (moxifloxacin) produced statistically significantly greater mean maximum and time-averaged QT/QTc intervals compared to placebo.

NONCLINICAL TOXICOLOGYCarcinogenesis, Mutagenesis, Impairment of FertilityThe carcinogenic potential of dexlansoprazole was assessed using lansoprazole studies. In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with lansoprazole at doses of 5 to 150 mg per kg per day, about 1 to 40 times the exposure on a body surface (mg/m2) basis of a 50 kg person of average height [1.46 m2 body surface area (BSA)] given the recommended human dose of lansoprazole 30 mg per day. Lansoprazole produced dose-related gastric ECL cell hyperplasia and ECL cell carcinoids in both male and female rats [see Clinical Pharmacology].In rats, lansoprazole also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, lansoprazole produced a dose-related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg per kg per day (4 to 40 times the recommended lansoprazole human dose based on BSA) exceeded the low background incidence (range = 1.4 to 10%) for this strain of rat. In a 24-month carcinogenicity study, CD-1 mice were treated orally with lansoprazole doses of 15 mg to 600 mg per kg per day, 2 to 80 times the recommended human dose based on BSA. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 mg and 600 mg lansoprazole per kg per day (40 to 80 times the recommended lansoprazole human dose based on BSA) and female mice treated with 150 mg to 600 mg lansoprazole per kg per day (20 to 80 times the recommended human dose based on BSA) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg per kg per day (10 to 80 times the recommended lansoprazole human dose based on BSA).The potential effects of dexlansoprazole on fertility and reproductive performance were assessed using lansoprazole studies. Lansoprazole at oral doses up to 150 mg per kg per day (40 times the recommended lansoprazole human dose based on BSA) was found to have no effect on fertility and reproductive performance of male and female rats.PATIENT COUNSELING INFORMATION[see FDA-Approved Patient Labeling in the full prescribing information]Information for PatientsTell your patients to watch for signs of an allergic reaction as these could be serious and may require that DEXILANT be discontinued.To ensure the safe and effective use of DEXILANT, this information and instructions provided in the FDA-approved patient labeling should be discussed with the patient. Inform patients of the following:DEXILANT is available as a delayed release capsule.DEXILANT may be taken without regard to food.DEXILANT should be swallowed whole.

follows: - Open capsule; - Sprinkle intact granules on one tablespoon of applesauce; - Swallow immediately.Distributed byTakeda Pharmaceuticals America, Inc.Deerfield, IL 60015U.S. Patent Nos. - 5,045,321; 5,093,132; 5,433,959; 6,462,058; 6,664,276; 6,939,971; and 7,285,668.DEXILANT is a trademark of Takeda Pharmaceuticals North America, Inc. and used under license by Takeda Pharmaceuticals America, Inc.All other trademark names are the property of their respective owners.©2009, 2010 Takeda Pharmaceuticals America, Inc.For more detailed information, see the full prescribing information for DEXILANT or contact Takeda Pharmaceuticals America, Inc. at 1-877-825-3327.KAP0110 R6-Brf; March 2010L-LPD-0310-2

Reference: 1. DEXILANT (dexlansoprazole) package insert, Takeda Pharmaceuticals America, Inc.

DEXILANT™, KAPIDEX™ (dexlansoprazole), and Dual Delayed Release™ are trademarks of Takeda Pharmaceuticals North America, Inc., and are used under license by Takeda Pharmaceuticals America, Inc.

©2010 Takeda Pharmaceuticals North America, Inc. LPD-01139 6/10 Printed in U.S.A.

11:00:13 AM

EDITORIAL


Resisting the Urge to Flatten HealthcareRobert E. Henry, Editor-in-Chief

The infuriating reality of healthcare is that it mustbe run in a systematic way, and that one aspect ofthat system must be policy (the other 2 are clini-

cal and business). And of course, policy means thatpoliticians ultimately weigh in and “decide” things fun-damentally outside their areas of expertise. Not knownfor consistent fiscal brilliance, their stamp on healthcareoften means that much of the downstream effects of leg-islation consist of crisis management aimed at containingthe clinical or economic ruin the legislation overlookedduring the planning phase.

Before we go into the latest example of how the newhealthcare legislation is spilling over its banks (or caus-ing a run on them?), there is a gem of a quote from theseminal movie A Man for All Seasons about a statesmanwith an unswerving conscience and a brilliant grasp ofnatural law, who insisted that his government’s legisla-tion conform to this reality. He was Sir Thomas More,and you guessed it, he was executed for his stance. Theissue then was the proposition that a king should runthe only church allowed in the country of England.When “asked” to sign the oath of allegiance, SirThomas refused. His logic bears repeating at every ses-sion of Congress: “Some men think the Earth is round,others think it flat; it is a matter capable of question.But if it is flat, will the King’s command make it round?And if it is round, will the King’s command flatten it?No, I will not sign.”

For policymakers in Congress and the White Houseresponsible for the Health Care and Education Reconcil -iation Act of 2010 (HCERA), their incentives and areasof knowledge are showing signs of detachment fromthose of the stakeholders in the rest of the country,whose job it is to carry out the legislation. One wondersif they have really asked themselves whether this legisla-tion is founded on their view of desirability without evi-dence of its compliance with natural laws of economicsand medicine, which owe no allegiance to any officials,elected or appointed—laws that will ultimately super-sede any man-made fiat.

The latest round—it is increasingly fitting to evoke

boxing imagery when describing interstakeholder dia-logue—involves Kathleen Sebelius, Secretary of the USDepartment of Health and Human Services, warningKaren Ignagni, the health insurance industry’s top lobby-ist, that health plans must not raise their premiums tocover increased costs occasioned by the HCERA. Herproclamation gives rise to concern that Ms Sebelius maybe dabbling in world-flattening legislative attempts: “Wewill not stand idly by as insurers blame their premiumhikes and increased profits on the requirement that theyprovide consumers with basic protections.”

I do not know if it is the use of the royal “we” thatsuggests arrogance, or the more troubling wordingthroughout the rest of that pithy, dangerous sentence.Instead of a neutral question as to whether insurers are“basing” their premium hikes on the HCERA’s newrequirements, she leaps to the pejorative “blame” con-clusion. This is not dialogue, but the launching ofsalvos. And the assumptions build as this revealing sen-tence continues. These business professionals in a freesociety are now operating under a “requirement” to pro-vide consumers with “basic protections.” The assump-tion is that Ms Sebelius knows exactly what constitutessuch protections, and that they do not fluctuate but areimmutable.

Operating on the notion that they practice their tradein a free society, the insurers are daring to ask why theyare so required. They obey economic laws that will standlong after this administration is gone, laws that state thatincreased benefits may be regarded by some as “basic pro-tections” but are by no means inevitable; they must bepaid for. And unlike the federal government, which, if itcontrolled healthcare, could provide (temporarily) thesebasic protections by devaluing the dollar and printingspurious money to pay for them, private industry canonly pay out benefits based on the monies paid into thesystem from plan members.

The autocracy of Ms Sebelius’s stance goes deep.There is a “let them [in this case, the insurers] eat cake”attitude inherent in her remarks. Somehow or other,insurers must come up with increased benefits without

increasing premiums. And the micromanagement of ourhealthcare, which is what has alarmed Americans eversince this unpopular, ideologically driven legislation wasproposed, is something we are expected to go along with,as if sacrificing fiscal sanity for whatever passes as “basicprotections” is not subject to debate.

Healthcare is ruled not by any Congress or adminis-tration, Democrat or Republican, but by the “iron trian-gle” of cost, quality, and access. Warp this triangle out ofshape, elongate one of its points, and you do so at the

expense of the other two. This world of healthcare, Ms Sebelius, is not flat; it is

not even round; it is triangular. And if you want to avoidruining a marvelous instrument providing care for somany Americans, listen to the other stakeholders andget in-step with the dance that medicine in the free mar-ket created. The rhythm is unforced, and it makes a lotof people happy. It is not that business does not want todance with the policy sector; it just does not want todance off the cliff. ■

EDITORIAL

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REGULATORY


Research on health communications has gainedprominence over the past few years.1 In theUnited States, healthcare consumers are expect-

ed to read and act on communications from varioussources, including federal and state governments, theSocial Security Administration, private insuranceplans, managed care organizations, and voluntaryhealth agencies. Written materials are not the onlymeans of acquiring health information, but they are themost widely used tool for disseminating crucial infor-mation. Therefore, it is necessary to evaluate the qual-ity of such communications for accuracy and to reduceredundancy and errors.

According to a 1992 national survey, most Americanelderly beneficiaries read at the 5th-grade level.2 There isan appropriate concern that healthcare materials are

written at higher grade levels and may not adequatelyeducate or benefit the intended population.3-6

Most studies in health communications measure pa -tient knowledge of a specific disease state.3-6 It is, however,important to measure patient comprehension of healthcarematerials in addition to their knowledge. Such compre-hension may be affected by a variety of factors, including,but not limited to, inadequate health literacy, readabilityof materials, and complexity of addressed topic(s), as wellas readers’ interest levels and cognitive abilities.

The Medicare program is divided into 4 parts: A, B,C, and D. Part D is the recent outpatient prescriptiondrug benefit introduced through the Medicare Modern -ization Act (MMA) of 2003, implemented on January 1,2006. Most people pay a monthly premium for this pre-scription coverage. Enrollment in Part D is voluntary,with penalties for late sign-ups.

Medicare Part DUnder Medicare Part D, distinct types of plans are

offered to beneficiaries—stand-alone prescription drug

Dr Aruru is Assistant Professor, Chicago College of Pharmacy,Midwestern University, Downers Grove, IL, and Dr Salmonis Professor of Health Policy & Administration, School ofPublic Health, University of Illinois at Chicago.

Assessment of Medicare Part DCommunications to BeneficiariesMeghana Aruru, PhD, MBA, BSPharm; J. Warren Salmon, PhD

Background: Older Americans receive healthcare benefits through the federal Medicareprogram. The Centers for Medicare & Medicaid Services provides comprehensive informa-tion to Medicare beneficiaries regarding benefits, plan options, and enrollment policies pri-marily through the annual Medicare & You handbook and the Medicare website. Few studieshave assessed the overall readability and, therefore, the usefulness of this handbook for ade-quately educating beneficiaries. Healthcare communications written at higher levels than thereaders’ comprehension levels cannot be well understood. Objective: To measure the readability of the 2008 Medicare & You handbook provided to allMedicare beneficiaries.Method: For our analysis, the 2008 version of the Medicare & You handbook was down-loaded from the Centers for Medicare & Medicaid Services website. Passages of ≥250 wordswere saved individually in Windows Notepad as text files. Shorter passages (ie, <250 words)were combined with the next continuing passage. Each file was then uploaded into theInternet-based Lexile analyzer (the Lexile Framework for Reading). Figures, pictures, andtables were not included in the analysis.Results: Approximately 70% of analyzed passages were written at approximately the 5th- to12th-grade levels (Lexile scores: 790L-1290L), whereas 30% of the passages were written atlevels above grade 12 (Lexile scores: 1310L-1910L).Conclusion: Medicare beneficiaries who have less than a high-school level education mayfind the passages analyzed in this study difficult to read and comprehend as discussed, indi-cating the need for simplified communication. Our study provides recommendations toimprove the handbook for better comprehension by beneficiaries.

Am Health Drug Benefits.2010;3(5):310-317.www.AHDBonline.comDisclosures are at end of text

Stakeholder Perspective,page 317

Assessment of Medicare Part D Communications


plans (PDPs) or Medicare Advantage PrescriptionDrug (MA-PD) plans incorporating prescription drugcoverage with other managed care benefits.7 In princi-ple, based on the MMA standard benefit design, aMedicare beneficiary is involved in cost-sharing. PartD’s standard benefit design has a unique feature knownas the coverage gap or doughnut hole.

Each year this coverage gap is expected to widen, andin 2010 the standard benefit package involves an annu-al deductible ($310), 25% of drug costs up to the initiallimit for the doughnut hole ($2830 in total costs for cov-ered drugs), and little cost-sharing beyond the upperlimit for the doughnut hole ($6440). This means thatbeneficiaries who have a standard benefit plan and donot receive low-income subsidies would be responsiblefor $4550 in out-of-pocket costs before reaching the cat-astrophic coverage limit of $6440.8 Although the stan-dard benefit must be offered by PDPs and MA-PDs, mostplans also offer actuarially equivalent plans. Some ofthese plans may involve partial or complete coverageduring the doughnut hole.8

Several new concepts were introduced within PartD, including the doughnut hole, formulary manage-ment, step therapy, and quantity limits.

It is important to realize that many elderly beneficiar-ies may not have been familiar with some or all of theseconcepts in the previous Medicare program. Beneficiariesreceive information from the Centers for Medicare &Medicaid Services (CMS) through its Medicare & Youhandbook, the Medicare website (www.medicare.gov),and a toll-free telephone number.

In Part D, formularies vary considerably within differ-ent plans and among different PDPs or MA-PDs.9Quantity limits are put in place by a plan sponsor torestrict the amount of drug prescribed (eg, 3 months).Step therapy requires that a certain drug be tried outbefore the prescribing of a newer and/or more expensivetherapy to prevent improper utilization. Prior authoriza-tion requires healthcare providers to seek approvalbefore providing certain drugs to beneficiaries.

These concepts are managed care tools used to con-trol prescription drug utilization. Although many peo-ple with previous insurance may be familiar with theseterms, many elderly beneficiaries may not be familiarwith these terms, either because of a lack of previousinsurance, dependence on caregivers/spouses/childrenfor insurance matters, and/or their own cognitive oreducational limitations.

Medicare Communications with Beneficiaries The Balanced Budget Act of 1997 mandated that

general and managed care plan comparison informationbe mailed to all current beneficiaries by October 15 of

each year, beginning in 1999. CMS (formerly known asthe Healthcare Financing Administration) initiated aNational Medicare Education Program (NMEP) to in -form and educate beneficiaries about Medicare+ Choiceplans and provide them with general and comparativeinformation about their health insurance options.10 “Thespecific objectives of the campaign are to ensure thatbeneficiaries have access to accurate and reliable infor-mation, are aware of the different health plan choicesavailable to them, understand the consequences ofchoosing different plans, and are able to use the infor-mation provided to them when making decisions.”10

The Medicare & You HandbookCMS would like Medicare beneficiaries to view the

Medicare program and its private sector partners as trust-ed and reliable sources of information.10,11 The agencydeveloped the consumer handbook Medicare & You toexplain health plan options to beneficiaries. This hand-book (formerly known as the Medicare Handbook) waspilot tested in 5 states and the Kansas City metropolitanstatistical area in the fall of 1998, when CMS mailed thehandbook to 5.1 million beneficiaries.12-14

The Medicare & You 2000 handbook was mailed to all39 million elderly and disabled beneficiaries in the fall of1999. Later versions were mailed each fall to beneficiar-ies. The education campaign also provided a toll-free

KEY POINTS

➤ The readability of Medicare information providedto beneficiaries has not been well studied.

➤ A 1992 national survey indicates that mostMedicare beneficiaries read at the 5th-grade level.

➤ The current study evaluated the readability level ofthe 2008 Medicare & You handbook used tocommunicate with Medicare beneficiaries.

➤ Of the 64 passages analyzed, 30% scored above the 12th-grade level, and 70% scored between the5th- and 12th-grade levels.

➤ This gap in readability presents a particular concernwith the introduction of Medicare Part D, whichincluded new concepts that might not have beenfamiliar to many beneficiaries

➤ A subanalysis of the 38 passages in Part D sectionsrevealed that about 10 passages had readingdifficulty level beyond grade 12, and 10 passageswere at 10th-grade reading level.

➤ The authors offer recommendations on how toimprove the readability level of Medicarecommunication with beneficiaries.

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telephone helpline; an Internet information database;support and training; counseling services; and state- andcommunity-based outreach efforts (Table 1).

The Medicare & You handbook is one of the keysources of information for Medicare beneficiaries—information that is extremely detailed and legitimate,because it comes from CMS and from several othersources, such as plan materials, state and local organiza-tional information, and the Medicare website. In 2008,there were 59 geographic-specific versions of the hand-book with drug and health plan comparison charts forparticular states. The 2008 handbook had approximate-ly 120 pages (depending on the version used) and wasissued in English, Spanish, Braille (English only), audio,and large print. Each fall, CMS mails a geographic-specific version of this handbook to all households ofpersons with Medicare coverage.

Assessment of Medicare CommunicationsRelatively few studies have examined the appropri-

ateness of the Medicare & You handbook for informingand educating beneficiaries. The handbooks and work-sheets used to compare plan information would be usefulto new beneficiaries if they were mailed up to 1 year inadvance, and would increase the likelihood of new ben-eficiaries actually using the worksheets to compare plansand make better-informed choices.12

Our study focused exclusively on this handbook,because it is the most comprehensive document regard-ing Medicare. Beneficiaries have access to other sourcesof Medicare-related information, but analyzing thesepieces of information is beyond the scope of this study.

In 2006, the US Government Accountability Office(GAO) analyzed 6 of 70 CMS documents on MedicarePart D and indicated that reading levels for analyzed pas-

sages ranged from 7th grade to post-college. The major-ity of American seniors read at or below the 5th-gradelevel, suggesting a significant scope for improvement.15Findings from a more recent GAO study indicate thatCMS’s model annual notice of change did not commu-nicate drug plan changes effectively to beneficiaries.15This study showed that “the language contained in themailings was at a reading level too high for beneficiaries,and it contained irrelevant information.”15

Other studies conclude that based on reading materi-als, individuals aged ≥65 years are less proficient thanyounger adults in locating information in documents tomake health-related decisions.16 A 2003 national surveyon adult literacy demonstrated that 27% of Medicarebeneficiaries were unable to understand information inshort, simple texts.17

In light of evidence that some older individuals facechallenges in reading and retaining written information,15the design and evaluation of appropriate writing materi-als for the elderly population are particularly important.Readability testing of written communications may be afirst step toward compiling healthcare materials that arecomprehensible and beneficial for the intended readers.

Evaluating ReadabilityReadability of healthcare materials is an emerging

yet underrated area of academic research. Readability isthe ease or comfort of reading text and includes legibil-ity (ie, words can be read) and comprehension (ie,understanding the text). In the 1930s, psychologistsstudying the processing of written information con-cluded that longer sentences (>20 words) are difficultto grasp, and readers find it easier to understand simplewords.16 Indices used to measure readability depend onsentence length and the number of “hard words” thatappear in each sentence.18

Readability analyses—primarily used in schools toascertain that students can read and comprehend mate-rials at particular grade levels—are a necessary and use-ful tool when preparing important and timely informa-tion, such as Part D prescription drug coverage. Previousstudies have shown that readability of written healthcarecommunication is consistently beyond average patients’reading grade levels.3-6

As mentioned earlier, approximately 20% of the USadult population cannot read beyond a 5th-grade level.2It is therefore important that all adult healthcare mate-rials be written at a 5th-grade level or lower to ade-quately educate the target population.

MethodsOur study measured the readability of the CMS-

produced 2008 Medicare & You handbook, a compre-

Table 1 Components of CMS Educational Campaign

Beneficiary mailings that included the Medicare & Youhandbook (CMS mailed the Medicare & You 2006 handbook in October 2005)

Toll-free telephone line: 1-800-Medicare

Website portal: www.Medicare.gov

Alliances with national and local organizations

National Train-the-Trainer program

State- and community-based special information campaigns

Enhanced beneficiary counseling from State HealthInsurance Assistance programs

Targeted and comprehensive assessment of outreach efforts

CMS indicates Centers for Medicare & Medicaid Services.



hensive, lengthy document detailing plan options andbenefits for Medicare beneficiaries.

DataWe downloaded the 2008 English version of the

Medicare & You handbook from the CMS website. Basedon the online Lexile Framework for Reading (www.lexile.com) measurement instructions, all passages with >250words were saved individually in Windows XP Notepadas text files. Passages with <250 words were combinedwith the next continuing passage.

A total of 64 passages were analyzed using the LexileFramework for Reading (permission to use and includeresults in the study was obtained before beginning thestudy). Tables, illustrations, and figures were not includ-ed in the analysis.

InstrumentLexile measures have been used in the assessment of

adult communications.19-21 Assessing the readability ofhealthcare materials is a fairly new endeavor. TheLexile Framework for Reading was developed with fed-eral funding in the 1980s. Older methods were moreroutine for school level assessments (Flesch-Kincaid,Dale-Chall, Simple Measure of Gobbledygook) andhave limited use in measuring the readability of adultcommunications.

The Lexile formula is based on sentence length andword frequency counts. Based on the Lexile theory ofcomprehension, passages with higher scores (between1800L and 1900L) are more difficult to read than pas-sages with lower scores (between 1300L and 1400L).

Grade levels were calculated by averaging the corre-sponding grade regions of the Lexile scores. For example,a Lexile score of 670 would fall into 2 regions—3rd and4th grade. This score was assigned the average of these 2grade levels—3.5.

ResultsNearly 30% of the Medicare & You handbook (19 of

64 passages) scored above 12th-grade readability lev-els, and 70% of the handbook (45 of 64 passages)scored from 5th- to 12th-grade readability levels(Table 2). An average grade level of 10.23 for the

handbook suggests that there were more passages athigher reading levels.

Beyond the 12th grade, the number of years of educa-tion to achieve advanced degrees may vary; therefore,averaging the number of years of schooling beyond the12th grade may lead to errors in estimation. Averagegrade levels were therefore not computed for the 19 pas-sages (ie,˜30% of the material) that were beyond the12th-grade readability range (Table 2). Table 3 presents the grade-level readability of the 45

passages that were within the 5th- to 12th-grade read-ability range. Few passages scored (Lexile scores) atlower grade levels. Only 2 passages were found to corre-spond to an approximately 7th-grade level (actual level,6.5), and only 1 passage scored a Lexile value that corre-sponded to an approximately 5th-grade reading level.

Subanalysis: Lexile Scores for the Part D SectionsBecause Medicare Part D introduced new concepts

that may have been unfamiliar to beneficiaries accus-tomed to the Medicare program for Part A and Part B,a subanalysis of Part D sections was necessary.

