october 2011, vol 1, no 3

Since the turn of the century, 2 thingshave become clear in healthcare.First, change, especially in group

practice, is happening at a rate that we havenever seen before. Second, we are in themidst of an information technology (IT)evolution. To keep up with these ongoingchanges, it has become imperative thatgroup practices incorporate technologywhile re maining nimble with their capital,both cash and equipment. The questionbecomes how to fund projects in a way that

meets both short- and long-term goals.Many practices are beginning

to qualify for the Health In-for mation Technology forEconomic and Clin icalHealth (HITECH) Actand receive funding.Are you? What are

From the publishers of

©2011 Engage Healthcare Communications, LLC

www.OncPracticeManagement.com

ONCOLOGY PRACTICEMANAGEMENT

™

OCTOBER 2011 VOLUME 1• NUMBER 3

PROCESS IMPROVEMENTS TO ENHANCE PATIENT CARE™

Finding Money for TechnologyHow to Fund EHR, IT, and Medical Equipment ProjectsBy Colleen O’Donnell

All eyes are on Washington thisfall, as deliberations begin on rec-ommendations from the congres -

s ional joint “super” committee. Congressand the president failed to achieve resolu-tion regarding the debt ceiling this sum-mer, and now this newly created 12-per-son committee will recommend at least$1.5 trillion in additional deficit reduc-tion measures through 2021, by No -vember 23, 2011. If a majority of the com-

mittee members endorse a proposal, thatproposal is guaranteed to go to a floor votein both the House and Senate byDecember 23 without amendment orSenate filibuster. Because these proposalscould be passed with any combination ofRepublican and Democratic votes thatadd up to a majority, despite pundit warn-ings that a stalemate could occur, congres -sional leaders could choose to move for-

November 2011: The Import of Thanksgiving Pales in Comparisonwith “Super” Committee OutcomeBy Dawn Holcombe, MBA, FACMPE, ACHE

Continued on page 14

Federal Auditsof E/M ServicesA Top 10 Survival GuideBy Michael Calahan, PA, MBA

It is no secret federal auditors promiseto assail providers through a variety ofstrong recoupment initiatives. Eval -

uation and management (E/M) servicesare primed for this offensive. No longerable to report consultation codes to theCenters for Medicare & MedicaidServices (CMS), oncologists must im -prove E/M reporting strategies for routinecognitive services, such as office visits andinpatient hospital visits. This increasesthe impact of E/M services on practicerevenue and elevates these mundaneservices to “juicy” targets for federal pro-grams such as the Comprehensive ErrorRate Testing and Recovery Audit Con -tractor initiatives.What should oncologists do in the face

of this scrutiny? Start by learning whichContinued on page 6

PATIENT AND PROVIDER ACCESS

Brought to you by the Association of

Community Cancer Centers

The SGR, Prompt-Pay Discounts,

and Cuts in Medicare

Reimbursement.....28

NEW C

OLUM

N...Continued on page 5

VELCADE and Millennium are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139

Copyright © 2010, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA V-10-0196 11/10

In This Issue

3October 2011 I www.OncPracticeManagement.com I

PUBLISHING STAFF

PublisherNicholas [email protected]

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Editorial DirectorDalia Buffery

EditorDawn [email protected]

Production ManagerMarie R. S. Borelli

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MISSION STATEMENT

Oncology healthcare requires providers tofocus attention on financial concerns andstrategic decisions that affect the bottomline. To continue to provide the high-quality care cancer patients deserve,providers must master the ever-changingbusiness of oncology. Oncology PracticeManagement will offer process solutionsfor members of the cancer care team—medical, surgical, and radiation oncolo-gists, as well as executives, administrators,and coders/billers—to assist them in reim-bursement, staffing, electronic healthrecords, REMS, and compliance withstate and federal regulations.

VOPM3

Oncology Practice Management™ is published 4 times a year by Engage Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205A, MonroeTownship, NJ 08831. Copyright © 2011 by Engage Healthcare Communications, LLC. All rights reserved. Oncology Practice Management™ is a registeredtrademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now orhereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permissionfrom the publisher. Printed in the United States of America. ISSN: applied for.

The ideas and opinions expressed in Oncology Practice Management™ do not necessarily reflect those of the editorial board, the editors, or the publisher.Publication of an advertisement or other product mentioned in Oncology Practice Management™ should not be construed as an endorsement of the product orthe manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the editorsnor the publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentionedin this publication.

Postmaster: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Oncology PracticeManagement™, 241 Forsgate Drive, Suite 205A, Monroe Township, NJ 08831. Fax: 732-992-1881. Yearly subscription rates: 1 year: $99.00 USD; 2 years:$149.00 USD; 3 years: $199.00 USD.

FEATURESMODELS OF CAREExploring Ways to Translate the Medical Home Modelinto Oncology................................................................4

REIMBURSEMENTImproving Previsit Processes to Maximize Postvisit Collections ......................................................12By Sarah W. Rock, MSOD; Debra Gregory

Getting from ICD-9 to ICD-10......................................24By Richard Vander Burg, RN, BSN

DATA MANAGEMENTImproving Oncology Service Line Management ......21By Brian Cassel, PhD; Lisa Shickle, MS

CASE STUDYDana-Farber/New Hampshire Oncology-Hematology ..............................................22

DEPARTMENTSPhysician Wealth Managementwith Lawrence B. Keller, CLU, ChFC, CFP®

Disability Insurance Planning ..........................................27

Patient and Provider Accessbrought to you by the Association of Community Cancer Centers

Hurdles to Appropriate Reimbursement ......................28By Sydney Abbott, JD

O

4 I ONCOLOGY PRACTICE MANAGEMENT I October 2011 I Special Edition

Models of Care

Ronald Barkley, MS, JDPresidentCancer Center BusinessDevelopment GroupBedford, NH

Peggy Barton, RNPractice ManagerToledo ClinicToledo, OH

Risë Marie ClelandPresidentOplinc, IncLawton, OK

Bruce A. Cutter, MDPresidentCutter HealthCareConsultingSpokane, WA

Craig Deligdish, MDMedical DirectorFlorida ComprehensiveCancer NetworkMelbourne, FL

Patrick A.Grusenmeyer, ScD,FACHEPresidentChristiana Care HealthInitiativesNewark, DE

Teri U. Guidi, MBA,FAAMAPresident & CEOOncology ManagementConsulting GroupPipersville, PA

Ruth Lander, RN,FACMPEPractice AdministratorColumbus Oncology & Hematology Associates, IncColumbus, OH

Bonnie J. Miller, RN,BSN, OCN, FAAMAAdministrative DirectorWomen’s Cancer CenterFox Chase CancerCenterPhiladelphia, PA

Cindy C. Parman, CPC,CPC-H, RCCCSI Coding Strategies IncPowder Springs, GA

Jeffrey A. Scott, MDSenior Vice PresidentCardinal HealthDublin, OH

Carla C. Wood, CPC, MS PresidentAltos Solutions, IncLos Altos, CA

Dawn Holcombe, MBA, FACMPE, ACHEPresident

DGH ConsultingSouth Windsor, Connecticut

Editorial Advisory Board

Editor-in-Chief

With today’s focus on the National Committee for QualityAssurance’s Patient-Centered Medical Home (PCMH) asa viable option for healthcare delivery and cost reform, a

group of researchers explored how best to translate the concept fromthe primary care model to oncology care. What they found is that anOncology Medical Home (OMH) model may revolutionize cancercare and reimbursement (J Clin Oncol. 2011;29[suppl]:Abstract e16641).With their background in identifying breast cancer care coordina-

tion challenges, Trosman and colleagues interviewed patients,providers, and payers regarding which characteristics would be mostdesirable in an OMH for breast cancer care. Four characteristicsemerged as important features to include when developing a modelfor oncology:1. Each OMH should have a lead physician, in this case, an oncol-ogist or breast surgeon, for the entire episode of cancer care.Survivorship care should be transferred back to the primary carephysician, with a corresponding PCMH.

2. A lead physician should facilitate care across the multidiscipli-nary cancer care team, including surgical, medical, and radiationoncology; radiology; supportive care; and primary care.

3. Each patient’s care and care team should be managed as a proj-ect, with key events sequenced and timed in a plan, by a “careproject manager.”

4.A unique reimbursement model should be implemented that in -centivizes team participation and coordination. Most (89%) patients reported a strong desire for a lead physician,

but only one third (33%) noted an interest in the reimbursementreform potential. Providers expressed high interest in all 4 charac-teristics (73%-85%). Most (88%) payers recognized the potential fora new reimbursement model; however, they disclosed their uncer-tainty with the specifics of the remaining 3 characteristics.OMH pilots, such as the first recognized OMH Consultants in

Medical Oncology and Hematology, are needed to inform specificimplementation strategies. As the first OMH, the process took approx-imately 7 years to implement. However, practice lead physician John D.Sprandio, MD, told Oncology Practice Management that, with that expe-rience behind them, his group has helped streamline the process for oth-ers, which he foresees as taking only 1 year for other groups. l

Exploring Ways toTranslate the MedicalHome Model intoOncologyPatients, Providers, and Payers Provide Some AnswersBy Dawn Lagrosa

Staffing

the best funding options to coverupfront costs? Does your existingtechnology need to be upgraded? Ifyou have answered yes to any of thesequestions, this article provides sugges-tions on how to get started exploringfunding options (Sidebar).Reaching out to other practices in

your area and specialty to under-stand what they have done and aredoing can be very helpful. What aretheir experiences and successes? Askabout implementation time and theuseful life of the equipment. Try tounderstand how your peers selected asystem and paid for it. You can gath-er valuable information by joiningLinkedIn groups devoted to grouppractices and electronic healthrecord (EHR) implementation,among other topics.When diving into a project like

implementing an EHR system, thecosts can be overwhelming. Consult -ing, software, hardware, implementa-tion, and training are all part of theinvestment. There are many fundingoptions available, and it is importantto understand the benefits of eachand how they can work together. It isimportant to think about fundingearly, and try to consider what willhappen as you navigate your waythrough the technology path.

Funding Options

1Bank Financing. Your local bankis most likely familiar with yourpractice and can provide a traditionalloan. This is typically a very easy wayto look at financing, and one that youmay have already used. A drawback isthat some banks require compensat-ing balances, large down payments,and/or limit the amount that might beavailable on your line of credit.