Part D sections were found on pages 37 to 74 inSection 2 of the handbook, and on pages 76 to 88 inSection 3. Some information in Section 3—such asinformation about grievances—is common to all the dif-ferent Medicare programs (Parts A, B, C, D). However,

Table 2 Lexile Results for the Medicare & You 2008 Handbook

Grade level Passages, N (%)Lexile scores,

rangeAverage Lexile

score Grade level Average grade

level

<12th grade 45 (70.31) 790L-1290L 1163.78 4.5-11.5 10.23

>12th grade 19 (29.69) 1310L-1910L 1442.5 >12 N/A

Table 3 Frequencies of the Medicare & You Handbook Passagesat Approximate Grade Levels 5-12

Passages, N (Total = 45) Grade level

Percentage of total handbook

1 4.5 2.2

1 6.0 2.2

2 6.5 4.4

2 8.5 4.4

4 7.5 8.88

5 10.5 11.11

15 11.0 33.33

15 11.5 33.33

because information to file for appeals and exceptionsmay be more important in the context of Part D, thisinformation was included in the subanalysis.

Lexile measures were computed for Part D passages.There were a total of 38 passages with ≥250 words. Themean Lexile score for these passages was 1243.68L, with aminimum score of 970L and a maximum score of 1690L.

Of the 38 passages on Medicare Part D, 10 passages(26%) showed a difficulty level beyond 12th grade.Approximately 10 passages (26% of the Part D sections)had a 12th-grade reading level and 10 passages (26%)had a 10th-grade reading level. Only 1 of 38 (2.6%) pas-sages had an approximate 6th-grade reading difficultylevel, and the remaining 7 passages (18%) had grade-level difficulties ranging from 7th to 9th grade.

DiscussionThe Medicare & You handbook could be a much more

useful tool for informing and educating beneficiaries. Itcontains pertinent information about plan choices,appeals, grievances, and exceptions, but omits a basicunderstanding of the societal context of the program,fails to list current challenges facing the program, anddoes not do an adequate job of explaining the meaningof Medicare reform for beneficiaries and their families.22Changes in the recent congressional legislation will war-rant explanation of governmental influence on theMedicare program.

The problem with written educational materials isthat there is often a gap between the reader’s Lexilemeasure (ability to read and understand text) and textLexile measures. The Medicare handbook’s Lexile scoresindicate an average grade level of approximately 10thgrade. This may be higher than the average beneficiary’sreading level and their grade level of education.Nineteen passages of 64 (30% of the handbook) werebeyond the 12th-grade education level, indicating thatthese passages may not be readable or comprehensible bythe average beneficiary.

The Medicare handbook is a standardized documentthat provides information on how to enroll, types ofplans, procedures for grievances, and a definition ofterms, but it does not conform to an individual’s specificsituation. For example, if a beneficiary who may be eligi-ble for a low-income subsidy is enrolled in a plan andwould like to change it, there is very little information inthe handbook on how to do so.

Healthcare communicators face numerous problemswhen dealing with a large subset of the population. Withthe increased complexity of Part D and the need tosecure proper and safe use of pharmacotherapy, benefici-aries and their families have a greater need to understandinstructions, follow procedures, interpret coverage infor-

mation and forms, and then act on all these steps tomake the best decision for their health.

This is vital to properly selecting a drug plan for theirprescription benefit. This process—daunting enough forpeople with adequate literacy skills—can compromisethe health and safety of persons with low literacy skills, aswell as of US residents with limited English proficiency.23

At the beginning of the implementation of Part D in2006, there were many plans (approximately 30-60,depending on the state) available to Medicare benefi-ciaries.24 During the first 2 years of implementation,22.5 million (53%) beneficiaries signed up for Part D.25A significant majority of Part D beneficiaries reportedthat the benefit was too complicated, and observerssuggested that such complexity might have thwartedsome beneficiaries in finding a suitable plan.26Assessing the impact of Part D on healthcare utiliza-tion by the elderly is extremely important to evaluatingthe program’s viability.

The introduction of private plans into Medicare hascreated a market scenario in which beneficiaries are freeto choose from a number of different plan offerings.Whether offering multiple plans affects healthcare uti-lization, adherence to medication, or improved qualityof life for the elderly is not yet known. This may be part-ly because Part D is a newer program, and obtaining alongitudinal database of Part D beneficiaries to demon-strate such outcomes will take time. CMS is just nowassembling such data for researchers.

To evaluate Part D’s sustainability, it is important tounderstand whether elderly beneficiaries are able tomake the type of informed choices that are expected ofthem. Medicare is a social policy program introduced asa benefit by right of citizenship. In this social policy, theintroduction of private parties has also brought aboutmanaged care techniques, such as formulary restrictions,copayments, coinsurances, step therapy, quantity limits,the doughnut hole, penalties for late sign-ups, and annu-al enrollment periods. It is important to recognize thatthese concepts may be unknown to many elderly benefi-ciaries, who may not be cognitively intact to processthem along with the additional burden of weighing andsifting multiple plan options, some of which may not besignificantly different from one another.

For beneficiaries who are disabled or have cognitiveimpairments, the burden of selecting, enrolling in, andutilizing plan benefits may rest on their caregivers, fami-lies, or even the long-term care facilities where theyreside. Because of penalties for late sign-ups that may lastfor the beneficiary’s entire plan period, it is important toensure that beneficiaries sign up in a timely manner.Decision-making for elderly beneficiaries to enroll in aPart D plan is certainly not easy, and caregivers who

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have assisted seniors will agree that this decision-makingrequires a certain level of knowledge, literacy, and cog-nition to navigate the plethora of choices available.Existing beneficiaries also need to reevaluate their planchoices to ensure their optimal outcomes.

Because CMS is the administering agency forMedicare and Medicaid, it can be assumed that any com-munication coming from the agency would be completeand be accurately designed to benefit seniors. As previ-ously noted, CMS ideologically claims that it would likebeneficiaries to make informed choices and perceive theMedicare program and its private partners as trusted andreliable sources of information.10 However, Medicarecommunications have not always been written at bene-ficiaries’ educational and/or health literacy levels.

The readability problem with Medicare documents isneither new nor unique to Medicare publications. In thecase of David v Heckler, the husband of a female patientin New York received a letter from the Department ofHealth and Human Services (DHHS) in 1984 when hiswife died of cancer.27 Like many Medicare beneficiaries,the patient’s husband received far less remunerationthan what he had expected. The letter explained why hereceived such little remuneration. His inability to under-stand the letter brought Legal Services Corporation tofile a class action suit on behalf of all Medicare benefici-aries in the state of New York. Legal Services pointed outthat 48% of the Medicare population had less than a9th-grade education. Dr Edward Fry (originator of theFry Readability Graph) testified that the letter was writ-ten at grade-16 level, or at a level suitable for personswith a college-level education. As a result, the judgeordered DHHS Secretary Margaret Heckler to take“prompt action” to improve the readability of Medicarecommunications.27

There is still significant scope for improvement.According to Dr Fry’s testimony, inclusion of tables andpictorial depictions may improve the readability of adocument.27 The 2008 Medicare & You handbook is com-prised mostly of text, with few tables and charts. Almostall the tables and figures are placed toward the end of thebook, and for the Part D sections, 26% of the 38 passageshad a readability level beyond 12th grade.

The Part D private market is not inherently stable.Since 2006, several plans opted out of the program,thereby necessitating that beneficiaries reevaluate theirchoices for the next year.

Policymakers may benefit by continuing to monitorbeneficiary satisfaction with plans and learn importantinformation through research on how well beneficiariescomprehend plan benefits and key factors behind suchdecision-making. Few studies have assessed elderly bene-ficiaries’ knowledge about Medicare, and even fewer have

evaluated comprehension of the newer Part D concepts.As the federal government anticipates the rollout of

various programs to reform the healthcare system, com-prehension of all new directions is vital for the public’sunderstanding, support, and benefit. In 2010, PresidentObama signed the Health Care Reform Bill, whichincludes future recommendations and implications forMedicare, particularly Part D.

Effects of the 2010 Healthcare Reform on Part DUnder the new Patient Protection and Affordable

Care Act (PPACA) of 2010, there is a provision for a“voluntary agreement with the Pharmaceutical Researchand Manufacturers of America (PhRMA) to provide dis-counts of 50% for brand-name drugs used by Part Denrollees in the Part D coverage gap. Manufacturers ofprescription drugs will be required to enter into agree-ments with Medicare Part D drug plan sponsors to pro-vide discounts on drugs provided to plan enrollees in thecoverage gap period beginning January 1, 2011.”9

The discount amount, along with the actual amountpaid by the enrollee, will be counted toward costsincurred by the enrollee. Beneficiaries receiving anylow-income subsidies or manufacturer discounts are noteligible for this discount. The PPACA mandates partic-ipation in this program by manufacturers, further statingthat, “Drugs sold and marketed in the US by a manufac-turer will not be covered under Part D unless the manu-facturer agrees to participate in the discount program.”9

Section 1101 of the Health Care and EducationReconciliation Act of 2010 added provisions to close thecoverage gap (ie, doughnut hole) over the course of 10years, by 2020.28 Medicare Part D beneficiaries enteringthe doughnut hole in 2010 would also receive a $250rebate. Cost-sharing in the doughnut hole for brand-name drugs (minus the $250 rebate) has dropped from100% to 25%.9 Subsequent reductions in cost-sharing onthe enrollee’s part will occur over the span of 10 years,thereby closing the coverage gap completely by 2020.Generic drugs are not a part of the 50% discount pro-gram, and beneficiary cost-sharing in the doughnut holewill be reduced to 25% by 2020 (Part D will pay for 75%of the generic drug’s costs).9

LimitationsReadability formulas do not measure persistence, an

important aspect of comprehension. Engaging readingmaterial written at the appropriate comprehension levelwill likely induce persistence to read, which is importantin today’s healthcare system. Elderly beneficiaries needto not only read and comprehend but also to continuereading information provided to derive maximum utili-ty. Constant involvement to protect one’s health is a



salient necessity in the US healthcare system of late,given the high prevalence of underinsurance amidsthealth equity issues. Several older studies in the field ofreadability research have shown significant relationshipsbetween persistence and readability.29,30

Our study did not measure persistence, nor did itinvolve readers to assess their readability levels. Furtheranalysis is needed to ascertain whether certain por-tions of the Medicare handbook text should be rewrit-ten to improve comprehensibility for beneficiaries andtheir families.

ConclusionsMedicare communications to beneficiaries are vast

and extensive. Few studies have examined the extentand usefulness of such materials in educating beneficiar-ies properly to make appropriate choices. In a consumer-oriented society, it is crucial that beneficiaries under-stand their choices before they make them. The breadthand depth of information may serve to further confuseand overwhelm elderly beneficiaries.

Although the NMEP—of which the Medicare & Youhandbook is a component—gets evaluated on a periodicbasis, the question remains whether this communicationis comprehensible to, or even readable by, beneficiaries.It must be noted that the 2010 English version of thehandbook has incorporated only few changes. For exam-ple, the glossary of terms is at the beginning of the book,unlike in previous versions. A summary of the 4 parts ofMedicare is provided at the beginning for quick refer-ence, including contact information for various services.

Nevertheless, the new Part D prescription drug bene-fit is philosophically and programmatically differentfrom the previous original parts. As such, the followingrecommendations are offered for improving the commu-nications, based on our analysis of the 2008 handbook. A. Consider writing Part D as a separate supplement. Medi -

care Part D is a new benefit, which is very differentfrom Part A and Part B. To better understand Part Dconcepts, it would be useful to have a separate sup-plement or addendum on Part D to differentiate phar-macy benefits from hospital and medical benefits.

B. Include new information about dual eligibility and low-income subsidies. For beneficiaries who fall into eithercategory, a separate section on hardship and affordingMedicare Part D may be appropriate, as opposed toinclusion in the overall text. The legislative objec-tive of Part D, after all, was to alleviate financial bar-riers to drug access.

C. Include charts, figures, tables, or graphs to help somebeneficiaries better understand their choices.Most ben-eficiaries may find reading continuous text difficultbecause of visual problems, declining cognition, or

other problems. Therefore, inclusion of visual aids,such as charts or figures, may become more appeal-ing to these beneficiaries and thereby aid in thelearning process.

D. Add several case vignettes. In the entire section onPart D, only 1 case example was used (for step thera-py). Using more case studies or examples to demon-strate or simulate real-life situations may help bene-ficiaries understand how these concepts work.

E. Arrange Part D sections in a single supplement to im -prove the continuity of content. Part D sections arespread out on pages 52-66, 84, 87-88, 99-101, and107-111 of the handbook.

F. Provide for separate sections on enrollment andappeals/grievances. Writing the Part D supplement as2 separate sections—plan enrollment and planappeals/grievances—may help to improve the clarityof these concepts.Periodically rechecking the document by CMS after

incorporating changes would be a useful means of ascer-taining whether readability of the material has im -proved. All these are practical targets for improving thereading material. Our analysis is especially relevant tothe CMS staff and their private partners who need toconsider our findings in reworking the Medicare & Youhandbook and all other communications to Part D ben-eficiaries. We recommend further periodic retesting ofthe handbook with readers for a better assessment of itscomprehensibility. ■

Disclosure StatementDr Aruru and Dr Salmon have nothing to disclose.

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and demand for information. Health Care Financ Rev. 1999;21:129-131.12. Harris-Kojetin LD, McCormack LA, Jael EMF, Lissy KL. Beneficiaries’ percep-tions of new Medicare health plan choice print materials. Health Care Financ Rev.2001;23:21-35.13. Goldstein E, Teichman L, Crawley B, et al. Lessons learned from the NationalMedicare & You Education Program. Health Care Financ Rev. 2001;23:5-20.14. Carman KL, Short PF, Farley DO, et al. Epilogue: early lessons from CAHPSdemonstrations and evaluations. Consumer Assessment of Health Plans Study. MedCare. 1999;37(suppl 3):MS97-MS105.15.US Government Accountability Office. Medicare Part D. Opportunities exist forimproving information sent to enrollees and scheduling the annual election period.2008. www.gao.gov/new.items/d094.pdf. Accessed January 2010.16. Hibbard J, Greene J, Tusler M. An assessment of beneficiary knowledge of Medicarecoverage options and the prescription drug benefit. May 2006. http://assets.aarp.org/rgcenter/health/2006_12_medicare.pdf. Accessed September 9, 2009.17. Kutner M, Greenberg E, Jin Y, Paulsen C; for the National Center for EducationStatistics, Institute of Education Sciences. The health literacy of America’s adults:results from the 2003 National Assessment of Adult Literacy. 2006. US Departmentof Education (NCES 2006–483). http://nces.ed.gov/pubs2006/2006483_1.pdf.Accessed January 10, 2010.18.Hall JC. The readability of original articles in surgical journals. ANZ J Surg. 2006;76:68-70.19.Wolf MS, Davis TC, Shrank WH, et al. A critical review of FDA approved med-ication guides. Patient Educ and Counsel. 2006;62:316-322.

20.Wolf MS, Davis TC, Tilson HH, et al. Misunderstanding of prescription drug warn-ing labels among patients with low literacy. Am J Health Syst Pharm. 2006;63:1048-1055.21.Wolf MS, Chang CH, Davis T, Makoul G. Development and validation of theCommunication and Attitudinal Self-Efficacy scale for cancer (CASE-cancer).Patient Educ Couns. 2005;57:333-341.22. Bernstein J, Stevens RA. Public opinion, knowledge, and Medicare reform.Health Aff (Millwood). 1999;18:180-193.23. Villarruel AM, Portillo CJ, Kane P. Communicating with limited English profi-ciency persons: implications for nursing practice. Nurs Outlook. 1999;47:262-270.24. Kaiser Family Foundation. Medicare Part D Plan Enrollment and Plan Charac -teristics. 2006. www.kff.org/medicare/upload/7426-02.pdf. Accessed February 6, 2010. 25. Polinski JM, Bhandari A, Saya UY, et al. Medicare beneficiaries knowledge ofand choices regarding Part D, 2005 to the present. Ethics, Public Policy Med Econ.2010;58:950-966.26.Hoadley J. Medicare Part D: simplifying the program and improving the value ofinformation for beneficiaries. Issue brief (Commonw Fund). 2008;39:1-15. 27. David v Heckler, 591 F.Supp. 1033 (E.D.N.Y., 1984). www.fastcase.com/Google/Start.aspx?C=cc0de5afbc82ca7abc8929ad8494150ba890ba54220920cc&D=a281b2e1feb0792396a4e9215f1b84ba2c9da8d14688d101. Accessed February 1, 2010.28. Health Care and Education Reconciliation Act of 2010, H.R. 4872, §1101. 29. Schramm W. Measuring another dimension of newspaper readership. JournalismQuarterly. 1947;24:293-306. 30. Swanson CE. Readability and readership: a controlled experiment. JournalismQuarterly. 1948;25:339-343.



Medicare Part D Education Materials Must Address Recipients’ Literacy LevelPOLICYMAKERS: The Medicare Part D drug

benefit began on January 1, 2006, after a 2-yearrestricted period of a drug discount card benefit for sen-iors and Medicare enrollees. Part D has engenderedmuch discussion and remains a controversial program,with a mixed track record. Part D is administered bythe Centers for Medicare & Medicaid Services (CMS)through stand-alone prescription drug plans orMedicare Advantage plans. CMS began overseeingthis program without any experience in managing anoutpatient drug benefit and should be commended fortheir early and continuing efforts.

Remaining hurdles, however, need to be addressedbefore the program can reach its goals. One hurdle isthe enrolling of eligible Medicare recipients in PartD: an estimated 12% of eligible recipients remainwith no Part D drug coverage, as well as 13% of thoseaged <65 years who are disabled.1 Program enrollmentcosts have increased and are a hindrance to manyMedicare recipients.2 As a component of the PatientProtection and Affordable Care Act, Part D enrolleeswill begin to receive a $250 payment starting inOctober 2010 to help defer expenses within the cov-erage gap (doughnut hole).2

Lack of drug coverage may result from many otherfactors, including the readability of Medicare Part Dmaterials. Considering that 64% of those who are dis-abled, aged <65 years, and with Medicare coverage areestimated to have a cognitive and/or mental impair-ment,1 readability becomes a crucial consideration.

Among those aged ≥65 years, an estimated 23% have acognitive/mental impairment.1

In light of these facts, the study by Aruru andSalmon provides a significant addition to the litera-ture. The authors’ findings that 70% of the Medicare& You handbook is written at a 5th- to 12th-gradereading comprehension level, and 30% of the hand-book is written at a level above grade 12, highlight adramatic problem within Medicare materials meantto enable understanding of this important socialinsurance program.

The authors provide specific suggestions for Part Dinformative materials. Their suggestion to separate outa segment on Medicare Part D is a cogent one, and asthey note, Part D may be foreign to Medicare enrolleesand their families. The suggested use of case studyvignettes as a teaching tool is also good. The authors’evaluation points to Medicare Part D materials as espe-cially complex from a readability perspective: CMSneeds to address this shortcoming in its future promo-tional and education materials.

References1. Kaiser Family Foundation. Medicare Fact Sheet. Medicare and nonelderlypeople with disabilities. September 2010. www.kff.org/medicare/upload/8100.pdf.Accessed September 22, 2010.2. Hoadley J, Summers L, Hargrave E, et al. Medicare Part D Spotlight. Medicareprescription drug plans in 2010 and key changes over five years: summary of find-ings. September 2010. Kaiser Family Foundation. November 2009.http://kff.org/medicare/upload/8096.pdf. Accessed September 22, 2010.

Jack E. Fincham, PhD, RPhProfessor of Pharmacy Practice and Administration

University of Missouri–Kansas City

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In the United States, brand-name price inflation forprescription drugs has outpaced overall prescriptiondrug price inflation.1,2 Although certain forces in the

market may account for this situation, this study focusedon the lack of adequate and accurate information that isneeded in the market to optimize utilization of prescrip-tion drugs and mediate costs.

Lack of Cost InformationOften, there is a lack of cost-related information on

prescription drugs, which is evident from discussions sur-rounding the contracts between manufacturers andinsurers who declare price and rebate information as

“proprietary and confidential”3 when there is a lack ofdata quantifying added value for new treatment options,4or information related to actual acquisition costs for eco-nomic research. Evidence has shown that patients,providers, and other decision makers do not know thenet cost of prescription drugs.5-7 Given this lack of cost-related information, there is growing pressure from awhole system perspective, both public and private, forthe healthcare system to take a closer look at costs whenconsidering drug formularies as a strategy to help remedysome of the issues of escalating costs in the market.

Prescription Drug Utilization and Cost ComplexitiesPrescription drug expenditure growth represents a

part of the healthcare system that is closely watched.Prescription drug expenditures trends from 2007 to 2008showed that spending increased by 1.8%—with totalspending increasing from $279.6 billion to $284.7 bil-lion.8 Spending on this segment of healthcare is notimmune to external economic forces. The recentdecades’ expansion of spending for prescription drugswas projected to continue in 2010 to 4.5%, and contin-ue to rise in the future as a result of the overall improv-

Dr Kjos is Assistant Professor, Social and AdministrativePharmacy, College of Pharmacy and Health Sciences, DrakeUniversity, Des Moines, IA; Dr Schommer is Professor,College of Pharmacy, University of Minnesota, Minneapolis;Dr Yuan is a Statistician for IMS Health, Inc., PlymouthMeeting, PA. Some of the information described in this articlewas presented at the 155th and 156th annual meetings of theAmerican Pharmacists Association, San Diego, CA, March2008, and San Antonio, TX, April 2009, respectively.