2Grants. There are many optionsfor grants, including state andlocal government grants, payers, orlocal hospitals. Many can be found

by doing research on Foundationcenter.org. Grants can be time-con-suming, and may require you to hiresomeone to complete all necessaryforms and paperwork. Therefore, theprocess could potentially limit yourvendor choices. This is an area inwhich working with other practicescan be helpful. Several organizationscan team up to obtain grant fundingfor their projects. There is value insharing the responsibilities.

3HITECH Act. This Act providesup to $64,000 per doctor over 5years. Many practices have been ableto prove meaningful use and havealready collected their first year pay-ment. This is an exciting opportunityfor many practices and worth pursu-ing. Ad ditional information is avail-

able through organi-zations such as theMedical Group Man -agement As sociation,American Me d icalGroup As sociation,Health care Infor -mation and Man age - ment Systems So ci -ety, Am erican HealthInfor mation Man -agement Asso ciation, as well as theOffice for the National Co ordinatorfor Health Information Technology.

4Leasing. Leasing options can pro-vide 100% financing for consult-ing, software, hardware, and imple-mentation. Leasing is an alternativeto your banking relationship thatallows you to conserve your cash andworking capital. Customized struc-tures like deferred payments and skippayments often are available. It isimportant to consider the flexibility ofa leasing arrangement, specifically forthe hardware portion of your technol-ogy. Having the ability to upgrade andchange hardware when it becomesobsolete, or easily add additional tech-nology when needed, is one of themany benefits of a leasing program.Furthermore, the ability to avoidexpensive out-of-warranty mainte-nance costs is vital. It is important tounderstand leasing terms and condi-tions and ask questions about how theprogram works.

You may decide that using a com-bination of the available optionsprovides you with the best solutionand gives you the most flexibility. l

Colleen O’Donnell is vice president ofthe Physician Group Practice division atInsight Financial Services, LLC, a les-sor specializing in leasing solutions fortechnology and medical equipment—www.ifsleasing.com.

Finding Money…Continued from the cover

Steps for EvaluatingFunding Options

• Start early, and consider alloptions.

• Ask your peers for help, asthey have experience andunderstand what you aregoing through and can offer valuable assistance.

• Ask for references.

October 2011 I www.OncPracticeManagement.com I 5

It is important to thinkabout funding early,and try to considerwhat will happen as you navigate your way through thetechnology path.

Finance

Reimbursement

audit findings yield valuable oppor-tunities for clinical documentationimprovement as well as stronger E/Mcoding. Here are my “Top 10” auditfindings together with survival tips.

1No response to additional doc -umentation requests (ADRs).Most often, physician services aredowncoded or denied by auditorsbecause of no response to ADRs.

Survival tipsEvery provider office should log thereceipt, track the processing, andconfirm the fulfillment of these med-ical record (MR) requests to avoidunnecessary repayments.

2Unsigned, illegible, or indeter-minate MRs. Unsigned MRs,illegible provider signatures, and/orthe inability to differentiate ancil-lary staff notes from treating providernotes account for a preponderance ofaudit findings.

Survival tipsChange Request 6698 (March 1,2010) requires legible signatures tocertify services; illegible signaturessubmitted without signature logs/attestations are adjudged as “indeter-minate,” and e quated to unsigneddocumentation. Mixing ancillarystaff notes in the body of the clinicalnote without signature clarificationis tantamount to uncertified records.Providers and ancillary staff musteach sign/date clinical note contri-butions, thereby clarifying author-ship. Excluding certain hospicenotes/orders stamped signatures arenot valid.

3Review of systems (ROS) miss-ing or poorly documented. Re -cording the history portion of E/Mservices is the weakest area ofprovider documentation. Within thehistory, the most overlooked element

is the ROS that, when poorly docu-mented, severely limits the level ofE/M service legitimately billed.

Survival tipsHave ancillary staff obtain the ROS;providers should verify and authenti-cate these data. If obtaining on aseparate questionnaire, “bridge”these data to the actual visit notes.

4Poor documentation for E/Mcode Current Procedural Ter -minology (CPT) 99211. CPT99211 is designed for minimal prob-lems requiring “quick” visits carriedout by ancillary staff, supervised bythe treating provider. Adequatelysubstantiated in the MR documenta-tion, CPT 99211 can be reported formyriad services.

Survival tipsCPT 99211 represents a true E/Mservice; therefore, the MR documen-tation must convey both evaluationand management facets. Because aCPT 99211 service is typically fur-nished by ancillary staff under theprovider’s direct supervision, CPT99211 is reported as “incident to”and the provider must certify thechart notes.

5Misapplication of modifier 25.Modifier 25 is reported with anE/M service when significant, sepa-

rately identifiable services are ren-dered by the same physician on thesame day of a procedure or other serv-ice. Common problem areas include:(a) modifier 25 incorrectly reportedwith a non-E/M service, for example,CPT 93000 to 93025 for EKG; and(b) modifier 25 reported with an E/Mcode when the patient presentedsolely for a prescheduled minor proce-dure, for example, joint injection.

Survival tipsModifier 25 is designed to allow cer-tain E/M services to bypass systemedits. Without proper usage, theMedicare carrier may impose claims-delaying prepayment screens anddocumentation reviews.

6Time used as the key compo-nent for the E/M service. Pro -

viders can report noontime-basedE/M services using time as the keycomponent (instead of the 3 keycomponents of history, physicalexamination [PE], and medical deci-sion making [MDM]) when counsel-ing and/or coordination of care con-stitute 50% or greater of the totalface-to-face time; however, auditorsfind no times documented in theMRs.

Survival tipsDocument 2 strata of times whenusing this option: (1) total face-to-face time for the entire encounter;and (2) total time spent in counsel-ing and/or coordination of care.Content of the counseling/coordina-tion of care must be documented.

7“4x4 rule”: expanded problemfocused (EPF) or detailed exam-

ination? Confusion surrounds thesespecific examination levels becausethe official documentation guide-lines (DGs) are ambiguous for bothlevels by stating they must contain“2 to 7 elements.” This causes pro -

Federal Audits…Continued from the cover

Mixing ancillary staffnotes in the body ofthe clinical notewithout signatureclarification istantamount touncertified records.

I ONCOLOGY PRACTICE MANAGEMENT I October 2011 I Special Edition6

Reimbursement

Reimbursement

vider misinterpretation and resultsin audit findings of “insufficient doc-umentation for detailed exams.”

Survival tipsKnow the “4x4 rule,” which compris-es 4 PE elements examined in 4 bodyareas/organ systems (fully document-ed). For providers, this rule is a quickmethod to avoid misinterpretation;for auditors, it allows efficient assess-ment and exact PE-level differentia-tion. Providers should check withtheir Medi care carrier to ascertain theDGs for EPF and detailed PEs.

8Misreporting of CPT 99499(unlisted E/M service). CMSaddresses CPT 99499 in the Medi -care Claims Processing Manual 100-04 Chapter 12§30, stating “theCarrier has the discretion to value theservice” coded with CPT 99499. Thecarrier is in control, and many carriersmaintain that CPT 99499 should bereported only rarely. This is becauseadjudicators must review documenta-tion and apply individual considera-tion protocols for correct pricing.

Survival tipsReport CPT 99499 in rare circum-stances and only per your carriers’instructions.

9Misapplication of modifier 24.When reporting unrelated E/M

services during the global surgicalperiod of a major procedure (90 days)or of a minor procedure (up to 10days), the MR documentation mustsupport the E/M code appended withmodifier 24. MR documentationmust detail why the service should beallowed outside the global period.

Survival tipsThis is one of the few E/M areas regu-larly on the Office of Inspector Gen -eral Annual Work Plan. Implementsteps to prevent inadvertent reporting

of E/M services included in the statuspost convalescence: careful docu-mentation and ICD-9-CM coding areessential.

10Key components of E/M ser -vices not fully documented

or missing. For most E/M services, 3key components govern code selec-tion: (1) history; (2) PE; and (3)

MDM. These components must beincluded in the documentation fornew office visits and initial inpatientservices. If only 2 key componentsare required to be documented, forexample, CPT 99212 to 99215 orCPT 99231 to 99233, at least 2 com-ponents must meet the service’s low-est thresholds.

Survival tipsError 1—History: Poorly record-

ed data including chief complaint(CC); history of present illness(HPI); and past medical, family/social history (PFSH). Contra -dictory data among these elementsare also a common error, for exam-ple, CC states one reason for thevisit but the HPI details a differentproblem. Some carriers require theCC and HPI to be documented bythe treating pro vider only. Termssuch as “noncontributory” under thePFSH or ROS may be invalid; know

your carrier’s preferences.Error 2—PE: Missing or insuffi-

cient information. A common PEstatement is “no change from priorvisit,” but when 3 key componentsare required, this brief statement isinadequate. “Negative” and “withinnormal limits” notations are accept-able forms of documentation forunaffected areas/organ systems only. Error 3—MDM:Truncated or dis-

organized data. MDM informationconveys the complexity/risk of theservice and therefore must be fullydocumented. Disorganized MDMdata can cause mistakes in copyingthe requested MRs. Pro viders shouldalways create a data bridge betweenthe body of the visit text and othersupporting visit documents such as anROS questionnaire. Data bridges arecritical when the provider hasreviewed old MRs, ordered tests/studies, carried forward or reviseddiagnoses and medications, etc. l

Michael Calahan, PA, MBA, is thedirector of physician compliance serv-ices at KForce Healthcare, Inc. Heworks with physicians for coding andrevenue cycle management as well as inthe facility inpatient/outpatient arenas.He can be contacted at [email protected] or [email protected].

Pro viders should alwayscreate a data bridgebetween the body ofthe visit text and othersupporting visitdocuments such as a review-of-systemsquestionnaire.


Reimbursement

NEW FOR 2012

Submit your questions to [email protected]

OUR EXPERTS ANSWER YOUR QUESTIONS

Do you have a practice management challenge blocking your path to success?Let our team of administrators, lawyers,

and consultants guide your way. OPMSM1011

IndicationYERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.1

REFERENCES 1. 2.

3.

Announcing YERVOY™ (ipilimumab) HCPCS Code C9284

The accurate completion of reimbursement- or coverage-related documentation is the responsibility of the healthcare provider and patient. Bristol-Myers Squibb and its agents make no guarantee regarding reimbursement for any serviceor item. This coding guidance is not intended to provide specifi c directions on requesting prior authorization or submitting claims for YERVOY and does not provide a guarantee of receiving prior authorization or reimbursement. Coding forYERVOY is dependent on the insurer and the care setting in which the drug will be administered. Oncology practices need to make coding decisions based on the diagnosis and treatment of each patient and the specifi c insurer requirements.