A Comparison of Drug Formularies andthe Potential for Cost-SavingsAndrea L. Kjos, PharmD, PhD; Jon C. Schommer, PhD; Yingli Yuan, PhD

Background: Brand-name drug costs have been escalating in the United States, and thereasons for this are not immediately clear. A lack of adequate and accurate information aboutdrug effectiveness, safety, and cost has implications for drug utilization and cost. Objective: To explore the extent to which health plan formularies were consistent with rec-ommended drug listings and identify what would be the potential cost-savings on total drugexpenditures if the utilization rate of the recommended therapies was increased. Method: This study compared publicly available recommended drug listings with the formu-laries of 8 major health plans in Minnesota. Data from 1 of the health plans underwent an in-depth case analysis to evaluate the potential impact on pharmaceutical expenditures, usingincreased utilization rate scenarios of the recommended drugs. Results: Health plans were similar with respect to degree of coverage for the recommend-ed drugs. However, the case analysis showed that by increasing the utilization rate of rec-ommended drugs, a potential cost-savings of more than 50% could be realized for the eval-uated health plan for some therapeutic categories.Conclusion: This study demonstrates an approach to assessing drug formularies usingpublicly available, recommended drug lists that incorporated evidence for effectiveness, safe-ty, and cost. By using the application of this type of reliable information, formulary changescan be guided to incentivize value-based utilization for patient populations.


Andrea L. Kjos


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ing economy, price increases for generic medications,and other factors.9

The utilization process that impacts spending onprescriptions is complex. Healthcare providers andconsumers are faced with difficult decisions and oftencompeting perspectives that shape the choice of pre-scription medications.10 Ideally, these decisions aremade based on the best information and evidence thatis available to achieve optimal patient outcomes withrespect to effectiveness and safety, in addition to costand value. Given the recent economic downturn, dis-cussions of cost, whether pertaining to cost-effective-ness11 or out-of-pocket expenditures,12 are an importantcomponent of understanding prescription drug choiceand utilization trends.

Cost is not the sole driver for choice of therapeuticproducts by patients; it is just one factor interwoven intoa network of utilization dynamics involving multiplestakeholders. The choice of a prescription drug may beinfluenced by a variety of coexisting factors inside andoutside the healthcare system, including the physician orpharmacist13; insurance or health plan14; promotionalmarketing15; and public policy.16 In addition, these deci-sions are often constrained by a perceived lack of evi-

dence for comparative effectiveness,17 perceived lack ofinformation about total net cost to the system or to thepatient,5,6 or perceived lack of transparency with respectto incentives (positive or negative) that influence theformulary status.7

One example that demonstrated this lack of informa-tion for comparative effectiveness was the creation of acommissioned task force to provide guidance on the useof secondary databases as a way to supplement availableclinical trial information on comparative effectiveness ofprescription drugs.17 An example demonstrating a lack ofcost information was given by Shrank and colleagues,who reported that prescribers are often not aware ofpatients’ costs for prescriptions and do not feel responsi-ble for managing these costs.6

A different example suggesting the presence ofuneven information was discussed in a report from thePharmacy Benefit Management Institute, which indicat-ed that only about half (52.3%) of surveyed employersperceived the nature of the financial relationship withtheir pharmacy benefit manager as transparent.7 Allthese are examples of how a lack of information is tied tovarious stakeholders of prescription drug utilization.

Key Research QuestionsThis lack of information with respect to prescription

drug effectiveness, safety, and cost, in combination withthe prominent role of managed care in prescription uti-lization, presents the following study questions: 1.What is the extent of similarity between health plans’

formularies and a recommended drug listing from anoutside source?

2.What would be the potential for cost-savings if a drugformulary was modified to be more aligned with theserecommended products?Given these questions, there is a need to critically

examine public and private drug benefit programs andrelated utilization with respect to the potential for cost-savings through the guidance of a recommended druglist. Past research has examined the potential economicbenefit of prescription benefit plans increasing utiliza-tion of generically available prescriptions.18,19 To date,however, no comparable research has examined the cur-rent state of health plans or the potential financialimpact when drug effectiveness, safety, and cost are usedas considerations for a projected formulary change.

To contribute to formulary research that demon-strates the importance of information related to effec-tiveness, safety, and cost, as well as the potential cost-savings from using approaches that apply these types ofinformation, this study had 3 objectives: 1. To explore the extent to which health plan formularies

were consistent with a recommended listing of drugs

KEY POINTS

➤ Evidence has shown that patients, providers, andother decision makers do not know the net cost ofprescription drugs.

➤ This study compared formulary lists from 8 healthplans and drug utilization and cost data from 1health plan in Minnesota with publicly availabledrug list recommendations to identify degree ofcoverage and what would be the potential cost-savings on total drug expenditures if the utilizationrate of the recommended drugs increased.

➤ Results showed a high variation among the 8 plansbetween therapeutic categories for recommendeddrug coverage.

➤ The plans were similar in coverage of recommendeddrugs across a single therapeutic category.

➤ Increased coverage of recommended drugs wasshown to produce greater potential cost-savings tothe health plan.

➤ These findings demonstrate a way to prioritizeformulary changes and subsequent prescriptionutilization for patient populations. Improvement ofdrug formularies lowers overall prescription drugcosts and has the potential to promote a morebalanced pharmaceutical market to combat theongoing rise of prescription drug prices.

Drug Formularies and the Potential for Cost-Savings


2. To document the extent to which 1 plan’s actual drugutilization patterns were consistent with the listing ofrecommended drugs

3. To identify the potential cost-savings on total drugexpenditures from increasing the proportion of rec-ommended drug therapies.

Methods This study was conducted in 2 parts. Part 1 com-

pared a publicly available listing of recommendeddrugs20 against the formularies of 8 major health plansin Minnesota. (The names of the plans are not dis-closed for several reasons. First, our goal was not to cat-egorize plans or make judgments as to the individuallevel of plan prescription coverage but to demonstratea standardized comparison approach to evaluate pre-scription drug formularies. Second, formulary informa-tion changes frequently and, therefore, may not be anaccurate representation of the coverage for the plan atthe current time. Third, it was consistent with ourInstitutional Review Board approval, because confi-dentiality was to be maintained for the unit of analysis,or in this case, the health plan. Finally, in Minnesotanearly all health plan formularies were publicly avail-able on each of their respective websites.)

Using the findings from Part 1, we included in Part 2 acase study of a self-insured employer’s drug benefit plan toevaluate the potential impact on utilization and expendi-tures if the use of recommended therapies was increased.

Our study was based on data from publicly availableinformation on safety, effectiveness, and medicationscost.20 This information is referred to in this article as“recommended” drugs or medication reports. The basesfor comparison were the specified recommended med-ication reports.

The recommended medication reports were publiclyavailable online in reports called Best Buy Drugs.21Consumer Reports Health Best Buy Drugs is an educa-tional program of Consumers Union. Consumers Unioncompiled these reports based on other independentsources.21 The first source consisted of scientific reviewsfrom the Drug Effectiveness Review Project (DERP).21DERP is a 13-state initiative, based at Oregon Health &Science University, that compares drugs based on effec-tiveness and safety for state Medicaid programs andplaces their reports in the public domain.22 The secondsource incorporated was information provided by theAgency for Healthcare Research and Quality.21 The costinformation provided in the reports came from nationalaverage prescription prices as would be reflected forcash-paying customers.21

These medication reports are divided into therapeuticcategories and are updated regularly to reflect changes in

brand and generic drug status, emerging evidence, andprice. These report profiles designate a choice of whichdrug(s) within each therapeutic category is to be inter-preted as an overall recommended choice when factorsof effectiveness, safety, and cost are considered together.

Within each report profile is a list of often-prescribedmedications for each therapeutic class, along withdosages, prices, and other pertinent prescribing informa-tion (eg, indications or other dosage forms). Each reportcontains information on all the drugs evaluated and theresulting recommended medication(s). Every therapeu-tic category contains specific recommended drugs basedon effectiveness, safety, and cost. Table 1 provides anoverview of the therapeutic drug categories that areincluded in this study.

Part 1: Data CollectionPart 1 of the study involved compiling a comprehen-

sive medication list for the available drug categories, usingthe publicly available information for the recommendedmedication reports. In essence, a new formulary was cre-ated based on the recommended medication reports. Eachtherapeutic category’s list was then supplemented withMedi-Span Price-Chek PC data (Medi-Span). The Medi-Span data were used to give complete information foreach drug entity in each identified drug category.

Table 1 Profiled Categories for Recommended Drugs

Therapeutic/drug category

ACE inhibitorsADHDAlzheimer’s diseaseAntidepressantsAntihistaminesAntipsychoticsBeta-blockersCalcium channel blockersDiabetes (oral)Hormones (estrogenic, for menopause)InsomniaNSAIDsOveractive bladderProton pump inhibitorsStatinsTriptans (migraine)

ACE indicates angiotensin-converting enzyme; ADHD, attention-deficit/hyperactivity disorder; NSAIDs, nonsteroidal anti-inflammatory drugs.

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Once the recommended information was reconciledwith the Medi-Span data, the drug lists were catego-rized according to all drugs in a therapeutic category,drugs reviewed by the publicly available informationreports, and drugs chosen as a recommended drug. InPart 1, we used reports from a publicly available infor-mation source and their recommendations20-22 and thenexpanded this information back into a fully populateddatabase of complete medication information for eachtherapeutic category.

We compared data from the 8 health plan formularieswith the recommended drugs within each therapeuticcategory. Data were summarized by computing the totalnumber of drug entities in the therapeutic category, thenumber of drug entities covered by each health plan, andthe number of recommended drugs covered by eachhealth plan. For each health plan, we calculated the per-centage of covered drugs that are recommended drugsbased on the total number of drug entities covered.

The health plans evaluated for Part 1 covered livesthrough private employee-based sponsorship, as well aspublic programs; therefore, a mix of public and privatesponsorship was represented. Exceptions, or specialrequirements for plan coverage, were noted wheneverthe information was available for each of the 8 healthplans. All data used in Part 1 were obtained during cal-endar year 2007.

Part 2: Case AnalysisIn Part 2 we used an in-depth case analysis of cost and

utilization information for 1 of the 8 health plans. Thiswas a private, employer-sponsored plan. In addition, inthis part of the study we evaluated potential cost-savingsthat could theoretically be obtained if drug utilizationaligned with the recommended medications reports. Forthis potential cost-savings we used 2 different summativeand percentage calculation strategies to illustrate possi-ble scenarios.

For Part 2, detailed data were obtained from a majoremployer (with 36,924 covered lives) for calendar year2007, which was 1 of the 8 evaluated health plans eval-uated in Part 1. The National Drug Code level drugdata were matched to the list of recommended drug(s)within each of the therapeutic categories. As in Part 1,drug description data were used from Medi-Span’sPrice-Chek PC to facilitate the matching of recom-mended drugs with the actual drug utilization data forthis health plan.

Next, the share of prescription volume (measured asdays of therapy) filled with recommended drugs wasdetermined. The actual amount of total drug expendi-tures (ie, plan and member cost) for these prescriptionswas determined. The actual cost of recommended drugs

was then identified, using the same 2007 employer data. Total drug expenditures were projected, assuming

that 100% or 85% of prescriptions were filled with rec-ommended drugs at the actual reported cost rather thanwith the actual drugs used at their actual cost. The dif-ferences in total drug expenditures using the employer’sactual data were compared with projected drug expendi-tures using publicly available recommended drugs to findthe potential cost-savings.

Theoretically, one could use the recommended drugfor 100% of the prescriptions filled by a given drug ben-efit plan. However, as most clinicians realize, there aretimes when the first-line recommended drug may not bethe best drug for a given patient. Assuming that the first-line preferred drug is appropriate 85% of the time, andthat other drugs are appropriate 15% of the time, weused an 85% recommended drug rate to provide a morerealistic estimate of the cost impact from using recom-mended drugs.

ResultsData used in Part 1 of this study described the extent

to which the 8 health plan formularies were consistentwith recommended drugs. Data for this comparison weresummarized by computing total medication coverage ineach therapeutic category and recommended drug cov-erage. These data were translated into percentages forinterpretation, giving a percentage of recommendedcoverage. These percentages were calculated using thenumber of recommended drugs divided by the totalnumber of medications in each health plan for eachtherapeutic category.

Part 1 of the analysis is summarized in Figure 1.Results show the cumulative percentages of recommend-ed drugs covered by each health plan (identified as A-H). Across all health plans, cumulative totals were sim-ilar. In contrast, a high variation is seen betweentherapeutic categories for recommended drug coverage.For example, recommended drugs in the triptan andstatin categories had greater recommended drug cover-age (ranges, 54%-100% and 29%-61%, respectively)compared with oral diabetic or antipsychotic medica-tions (ranges, 22%-38% and 19%-38%, respectively).

However, health plans were similar in recommendeddrug coverage across a single therapeutic category. Forexample, oral diabetic medications had a 22% to 38%recommended drug coverage range across all healthplans. Antidepressant medications ranged from 8% to12% across all plans.

In sum, the study objective of measuring consistencybetween health plan formularies and recommended druglistings showed that some drug categories had greaterconsistency with the recommended drugs. Health plans



ADEP 11%APSY 19%

OVBL 50%

BB 50%

CCB 54%

DIAB 34%

HORM 45%

INSOM 22%

NSAIDs 14%

STAT 57%

TRIP 55%

ACE 27%

ADHD 28%

ALZH 40%

ADEP 8%

OVBL 27%

BB 64%

CCB 55%

DIAB 28%

HORM 47%

NSAIDs 19%

TRIP 83%

STAT 53%

INSOM 7%

APSY 21%

ACE 34%

ADHD 18%

ALZH 83% ADEP 12%

BB 57%

CCB 38%

DIAB 28%

HORM 59%

INSOM 17%

NSAIDs 23%

STAT 56%

TRIP 55%

APSY 38%

ACE 22%

ADHD 29%

ALZH 33%

OVBL 33%

BB 59%

CCB 41%

DIAB 37%

HORM 43%

INSOM 15%NSAIDs 17%

PPI 33%

STAT 52%

TRIP 82%

APSY 29%

ACE 24%

ADHD 33%

ALZH 64%

ADEP 11%AHIST 8%

OVBL 60%

BB 47%

CCB 40%

DIAB 22%

HORM 61%

NSAIDs 28%

PPI 13%

TRIP 55%

STAT 61%

APSY 29%

ACE 22%ADHD 15%

ALZH 54%

ADEP 10%AHIST 23%

ADEP 9%

OVBL 38%

BB 64%

CCB 61%

DIAB 38%

HORM 50%

INSOM 10%

NSAIDs 30%

PPI 25%

STAT 42%

TRIP 67%

APSY 38%

ACE 33%

ADHD 23%

ALZH 64%

AHIST 60%

ADEP 8%

OVBL 27%

CCB 51%

HORM 51%

INSOM 13%NSAIDs 11%

PPI 17%

STAT 29%

TRIP 100%

DIAB 31%

BB 48%

APSY 27%

ACE 19%

ADHD 16%

ALZH 50%

AHIST 27%

APSY 19%

OVBL 50%

BB 53%

CCB 54%

DIAB 34%

HORM 46%

INSOM 22%

NSAIDs 15%PPI 14%

STAT 57%

TRIP 54%

ADEP 11%

ACE 27%

ADHD 28%

ALZH 40%

AHIST 27%

NOTE: Percentage calculated as number of recommended drugs covered divided by total number of drugs in each health plan (A-H) for each therapeu-tic/drug category. Maximum cumulative percent would be 100% x 16 = 1600%. Several plans did not cover any recommended drugs in some categories.ACE indicates angiotensin-converting enzyme inhibitors; ADEP, antidepressants; ADHD, attention-deficit/hyperactivity disorder; AHIST, antihistamines;ALZH, Alzheimer’s disease; APSY, antipsychotics; BB, beta-blockers; CCB, calcium channel blockers; DIAB, diabetes; HORM, hormones; INSOM,insomnia; NSAIDs, nonsteroidal anti-inflammatory drugs; OVBL, overactive bladder; PPI, proton pump inhibitors; STAT, statins; TRIP, triptans.

A B C D E F G H

700%

600%

500%

400%

300%

200%

100%

0%

Health plans

Figure 1 Cumulative Percentage of Recommended Therapeutic/Drug Coverage, by Health Plan (A-H)

Cumulative percentage

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were largely consistent with one another in terms of per-centages of recommended drug coverage.

Part 2 of the analysis determined the extent of con-sistency between the recommended drugs and the uti-lization data from 1 of the 8 health plans. Recommendeddrugs accounted for an average of 39% of the days oftherapy used by the drug plan in 2007. The recommend-ed drug share by days of therapy ranged from a low of 6%(antihistamines) to a high of 89% (Alzheimer’s diseasedrugs) across the categories studied.

Cost-savings could have been realized in 13 of the16 categories through increased use of the recommend-

ed drugs. The overall savings from the use of recom-mended drugs for 100% of prescriptions would haveresulted in a 52% savings in total drug expenditures.The use of recommended drugs for 85% of prescriptionswould have produced a 41% savings across the thera-peutic categories.

Figure 2, Table 2, and Table 3 show cost summaryand potential cost-savings information. In Figure 2, onlycategories with cost-savings are shown. Of the 16 cate-gories evaluated, 12 displayed a potential for cost-savingsin the 85% recommended drug utilization scenarios(Figure 2 and Table 3). Table 3 displays cost-savings as a

aTotal cost associated with filled prescriptions. Cost calculations based on sum of actual ingredient cost to the health plan, dispensing feecharged by pharmacy, and any taxes incurred by the sale.ACE indicates angiotensin-converting enzyme; ADHD, attention-deficit/hyperactivity disorder; NSAIDs, nonsteroidal anti-inflammatory drugs.

Antidepressants

Statins

Proton pump inhibitors

Beta-blockers

ACE inhibitors

Antihistamines

Diabetes, oral

Insomnia (after generic Ambien)

NSAIDs

Hormones (estrogenic)

Calcium channel blockers

ADHD

3,036,7712,647,926

2,141,476

2,270,344 523,061

374,715

1,699,654 1,310,724

1,087,613

275,179 71,777

14,905

201,406 77,989 55,177

712,542 657,646

552,431

430,032 287,873

170,371

421,314 333,921

271,680

216,269 182,839

125,808

320,905 182,465

143,271

313,571 35,682 16,548

644,265 403,882

327,413

Figure 2 Total Cost and Potential Cost-Savings with 85% and 100% Recommended Drug Utilization, $

Total costa

Savings w/ 100% utilization

Savings w/ 85% utilization

$500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000 $3,000,000 $3,500,000



Table 2 2007 Total and Projected Cost-Savings for 1 Health Plan (36,924 members)


Total Rxactual, Na

Total costactual, $b

Total cost/dayactual, $c

Total cost/day

recommended, $d

Total cost-savings if 85% recommended utilization, $e

Total cost-savings if 100%recommended utilization, $f Comments

Antidepressants 35,557 3,036,771 2.14 0.26 2,141,476 2,647,926 High utilization, cost,and potential savings

Statins 20,558 2,270,344 2.22 1.66 374,715 523,061 High utilization, cost,and potential savings

Proton pumpinhibitors

12,266 1,699,654 3.37 0.78 1,087,613 1,310,724 High utilization, cost,and potential savings

Migraine 3051 878,125 16.98 17.42 (8491cost

increase)

(34,335cost

increase)

Older drugs not as safe Recommended drugs have higher cost

Antipsychotics 3153 787,230 8.38 11.12 (213,901cost

increase)

(264,456cost

increase)

Older drugs not as safe Recommended drugs have higher cost

Antihistamines 9228 712,542 1.98 0.15 552,431 657,646 High utilization, cost,and potential savings

ADHD 4770 644,265 3.87 1.39 327,413 403,882

Diabetes, oral 7758 430,032 1.28 0.42 170,371 287,873

Insomnia (aftergeneric Ambien)

7662 421,314 2.11 0.42 271,680 333,921

Hormones(estrogenic)

5045 320,905 1.16 0.52 143,271 182,465

Calcium channelblockers

4912 313,571 1.39 1.25 16,548 35,682

Beta-blockers 11,996 275,179 0.47 0.35 14,905 71,777

NSAIDs 5731 216,269 1.33 0.25 125,808 182,839

ACE inhibitors 11,872 201,406 0.35 0.21 55,177 77,989

Overactive bladder

997 96,124 2.66 3.49 (28,295cost

increase)

(36,683cost

increase)

Older drugs not as safeRecommended drugs have higher cost

Alzheimer’s disease

81 20,084 6.05 5.71 (1823cost

increase)

1778 Mixed results, savings only demon-strated at 100%

Totals 145,856 12,510,561 3.49 2.79 5,101,464 6,472,948aTotal prescriptions filled during calendar year 2007. bTotal actual cost associated with filled prescriptions; cost calculations based on sum of actual ingredient cost to the health plan, dispensing fee charged by the pharmacy, and any taxesincurred by the sale. cTotal cost per day of therapy calculated based on a typical 30-day supply at the most common dosage and used the same cost calculation as “total cost actual.” dTotal cost per day of therapy of the recommended medication; if >1 drug was specified as recommended, the less expensive option is represented. eTotal cost-savings if utilization was shifted to 85% of all prescriptions in the therapeutic category were written for recommended drugs. Calculations made based on determining the totalnumber of prescriptions for 85% of all prescriptions and multiplying the actual cost, then subtracting the actual cost of 85% utilization from the total actual cost. fTotal cost-savings if utilization was shifted to 100% and all prescriptions were for recommended drugs.ACE indicates angiotensin-converting enzyme; ADHD, attention-deficit/hyperactivity disorder; NSAIDs, nonsteroidal anti-inflammatory drugs.

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percentage of dollars potentially saved if utilizationwere shifted to either 85% or 100% of the recommend-ed drug use. In addition, Table 2 shows the therapeuticcategories (highlighted) with highest overall utilizationand the highest potential cost-savings from increaseduse of recommended drugs. Anti depressants had thehighest overall potential cost-savings—71% (Table 3).

Discussion The relatively high cost differential ($2.14 vs $0.26)

seen between nonrecommended and recommendedantidepressant drugs makes potential cost-savings sub-

stantial ($2,647,926/yr) if all (100%) plan memberswere to switch to a recommended antidepressant med-ication. For statins, potential cost-savings were not ashigh ($523,061/yr). Potential cost-savings for protonpump inhibitors were similar to those of antidepressants,showing a large differential in average cost of therapy fornonrecommended and recommended drugs ($3.37 vs$0.78). This, compounded by the high utilization(12,266 total prescriptions in 2007), yielded a largepotential cost-savings of $1,310,724 annually.