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS YERVOY can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs) and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Important Safety Information

Boxed WARNING regarding immune-mediated adverse reactions

Recommended Dose Modifi cations

Immune-mediated Enterocolitis:

Immune-mediated Hepatitis:

Immune-mediated Dermatitis:

Immune-mediated Neuropathies:

Immune-mediated Endocrinopathies:

Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:

Pregnancy & Nursing:

Common Adverse Reactions:

Important Safety Information (cont)

YERVOY™ (ipilimumab) Injection, for intravenous infusion

Brief Summary of Prescribing Information. For complete prescribing information consult official package insert.

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONSYERVOY (ipilimumab) can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions. [See Dosage and Administration (2.2) in Full Prescribing Information]

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests and thyroid function tests at baseline and before each dose. [See Warnings and Precautions]

INDICATIONS AND USAGE

YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

YERVOY can result in severe and fatal immune-mediated reactions due to T-cell activation and proliferation. [See Boxed Warning]

Immune-mediated Enterocolitis

In Study 1, severe, life-threatening, or fatal (diarrhea of 7 or more stools above baseline, fever, ileus, peritoneal signs; Grade 3–5) immune-mediated enterocolitis occurred in 34 (7%) YERVOY-treated patients, and moderate (diarrhea with up to 6 stools above baseline, abdominal pain, mucus or blood in stool; Grade 2) enterocolitis occurred in 28 (5%) YERVOY-treated patients. Across all YERVOY-treated patients (n=511), 5 (1%) patients developed intestinal perforation, 4 (0.8%) patients died as a result of complications, and 26 (5%) patients were hospitalized for severe enterocolitis.

The median time to onset was 7.4 weeks (range 1.6–13.4) and 6.3 weeks (range 0.3–18.9) after the initiation of YERVOY for patients with Grade 3–5 enterocolitis and with Grade 2 enterocolitis, respectively.

Twenty-nine patients (85%) with Grade 3–5 enterocolitis were treated with high-dose (≥40 mg prednisone equivalent per day) corticosteroids, with a median dose of 80 mg/day of prednisone or equivalent; the median duration of treatment was 2.3 weeks (ranging up to 13.9 weeks) followed by corticosteroid taper. Of the 28 patients with moderate enterocolitis, 46% were not treated with systemic corticosteroids, 29% were treated with <40 mg prednisone or equivalent per day for a median duration of 5.1 weeks, and 25% were treated with high-dose corticosteroids for a median duration of 10 days prior to corticosteroid taper. Infliximab was administered to 5 of the 62 patients (8%) with moderate, severe, or life-threatening immune-mediated enterocolitis following inadequate response to corticosteroids.

Of the 34 patients with Grade 3–5 enterocolitis, 74% experienced complete resolution, 3% experienced improvement to Grade 2 severity, and 24% did not improve. Among the 28 patients with Grade 2 enterocolitis, 79% experienced complete resolution, 11% improved, and 11% did not improve.

Monitor patients for signs and symptoms of enterocolitis (such as diarrhea, abdominal pain, mucus or blood in stool, with or without fever) and of bowel perforation (such as peritoneal signs and ileus). In symptomatic patients, rule out infectious etiologies and consider endoscopic evaluation for persistent or severe symptoms.

Permanently discontinue YERVOY in patients with severe enterocolitis and initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least one month. In clinical trials, rapid corticosteroid tapering resulted in recurrence or worsening symptoms of enterocolitis in some patients.

Withhold YERVOY dosing for moderate enterocolitis; administer anti-diarrheal treatment and, if persistent for more than one week, initiate systemic corticosteroids at a dose of 0.5 mg/kg/day prednisone or equivalent. [See Dosage and Administration (2.2) in Full Prescribing Information]

Immune-mediated Hepatitis

In Study 1, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations of more than 5 times the upper limit of normal or total bilirubin elevations more than 3 times the upper limit of normal; Grade 3–5) occurred in 8 (2%) YERVOY-treated patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4% of YERVOY-treated patients. An additional 13 (2.5%) patients experienced moderate hepatotoxicity manifested by liver function test abnormalities (AST or ALT elevations of more than 2.5 times but not more than 5 times the upper limit of normal or total bilirubin elevation of more than 1.5 times but not more than 3 times the upper limit of normal; Grade 2). The underlying pathology was not ascertained in all patients but in some instances included immune-mediated hepatitis. There were insufficient numbers of patients with biopsy-proven hepatitis to characterize the clinical course of this event.

Monitor liver function tests (hepatic transaminase and bilirubin levels) and assess patients for signs and symptoms of hepatotoxicity before each dose of YERVOY. In patients with hepatotoxicity, rule out infectious or malignant causes and increase frequency of liver function test monitoring until resolution.

Permanently discontinue YERVOY in patients with Grade 3–5 hepatotoxicity and administer systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent. When liver function tests show sustained improvement or return to baseline, initiate corticosteroid tapering and continue to taper over 1 month. Across the clinical development program for YERVOY, mycophenolate treatment has been administered in patients who have persistent severe hepatitis despite high-dose corticosteroids. Withhold YERVOY in patients with Grade 2 hepatotoxicity. [See Dosage and Administration (2.2) in Full Prescribing Information]

Immune-mediated Dermatitis

In Study 1, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3–5) occurred in 13 (2.5%) YERVOY-treated patients. One (0.2%) patient died as a result of toxic epidermal necrolysis and one additional patient required hospitalization for severe dermatitis. There were 63 (12%) patients with moderate (Grade 2) dermatitis.