Antihistamines had a lower utilization than the pre-vious 3 categories mentioned (9228 total prescriptionsin 2007); however, because of the very low daily cost forover-the-counter loratadine ($0.15/day), the potentialcost-savings still topped a half million ($657,646).

Some data in Table 2 show the opposite outcome—increased cost from increasing use of recommended drugs.A switch to the recommended drug could actuallyincrease health plan spending in these categories if 100%(or even 85%) of the patients were switched. For exam-ple, if 100% of the prescriptions were preferred medica-tions, it would cost the health plan $34,335, $264,456,and $36,683 more for migraine, antipsychotic, and over-active bladder medications, respectively. These resultsare also represented as percentages in Table 3.

The reason for these findings was that all these cate-gories contained older generic therapeutic agents thatmay be less effective (regardless of their lower cost), orhave an increased number of potential side effects com-pared with the newer, often branded, products.

The cost if 85% of drugs were prescribed as recom-mended was considered in Figure 2 and Tables 2 and 3,because this was seen as a more realistic portrayal of theactual potential cost-savings in place of the cost if 100%of drugs were prescribed as recommended.

Some therapeutic categories have the potential forhigh patient variability; therefore, the preferred drug maynot be the most optimal therapeutic choice. For exam-ple, with the antidepressant medications, patients areoften switched several times before finding an efficaciousoption and then maintaining it for the long-term.Overall, however, the trend for the cost if 85% of drugswere prescribed as recommended closely follows that ofcost if 100% of drugs were prescribed as recommended,in that there is still potential for cost-savings when usingthe 85% scenario for most therapeutic categories.

To summarize Part 2, using 1 major health plan as acase study, overall results showed that using recom-mended drug information as an approach for a pre-scription drug benefit could reduce costs by more than50% for some therapeutic categories (eg, antihista-mines, 78%; antidepressants, 71%; insomnia, 65%;proton pump inhibitors, 64%; nonsteroidal anti-

Table 3 Potential Cost-Savings, Percent Dollars, with85% or 100% Recommended Drug Utilization


85%Recommended

filled, %

100%Recommended

filled, %

Categories with potential for cost-savings

Antidepressants 70.5 87.2Statins 16.5 23.0Proton pumpinhibitors

64.0 77.1

Beta-blockers 5.4 12.3ACE inhibitors 27.4 31.2Antihistamines 77.5 92.3Diabetes, oral 39.6 66.9Insomnia 64.5 79.3NSAIDs 58.2 84.5Hormones (estrogenic) 44.6 56.9

Calcium channelblockers 5.3 11.4

ADHD 50.8 62.7

Categories without potential for cost-savings

Migraine –1.0 –3.9Antipsychotics –27.2 –33.6Overactive bladder –29.4 –38.2

Alzheimer’s disease

–9.1 8.9

Total potential cost-savingsa

40.8 51.7

aTotal potential cost-savings was calculated from the sum total costof all evaluated categories (including those that did not have apotential cost-savings) divided by the sum total of the cost if 85%or 100% of prescriptions were filled with recommended drugs.ACE indicates angiotensin-converting enzyme; ADHD, attention-deficit/hyperactivity disorder; NSAIDs, nonsteroidal anti-inflammatory drugs.



inflammatory drugs, 58%; Table 3). However, althoughnot all categories displayed a potential for cost-savings,an overall total potential cost-savings was calculated asa percentage from the sum total cost of all evaluatedcategories, including those without a potential cost-savings, divided by the total of the cost if 85% or 100%of prescriptions were filled with recommended drugs.This overall potential cost-savings was 40.8% if all 16drug categories were switched to 85% of recommendeddrugs and 51.7% if all 16 drug categories were switchedto 100% recommended drugs.

Limitations This study had several limitations. Only 8 health

plans in Minnesota were evaluated, and only 1 of the 8plans was evaluated in Part 2 of the study. The study onlyused Best Buy Drugs20 as the basis for the recommendeddrug used for comparison. This list could be challengedas having its own set of limitations, or perhaps as notbeing the optimal basis for comparison.

In addition, for this study, we assumed that formula-ry stakeholders are not influenced by competing incen-tives (eg, manufacturer rebates). We also assumed thatout-of-pocket incentives for patients are not relevantfor the comparison.

Finally, the prescription drug market is a rapidlychanging environment with changes in patent status,the number of generic manufacturers, and the ever-increasing number of available treatments, strengths,and dosage forms. Considering the fluid nature of thismarket, this study represents a cross-sectional view thatmay not reflect the current drug market.

ConclusionsAs prices for prescription drugs continue to rise, there

remains a lack of information to stakeholders—particu-larly cost information. This lack of information wasdescribed as one issue creating the potential for ineffi-ciencies in the market. Using a comparison of 8 majorhealth plans and 1 case study of utilization informationshowed that certain therapeutic drug categories have alarge potential for projected cost-savings. By using a rec-ommended drug list for modifying drug formularies,health plans could reduce their costs by nearly 41% if85% of prescriptions were shifted to recommendeddrugs, or nearly 52% if 100% of all prescriptions wereshifted to recommended drugs.

This study demonstrates an approach to assessingdrug formularies using a publicly available, onlineresource for recommended prescription drug informa-tion, based on effectiveness, safety, and cost. Stake -holders involved in drug formularies may benefit fromusing this type of information with respect to effective-

ness, safety, and cost to determine ways to improve out-comes and decrease costs. Aligning formularies with thebest available information may slow the rise of costsassociated with the use of medications.

The findings presented here are important to the drugformulary literature, because they demonstrate an appli-cation of reliable, recommended drug information basedon effectiveness, safety, and cost as a way to prioritize for-mulary changes and subsequent prescription utilizationfor patient populations. Not only could the improve-ment of drug formularies lower overall prescription drugcosts, it also has the potential to promote a more bal-anced pharmaceutical market to combat the ongoingrise of prescription drug prices. ■

AcknowledgmentFinancial support for this study was provided by the

Attorney General Consumer and Prescriber EducationGrant Program. The authors gratefully acknowledge theparticipation of Dr Stephen Schondelmeyer and DrMarcia Worley in the larger study, some of which find-ings are the basis for the current article.

Disclosure StatementDr Schommer is currently Principal Investigator for a grad-

uate student traineeship (a position held by 1 of his graduatestudents for 1 academic year), Novartis Pharmaceuticals, buthad no affiliation with this company at the time this researchwas conducted; Dr Yuan is an employee of IMS Health; DrKjos has nothing to disclose.

References1. Gross D, DeLeno Neuworth D, eds. Average manufacturer price increases forwidely used brand name and specialty prescription drugs reach record levels. AARPRx Watchdog Rep. April 2009;1-3. http://assets.aarp.org/www.aarp.org_/cs/health/rx_watchdog_apr09.pdf. Accessed January 4, 2010. 2. Schondelmeyer SW. Statement on prescription drug price inflation: are prices ris-ing too fast? Statement before Subcommittee on Health, Congress of the UnitedStates House of Representatives, December 8, 2009. http://energycommerce.house.gov/Press_111/20091208/schondelmeyer_testimony.pdf. Accessed January 4, 2010.3. Kemp K; for the Office of the Assistant Secretary for Planning and Evaluation, USDepartment of Health & Human Services. Conference summary: pharmaceuticalpricing practices, utilization, and costs. http://aspe.hhs.gov/health/reports/Drug-papers/kemp1.htm. Accessed January 4, 2010.4. Kleinke JD. The price of progress: prescription drugs in the health care market.Health Aff (Millwood). 2001;2:43-60.5. Kohl H, Shrank WH. Increasing generic drug use in Medicare Part D: the role ofgovernment. J Am Geriatr Soc. 2007;55:1106-1109.6. Shrank WH, Young HN, Ettner SL, et al. Do the incentives in 3-tier pharmaceu-tical benefit plans operate as intended? Results from a physician leadership survey.Am J Manag Care. 2005;11:16-22.7. Pharmacy Benefit Management Institute, LP. Prescription drug benefit cost andplan design report 2008-2009 edition. www.pbmi.com/2008_report/pdfs/Revised_Report_20112009.pdf. Accessed December 22, 2009. 8.Hoffman J, Doloresco F, Vermeulen L, et al. Projecting future drug expenditures—2010. Am J Health Syst Pharm. 2010;67:919-928. 9. Sisko A, Truffer C, Smith S, et al. Health spending projections through 2018:recession effects add uncertainty to the outlook. Health Aff (Millwood). 2009;28:w346-w357. Epub 2009 Feb 24. 10. Schommer JC, Worley MM, Kjos AL, et al. A thematic analysis for how patients,prescribers, experts, and patient advocates view the prescription choice process. ResSocial Adm Pharm. 2009;5:154-169. Epub 2009 Jan 21.11. Baio G, Russo P. A decision-theoretic framework for the application of cost-

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effectiveness analysis in regulatory processes. Pharmacoeconomics. 2009;27:645-655. 12. Schommer JC, Chen Y, Kjos AL, et al. Decision making regarding prescriptiondrugs: out-of-pocket pressures. Drug Benefit Trends. 2009;21:278-289. 13. Shrank WH, Stedman M, Ettner SL, et al. Patient, physician, pharmacy, andpharmacy benefit design factors related to generic medication use. J Gen Intern Med.2007;22:1298-1304. Epub 2007 Jul 24.14. Roebuck MC, Liberman JN. Impact of pharmacy benefit design on prescriptiondrug utilization: a fixed effects analysis of plan sponsor data. Health Serv Res.2009;44:988-1009. Epub 2009 Jan 28.15.Kyle GJ, Nissen LM, Tett SE. Pharmaceutical company influences on medicationprescribing and their potential impact on quality use of medicines. J Clin Pharm Ther.2008;33:553-559. 16. Kesselheim AS. Think globally, prescribe locally: how rational pharmaceuticalpolicy in the U.S. can improve global access to essential medicines. Am J Law Med.2008;34:125-139. 17. Berger ML, Mamdani M, Atkins D, Johnson ML. Good research practices forcomparative effectiveness research: defining, reporting and interpreting nonrandom-

ized studies of treatment effects using secondary data sources: the ISPOR GoodResearch Practices for Retrospective Database Analysis Task Force report—part I.Value Health. 2009;12:1044-1052. Epub 2009 Sep 29. 18. Fischer MA, Avorn J. Economic consequences of underuse of generic drugs: evi-dence from Medicaid and implications for prescription drug benefit plans. Health ServRes. 2003;38:1051-1063. 19. Haas JS, Phillips KA, Gerstenberger EP, Seger AC. Potential savings from sub-stituting generic drugs for brand-name drugs: medical expenditure panel survey,1997-2000. Ann Intern Med. 2005;142:891-897. 20. Consumers Union of U.S. Inc. Consumer Reports: Best Buy Drugs. 2009.www.consumerreports.org/health/best-buy-drugs/index.htm. Accessed January 4, 2010.21. Consumers Union of the U.S. Inc. About Consumer Reports Health: Best BuyDrugs. www.consumerreports.org/health/about/best-buy-drugs.htm#abtproject.Accessed July 26, 2010.22. Oregon Health & Science University. Drug Effectiveness Review Project(DERP). www.ohsu.edu/ohsuedu/research/policycenter/DERP/. Updated 2008.Accessed January 4, 2010.

Aligning Stakeholders Can Maximize the Opportunity for Cost-Savings on Drugs

PAYERS: Depending on their line of business,healthcare payers are constantly tasked with admin-istering a comprehensive and quality-based pharmacybenefit under the constraints of a budgeted portion ofeither a premium (commercial and Medicare plans)or capitation (Medicaid or state-sponsored plans).

Although the goal should be to maximize utiliza-tion from a preferred formulary or a recommendeddrug list, incentives that are not aligned with adher-ence to these preferred agents lead to missed oppor-tunities for cost-savings, increased cost-shifting toemployers and beneficiaries/members, and inefficien-cies within the healthcare system.

The authors of this new study/article demonstratethat (1) utilization of medications from preferred for-mularies or recommended drug lists are not currentlymaximized by health plans, and (2) opportunities forcost-savings are available; the challenge, however, isto align all stakeholders to maximize the opportunityfor savings.

The monies realized through greater adherence toa preferred formulary could potentially reduce premi-ums to employer groups, improve provider reimburse-ment, and broaden network access and mitigate cost-sharing through member copays, coinsurance, andmember premium contribution.

The challenges to payers lie in the identificationof true prescription cost and benefit design prefer-ence, and then relaying that information in a mean-ingful way to network prescribers and members/bene-

ficiaries, along with a message explaining how theycan personally benefit from greater adoption of thesetools, through things such as greater reimbursementor lower copays/premiums.

PATIENTS/MEMBERS: Medical benefit costtrends continue to escalate, and the prescriptioncomponent of a comprehensive medical coverage isnot exempt from this phenomenon. In the attempt tooffer a viable and affordable benefit plan to employergroups, health plans continue to cost-shift the risingexpense trends to end-user members/beneficiaries, bymeans of increased deductibles, increasing patientcopays/coinsurance, and premium-sharing.

The level of a beneficiary’s contribution has risen tothe point where patient adherence drops off whenmembers can no longer afford to bear “their” shareunder their current benefit design for drug coverage. Ifmembers/patients could better appreciate how theiralignment with preferred benefits—especially regard-ing pharmaceuticals and a preferred drug list—couldreduce their coverage expense and mitigate, perhapseven reduce, some of their cost-sharing obligation, wewould most likely see increased adoption of preferredproducts and lesser influence by outside factors, be itdirect-to-consumer pharmaceutical companies’ cam-paigns or direct-to-prescriber programs.

Jeff Januska, PharmDDirector of Pharmacy

CenCal Health, Santa Barbara, CA


GENERIC DRUG TRENDS

333www.AHDBonline.com l American Health & Drug BenefitsVol 3, No 5 l September/October 2010

In September 2010, the US Food and Drug Adminis -tration (FDA) conducted a webinar for the media toreview the basic information concerning FDA’s

approval of generic drugs1 in an attempt to promote thepublic’s understanding of generics and dispel commonmisconceptions about this growing branch of pharma-ceutical products that are surrounded by a veil of confu-sion and controversy. Although much of the informationprovided by the FDA in that webinar could be consid-ered common knowledge, such reiteration of the basicfacts should not be seen as redundant, considering thatthe “drug wars” among generic and brand-name phar-maceutical makers (that stem largely from cost con-cerns) often are positioned as issues related to patientsafety and product efficacy rather than finances.

Robert L. West, Deputy Director of the FDA’s Officeof Generic Drugs (OGD) conducted the webinar. MrWest’s foremost concern was the message of safety andefficacy of generics, while simultaneously acknowledg-ing that generic utilization continues to grow and bynow constitutes the bulk of all prescriptions written inthe United States.2 This in itself did not seem to pose aproblem for him. If generics “represent 70% of the totalprescriptions dispensed in the United States,”2 which isa considerable increase from “about 50% just a yearago,” according to Mr West,1 it would seem unnecessaryto tout generic drugs yet again as being as safe andeffective as brand-name drugs. Such a growth in theutilization rate should be sufficient evidence for thesequalities (patient safety and product efficacy).

Indeed, as has been discussed often on the pages ofAmerican Health & Drug Benefits, the numbers areimpressive. According to Mr West, “each year, morethan 2.6 billion prescriptions are filled in the U.S. [sic]using generic drugs”2 compared with “approximately1.2 billion brand-name prescriptions dispensed eachyear.”2 Nevertheless, writing prescriptions is no guaran-tee of patient adherence, and therein may lie the rub,which is where better education is needed.

To receive FDA approval for a generic drug, Mr

West indicated, the manufacturer must demonstratethat its product2:• Contains the same active ingredient as the brand-

name drug• Has the same strength of the active ingredient as in

the brand drug• Is of the same dosing formulation (eg, tablet, capsule)• Has the same route of administration as the brand

drug (eg, oral, injection).Furthermore, although generic drugs rely on evidence

collected in the original clinical studies conducted bythe brand drug manufacturer, generic manufacturersmust also demonstrate that the specific generic formula-tion carries bioequivalence and pharmaceutical equiva-lence to the brand-name drug.2 This is often the causefor concern and contention about the actual benefit ofand justification for generic product utilization.

This very concern was recently evaluated byFDA/OGD investigators (including many pharmacists)in a study published late last year.3 The investigatorscompared the evidence used by the FDA between 1996and 2007 to establish the bioequivalence of genericsand brand-name drugs.3 The goal of the study was toevaluate how well the bioequivalence measures used toapprove generics compared with those used for thebrand-name drugs. A total of 2070 studies were includ-ed in this analysis.

The results showed a mean standard deviation ofgeometric mean ratios of 1.00 ± 0.60 for drug peak plas-ma concentration (Cmax) and 1.00 ± 0.40 for areaunder the curve (AUC) plasma drug concentration.2,3

The average differences between generic and brand-name drugs in these measures (Cmax and AUC) were4.35% and 3.56%, respectively.3 And in 98% of thesestudies, the generic AUC differed from that of thebrand product by <10%.2,3 The investigators concludedthat these studies support the FDA’s use of its criteriafor the approval process of generic formulations forbrand-name products.3 This analysis, although scientif-ically sound, is anything but simple.

FDA’s Approval Process Borne Out by a Large Study: But Communicating Generics’Safety and Efficacy to the Public Leaves Much to Be DesiredBy Dalia Buffery, MA, ABD

Mr West admitted that the issue of bioequivalence isa frequent cause for misinformation, leading to consider-able inconsistent and inaccurate assertions about the dif-ference in the levels of the active ingredient that is pres-ent in the brand and the generic drug, resulting in claimsthat vary by more than a 40% difference, from –20% to+25%.2 The reason for this, the OGD Deputy Directorsuggests, is the complexity of the statistical analysesinvolved in the evidence for bioequivalence2; an intrigu-ing observation that merits consideration, yet his ownexplanation of generic bioequivalence to the publicrelied on this very same study as the basis for the FDA’sarticulation of this phenomenon.2

Indeed, in an ideal world, simpler calculations andexplanations may help a greater number of stakeholdersto accept or reject the bioequivalence of these 2 similaryet competing groups of products that theoretically havea unified goal of helping patients. Complexity is not toohelpful when seeking the understanding of consumers,especially with regard to drug therapy, of which payersand providers are well aware. Convincing patients to usemedications is often a long and arduous task, with which

pharmaceutical companies, too, have been struggling foryears. Yet the makers of brand-name products havefound innovative ways to illustrate to consumers whyusing pharmaceuticals can often help improve theirhealth and well-being. Using simple and clear languagethat does not require high-level education is crucial.

The FDA, and perhaps the makers of generic prod-ucts, must also find innovative and more patient-focusedways of simplifying the complex issues of bioequivalenceto consumers, who are after all, the ultimate target of thedrug companies but are often the ones who do not buyinto the very idea of generics (“cheap” is not always apositive and is often peculiarly suspect, especially whenit comes to the American consumer). Lack of under-standing of the true benefits of drug therapy is among thewell-known causes of patient lack of adherence.

Although the FDA’s effort to explain bioequivalenceis commendable, its very way of explanation and choiceof communication with the public leave much to bedesired. Improved channels of communication andclearer messages are needed to clarify a complex issue insimple but convincing words. ■

References1. US Food and Drug Administration. FDA basics webinar on generic drugs. Septem -ber 2010. www.fda.gov/AboutFDA/Transparency/Basics/ucm225778.htm. AccessedSeptember 27, 2010.2. West RL. Generic drugs. September 2010. www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM226568.pdf. Accessed September 27, 2010.3. Davit BM, Nwakama PE, Buehler GJ, et al. Comparing generic and innovator drugs:a review of 12 years of bioequivalence data from the United States Food and DrugAdministration. Ann Pharmacother. 2009;43:1583-1597.

GENERIC DRUG TRENDS

334 American Health & Drug Benefits l www.AHDBonline.com September/October 2010 l Vol 3, No 5

Bioequivalence is a frequent cause formisinformation, resulting in claims thatvary by more than a 40% difference, from –20% to +25%.

Wellness

-Base

d Healthcare Polic

y:

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REGULATORY

Background: Pay-for-performance initiatives have been suggested as a

quality of patient care and provide incentives to improve providers’ perfor

for Medicare & Medicaid Services has endorsed such programs to imp

Objective: To examine the state of quality initiatives endorsed by the

& Medicaid Services in which institutions, provider groups, and phy

incentives based on adherence to composite metrics.

Method: A literature search was conducted using the keywords “

“quality improvement,” “medical errors,” and “physician incentive pl

Results: Although quality of care has improved in healthcare settin

for-performance initiatives, what can be attributed to payer-incentiv

Studies demonstrate that, of the 25 hospitals classified by the

Medicaid Services to be in the lowest decile of quality improveme

cant progress in adhering to quality metrics after participation in the

however, were distributed based on a predetermined threshold e

Medicaid Services to be given only to participa

d by the 51 hospitals that were w

h institutions,

Pay-for-Performance Initia

Benefits for Improving Health

Amit Sura, MD, MBA; Nirav R. Shah, MD, MPH

For the past 2

drugs have fa

The Orphan Drug Act of

defined in the United Sta

dreds of thousands of d

the small populations in

cost of orphan drugs is

intensified economic pr

erage of orphan drugs.

insights on how payers

findings show that the

barring sweeping cha

to orphan agents and

stand payer impact o

prepared to develop

[AHDB. 2010;3(1):15

Orphan Dru

Manageme

We Approach

Rebecca Hyde; Diana D

REPRINTS of all past AHDB articles

AvailableAvailable

Reprints may be ordered for a nominal fee by contacting [email protected]

We Take Quality To Heart.

©2010 Mylan Pharmaceuticals Inc. MYNMKT392A

Over the past five decades, Mylan Pharmaceuticals has established the systems necessary to ensure the quality of thegeneric products that we manufacture. Every step in the processincludes quality controls and quality assurance measurements thatare integrated into the production procedures.

In addition to routine quality checks and re-checks, Mylan has dedicated resources and professionals that are focused on operational excellence. The objective is clear … to continuallyimprove the systems and procedures in place to be sure theywill result in quality generics.

At Mylan, every person in our domestic and global network takesquality very seriously, and it’s why we are proud that America’spharmacists rank our products highest in quality year after year.*

*U.S. Pharmacist Generic Company Surveys. 2006-2009

800.RX.MYLAN • www.mylanpharms.com


American Health & Drug Benefits offers an open forum for all healthcare stakeholders toexchange ideas and present their data, innovations, and initiatives to facilitate patient-centered healthcareand benefit design models that meet the needs of all stakeholders—Distributors, Employers, Evaluators,Manufacturers, Patients, Payers, Providers, Purchasers, Regulators, and Researchers.

Readers are invited to submit articles that aim at improving the quality of patient care and the US healthcaredelivery system in general and of benefit design strategies in particular. All articles will undergo a blind peerreview, and acceptance is based on that review.

AGING/DEMENTIA—With the aging of the USpopulation, there is a growing need for early imple-mentation of outcome-based preventive and therapeu-tic strategies for older people.

ALLERGIES—Allergies, such as allergic or seasonalrhinitis, affect millions of Americans daily, resultingin a significant economic burden and human cost.Under treatment and lack of adherence are commonobstacles to patient management.

ARTHRITIS—Musculoskeletal conditions, such asrheumatoid arthritis or osteoporosis, are on the increase,yet many patients are undiagnosed and untreated.Comparing new and available therapies is a key targetfor improving patient outcomes and reducing costs.

CANCER CARE—The growing focus on biologicagents dictates an enhanced study of these therapeu-tic options, including reimbursement policies, cost-management, industry trends, and the biologicpipeline updates.

CARDIOVASCULAR DISEASE—Still a leadingcause of morbidity and mortality among men andwomen. Original, outcome-based research on appro-priate therapies, cost-comparisons, emerging preven-tion strategies, and comparative effectiveness of bestpractices will enhance readers’ decision-making.

DIABETES, OBESITY—The increasing comorbidepidemics of these twin conditions mandates a thor-ough examination of best therapies, adherence issues,access, and prevention strategies. We invite articlesthat will address how to improve patient outcomesand best individualized patient care.

GASTROINTESTINAL CONDITIONS—Recognizing GI conditions, such as hepatitis C,Crohn’s disease, or inflammatory bowel disorder,remains a challenge.

INFECTIOUS DISEASES—The spread of commonand emerging pathogens within the hospital and inthe community remains a major concern requiringincreased vigilance.

MENTAL DISORDERS—Depression, bipolar disor-der, and schizophrenia exert a huge financial andhuman burden on individuals, employers, and payers.Topics of interest include comparative effectivenessanalyses, best practices, and reimbursement.

PAIN MANAGEMENT—Chronic pain is associatedwith a slew of complicated medical disorders and anenormous economic burden, yet pain medications arestill underused. Appropriate topics include best thera-pies, diagnosis, and clinicians’ anxiety about addictionissues and potential misuse.

Manuscripts should follow the Guidelines for Authors, available at www.AHDBonline.com For more information, call 732-992-1892

CALL FOR PAPERS

Areas of high interest include:

Clinical topics of interest include:

• Adherence Issues

• Benefit Design

• Comparative Effectiveness Analyses

• Cost-Effectiveness Analyses

• Decision-Making Tools

• Healthcare Trends

• Health Economics

• Health Plan Initiatives/Innovation

• Health Information Technology

• Innovation in Patient Care

• Off-Label Use/Misuse

• Original Research

• Pharmacoeconomics

• Reimbursement Strategies

• Wellness Programs

For your members with moderate to severe plaque psoriasis

Please see Important Safety Information and Brief Summary of Prescribing Information for STELARA™on the following pages.

www.STELARAinfo.com

IndicationSTELARA™ is indicated for the treatment of adult patients (18 years or older)with moderate to severe plaque psoriasis who are candidates for phototherapy orsystemic therapy.

DosingSTELARA™ is administered by subcutaneous injection.

• For patients weighing ≤100 kg (220 lbs), the recommended dose is 45 mg initiallyand 4 weeks later, followed by 45 mg every 12 weeks

• For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initiallyand 4 weeks later, followed by 90 mg every 12 weeks

In patients weighing >100 kg, 45 mg was also shown to be efficacious. However,90 mg resulted in greater efficacy in these patients.

The safety and efficacy of STELARA™ have not been evaluated beyond two years.

Dosage forms and strengthsSTELARA™ contains 90 mg of ustekinumab per mL.

• 45 mg/0.5 mL in a single-use, prefilled syringe, with an NDC number of 57894-060-03

• 90 mg/1 mL in a single-use, prefilled syringe, with an NDC number of 57894-061-03

IMPORTANT SAFETY INFORMATIONInfectionsSTELARA™ may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, andviral infections were reported. Infections requiring hospitalization included cellulitis, diverticulitis, osteomyelitis,gastroenteritis, pneumonia, and urinary tract infections. STELARA™ should not be given to patients with a clinicallyimportant active infection and should not be administered until the infection resolves or is adequately treated.Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. Exercise cautionwhen considering use of STELARA™ in patients with a chronic infection or a history of recurrent infection.

Theoretical Risk for Vulnerability to Particular InfectionsIndividuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections frommycobacterium, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fataloutcomes have been reported in such patients. It is not known whether patients with pharmacologic blockadeof IL-12/IL-23 from treatment with STELARA™ will be susceptible to these types of infections. Considerappropriate diagnostic testing as dictated by clinical circumstances.

Pre-Treatment Evaluation of Tuberculosis (TB)Evaluate patients for TB prior to initiating treatment with STELARA™. STELARA™ should not be given to patientswith active TB. Initiate treatment of latent TB before administering STELARA™. Patients should be monitoredclosely for signs and symptoms of active TB during and after treatment with STELARA™.

MalignanciesSTELARA™ is an immunosuppressant and may increase the risk of malignancy. Malignancies were reportedamong patients who received STELARA™ in clinical studies. The safety of STELARA™ has not been evaluatedin patients who have a history of malignancy or who have a known malignancy.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)One case of RPLS has been reported in a STELARA™-treated patient. If RPLS is suspected, discontinueSTELARA™ and administer appropriate treatment.RPLS is a neurological disorder, which is not caused by an infection or demyelination. RPLS can present withheadache, seizures, confusion, and visual disturbances. RPLS has been associated with fatal outcomes.

ImmunizationsPrior to initiating therapy with STELARA™, patients should receive all immunizations recommended by currentguidelines. Patients being treated with STELARA™ should not receive live vaccines. BCG vaccines should not begiven during treatment or within one year of initiating or discontinuing STELARA™. Exercise caution whenadministering live vaccines to household contacts of STELARA™ patients, as shedding and subsequenttransmission to STELARA™ patients may occur. Non-live vaccinations received during a course of STELARA™may not elicit an immune response sufficient to prevent disease.

Concomitant TherapiesThe safety of STELARA™ in combination with other immunosuppressive agents or phototherapy has not beenevaluated. Ultraviolet-induced skin cancers developed earlier and more frequently in mice genetically manipulatedto be deficient in both IL-12 and IL-23 or IL-12 alone. The relevance of these findings in mouse models formalignancy risk in humans is unknown.

Most Common Adverse ReactionsThe most common adverse reactions (≥3% and higher than that with placebo) in clinical trials for STELARA™45 mg, STELARA™ 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection(5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively.

Please see Brief Summary of Prescribing Information for STELARA™ on the following page.

Reference: STELARA™ Prescribing Information 12/2009. Horsham, PA: Centocor Ortho Biotech Inc.

representing the products of

www.STELARAinfo.com ©2010 Centocor Ortho Biotech Services, LLC 4/10 25STPMC10012

25US10030

Brief Summary of Prescribing Information for STELARA™ (ustekinumab) STELARA™ Injection, for subcutaneous useSee package insert for Full Prescribing InformationINDICATIONS AND USAGE: STELARA™ is indicated for the treatment of adult patients (18 yearsor older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemictherapy. CONTRAINDICATIONS: None. WARNINGS AND PRECAUTIONS: InfectionsSTELARA™ may increase the risk of infections and reactivation of latent infections. Seriousbacterial, fungal, and viral infections were observed in subjects receiving STELARA™ (see AdverseReactions). STELARA™ should not be given to patients with any clinically important activeinfection. STELARA™ should not be administered until the infection resolves or is adequatelytreated. Instruct patients to seek medical advice if signs or symptoms suggestive of an infectionoccur. Exercise caution when considering the use of STELARA™ in patients with a chronicinfection or a history of recurrent infection. Serious infections requiring hospitalization occurredin the psoriasis development program. These serious infections included cellulitis, diverticulitis,osteomyelitis, viral infections, gastroenteritis, pneumonia, and urinary tract infections. TheoreticalRisk for Vulnerability to Particular Infections Individuals genetically deficient in IL-12/IL-23are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous,environmental mycobacteria), salmonella (including nontyphi strains), and Bacillus Calmette-Guerin(BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. Itis not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment withSTELARA™ will be susceptible to these types of infections. Appropriate diagnostic testing shouldbe considered, e.g., tissue culture, stool culture, as dictated by clinical circumstances.Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis infection priorto initiating treatment with STELARA™. Do not administer STELARA™ to patients with activetuberculosis. Initiate treatment of latent tuberculosis prior to administering STELARA™. Consideranti-tuberculosis therapy prior to initiation of STELARA™ in patients with a past history of latentor active tuberculosis in whom an adequate course of treatment cannot be confirmed. Patientsreceiving STELARA™ should be monitored closely for signs and symptoms of active tuberculosisduring and after treatment. Malignancies STELARA™ is an immunosuppressant and mayincrease the risk of malignancy. Malignancies were reported among subjects who receivedSTELARA™ in clinical studies (see Adverse Reactions). In rodent models, inhibition ofIL-12/IL-23p40 increased the risk of malignancy (see Nonclinical Toxicology). The safety ofSTELARA™ has not been evaluated in patients who have a history of malignancy or who have aknown malignancy. Reversible Posterior Leukoencephalopathy Syndrome One case ofreversible posterior leukoencephalopathy syndrome (RPLS) was observed during the clinicaldevelopment program which included 3523 STELARA™-treated subjects. The subject, who hadreceived 12 doses of STELARA™ over approximately two years, presented with headache,seizures and confusion. No additional STELARA™ injections were administered and the subjectfully recovered with appropriate treatment. RPLS is a neurological disorder, which is not causedby demyelination or a known infectious agent. RPLS can present with headache, seizures,confusion and visual disturbances. Conditions with which it has been associated includepreeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy.Fatal outcomes have been reported. If RPLS is suspected, STELARA™ should be discontinuedand appropriate treatment administered. Immunizations Prior to initiating therapy withSTELARA™, patients should receive all immunizations appropriate for age as recommended bycurrent immunization guidelines. Patients being treated with STELARA™ should not receive livevaccines. BCG vaccines should not be given during treatment with STELARA™ or for one yearprior to initiating treatment or one year following discontinuation of treatment. Caution is advisedwhen administering live vaccines to household contacts of patients receiving STELARA™ becauseof the potential risk for shedding from the household contact and transmission to patient. Non-livevaccinations received during a course of STELARA™ may not elicit an immune response sufficientto prevent disease. Concomitant Therapies The safety of STELARA™ in combination with otherimmunosuppressive agents or phototherapy has not been evaluated. Ultraviolet-induced skincancers developed earlier and more frequently in mice genetically manipulated to be deficient inboth IL-12 and IL-23 or IL-12 alone (see Nonclinical Toxicology). ADVERSE REACTIONS: Thefollowing serious adverse reactions are discussed elsewhere in the label: Infections (see Warningsand Precautions); Malignancies (see Warnings and Precautions); and RPLS (see Warnings andPrecautions). Clinical Studies Experience The safety data reflect exposure to STELARA™ in2266 psoriasis subjects, including 1970 exposed for at least 6 months, 1285 exposed for at leastone year, and 373 exposed for at least 18 months. Because clinical trials are conducted underwidely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannotbe directly compared to rates in the clinical trials of another drug and may not reflect the ratesobserved in practice. Adverse reactions listed below are those that occurred at a rate of at least1% and at a higher rate in the STELARA™ groups than the placebo group during theplacebo-controlled period of STUDY 1 and STUDY 2. The numbers (percentages) of adversereactions reported for placebo-treated patients (n=665), patients treated with 45 mg STELARA™(n=664), and patients treated with 90 mg STELARA™ (n=666), respectively, were:Nasopharyngitis: 51 (8%), 56 (8%), 49 (7%); Upper respiratory tract infection: 30 (5%), 36 (5%),28 (4%); Headache: 23 (3%), 33 (5%), 32 (5%); Fatigue: 14 (2%), 18 (3%), 17 (3%); Diarrhea:12 (2%), 13 (2%), 13 (2%); Back pain: 8 (1%), 9 (1%), 14 (2%); Dizziness: 8 (1%), 8 (1%), 14(2%); Pharyngolaryngeal pain: 7 (1%), 9 (1%), 12 (2%); Pruritus: 9 (1%), 10 (2%), 9 (1%); Injectionsite erythema: 3 (<1%), 6 (1%), 13 (2%); Myalgia: 4 (1%), 7 (1%), 8 (1%); Depression: 3 (<1%),8 (1%), 4 (1%). Adverse drug reactions that occurred at rates less than 1% included: cellulitisand certain injection site reactions (pain, swelling, pruritus, induration, hemorrhage, bruising, andirritation). One case of RPLS occurred during clinical trials (see Warnings and Precautions).Infections In the placebo-controlled period of clinical studies of psoriasis subjects (averagefollow-up of 12.6 weeks for placebo-treated subjects and 13.4 weeks for STELARA™-treatedsubjects), 27% of STELARA™-treated subjects reported infections (1.39 per subject-year offollow-up) compared with 24% of placebo-treated subjects (1.21 per subject-year of follow-up).Serious infections occurred in 0.3% of STELARA™-treated subjects (0.01 per subject-year offollow-up) and in 0.4% of placebo-treated subjects (0.02 per subject-year of follow-up) (seeWarnings and Precautions). In the controlled and non-controlled portions of psoriasis clinical trials,61% of STELARA™-treated subjects reported infections (1.24 per subject-year of follow-up).

Serious infections were reported in 0.9% of subjects (0.01 per subject-year of follow-up).Malignancies In the controlled and non-controlled portions of psoriasis clinical trials, 0.4% ofSTELARA™-treated subjects reported malignancies excluding non-melanoma skin cancers (0.36per 100 subject-years of follow-up). Non-melanoma skin cancer was reported in 0.8% ofSTELARA™-treated subjects (0.80 per 100 subject-years of follow-up) (see Warnings andPrecautions). Serious malignancies included breast, colon, head and neck, kidney, prostate, andthyroid cancers. Immunogenicity The presence of ustekinumab in the serum can interfere withthe detection of anti-ustekinumab antibodies resulting in inconclusive results due to assayinterference. In STUDIES 1 and 2, antibody testing was done at time points when ustekinumabmay have been present in the serum. In STUDY 1 the last ustekinumab injection was betweenWeeks 28 and 48 and the last test for anti-ustekinumab antibodies was at Week 52. In STUDY 2the last ustekinumab injection was at Week 16 and the last test for anti-ustekinumab antibodieswas at Week 24. In STUDY 1 (N=743), antibody results were found to be positive, negative, andinconclusive in 38 (5%), 351 (47%), and 354 (48%) patients, respectively. In STUDY 2 (N=1198),antibody results were found to be positive, negative, and inconclusive in 33 (3%), 90 (8%), and1075 (90%) patients, respectively. The data reflect the percentage of subjects whose test resultswere positive for antibodies to ustekinumab in a bridging immunoassay, and are highly dependenton the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodypositivity in an assay may be influenced by several factors, including sample handling, timing ofsample collection, concomitant medications and underlying disease. For these reasons,comparison of the incidence of antibodies to ustekinumab with the incidence of antibodies toother products may be misleading. DRUG INTERACTIONS: Drug interaction studies have notbeen conducted with STELARA™. Live Vaccines Live vaccines should not be given concurrentlywith STELARA™ (see Warnings and Precautions). Concomitant Therapies The safety ofSTELARA™ in combination with immunosuppressive agents or phototherapy has not beenevaluated (see Warnings and Precautions). CYP450 Substrates The formation of CYP450enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF�, IFN)during chronic inflammation. Thus, ustekinumab could normalize the formation of CYP450enzymes. A role for IL-12 or IL-23 in the regulation of CYP450 enzymes has not been reported.However, upon initiation of ustekinumab in patients who are receiving concomitant CYP450substrates, particularly those with a narrow therapeutic index, monitoring for therapeutic effect(e.g., for warfarin) or drug concentration (e.g., for cyclosporine) should be considered and theindividual dose of the drug adjusted as needed (see Clinical Pharmacology). USE IN SPECIFICPOPULATIONS: Pregnancy Pregnancy Category B There are no studies of STELARA™ inpregnant women. STELARA™ should be used during pregnancy only if the potential benefitjustifies the potential risk to the fetus. No teratogenic effects were observed in the developmentaland reproductive toxicology studies performed in cynomolgus monkeys at doses up to 45 mg/kgustekinumab, which is 45 times (based on mg/kg) the highest intended clinical dose in psoriasispatients (approximately 1 mg/kg based on administration of a 90 mg dose to a 90 kg psoriasispatient). Ustekinumab was tested in two embryo-fetal development toxicity studies. Pregnantcynomolgus monkeys were administered ustekinumab at doses up to 45 mg/kg during the periodof organogenesis either twice weekly via subcutaneous injections or weekly by intravenousinjections. No significant adverse developmental effects were noted in either study. In anembryo-fetal development and pre- and post-natal development toxicity study, three groups of20 pregnant cynomolgus monkeys were administered subcutaneous doses of 0, 22.5, or 45 mg/kg ustekinumab twice weekly from the beginning of organogenesis in cynomolgus monkeysto Day 33 after delivery. There were no treatment-related effects on mortality, clinical signs, bodyweight, food consumption, hematology, or serum biochemistry in dams. Fetal losses occurred insix control monkeys, six 22.5 mg/kg-treated monkeys, and five 45 mg/kg-treated monkeys.Neonatal deaths occurred in one 22.5 mg/kg-treated monkey and in one 45 mg/kg-treatedmonkey. No ustekinumab-related abnormalities were observed in the neonates from birth throughsix months of age in clinical signs, body weight, hematology, or serum biochemistry. There wereno treatment-related effects on functional development until weaning, functional developmentafter weaning, morphological development, immunological development, and gross andhistopathological examinations of offsprings by the age of 6 months. Nursing Mothers Cautionshould be exercised when STELARA™ is administered to a nursing woman. The unknown risksto the infant from gastrointestinal or systemic exposure to ustekinumab should be weighed againstthe known benefits of breast-feeding. Ustekinumab is excreted in the milk of lactating monkeysadministered ustekinumab. IgG is excreted in human milk, so it is expected that STELARA™ willbe present in human milk. It is not known if ustekinumab is absorbed systemically after ingestion;however, published data suggest that antibodies in breast milk do not enter the neonatal andinfant circulation in substantial amounts. Pediatric Use Safety and effectiveness of STELARA™in pediatric patients have not been evaluated. Geriatric Use Of the 2266 psoriasis subjectsexposed to STELARA™, a total of 131 were 65 years or older, and 14 subjects were 75 years orolder. Although no differences in safety or efficacy were observed between older and youngersubjects, the number of subjects aged 65 and over is not sufficient to determine whether theyrespond differently from younger subjects. OVERDOSAGE: Single doses up to 4.5 mg/kgintravenously have been administered in clinical studies without dose-limiting toxicity. In case ofoverdosage, it is recommended that the patient be monitored for any signs or symptoms of adversereactions or effects and appropriate symptomatic treatment be instituted immediately. PATIENTCOUNSELING INFORMATION: Instruct patients to read the Medication Guide before startingSTELARA™ therapy and to reread the Medication Guide each time the prescription is renewed.Infections Inform patients that STELARA™ may lower the ability of their immune system to fightinfections. Instruct patients of the importance of communicating any history of infections to thedoctor, and contacting their doctor if they develop any symptoms of infection. Malignancies Patientsshould be counseled about the risk of malignancies while receiving STELARA™.Prefilled Syringe Manufactured by: Vial Manufactured by:Centocor Ortho Biotech Inc., Centocor Ortho Biotech Inc.,Horsham, PA 19044, Horsham, PA 19044,License No. 1821 at License No. 1821 atBaxter Pharmaceutical Solutions, Cilag AG,Bloomington, IN 47403 Schaffhausen, Switzerland1-800-457-6399 25US10041© Centocor Ortho Biotech Inc. 2009 December 2009

CLINICAL


Mr Lynch is Executive Director, Connecticut Center for Primary Care, and Medical Director forProHealth Physicians, Inc, Farmington, CT; Dr Cooke is President, PosiHealth, Inc, and ClinicalAssociate Professor, University of Maryland School of Pharmacy, Baltimore, MD; Dr Rosen is Medical Director for ProHealth Physicians, Inc, Farmington, CT; Dr Gandhi is Director, HealthEconomics and Outcomes Research for AstraZeneca LP, Wilmington, DE; and Dr Bullano is Director, Health Economics and Outcomes Research for AstraZeneca LP, Wilmington, DE.