The median time to onset of moderate, severe, or life-threatening immune-mediated dermatitis was 3.1 weeks and ranged up to 17.3 weeks from the initiation of YERVOY (ipilimumab).

Seven (54%) YERVOY-treated patients with severe dermatitis received high-dose corticosteroids (median dose 60 mg prednisone/day or equivalent) for up to 14.9 weeks followed by corticosteroid taper. Of these 7 patients, 6 had complete resolution; time to resolution ranged up to 15.6 weeks.

Of the 63 patients with moderate dermatitis, 25 (40%) were treated with systemic corticosteroids (median of 60 mg/day of prednisone or equivalent) for a median of 2.1 weeks, 7 (11%) were treated with only topical corticosteroids, and 31 (49%) did not receive systemic or topical corticosteroids. Forty-four (70%) patients with moderate dermatitis were reported to have complete resolution, 7 (11%) improved to mild (Grade 1) severity, and 12 (19%) had no reported improvement.

Monitor patients for signs and symptoms of dermatitis such as rash and pruritus. Unless an alternate etiology has been identified, signs or symptoms of dermatitis should be considered immune-mediated.

Permanently discontinue YERVOY in patients with Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations. Administer systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent. When dermatitis is controlled, corticosteroid tapering should occur over a period of at least 1 month. Withhold YERVOY dosing in patients with moderate to severe signs and symptoms. [See Dosage and Administration (2.2) in Full Prescribing Information]

For mild to moderate dermatitis, such as localized rash and pruritus, treat symptomatically. Administer topical or systemic corticosteroids if there is no improvement of symptoms within 1 week.

Immune-mediated Neuropathies

In Study 1, one case of fatal Guillain-Barré syndrome and one case of severe (Grade 3) peripheral motor neuropathy were reported. Across the clinical development program of YERVOY, myasthenia gravis and additional cases of Guillain-Barré syndrome have been reported.

Monitor for symptoms of motor or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, or paresthesia. Permanently discontinue YERVOY in patients with severe neuropathy (interfering with daily activities) such as Guillain-Barré-like syndromes. Institute medical intervention as appropriate for management of severe neuropathy. Consider initiation of systemic corticosteroids at a dose of 1 to 2 mg/kg/day prednisone or equivalent for severe neuropathies. Withhold YERVOY dosing in patients with moderate neuropathy (not interfering with daily activities). [See Dosage and Administration (2.2) in Full Prescribing Information]

Immune-mediated Endocrinopathies

In Study 1, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3–4) occurred in 9 (1.8%) YERVOY-treated patients. All 9 patients had hypopituitarism and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate endocrinopathy (requiring hormone replacement or medical intervention; Grade 2) occurred in 12 (2.3%) patients and consisted of hypothyroidism, adrenal insufficiency, hypopituitarism, and one case each of hyperthyroidism and Cushing’s syndrome. The median time to onset of moderate to severe immune-mediated endocrinopathy was 11 weeks and ranged up to 19.3 weeks after the initiation of YERVOY.

Of the 21 patients with moderate to life-threatening endocrinopathy, 17 patients required long-term hormone replacement therapy including, most commonly, adrenal hormones (n=10) and thyroid hormones (n=13).

Monitor patients for clinical signs and symptoms of hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper- or hypothyroidism. Patients may present with fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific symptoms which may resemble other causes such as brain metastasis or underlying disease. Unless an alternate etiology has been identified, signs or symptoms of endocrinopathies should be considered immune-mediated.

Monitor thyroid function tests and clinical chemistries at the start of treatment, before each dose, and as clinically indicated based on symptoms. In a limited number of patients, hypophysitis was diagnosed by imaging studies through enlargement of the pituitary gland.

Withhold YERVOY dosing in symptomatic patients. Initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent, and initiate appropriate hormone replacement therapy. [See Dosage and Administration (2.2) in Full Prescribing Information]

Other Immune-mediated Adverse Reactions, Including Ocular Manifestations

The following clinically significant immune-mediated adverse reactions were seen in less than 1% of YERVOY-treated patients in Study 1: nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia.

Across the clinical development program for YERVOY, the following likely immune-mediated adverse reactions were also reported with less than 1% incidence: myocarditis, angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis, leukocytoclastic vasculitis, erythema multiforme, psoriasis, pancreatitis, arthritis, and autoimmune thyroiditis.

Permanently discontinue YERVOY for clinically significant or severe immune-mediated adverse reactions. Initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day prednisone or equivalent for severe immune-mediated adverse reactions.

Administer corticosteroid eye drops to patients who develop uveitis, iritis, or episcleritis. Permanently discontinue YERVOY for immune-mediated ocular disease that is unresponsive to local immunosuppressive therapy. [See Dosage and Administration (2.2) in Full Prescribing Information]

ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling.

[see Warnings and Precautions].






A

n

e

[ d

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared with rates in other clinical trials or experience with therapeutics in the same class and may not reflect the rates observed in clinical practice.