Managing Dyslipidemia in PrimaryCare with Restricted Access to Lipid-Modifying TherapyJohn T. Lynch, MPH; Catherine E. Cooke, PharmD, BCPS, PAHM; Jonathan Rosen, MD; Sanjay Gandhi, PhD; Michael F. Bullano, PharmD

Background: Many patients with dyslipidemia do not achieve goal low-density lipoproteincholesterol levels. The barriers to achieving goal include inadequate assessment of cardio-vascular risk status, medication cost, formulary restrictions, patient lack of adherence, andinadequate counseling time. Removing barriers may improve goal attainment and reduce therisk for cardiovascular events. Objective: To identify opportunities to improve dyslipidemia management in primary care byexamining low-density lipoprotein cholesterol goal attainment in patients with unrestricted orrestricted access to lipid-modifying therapy.Method: A total of 5936 adult patients from a primary care practice with a low-densitylipoprotein measurement were categorized by coronary heart disease risk into 1 of 4 lipid-modifying therapy groups: unrestricted (fluvastatin, lovastatin, pravastatin, or simvastatinmonotherapy); restricted (atorvastatin, rosuvastatin, or simvastatin/ezetimibe fixed-dosecombination); other (lipid-modifying combination statin therapy or a nonstatin lipid-modifyingtherapy); and no lipid-modifying therapy. The primary outcome was low-density lipoproteincholesterol goal attainment by lipid-modifying therapy group. Logistic regression identifiedassociated demographic and clinical factors. Results: In this cohort, 78.1% of the patients achieved low-density lipoprotein cholesterolgoal levels. Overall goal attainment rates were lower in the high and very high coronary heartdisease risk categories, at 52.6% and 31.6%, respectively. For patients at elevated coronaryheart disease risk (high or very high), the rates of low-density lipoprotein cholesterol goalattainment were 14 to 16 percentage points higher for patients receiving restricted lipid-modifying therapy compared with patients receiving unrestricted lipid-modifying therapy (highcoronary heart disease risk: 68% vs 52%, respectively; very high coronary heart disease risk:42% vs 28%, respectively). Increasing age, male sex, and use of restricted lipid-modifyingtherapy were significantly associated with improved low-density lipoprotein cholesterol goalattainment. Of the 1298 patients who were not at low-density lipoprotein cholesterol goal,54.1% were not receiving any lipid-modifying therapy. For each coronary heart disease riskcategory, there was a significantly higher percent utilization of unrestricted lipid-modifyingtherapy compared with restricted lipid-modifying therapy (P <.001).Conclusion: A significant number of patients at elevated risk for coronary heart diseaseremain untreated or have low-density lipoprotein cholesterol levels above target. Removingbarriers to the use of restricted lipid-modifying agents in patients at risk for heart disease pro-vides an opportunity to improve low-density lipoprotein cholesterol levels.


John T. Lynch


Managing Dyslipidemia with Restricted Access to Lipid-Modifying Therapy


The National Cholesterol Education Program(NCEP) Adult Treatment Panel (ATP) III guide-lines and 2004 update stress the importance of

achieving low-density lipoprotein cholesterol (LDL-C)goals in patients with dyslipidemia.1,2 Patients at highercoronary heart disease (CHD) risk have lower LDL-Cgoals and require more aggressive lipid-modifying thera-py to achieve these goals than patients at lower CHDrisk. Reducing LDL-C with lipid-modifying therapy inpatients at higher CHD risk yields greater relative bene-fits in reducing the risk of CHD events compared withsuch treatment in patients at lower CHD risk.1,2

Despite awareness of the importance of appropriatelymanaging patients with dyslipidemia, evaluations of cur-rent practice reveal that only about 40% to 75% of allpatients with dyslipidemia achieve goal LDL-C levels.3-6The likelihood of goal attainment is inversely associatedwith cardiovascular (CV) risk.5,7 Reported rates of LDL-C goal attainment range from 50% to 98% in patients atlower CHD risk,3,5,8,9 and from 10% to 70% in patientsat higher CHD risk.5,6,8,10 Only about 20% to 30% ofpatients at very high risk achieve goal LDL-C levels.5,6

Several barriers to achieving goal LDL-C levels havebeen reported in the literature, including patient, physi-cian, and system barriers.11-14 A study of primary careproviders in the United States identified barriers to initi-ating statin therapy, such as concerns about cost, patientadherence, and lack of adequate counseling time.11 In amanaged care organization (MCO), cost and adherencewere also of concern and were found to be inversely relat-ed.12 Non-Medicaid MCO patients with higher copay-ments were more likely to discontinue statin therapysooner than those with lower copayments.12

MCOs use preferred drug lists (PDLs) to have animpact on prescribing. In one study of Medicaid recip-ients, significant decreases (range, 65%-97%) werefound in the proportion of statin prescriptions filled foroff-PDL (ie, restricted) medicines after the adoption ofa Medicaid PDL.13 Physicians have difficulty assigningCHD risk status and following guideline-recommendedinterventions.11 Other studies have confirmed thatphysicians are unaware of national guidelines for statinuse.14 When physicians underestimate CHD risk status,drug therapy restrictions may result in undertreatmentof patients with dyslipidemia, especially those at high-er CHD risk.

Removing barriers to achieving nationally recom-mended LDL-C goals in patients at increased CHD riskmay reduce the risk of CV events. The objective of ourstudy was to identify opportunities to improve dyslipi-demia management in primary care by examining LDL-C goal attainment in patients with unrestricted andrestricted access to lipid-modifying therapy.

MethodsStudy Population

Patients were retrospectively identified from thelargest primary care group practice in Connecticut,which serves approximately 320,000 patients. In addi-tion to the internal patient care database, this primarycare practice routinely receives data on hospitalizations,emergency department visits, and pharmacy claims fortheir patients insured by a regional MCO.

To be eligible for inclusion in this study, patients hadto be insured by the regional MCO, have at least 1 officevisit to the primary care group practice, and have at least1 LDL-C measurement during 2007. LDL-C valuesreported from the laboratory were calculated by using aformula that includes total cholesterol, high-densitylipoprotein cholesterol (HDL-C), and triglycerides;patients had to have these additional lipid parametersavailable for CHD risk stratification. Patients wereexcluded if they were younger than age 18 years onJanuary 1, 2007, or if they had no associated pharmacyclaims data.

Data CollectionData from the primary care practice and managed

care claims databases during 2007 were combined to cre-ate individual patient profiles. These patient profiles

KEY POINTS

➤ Despite widespread awareness of the importance oflipid management in patients with dyslipidemia,many patients do not achieve target cholesterollevels.

➤ Previous studies have reported barriers to achievinggoal LDL-C levels, which involve patients,physicians, and the healthcare system as a whole.

➤ This study included 5936 patients with medical and pharmacy coverage who had an LDL-Cmeasurement and were either receiving differenttypes of lipid-modifying therapies or no therapy.

➤ Pharmacy coverage restricted the initial lipid-modifying therapy with a step-edit on atorvastatin,rosuvastatin, and simvastatin/ezetimibe fixed-dosecombination.

➤ Cholesterol goal attainment was unaffected by thetype of lipid-modifying therapy used by patients atlow risk, but in patients at higher risk, more patientsreached LDL-C goal with one of the drugs includedin the restricted coverage category.

➤ This finding has implications to payers’ drugcoverage decisions and clinicians’ prescribingdecisions.

CLINICAL


contained information from office visits, hospitaliza-tions, and emergency department care. Patient profilescontained unique deidentified patient numbers, demo-graphic data (ie, age and sex), clinical data (ie, diag-noses/procedures and laboratory data), and prescriptionclaims data. Data on diagnoses and procedures wereobtained from office visits, hospitalizations, and emer-gency department care. Laboratory results includedLDL-C. Patient identities were masked throughout thestudy in a limited data set format in accordance with theHealth Insurance Portability and Accountability Act.

Coronary Heart Disease Risk StatusPatients were stratified into CHD risk categories of

low, moderate, high, and very high using a modifiedNCEP ATP III approach1,2 (see Appendix at www.AHDBonline.com). International Classification of Diseases, NinthRevision, Clinical Modification (ICD-9-CM) codes,Current Procedural Terminology, version 4 (CPT-4)codes, and pharmacy claims data were used to stratifypatients by hierarchy into the highest risk category.

Patients were considered to be at high CHD risk (goalLDL-C <100 mg/dL) if they had any ICD-9-CM codesfor myocardial infarction, other ischemic heart disease,angina pectoris, symptomatic carotid artery disease,peripheral arterial disease, abdominal aortic aneurysm,or diabetes mellitus; any CPT-4 claims for coronaryartery bypass graft or percutaneous transluminal coro-nary angioplasty; or any pharmacy claims for antidiabet-ic agents. Patients identified as having high CHD risk(clinical CHD) were considered to be at very high CHDrisk (goal LDL-C <70 mg/dL) if they also had claimsindicating diabetes, intermediate coronary syndrome,or dysmetabolic syndrome X (metabolic syndrome).Patients with diabetes must also have had other comorbidcodes within the high CHD risk category to be classifiedas having very high CHD risk.

The remaining patients with at least 2 risk factorswere considered to be at moderate risk (goal LDL-C<130 mg/dL).1,2 Risk factors included age ≥45 years formen or age ≥55 years for women, HDL-C <40 mg/dL,and hypertension as defined by ICD-9-CM codes or bypharmacy claims for an antihypertensive medication.Patients who did not meet the criteria for very high,high, or moderate CHD risk categories were placed intothe low CHD risk (goal LDL-C <160 mg/dL) category.

Outcome MeasuresThe primary outcome measure was the percentage of

patients achieving LDL-C goals. In accordance with theNCEP ATP III guidelines and the 2004 update,1,2 LDL-Cgoals were defined as <160 mg/dL for the low CHD riskcategory, <130 mg/dL for the moderate CHD risk cate-

gory, <100 mg/dL for the high CHD risk category, and<70 mg/dL for the very high CHD risk category. Forpatients with more than 1 LDL-C value, the most recentvalue was utilized. An analysis was conducted in patientswho had not achieved goal LDL-C values to identifyopportunities to improve dyslipidemia management inthis practice.

Dyslipidemia Treatment PatternsThe use of lipid-modifying therapy was determined

from the pharmacy claims and grouped based on themechanistic types of lipid-modifying therapy andexpected patterns of therapy (eg, monotherapy or com-bination therapy). Types of lipid-modifying therapyincluded statins (atorvastatin, fluvastatin, lovastatin,pravastatin, rosuvastatin, or simvastatin); simvastatin/ezetimibe fixed-dose combination; fibrates (fenofibrateor gemfibrozil); niacin; cholesterol absorption inhibitors(ezetimibe); and bile acid sequestrants (cholestyramineor colestipol).

Patients receiving a statin as monotherapy or the sim-vastatin/ezetimibe fixed-dose combination were furtherclassified into “unrestricted” and “restricted” categories.

The unrestricted and restricted lipid-modifying ther-apy categories were based on a step-therapy programinstituted by the regional MCO during the study exam-ination period (ie, 2007). As part of the program,patients were required to “step through” (ie, cumulativepharmacy fills for at least a 90-day supply) therapy witheither lovastatin or simvastatin. After this trial, patientswould become “eligible” to receive atorvastatin, rosuva -statin, or simvastatin/ezetimibe fixed-dose combinationtherapy under their prescription benefit.

For circumstances in which patients were prescribed arestricted medication and elected not to follow the step-therapy program, they would pay the full cost of theirrestricted lipid-modifying therapy medication out ofpocket. Accordingly, the restricted statin lipid-modify-ing therapy group included patients receiving atorva -statin or rosuvastatin monotherapy or the simvastatin/ezetimibe fixed-dose combination.

The unrestricted statin group contained patients whowere receiving fluvastatin, lovastatin, pravastatin, orsimvastatin monotherapy.

Patients observed taking more than 1 lipid-modifyingtherapy type (ie, multipill combination therapy) or anon−statin-containing lipid-modifying therapy werecategorized into the “other” group.

The last group—no lipid-modifying therapy—includ-ed patients who had no prescription claims observed forany lipid-modifying therapy type. For patients whoswitched therapy, the most recent prescription was usedto categorize into a lipid-modifying therapy group.



Statistical Analysis Descriptive statistics were used to report sample char-

acteristics, treatment patterns, and NCEP ATP III LDL-C goal attainment rates. Categorical variables are report-ed as frequencies and percentages, and continuousvariables are reported as mean ± standard deviation. Chi-square tests were used to compare LDL-C goal attain-ment among the lipid-modifying therapy groups, anddemographic and clinical factors associated with LDL-Cgoal attainment were evaluated using logistic regression.Statistical significance was set at an accepted alpha(P <.05). All statistical analyses were performed usingSAS version 9.1 (SAS Institute, Cary, NC) and Stataversion 8.1 (Stata Corporation, College Station, TX).

ResultsMember Demographics

A total of 5936 patients met the study inclusion cri-teria, which represented 17% of the patients seen in thislarge group practice who were also insured by the region-al MCO (Figure 1). The baseline characteristics of thesepatients are presented in Table 1. In this primary caresetting, the majority of patients were categorized as hav-ing low CHD risk (58.6%). A total of 2458 patients(41.4%) were at an elevated CHD risk: 24.6% at mod-erate, 14.9% at high, and 1.9% at very high CHD risk.Hypertension was the most common risk factor, found in45.3% of patients. Diabetes was present in 12.2% of thecohort, which automatically placed these patients intohigh or very high CHD risk categories.

Of the 1626 patients who received statin monothera-py or a simvastatin/ezetimibe fixed-dose combination,986 and 658 patients were categorized as unrestrictedand restricted lipid-modifying therapy, respectively(Table 2). This equates to an approximate 60/40 split inthe 1626 patients receiving statin-based therapy.Unrestricted lipid-modifying therapy utilization washigher than restricted lipid-modifying therapy for eachCHD risk category. Of note, 3849 patients (64.8%) werenot treated with any lipid-modifying therapy; most ofthem were in the low CHD risk category (n = 2739).

LDL-C Goal AttainmentA total of 4638 patients (78.1%) met their LDL-C

goal levels. As CHD risk increased, the percentage ofpatients achieving goal LDL-C decreased (low, 90.8%;moderate, 67.1%; high, 52.6%; very high, 31.6%). Asimilar pattern of decreasing goal attainment withincreasing CHD risk was found in patients in the otherlipid-modifying therapy group (low, 84.7%; moderate,64.0%; high, 58.1%; very high, 31.3%).

For all CHD risk categories except the lowest, goalachievement increased as drug therapy progressed from

Figure 1 Large Patient Population in Primary Care Group Practice

Patients with commercial insurance from regional

managed care organization N = 35,669

Excluded patients aged <18 yearsN = 9957

Adults with commercial insurance from regional

managed care organizationN = 25,712

Adults with ≥1 visit to primary care provider in 2007

N = 10,403

Patients with ≥1 LDL-C value in 2007N = 5936

Excluded patients without any office visits or

prescription data in 2007N = 15,309

Excluded patients without any LDL-C values

N = 4467

NOTE: The total population in this practice is approximately 320,000.LDL-C indicates low-density lipoprotein cholesterol.

➤

➤

➤➤

➤

➤

Table 1 Baseline Patient Characteristics

CharacteristicaPatientsN (%)

Age (yrs), mean ± SD [range] 44.9 ± 13.5 [18-92]

Men, any age Men ≥45 yrs

2984 (50.3) 2169 (36.5)

Women, any age Women ≥55 yrs

2952 (49.7) 996 (16.8)

Diagnosis Diabetes or on antidiabetic medication Hypertension or on antihypertensive therapy

724 (12.2) 2688 (45.3)

CHD risk status Low Moderate High Very high

3478 (58.6) 1461 (24.6) 883 (14.9) 114 (1.9)

aData on ethnicity not collected. Total patients = 5936. CHD indicates coronary heart disease; SD, standard deviation.

no therapy to unrestricted therapy to restricted therapy(P <.001) (Figure 2). For patients at elevated CHD risk(high or very high), the rates of LDL-C goal attainmentwere 14 to 16 percentage points higher for patientsreceiving restricted lipid-modifying therapy comparedwith patients receiving unrestricted lipid-modifyingtherapy (high CHD risk: 68%-52%; very high CHDrisk: 42%-28%).

Factors in the multivariable logistic regression modelthat were significantly associated with improved LDL-Cgoal attainment were increasing age (odds ratio, 1.04;95% confidence interval [CI], 1.02-1.06), male sex (oddsratio, 1.37; 95% CI, 1.07-1.76), and use of restricted

lipid-modifying therapy (odds ratio, 1.46; 95% CI, 1.14-1.86). Patients at moderate (odds ratio, 0.34; 95% CI,0.25-0.48), high (odds ratio, 0.17; 95% CI, 0.12-0.23),and very high (odds ratio, 0.05; 95% CI, 0.03-0.09)CHD risk were less likely to achieve LDL-C goal whencompared with patients at low risk (data not shown).

Patients Not at LDL-C GoalAs CHD risk increased, the percentage of patients

not achieving goal LDL-C increased (low, 9.2%; moder-ate, 32.9%; high, 47.4%; very high, 68.4%). Furtherexamination of the 1298 patients who were not at LDL-C goal revealed that 702 (54.1%) patients were not

CLINICAL


Table 2 Lipid-Modifying Therapy Utilization, by CHD Risk Group

Therapy group, by CHD risk category, N (%)

LMT groupLow risk (N = 3478)

Moderate risk (N = 1461)

High risk (N = 883)

Very high risk (N = 114)

All patients (N = 5936)

No therapy 2739 (78.8) 799 (54.7) 298 (33.7) 13 (11.4) 3849 (64.8)

Unrestricted therapiesa 392 (11.3) 312 (21.4) 228 (25.8) 36 (31.6) 968 (16.3)

Restricted therapiesb 229 (6.6) 211 (14.4) 185 (21.0) 33 (28.9) 658 (11.1)

Other lipid therapyc 118 (3.4) 139 (9.5) 172 (19.5) 32 (28.1) 461 (7.8)aFluvastatin, pravastatin, lovastatin, or simvastatin monotherapy. bAtorvastatin monotherapy, rosuvastatin monotherapy, or simvastatin/ezetimibe fixed-dose combination. cFibrates, niacin, ezetimibe, and bile acid sequestrants as monotherapy alone or in multipill combination therapy. CHD indicates coronary heart disease; LMT, lipid-modifying therapy.

Figure 2 LDL-C Goal Attainment, by Lipid-Modifying Therapy Group

LMT groups:NoneUnrestrictedRestricted(N = 5475)

92 (2524/2739)

86 (337/392)

86(197/229)

79 (166/211)

63 (501/799)

72 (224/312) 68

(126/185)

40 (120/298)

52 (118/228)

42 (14/33)

15 (2/13)

28 (10/36)

100

90

80

70

60

50

40

30

20

10

0Low Moderate High Very high

CHD risk categories

CHD indicates coronary heart disease; LDL-C, low-density lipoprotein cholesterol; LMT, lipid-modifying therapy.

Patie

nts

achi

evin

g go

al L

DL-C

, %

receiving any lipid-modifying therapy, 279 (21.5%) werereceiving unrestricted lipid-modifying therapy, 155(11.9%) were receiving restricted lipid-modifying thera-py, and 162 (12.5%) were receiving other lipid-modify-ing therapy.

Among patients not achieving goal with either unre-stricted or restricted lipid-modifying therapy (n = 434),many more patients were receiving unrestricted lipid-modifying therapy than restricted lipid-modifying thera-py (57.8%-63.2% vs 33.8%-42.2%), and this trend wassignificant across low, moderate, and high CHD risk cat-egories (P <.001; Figure 3). Patients receiving unre-stricted lipid-modifying therapy required, on average, anadditional 17.9% reduction in LDL-C levels to achievegoal LDL-C, with the high and very high CHD risk cat-egories requiring the largest reductions, at 22.7% and21.7%, respectively.

DiscussionThe intent of our study was to identify targets for

quality improvement initiatives. Clearly, the data sup-port attention in the higher CHD risk categories.About half of the patients in the high CHD risk cate-gory and two thirds of the patients in the very highCHD risk category did not achieve goal LDL-C levels.These patients represent the largest healthcare bur-den.1,2 They are more likely to suffer adverse CV out-comes and associated costs than patients at lower CHDrisk. National guidelines have stressed the importanceof aggressively managing this population, yet currentpractice yields suboptimal results.1,2

Patients at higher CHD risk have lower LDL-C goals,and more difficulty attaining goal LDL-C.4-8,15,16 In addi-tion to CHD risk status, greater percentage LDL-Creduction and lack of titration have been associated withdecreased likelihood of achieving goal.15-18 In a study ofpatients newly initiated on statin therapy, the percent-age of LDL-C reduction required to achieve goal wasfound to independently predict goal attainment.16

Patients who required at least a 15% reduction in LDL-C level or who were at elevated CHD risk were less like-ly to achieve goal compared with patients who requiredless than a 15% reduction or who were low risk.16

Despite having pharmacy coverage, patients andphysicians in our study faced restrictions in choice oflipid-modifying therapy. The restricted lipid-modifyingtherapy options were atorvastatin, rosuvastatin, andsimvastatin/ezetimibe fixed-dose combination. Theseagents demonstrate superior percentage reductions inLDL-C values versus agents included in the unrestrict-ed lipid-modifying therapy group across various prac-tice settings.19-24

In our study, goal attainment was unaffected by lipid-

modifying therapy use in the low CHD risk category, butmore patients in the moderate, high, and very highCHD risk categories achieved goal LDL-C if they werereceiving restricted lipid-modifying therapy. The dispar-ity in LDL-C goal attainment between restricted andunrestricted lipid-modifying therapy groups was greaterin higher CHD risk categories.

Patients in the high and very high CHD risk cate-gories were more likely to achieve LDL-C goal if theywere receiving restricted lipid-modifying therapy com-pared with unrestricted lipid-modifying therapy. In addi-tion, for patients not at LDL-C goal, the use of unre-stricted agents was greater in all of the CHD riskcategories compared with the use of restricted lipid-mod-ifying therapy. Agents in the unrestricted lipid-modify-ing therapy group could have been titrated to higherdoses or switched to restricted agents with increasedLDL-C lowering potential. However, evidence demon-strates that such modifications occur infrequently.15,17,18

In a recent study of 1654 patients newly initiated withsimvastatin therapy, only 45.6% were found to be atLDL-C goal.17 In those patients who did not achieveLDL-C goal, a majority (85.4%) were not titrated fromthe initial simvastatin dose or switched to another statin.17

In a study of high CHD risk patients treated in a pri-mary care setting within a Veterans AdministrationMedical Center, only 16% of patient visits resulted in anincreased statin dose in patients with uncontrolled LDL-C levels.18 Similar results were found in a study by



65.1

42.234.933.8

66.263.2 57.8

Utili

zatio

n, %

CHD risk groups

Lowa Moderatea Higha Very high(N = 87) (N = 133) (N = 169) (N = 45)

aP <.001 for comparison of restricted versus unrestricted LMT use.CHD indicates coronary heart disease; LDL-C, low-density lipoprotein cholesterol;LMT, lipid-modifying therapy.