The clinical development program excluded patients with active autoimmune disease or those receiving systemic immunosuppression for organ transplantation. Exposure to YERVOY (ipilimumab) 3 mg/kg for four doses given by intravenous infusion in previously treated patients with unresectable or metastatic melanoma was assessed in a randomized, double-blind clinical study (Study 1). [See Clinical Studies (14) in Full Prescribing Information] One hundred thirty-one patients (median age 57 years, 60% male) received YERVOY as a single agent, 380 patients (median age 56 years, 61% male) received YERVOY with an investigational gp100 peptide vaccine (gp100), and 132 patients (median age 57 years, 54% male) received gp100 peptide vaccine alone. Patients in the study received a median of 4 doses (range 1 to 4 doses). YERVOY was discontinued for adverse reactions in 10% of patients.

The most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue, diarrhea, pruritus, rash, and colitis.

Table 1 presents selected adverse reactions from Study 1, which occurred in at least 5% of patients in the YERVOY-containing arms and with at least 5% increased incidence over the control gp100 arm for all-grade events and at least 1% incidence over the control group for Grade 3–5 events.

Table 1: Selected Adverse Reactions in Study 1

Percentage (%) of Patientsa

YERVOY 3 mg/kg n=131

YERVOY 3 mg/kg+gp100

n=380

gp100 n=132

System Organ Class/ Preferred Term

Any Grade

Grade3–5

Any Grade

Grade3–5

Any Grade

Grade 3–5

Gastrointestinal Disorders Diarrhea ColitisSkin and Subcutaneous Tissue Disorders Pruritus RashGeneral Disorders and Administration Site Conditions Fatigue

328

3129

41

55

02

7

375

2125

34

43

<12

5

202

118

31

10

00

3

a Incidences presented in this table are based on reports of adverse events regardless of causality.

Table 2 presents the per-patient incidence of severe, life-threatening, or fatal immune-mediated adverse reactions from Study 1.

Table 2: Severe to Fatal Immune-mediated Adverse Reactions in Study 1

Percentage (%) of Patients

YERVOY3 mg/kgn=131

YERVOY3 mg/kg+gp100

n=380

Any Immune-mediated Adverse ReactionEnterocolitisa,b

Hepatotoxicitya

Dermatitisa

Neuropathya

Endocrinopathy Hypopituitarism Adrenal insufficiencyOther Pneumonitis Meningitis Nephritis Eosinophiliac

Pericarditisa,c

157121440

00110

12723

<1111

<1<100

<1

a Including fatal outcome. b Including intestinal perforation. c Underlying etiology not established.

Across clinical studies that utilized YERVOY doses ranging from 0.3 to 10 mg/kg, the following adverse reactions were also reported (incidence less than 1% unless otherwise noted): urticaria (2%), large intestinal ulcer, esophagitis, acute respiratory distress syndrome, renal failure, and infusion reaction.

Based on the experience in the entire clinical program for melanoma, the incidence and severity of enterocolitis and hepatitis appear to be dose dependent.

Immunogenicity

In clinical studies, 1.1% of 1024 evaluable patients tested positive for binding antibodies against ipilimumab in an electrochemiluminescent (ECL) based assay. This assay has substantial limitations in detecting anti-ipilimumab antibodies in the presence of ipilimumab. Infusion-related or peri-infusional reactions consistent with hypersensitivity or anaphylaxis were not reported in these 11 patients nor were neutralizing antibodies against ipilimumab detected.

Because trough levels of ipilimumab interfere with the ECL assay results, a subset analysis was performed in the dose cohort with the lowest trough levels. In this analysis, 6.9% of 58 evaluable patients, who were treated with 0.3 mg/kg dose, tested positive for binding antibodies against ipilimumab.

Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to YERVOY with the incidences of antibodies to other products may be misleading.

DRUG INTERACTIONS

No formal drug-drug interaction studies have been conducted with YERVOY (ipilimumab).

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of YERVOY in pregnant women. Use YERVOY during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In a combined study of embryo-fetal and peri-postnatal development, severe toxicities including increased incidences of third-trimester abortion, stillbirth, premature delivery, low birth weight, and infant mortality occurred following intravenous administration of ipilimumab to pregnant cynomolgus monkeys every 21 days from the onset of organogenesis through parturition at doses of 2.6 or 7.2 times the recommended human dose of 3 mg/kg (by AUC). [See Nonclinical Toxicology (13.2) in Full Prescribing Information]

In genetically engineered mice in which the gene for CTLA-4 has been deleted (a “knockout mouse”), offspring lacking CTLA-4 were born apparently healthy, but died within 3–4 weeks due to multi-organ infiltration and damage by lymphocytes.

Human IgG1 is known to cross the placental barrier and ipilimumab is an IgG1; therefore, ipilimumab has the potential to be transmitted from the mother to the developing fetus.

Nursing Mothers

It is not known whether ipilimumab is secreted in human milk. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from YERVOY, a decision should be made whether to discontinue nursing or to discontinue YERVOY, taking into account the importance of YERVOY to the mother.

Pediatric Use

Safety and effectiveness of YERVOY have not been established in pediatric patients.

Geriatric Use

Of the 511 patients treated with YERVOY at 3 mg/kg, 28% were 65 years and over. No overall differences in safety or efficacy were reported between the elderly patients (65 years and over) and younger patients (less than 65 years).