LMT groups:RestrictedUnrestricted

36.8

Figure 3 Use of Unrestricted and Restricted LMT in Patients Not at LDL-C Goal Levels

100

80

60

40

20

0

Lindgren and colleagues, who examined 1166 patientswith uncontrolled LDL-C values at 3 months.15 In 87.3%of these patients, there were no changes to the lipid-modifying therapy regimen. Of the 12.7% of patientswith changes, approximately 74% had a change in thedose of the original lipid-modifying therapy, and 26%were prescribed a different lipid-modifying therapy. At12 months, only 7.9% of the original cohort hadattained LDL-C goal levels.15

Few patients who are not controlled on their initialregimen achieve goal LDL-C levels.15,25 In a prospectivestudy of patients at high CHD risk with uncontrolledLDL-C levels, only 14% attained goal within 6 months.25This low level of goal attainment occurred despite a pro-tocol that instructed the study sites to titrate the pre-scribed statin as necessary to achieve LDL-C goal <100mg/dL. Clinical inertia (eg, lack of titration) or patientnonadherence to lipid-modifying therapy can partlyexplain why even after longer follow-up, LDL-C goalattainment remains elusive. For patients who do havechanges to their lipid-modifying therapy regimen, thereis an increased risk for nonpersistence. In a study ofpatients with comorbid hypertension and dyslipidemia,patients who had changes to their lipid-modifying ther-apy were less likely to persist with their lipid-modifyingtherapy compared with those who remained on their ini-tial lipid-modifying therapy regimen.26

To effectively manage formulary restrictions, system-atic interventions are needed to improve LDL-C goalattainment. One study showed that using an education-al intervention improved LDL-C goal attainment ratesfrom 49% to 62%.18 After receiving this education, cli-nicians were more likely to increase the statin dose.18Another study demonstrated that clinical pharmacistinvolvement improved LDL-C goal attainment rates by17%, after a therapeutic conversion from one statin toother statins or statin combination products.27 Althoughthese programs are effective, they are often only pilotstudies and are not sustained for long periods.

LimitationsAn overestimation of LDL-C goal attainment might

have occurred in this study, because patients were con-servatively segmented into CHD risk categories. Data,such as family history of CHD, smoking status, andblood pressure measurements, were unavailable.Without these data, there was no way to determine thecomplete number of CHD risk factors or to calculate 10-year risk of having a CHD event. These additional datamay have categorized patients into higher CHD risk cat-egories, with more aggressive LDL-C goals. The resultwould likely have been a greater percentage of patientshaving LDL-C levels not at goal.

In addition, some patients might have received drugsamples, and there was no way of accounting for this sup-ply of medication. The impact of samples without anyprescription claims could affect lipid-modifying therapygroup categorization and rate of LDL-C goal attainmentby lipid-modifying therapy group. Similarly, patientswho paid cash for their lipid-modifying therapies couldhave been miscategorized by lipid-modifying therapygroup, which could affect the rate of LDL-C goal attain-ment per lipid-modifying therapy group.

Finally, we did not obtain information on medicationadherence. Patients with poor medication adherence areless likely to achieve goal LDL-C values. If the percent-age of patients who were nonadherent was different inthe various lipid-modifying therapy groups, this couldaffect the discrepancy in LDL-C goal attainment.

ConclusionA significant number of patients at elevated risk for

CHD remain untreated or have LDL-C levels abovetarget; these patients are either not receiving lipid-modifying therapy or their current regimens are subop-timal. In this study, although patients receivingrestricted lipid-modifying therapy agents were morelikely to achieve LDL-C goal, the use of these agentswas relatively low. These patterns of lipid-modifyingtherapy use may be helpful to discern approaches toachieve higher LDL-C goal attainment rates.Removing barriers to the use of restricted agents inpatients at elevated CHD risk provides an opportunityto achieve goal LDL-C levels aimed at decreasing therisk of subsequent CV disease events.

It is imperative that clinicians have the opportunityto individualize lipid-modifying therapy according tothe patient’s CHD risk status and LDL-C goal, with theintent of achieving goal LDL-C with the initial thera-py prescribed. To enable clinicians and patients toachieve goals, unrestricted access to initial lipid-modi-fying therapy regimens that are expected to achievegoal should be a standard formulary strategy for patientsat high CHD risk. ■

AcknowledgmentThis study was supported by funding from AstraZeneca.

Disclosure StatementMr Lynch and Dr Rosen receive research grant support

from AstraZeneca and Novartis; Dr Cooke receives researchgrant support from AstraZeneca, Novartis, and Pfizer; DrsGandhi and Bullano are employees of AstraZeneca LP.

References1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterolin Adults. Executive summary of the Third Report of the National CholesterolEducation Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment

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of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.2. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials forthe National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation. 2004;110:227-239. Erratum in: Circulation. 2004;110:763.3. Van Ganse E, Souchet T, Laforest L, et al. Ineffectiveness of lipid-lowering therapyin primary care. Br J Clin Pharmacol. 2005;59:456-463.4. Stacy TA, Egger A. Results of retrospective chart review to determine improvementin lipid goal attainment in patients treated by high-volume prescribers of lipid-modi-fying drugs. J Manag Care Pharm. 2006;12:745-751.5. Waters DD, Brotons C, Chiang CW, et al. Lipid Treatment Assessment Project 2:a multinational survey to evaluate the proportion of patients achieving low-densitylipoprotein cholesterol goals. Circulation. 2009;120:28-34.6. Van Ganse E, Laforest L, Alemao E, et al. Lipid-modifying therapy and attainmentof cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy(REALITY) study. Curr Med Res Opin. 2005;21:1389-1399.7. Laforest L, Moulin P, Souchet T, et al. Correlates of LDL-cholesterol goal attain-ment in patients under lipid lowering therapy. Atherosclerosis. 2008;199:368-377. Epub2008 Jan 11.8. Latts LM. Assessing the results: phase 1 hyperlipidemia outcomes in 27 healthplans. Am J Med. 2001;110(suppl 6A):17-23.9. Davidson MH, Maki KC, Pearson TA, et al. Results of the National CholesterolEducation (NCEP) Program Evaluation Project Utilizing Novel E-Technology (NEP-TUNE) II survey and implications for treatment under the recent NCEP writinggroup recommendations. Am J Cardiol. 2005;96:556-563.10. Hilleman DE, Monaghan MS, Ashby CL, et al. Physician-prompting statin ther-apy intervention improves outcomes in patients with coronary heart disease.Pharmacotherapy. 2001;21:1415-1421.11. Doroodchi H, Abdolrasulnia M, Foster JA, et al. Knowledge and attitudes of pri-mary care physicians in the management of patients at risk for cardiovascular events.BMC Fam Pract. 2008;9:42.12. Ellis JJ, Erickson SR, Stevenson JG, et al. Suboptimal statin adherence and dis-continuation in primary and secondary prevention populations. J Gen Intern Med.2004;19:638-645.13. Headen AE Jr, Masia NA, Axelsen KJ. Effects of medicaid access restrictions onstatin utilisation for patients treated by physicians practising in poor and minorityneighbourhoods. Pharmacoeconomics. 2006;24(suppl 3):41-53.14. Tsang JL, Mendelsohn A, Tan MK, et al; for the Vascular Protection Registry andGuidelines Oriented Approach to Lipid Lowering Registry Investigators. Discordancebetween physicians’ estimation of patient cardiovascular risk and use of evidence-based medical therapy. Am J Cardiol. 2008;102:1142-1145. Epub 2008 Aug 15.15. Lindgren P, Borgström F, Stålhammar J, et al. Determinants of cholesterol goalattainment at 12 months in patients with hypercholesterolaemia not at consensus

goal after 3 months of treatment with lipid-lowering drugs. Int J Clin Pract. 2007;61:1410-1414.16. Kamat SA, Gandhi SK, Davidson M. Comparative effectiveness of rosuvastatinversus other statin therapies in patients at increased risk of failure to achieve low-den-sity lipoprotein goals. Curr Med Res Opin. 2007;23:1121-1130. 17. Willey VJ, Bullano MF, Shoetan NN, Gandhi SK. Therapy modifications andlow-density lipoprotein cholesterol goal attainment rates associated with the initia-tion of generic simvastatin. Curr Med Res Opin. 2010;26:121-128.18. Goldberg KC, Melnyk SD, Simel DL. Overcoming inertia: improvement inachieving target low-density lipoprotein cholesterol. Am J Manag Care. 2007;13:530-534.19. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy studyof atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patientswith hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81:582-587.Erratum in: Am J Cardiol. 1998;82:128.20. McKenney JM, Jones PH, Adamczyk MA, et al; for the STELLAR study group.Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, andpravastatin in achieving lipid goals: results from the STELLAR trial. Curr Med ResOpin. 2003;19:689-698.21. Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, double-blind, place-bo-controlled, factorial design study to evaluate the lipid-altering efficacy and safetyprofile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatinmonotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004;26:1758-1773.22. Ohsfeldt RL, Gandhi SK, Fox KM, et al. Effectiveness and cost-effectiveness ofrosuvastatin, atorvastatin, and simvastatin among high-risk patients in usual clinicalpractice. Am J Manag Care. 2006;12(15 suppl):412-423.23. Bullano MF, Wertz DA, Yang GW, et al. Effect of rosuvastatin compared withother statins on lipid levels and National Cholesterol Education Program goal attain-ment for low-density lipoprotein cholesterol in a usual care setting. Pharmacotherapy.2006;26:469-478.24. Bullano MF, Kamat S, Wertz DA, et al. Effectiveness of rosuvastatin versus ator-vastatin in reducing lipid levels and achieving low-density lipoprotein cholesterolgoals in a usual care setting. Am J Health Syst Pharm. 2007;64:276-284.25. Foley KA, Simpson RJ Jr, Crouse JR 3rd, et al. Effectiveness of statin titration onlow-density lipoprotein cholesterol goal attainment in patients at high risk of athero-genic events. Am J Cardiol. 2003;92:79-81. 26. Robertson TA, Cooke CE, Wang J, et al. Effect of medication burden on persist-ent use of lipid-lowering drugs among patients with hypertension. Am J Manag Care.2008;14:710-716.27. Miller AE, Hansen LB, Saseen JJ. Switching statin therapy using a pharmacist-managed therapeutic conversion program versus usual care conversion among indi-gent patients. Pharmacotherapy. 2008;28:553-561.



Appropriate Medication Selection Key to Cost-Effective Therapy, Patient AdherenceMEDICAL/PHARMACY DIRECTORS: Because

of the high cost of treatment and the clinical seque-lae of cardiovascular disease, primary and secondarypreventive measures are continually on payers’minds. Cholesterol-lowering drugs are among thetop-budgeted therapeutic classes for most payers,making this class a priority category for appropriateutilization management.

In their study, Lynch and colleagues addressedimportant issues in cholesterol management. Basedon their data relevant to low-density lipoprotein cho-lesterol (LDL-C) goal attainment, particularly in

those who are at high and very high risk for coronaryheart disease (CHD), better cholesterol managementis paramount for the prevention of cardiovascularevents. An interesting follow-up to this study wouldinclude the doses used and adherence and persistencepatterns within the risk groups of patients with CHD.

In the introduction, the authors cite a study show-ing that high copay cost is inversely related to patientmedication adherence. One of the keys to the deliv-ery of and payment for cost-effective therapy isappropriate therapy selection.

In the current study, the largest group of treated


Continued

CLINICAL


and untreated patients is within the low CHD riskgroup. In this group, treating patients with morepotent and more expensive brand-name statin thera-py did not produce better results based on the per-centage of patients achieving their goal LDL-C level.In reviewing these data, it appears that the most cost-effective therapy was not selected for the largestgroup of patients. One can, therefore, understand therationale for some type of utilization management—in this case step-therapy requirement—for this groupof patients.

One alternative to the 90-day supply requirementof a generic, less-potent statin may be the explorationof a step-therapy requirement (or noncoverage) appli-cable only to the lower doses of the brand-namestatins. This may provide more options for patientswho initially require greater levels of LDL-C reduc-tions, without wasting money to achieve LDL-C lev-els that could be achieved, for example, with simvas-tatin 40 mg/day. This approach may emphasize theimportance of appropriate statin and dose selection.

The data presented by Lynch and colleagues high-light the importance of provider education regardingnot only initial medication selection but also theneed for adequate dose titration that is necessary forLDL-C goal attainment.PATIENTS: Adherence to cholesterol-lowering

therapy has historically been poor. In fact, a recentanalysis determined that statin adherence and per-sistence is worse than adherence to oral antidiabetesmedications or angiotensin receptor blockers.1

In addition to providers, patients also need con-tinual education concerning the importance of cho-lesterol management. All barriers to medicationadherence should be addressed to identify solutions,including cost-effective alternatives, when appropriate.

1. Yeaw J, Benner JS, Walt JG, et al. Comparing adherence and persistence across6 chronic medication classes. J Manag Care Pharm. 2009;15:728-740.

Matthew Mitchell, PharmD, MBAManager, Pharmacy Services

SelectHealth, Salt Lake City, UT

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INDUSTRY TRENDS


The Patient Protection and Affordable Care Act(PPACA)1 and the Health Care and EducationReconciliation Act2 of 2010 may be the first steps

in the process of federal healthcare reform, but many ofthe provisions of the PPACA represent further move-ment on a path that has been laid out over the pastdecade by policymakers in the public and the privatesectors—the historical aim of increasing value in health-care. As healthcare reform changes the shape of the UShealthcare system, the PPACA sends a strong signal thatquality will be a central driver of this change.

In an environment that rewards value and quality,attention to outcomes measurement and improvementwill be essential to the success of organizations acrossthe healthcare system. This includes health plans andthe physicians and institutions with which they inter-act. The volume and complexity of healthcare qualitydata will increase quickly. Investment in the infrastruc-ture and programs needed to support quality measure-ment, reporting, and improvement will likely be drivenby the simultaneous increase in demands for trans-parency and accountability at all levels of the health-care system.

The PPACA, as well as the regulations and legisla-tion that will follow, are driven by forces that rely pro-foundly on the measurement of health system perfor -mance in 2 core areas—the expansion of insurance tomore Americans, and an effort to ensure consumer pro-tection and affordability. But PPACA signals that theseforces will drive the next stages of change—paymentreform and delivery system reform.

Payment reform is, and increasingly will be, drivenby the trend toward value-based rather than service-based purchasing. As quality becomes part of the foun-dation for economic success at all levels of the health-care system, increased coordination of care and moresophisticated population management will be neces-sary. The link between demonstrated performance andeconomic success, which began more than a decadeago, will move from the periphery to the center ofhealthcare. Healthcare organizations, and individual

physicians, will have to respond. Now is the time forthem to prepare.

Opportunities for Quality Outcomes Measurement and Reporting

With the expansion of insurance and consumer pro-tection forming the backbone of healthcare reform, thelanguage of the acts themselves speaks not only toaffordability but also to value. Value-based purchasingstrategies, beginning with health plans and ending withthe consumer, will create pressure on institutions to per-form. Performance must become quantifiable, so thedevelopment of metrics to measure all facets of health-care performance will be a key element of the reformprocess and is explicitly funded by the reform legislation,as discussed below.

Much of the language in the PPACA speaks to agreater awareness of coordination of care and howimproved coordination at each level of the systemincreases value for the patient and decreases costthrough enabling better clinical outcomes and theelimination of wasteful and redundant medical spend-ing. One bonus that creates a powerful incentive forcare management programs is the Care Coordinationand Management Performance Bonus for MedicareAdvan tage (MA) plans.

The following excerpt from the PPACA explainsthis particular bonus and points to health reform prior-ities in terms of clinical and quality outcomes:

“For years beginning with 2014…in the case of an MAplan that conducts 1 or more programs described [as]…

(i) Care management programs that—(I) target individuals with 1 or more chronic

conditions;(II) identify gaps in care; and(III) facilitate improved care by using additional

resources like nurses, nurse practitioners,and physician assistants.

(ii) Programs that focus on patient education and self-management of health conditions, includinginterventions that—

Healthcare Reform: Quality OutcomesMeasurement and Reporting Cary Sennett, MD, PhD Chief Medical Officer, MedAssurant, Inc

This article is based in part on a presentation at the annual meeting of the America’s Health Insurance Plans in May 2010 in Las Vegas, NV.

INDUSTRY TRENDS


(I) help manage chronic conditions;(II) reduce declines in health status; and(III) foster patient and provider collaboration.

[The bonus would be] equal to the product of—(i) 0.5% of the national monthly per capita cost for

expenditures for individuals enrolled under theoriginal Medicare fee-for-service program for theyear; and

(ii) The total number of programs.”1

Older systems of quality measurement will beexpanded. For example, the Physician Quality Report -ing Initiative (PQRI) introduced by the Centers forMedicare & Medicaid Services (CMS), which onceoffered Medicare reimbursement for providers who report-ed a limited set of metrics, will likely become a require-ment, and quality reporting will no longer be an option.Investment in systems to support the measurement andreporting of metrics related to PQRI should increase asphysicians face stronger incentives to participate.

Starting in 2010, CMS’s Five-Star Quality Rating sys-tem—a performance rating system for MA plans—will beused to create bonuses for plans that achieve 4 or 5 qual-ity stars. Increased reimbursement will be determined bya plan’s ability to effectively demonstrate performance.The PPACA defines these quality performance bonuseson an incremental scale, with plans eligible for a 1.5%bonus in 2012 and up to a 5% bonus in 2014.

These new financial incentives are bound to signifi-cantly shape health plan priorities in the future.

Implications for Quality Outcomes Measurement and Reporting

The most notable implication of healthcare reformon quality outcomes measurement and reporting is thatquality, explicitly measured, will be more tightly linkedto overall economic success through the emergence ofachievement-based bonuses, value-based purchasing,and exchange-enabled competition among health insur-ers. The demand for transparency and enhanced publicreporting create a significant challenge to institutions,which will have to be able to use data for the quantita-tive measurement of performance and to understandhow to use that information to guide efforts to improveperformance.

Pilot programs, such as accountable care organiza-tions (ACOs) and the Medicare bundled payment pro-gram, are evidence that clinical outcomes will be impli-cated in the determination of the monetary value ofhealthcare. Subsequent quality-based competitionbetween managed care plans and delivery system–basedentities (eg, ACOs) could also emerge as consumers areoffered new options and have more information toguide choice.

Health insurers will not be the only level of the sys-tem affected by these changes; providers contracted withhealth plans will be under additional pressure to measureand improve care. Measured and reported quality in theclinic setting may enhance opportunities for healthplans to value-purchase and may create opportunities forhealth plans to support their networks with programs tofurther enable improvement.

Driven by the $75 million annually appropriated bythe PPACA for quality measure development between2010 and 2014, quality metrics will advance across abroader surface. More robust measures of clinical qualityand outcomes will emerge, including measures to assess: • Health outcomes and functional status of patients• Management and coordination of care across episodes

of care• Care transitions for patients across the continuum of

providers, healthcare settings, and health plans.With CMS’s triennial assessment of gaps in quality

measures, the expectation is that there will be more spe-cific metrics for the assessment of coordination of careand metrics to accurately address safety, efficiency, andpatient experience. This broader set of metrics—manymuch more complex than those available today—willrequire more complex calculations to measure quality.At the same time, healthcare organizations—fromhealth plans to individual physicians—will find furtherchallenges, managing and improving the more complexcare processes on which these broader and more robustmetrics will shine a light.

How Health Plans Can Prepare for IncreasingDemands for Quality Data Management

Strategic investment will not only lead to positiveand significant return on investments (ROIs); it willalso enable health plans to create more value for theircovered members.

Invest in MeasurementThe HEDIS (Healthcare Effectiveness Data and

Information Set) measures developed by the National

Starting in 2010, CMS’s Five-Star QualityRating system—a performance rating systemfor MA plans—will be used to createbonuses for plans that achieve 4 or 5 qualitystars. Increased reimbursement will bedetermined by a plan’s ability to effectivelydemonstrate performance.

Committee for Quality Assurance are an importantstarting point, but a starting point nonetheless. First,health plans must assess themselves comparativelyagainst the competition. They will need to define theinternal processes that influence the accepted measuresof quality to understand why they rank the way they do.Beyond comparative assessment, health plans will needan infrastructure for compiling information about theproviders with whom they contract; quality measureswill include data related to clinical outcomes for whichthe providers are responsible. As healthcare reformdrives accountability, it will be the responsibility of thehealth plan to determine and constantly improve thevalue of the providers who comprise their network.

Invest in ImprovementHealth plans should be aware that the 2012 MA reim-

bursements will be based on the 2011 CMS Five-StarQuality Rating system. Improve ment in those areas willincrease reimbursement almost immediately. The key isknowing where you are starting, understanding whatmeasures represent the best opportunity for improvementin the Five-Star Quality Rating system, and then focus-ing resources on making the changes that will lead to thelargest improvement in the plan’s overall star rating.

Buy on Value and Partner with Providers toImprove Value

Just as purchasers are beginning to buy based onvalue, so should health plans. Provider evaluation and

assessment form the basis for contract decision-makingand allow plans to work with providers to improve per-formance and quality metrics. Pay-for-performance andother value-based purchasing strategies reinforceaccountability at all levels of the system. Risk-sharingbetween health plans and providers will be combinedwith information-sharing and investment in other pro-grams to support provider performance improvement forthe benefit of the purchaser, provider, and payer—and,of course, the patient.

ConclusionWith pressure to create a more value-driven, trans-

parent, and accountable marketplace, and with appro-priated funding for quality measure development, thePPACA is going to drive significant increases in theextent and complexity of reporting requirements at alllevels of the healthcare system. The PPACA’s commit-ment to patient protection, expansion of insurance cov-erage, and affordability demands investment on the partof CMS, health plans, and providers. With the rise ofvalue-based purchasing, health plans will have to bemore transparent regarding their performance and willhave to demonstrate that they are delivering andimproving value across their entire network. The poten-tial ROI is significant for quality measurement andreporting, and for systems that enable documentableimprovements. The PPACA has established bonusincentives in the language of reform to begin rewardinghealth plans and providers almost immediately forachievement, and appears to guarantee that investmenttoday will lead to economic success and better qualityhealthcare for patients in the very near future. ■

References1. Patient Protection and Affordable Care Act, H.R. 3590. http://democrats.senate.gov/reform/patient-protection-affordable-care-act-as-passed.pdf. Accessed July 19, 2010.2. Health Care and Education Reconciliation Act of 2010, H.R. 4872. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=111_cong_bills&docid=f:h4872enr.txt.pdf. Accessed July 19, 2010.

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Victoza® (liraglutide [rDNA origin] injection)Rx onlyBRIEF SUMMARY. Please consult package insert for full prescribing information.

WARNING: RISK OF THYROID C-CELL TUMORS: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Based on the findings in rodents, monitoring with serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors [see Contraindications and Warnings and Precautions].

INDICATIONS AND USAGE: Victoza® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Important Limitations of Use: Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, pre-scribe Victoza® only to patients for whom the potential benefits are considered to outweigh the potential risk. Victoza® is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. In clinical trials of Victoza®, there were more cases of pancreatitis with Victoza® than with comparators. Victoza® has not been studied sufficiently in patients with a history of pancreatitis to determine whether these patients are at increased risk for pancreatitis while using Victoza®. Use with caution in patients with a history of pancreatitis. Victoza® is not a substitute for insulin. Victoza® should not be used in patients with type 1 dia-betes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. The concurrent use of Victoza® and insulin has not been studied.CONTRAINDICATIONS: Victoza® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syn-drome type 2 (MEN 2).WARNINGS AND PRECAUTIONS: Risk of Thyroid C-cell Tumors: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice. Malignant thyroid C-cell carcinomas were detected in rats and mice. A statistically significant increase in cancer was observed in rats receiving liraglutide at 8-times clinical exposure compared to controls. It is unknown whether Victoza® will cause thyroid C-cell tumors, including medullary thyroid car-cinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors could not be determined by clinical or nonclinical studies [see Boxed Warning, Contra-indications]. In the clinical trials, there have been 4 reported cases of thyroid C-cell hyperplasia among Victoza®-treated patients and 1 case in a comparator-treated patient (1.3 vs. 0.6 cases per 1000 patient-years). One additional case of thyroid C-cell hyperplasia in a Victoza®-treated patient and 1 case of MTC in a comparator-treated patient have subsequently been reported. This comparator-treated patient with MTC had pre-treatment serum calcitonin concentrations >1000 ng/L suggesting pre-existing disease. All of these cases were diagnosed after thyroidectomy, which was prompted by abnormal results on routine, protocol-specified measurements of serum calcitonin. Four of the five liraglutide-treated patients had elevated calcitonin concentrations at baseline and throughout the trial. One liraglutide and one non-liraglutide-treated patient devel-oped elevated calcitonin concentrations while on treatment. Calcitonin, a biological marker of MTC, was measured throughout the clinical development program. The serum calcitonin assay used in the Victoza® clinical trials had a lower limit of quantification (LLOQ) of 0.7 ng/L and the upper limit of the reference range was 5.0 ng/L for women and 8.4 ng/L for men. At Weeks 26 and 52 in the clinical trials, adjusted mean serum calcitonin concentrations were higher in Victoza®-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator. At these timepoints, the adjusted mean serum calcitonin values (~ 1.0 ng/L) were just above the LLOQ with between-group differences in adjusted mean serum calcitonin values of approximately 0.1 ng/L or less. Among patients with pre-treatment serum calcitonin below the upper limit of the reference range, shifts to above the upper limit of the reference range which persisted in subsequent measurements occurred most frequently among patients treated with Victoza® 1.8 mg/day. In trials with on-treatment serum calcitonin measurements out to 5-6 months, 1.9% of patients treated with Victoza® 1.8 mg/day developed new and persistent calci-tonin elevations above the upper limit of the reference range compared to 0.8-1.1% of patients treated with control medication or the 0.6 and 1.2 mg doses of Victoza®. In trials with on-treat-ment serum calcitonin measurements out to 12 months, 1.3% of patients treated with Victoza® 1.8 mg/day had new and persistent elevations of calcitonin from below or within the reference range to above the upper limit of the reference range, compared to 0.6%, 0% and 1.0% of patients treated with Victoza® 1.2 mg, placebo and active control, respectively. Otherwise, Victoza® did not produce consistent dose-dependent or time-dependent increases in serum calcitonin. Patients with MTC usually have calcitonin values >50 ng/L. In Victoza® clinical trials, among patients with pre-treatment serum calcitonin <50 ng/L, one Victoza®-treated patient and no comparator-treated patients developed serum calcitonin >50 ng/L. The Victoza®-treated patient who developed serum calcitonin >50 ng/L had an elevated pre-treatment serum calcitonin of 10.7 ng/L that increased to 30.7 ng/L at Week 12 and 53.5 ng/L at the end of the 6-month trial. Follow-up serum calci-tonin was 22.3 ng/L more than 2.5 years after the last dose of Victoza®. The largest increase in serum calcitonin in a comparator-treated patient was seen with glimepiride in a patient whose serum calcitonin increased from 19.3 ng/L at baseline to 44.8 ng/L at Week 65 and 38.1 ng/L at Week 104. Among patients who began with serum calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of Victoza®-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients, with an incidence of 1.1% among patients treated with 1.8 mg/day of Victoza®. The clinical significance of these findings is unknown. Counsel patients regarding the risk for MTC and the symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness). It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate the potential risk of MTC, and such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinolo-gist for further evaluation. Although routine monitoring of serum calcitonin is of uncertain value in patients treated with Victoza®, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation. Pancreatitis: In clinical

trials of Victoza®, there were 7 cases of pancreatitis among Victoza®-treated patients and 1 case among comparator-treated patients (2.2 vs. 0.6 cases per 1000 patient-years). Five cases with Victoza® were reported as acute pancreatitis and two cases with Victoza® were reported as chronic pancreatitis. In one case in a Victoza®-treated patient, pancreatitis, with necrosis, was observed and led to death; however clinical causality could not be established. One additional case of pan-creatitis has subsequently been reported in a Victoza®-treated patient. Some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse. There are no con-clusive data establishing a risk of pancreatitis with Victoza® treatment. After initiation of Victoza®, and after dose increases, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Victoza® and other potentially suspect medications should be discontinued promptly, confirmatory tests should be performed and appropriate management should be initiated. If pancreatitis is confirmed, Victoza® should not be restarted. Use with caution in patients with a history of pancreatitis. Use with Medications Known to Cause Hypoglycemia: Patients receiving Victoza® in combination with an insulin secretagogue (e.g., sulfonylurea) may have an increased risk of hypoglycemia. In the clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treat-ment occurred in 7 Victoza®-treated patients and in no comparator-treated patients. Six of these 7 patients treated with Victoza® were also taking a sulfonylurea. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea or other insulin secretagogues [see Adverse Reactions]. Macrovascular Outcomes: There have been no clinical studies establishing con-clusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug.ADVERSE REACTIONS: Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Victoza® was evaluated in a 52-week monotherapy trial and in four 26-week, add-on combination therapy trials. In the monotherapy trial, patients were treated with Victoza® 1.2 mg daily, Victoza® 1.8 mg daily, or glimepiride 8 mg daily. In the add-on to metformin trial, patients were treated with Victoza® 0.6 mg, Victoza® 1.2 mg, Victoza® 1.8 mg, placebo, or glimepiride 4 mg. In the add-on to glimepiride trial, patients were treated with Victoza® 0.6 mg, Victoza® 1.2 mg, Victoza® 1.8 mg, placebo, or rosiglitazone 4 mg. In the add-on to metformin + glimepiride trial, patients were treated with Victoza® 1.8 mg, placebo, or insulin glargine. In the add-on to metformin + rosiglitazone trial, patients were treated with Victoza® 1.2 mg, Victoza® 1.8 mg or placebo. Withdrawals: The incidence of withdrawal due to adverse events was 7.8% for Victoza®-treated patients and 3.4% for comparator-treated patients in the five controlled trials of 26 weeks duration or longer. This difference was driven by withdrawals due to gastrointestinal adverse reactions, which occurred in 5.0% of Victoza®-treated patients and 0.5% of comparator-treated patients. The most common adverse reactions leading to withdrawal for Victoza®-treated patients were nausea (2.8% versus 0% for comparator) and vomiting (1.5% versus 0.1% for comparator). Withdrawal due to gastrointestinal adverse events mainly occurred during the first 2-3 months of the trials. Tables 1 and 2 summarize the adverse events reported in ≥5% of Victoza®-treated patients in the five controlled trials of 26 weeks duration or longer.Table 1: Adverse events reported in ≥ 5% of Victoza®-treated patients or ≥5% of glimepiride-treated patients: 52-week monotherapy trial

All Victoza® N = 497 Glimepiride N = 248Adverse Event Term (%) (%)Nausea 28.4 8.5Diarrhea 17.1 8.9Vomiting 10.9 3.6Constipation 9.9 4.8Upper Respiratory Tract Infection 9.5 5.6Headache 9.1 9.3Influenza 7.4 3.6Urinary Tract Infection 6.0 4.0Dizziness 5.8 5.2Sinusitis 5.6 6.0Nasopharyngitis 5.2 5.2Back Pain 5.0 4.4Hypertension 3.0 6.0

Table 2: Adverse events reported in ≥ 5% of Victoza®-treated patients and occur-ring more frequently with Victoza® compared to placebo: 26-week combination therapy trials

Add-on to Metformin TrialAll Victoza® +

Metformin N = 724

Placebo + Metformin N = 121

Glimepiride + Metformin N = 242

Adverse Event Term (%) (%) (%)Nausea 15.2 4.1 3.3Diarrhea 10.9 4.1 3.7Headache 9.0 6.6 9.5Vomiting 6.5 0.8 0.4

Add-on to Glimepiride TrialAll Victoza® +

Glimepiride N = 695Placebo + Glimepiride

N = 114Rosiglitazone +

Glimepiride N = 231Adverse Event Term (%) (%) (%)Nausea 7.5 1.8 2.6Diarrhea 7.2 1.8 2.2Constipation 5.3 0.9 1.7Dyspepsia 5.2 0.9 2.6

Add-on to Metformin + GlimepirideVictoza® 1.8 + Metformin + Glimepiride

N =230

Placebo + Metformin + Glimepiride

N =114

Glargine + Metformin + Glimepiride

N =232

Adverse Event Term (%) (%) (%)Nausea 13.9 3.5 1.3Diarrhea 10.0 5.3 1.3Headache 9.6 7.9 5.6Dyspepsia 6.5 0.9 1.7Vomiting 6.5 3.5 0.4

Add-on to Metformin + RosiglitazoneAll Victoza® + Metformin +

Rosiglitazone N = 355Placebo + Metformin

+ Rosiglitazone N = 175Adverse Event Term (%) (%)Nausea 34.6 8.6Diarrhea 14.1 6.3Vomiting 12.4 2.9Decreased Appetite 9.3 1.1Anorexia 9.0 0.0Headache 8.2 4.6Constipation 5.1 1.1Fatigue 5.1 1.7

Gastrointestinal adverse events: In the five clinical trials of 26 weeks duration or longer, gastroin-testinal adverse events were reported in 41% of Victoza®-treated patients and were dose-related. Gastrointestinal adverse events occurred in 17% of comparator-treated patients. Events that occurred more commonly among Victoza®-treated patients included nausea, vomiting, diar-rhea, dyspepsia and constipation. In clinical trials of 26 weeks duration or longer, the percentage of patients who reported nausea declined over time. Approximately 13% of Victoza®-treated patients and 2% of comparator-treated patients reported nausea during the first 2 weeks of treat-ment. Immunogenicity: Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals, patients treated with Victoza® may develop anti-liraglutide antibodies. Approximately 50-70% of Victoza®-treated patients in the five clinical trials of 26 weeks dura-tion or longer were tested for the presence of anti-liraglutide antibodies at the end of treatment. Low titers (concentrations not requiring dilution of serum) of anti-liraglutide antibodies were detected in 8.6% of these Victoza®-treated patients. Sampling was not performed uniformly across all patients in the clinical trials, and this may have resulted in an underestimate of the actual percentage of patients who developed antibodies. Cross-reacting anti-liraglutide antibod-ies to native glucagon-like peptide-1 (GLP-1) occurred in 6.9% of the Victoza®-treated patients in the 52-week monotherapy trial and in 4.8% of the Victoza®-treated patients in the 26-week add-on combination therapy trials. These cross-reacting antibodies were not tested for neutral-izing effect against native GLP-1, and thus the potential for clinically significant neutralization of native GLP-1 was not assessed. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 2.3% of the Victoza®-treated patients in the 52-week monotherapy trial and in 1.0% of the Victoza®-treated patients in the 26-week add-on combination therapy trials. Among Victoza®-treated patients who developed anti-liraglutide antibodies, the most common category of adverse events was that of infections, which occurred among 40% of these patients compared to 36%, 34% and 35% of antibody-negative Victoza®-treated, placebo-treated and active-control-treated patients, respectively. The specific infections which occurred with greater frequency among Victoza®-treated antibody-positive patients were primarily nonserious upper respiratory tract infections, which occurred among 11% of Victoza®-treated antibody-positive patients; and among 7%, 7% and 5% of antibody-negative Victoza®-treated, placebo-treated and active-control-treated patients, respectively. Among Victoza®-treated antibody-negative patients, the most common category of adverse events was that of gastrointestinal events, which occurred in 43%, 18% and 19% of antibody-negative Victoza®-treated, placebo-treated and active-con-trol-treated patients, respectively. Antibody formation was not associated with reduced efficacy of Victoza® when comparing mean HbA1c of all antibody-positive and all antibody-negative patients. However, the 3 patients with the highest titers of anti-liraglutide antibodies had no reduction in HbA1c with Victoza® treatment. In clinical trials of Victoza®, events from a composite of adverse events potentially related to immunogenicity (e.g. urticaria, angioedema) occurred among 0.8% of Victoza®-treated patients and among 0.4% of comparator-treated patients. Urticaria accounted for approximately one-half of the events in this composite for Victoza®-treated patients. Patients who developed anti-liraglutide antibodies were not more likely to develop events from the immu-nogenicity events composite than were patients who did not develop anti-liraglutide antibodies. Injection site reactions: Injection site reactions (e.g., injection site rash, erythema) were reported in approximately 2% of Victoza®-treated patients in the five clinical trials of at least 26 weeks duration. Less than 0.2% of Victoza®-treated patients discontinued due to injection site reactions. Papillary thyroid carcinoma: In clinical trials of Victoza®, there were 6 reported cases of papillary thyroid carcinoma in patients treated with Victoza® and 1 case in a comparator-treated patient (1.9 vs. 0.6 cases per 1000 patient-years). Most of these papillary thyroid carcinomas were <1 cm in greatest diameter and were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings on protocol-specified screening with serum calcitonin or thyroid ultra-sound. Hypoglycemia: In the clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treatment occurred in 7 Victoza®-treated patients (2.6 cases per 1000 patient-years) and in no comparator-treated patients. Six of these 7 patients treated

with Victoza® were also taking a sulfonylurea. One other patient was taking Victoza® in combina-tion with metformin but had another likely explanation for the hypoglycemia (this event occurred during hospitalization and after insulin infusion) (Table 3). Two additional cases of hypoglyce-mia requiring the assistance of another person for treatment have subsequently been reported in patients who were not taking a concomitant sulfonylurea. Both patients were receiving Victoza®, one as monotherapy and the other in combination with metformin. Both patients had another likely explanation for the hypoglycemia (one received insulin during a frequently-sampled intra-venous glucose tolerance test, and the other had intracranial hemorrhage and uncertain food intake).Table 3: Incidence (%) and Rate (episodes/patient year) of Hypoglycemia in the 52-Week Monotherapy Trial and in the 26-Week Combination Therapy Trials

Victoza® Treatment

Active Comparator

Placebo Comparator

Monotherapy Victoza®

(N = 497)Glimepiride

(N = 248)None

Patient not able to self−treat 0 0 —Patient able to self−treat 9.7 (0.24) 25.0 (1.66) —Not classified 1.2 (0.03) 2.4 (0.04) —Add-on to Metformin

Victoza® + Metformin (N = 724)

Glimepiride + Metformin (N = 242)

Placebo + Metformin (N = 121)

Patient not able to self−treat 0.1 (0.001) 0 0Patient able to self−treat 3.6 (0.05) 22.3 (0.87) 2.5 (0.06)Add-on to Glimepiride Victoza® +

Glimepiride (N = 695)

Rosiglitazone + Glimepiride

(N = 231)

Placebo + Glimepiride

(N = 114)Patient not able to self−treat 0.1 (0.003) 0 0Patient able to self−treat 7.5 (0.38) 4.3 (0.12) 2.6 (0.17)Not classified 0.9 (0.05) 0.9 (0.02) 0Add-on to Metformin + Rosiglitazone

Victoza® + Metformin +

Rosiglitazone (N = 355)

None

Placebo + Metformin +

Rosiglitazone (N = 175)

Patient not able to self−treat 0 — 0Patient able to self−treat 7.9 (0.49) — 4.6 (0.15)Not classified 0.6 (0.01) — 1.1 (0.03)Add-on to Metformin + Glimepiride

Victoza® + Metformin + Glimepiride

(N = 230)

Insulin glargine + Metformin + Glimepiride

(N = 232)

Placebo + Metformin + Glimepiride

(N = 114)Patient not able to self−treat 2.2 (0.06) 0 0Patient able to self−treat 27.4 (1.16) 28.9 (1.29) 16.7 (0.95)Not classified 0 1.7 (0.04) 0

In a pooled analysis of clinical trials, the incidence rate (per 1,000 patient-years) for malig-nant neoplasms (based on investigator-reported events, medical history, pathology reports, and surgical reports from both blinded and open-label study periods) was 10.9 for Victoza®, 6.3 for placebo, and 7.2 for active comparator. After excluding papillary thyroid carcinoma events [see Adverse Reactions], no particular cancer cell type predominated. Seven malignant neoplasm events were reported beyond 1 year of exposure to study medication, six events among Victoza®-treated patients (4 colon, 1 prostate and 1 nasopharyngeal), no events with placebo and one event with active comparator (colon). Causality has not been established. Laboratory Tests: In the five clinical trials of at least 26 weeks duration, mildly elevated serum bilirubin concentra-tions (elevations to no more than twice the upper limit of the reference range) occurred in 4.0% of Victoza®-treated patients, 2.1% of placebo-treated patients and 3.5% of active-comparator-treated patients. This finding was not accompanied by abnormalities in other liver tests. The significance of this isolated finding is unknown.OVERDOSAGE: In a clinical trial, one patient with type 2 diabetes experienced a single overdose of Victoza® 17.4 mg subcutaneous (10 times the maximum recommended dose). Effects of the overdose included severe nausea and vomiting requiring hospitalization. No hypoglycemia was reported. The patient recovered without complications. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.More detailed information is available on request. For information about Victoza® contact: Novo Nordisk Inc., 100 College Road West, Princeton, New Jersey 08540, 1−877-484-2869Date of Issue: January 2010 Version: 1Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, DenmarkVictoza® is a registered trademark of Novo Nordisk A/S. Victoza® is covered by US Patent Nos. 6,268,343; 6,458,924; and 7,235,627 and other patents pending. Victoza® Pen is covered by US Patent Nos. 6,004,297; 6,235,004; 6,582,404 and other patents pending.© 2010 Novo Nordisk A/S 140586-R1 4/2010

© 2010 Novo Nordisk A/S 141395 May 2010

Victoza® is a registered trademark of Novo Nordisk A/S.

Visit VictozaPro.com to learn more.

Targets beta cells

Provides powerful andsustained reductions in A1C*

Can provide the additional benefi t of weight loss

Safety and tolerability were studied in clinical trials that included nearly 4000 patients

Victoza® is not indicated for the management of obesity, and weight change was a secondary end point in clinical trials.

Once-daily Victoza®:

Indications and usageVictoza® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Because of the uncertain relevance of the rodent thyroid C-cell tumor fi ndings to humans, prescribe Victoza® only to patients for whom the potential benefi ts are considered to outweigh the potential risk. Victoza® is not recommended as fi rst-line therapy for patients who have inadequate glycemic control on diet and exercise. In clinical trials of Victoza®, there were more cases of pancreatitis with Victoza® than with comparators. Victoza® has not been studied suffi ciently in patients with a history of pancreatitis to determine whether these patients are at increased risk for pancreatitis while using Victoza®. Use with caution in patients with a history of pancreatitis. Victoza® is not a substitute for insulin. Victoza® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. The concurrent use of Victoza® and insulin has not been studied.

Important safety informationLiraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Based on the fi ndings in rodents, monitoring with serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

If pancreatitis is suspected, Victoza® should be discontinued. Victoza® should not be re-initiated if pancreatitis is confi rmed. When Victoza® is used with an insulin secretagogue (e.g. a sulfonylurea) serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia. There have been no studies establishing conclusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug. The most common adverse reactions, reported in ≥5% of patients treated with Victoza® and more commonly than in patients treated with placebo, are headache, nausea, diarrhea, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials. Victoza® has not been studied in type 2 diabetes patients below 18 years of age and is not recommended for use in pediatric patients. Victoza® should be used with caution in patients with renal impairment and in patients with hepatic impairment.

Please see brief summary of Prescribing Information on adjacent page.

* Victoza® was evaluated in a 52-week monotherapy trial and in four 26-week, add-on combination trials.

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