Renal Impairment

No formal studies of YERVOY in patients with renal impairment have been conducted. [See Clinical Pharmacology (12.3) in Full Prescribing Information]

Hepatic Impairment

No formal studies of YERVOY in patients with hepatic impairment have been conducted. [See Clinical Pharmacology (12.3) in Full Prescribing Information]

OVERDOSAGE

There is no information on overdosage with YERVOY.

PATIENT COUNSELING INFORMATION

See MEDICATION GUIDE in Full Prescribing Information.

Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA

1281558A2 IP-B0001A-03-11 Issued: March 2011


Reimbursement

As most of us know, poor pre-visit processes create havocon a practice’s ability to post,

bill, and collect for services rendered(Petaschnick J. Health Care Collector.2007;20:1,10-12). A previsit processthat is laden with errors, variation,and waste will result in an increase notonly in denials and lost revenue, butalso in cost associated with catchingand correcting errors on the back end. Previsit processes also can be tied

directly to patient satisfaction. Per -haps the most obvious is the dissatis-faction that arises when charges aredenied as a result of incorrect billing(Lloyd J. Receivables Report. 2011;26:1,10). Dissatisfaction can be com-pounded when patients experienceanxiety and worry associated with alack of understanding about their out-of-pocket liability before they havereceived services. Because the finan-cial obligation for oncology patientscontinues to grow, patients now areseeking alternatives and options,both medically and financially.To decrease the cost of collections

and to meet the patient’s expecta-tion to be educated fully about theirfinancial liability, Kansas City Can -cer Center, a multispecialty oncolo-

gy and hematology practice with 7primary sites of service in the KansasCity metro area, evaluated its previsitprocesses to incorporate a complete,accurate, and timely verification ofbenefits before rendering services.

Identifying the ProblemsIn the winter of 2009, Kansas City

Cancer Center practice leadershipidentified a clear opportunity to

decrease the number of deniedclaims. Upon closer examination,they found that 3 of the top 5 denial codes resulted directly from a failure to collect and/or verify the appropriate information at thetime of preregistration. These denialcodes included: Services Covered by Another Payer, Services NotCovered by This Payer, andCoverage Termed.To evaluate the preregistration

process in more detail, the practiceassembled a cross-functional team

and created a standard definition of“complete preregistration”: collecting100% of the following data elementsbefore the date of service, with 100%accuracy, 100% of the time: • Patient name (first, middle, last)• Address• Date of birth• Gender• Primary and secondary policy andgroup numbers

• Plan addresses• Subscriber demographics (name,date of birth, gender, SocialSecurity number, and employer). Next, the practice measured how

well this standard was being met. Bycounting both missing and inaccu-rate data, the team calculated adefect rate of 52%. This deficiencywas causing work to be duplicated inthe form of error correction and timespent locating missing information.In addition, there consistently weredefects that made it downstream,which resulted in denials and addi-tional replicated work.At this point, they set out to deter-

mine the root causes of the incom-plete preregistrations in order to applythe most effective solutions. Theyidentified variation in process be -tween multiple sites of service; exces-sive touches or hand-offs withoutclearly defined roles, responsibilities,or accountability; use of inadequateor outdated paper forms resulting in missing, inaccurate, or illegibleinformation; and simple errors inobtaining and recording data ele-ments such as group numbers, insur-ance plans, dates of birth, subscriberinformation, and plan numbers.

Improving Previsit Processes to MaximizePostvisit CollectionsLiaisons Complete Accurate and Timely PreregistrationsBy Sarah W. Rock, MSOD; Debra Gregory

Sarah W. Rock, MSOD Debra Gregory


After a new patient is scheduled at any location, apreregistration liaisoncontacts the patientwithin 48 hours toobtain his or heraddress, phonenumber, emergencycontacts, andinsurance information.

WillWeexhaust all possibilities.

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718.482.1800 1


Advocacy

ward with the com-mittee’s recommen-dations.This leaves in -

cred ible power in thehands of the jointcommittee, but alsogreat risk. The $1.5trillion they havebeen tasked to cut isa paltry percent ofthe total debt prob-lem our country faces.

It will not make a significant impactin the long run. However, the bruntof either their action or the auto-matic 2% overall Medicare cuts thatwill be triggered if they take noaction will fall on the providers whocare for Medicare patients. At leasthalf of all oncology patients nation-wide use Medicare insurance, so theripple effects for oncologists will be severe.Already rumors are swirling of

potential cuts following the first com-mittee meeting. With many possibletargets pulled off the table for thecommittee, one prime target for cutsthat remains is physician services forMedicare patients. Oncology servicesand costs could be affected signifi-cantly and adversely for Medicarepatients and providers if certain typesof cuts happen, either driven by thejoint committee or by the automatedmandatory universal cuts that wouldbe triggered should the committeenot act by November 23.

Impact of Drug PricingChangesOncology drugs are billed through

the physician services process, sodrug reimbursement to physicianswho buy drugs out of pocket andseek reimbursement after treatmentis vulnerable.Oncology drugs are currently

reimbursed by Medicare at averagesales price (ASP) plus 6%. The ASP

is calculated based on prices reportedby manufactures when a drug is sold.However, each drug is not solddirectly to physicians’ offices, butinstead to oncology drug distributors,who collect a margin to cover theiroperations (usually about 2%). Thismeans that physicians already re -ceive a real net reimbursement ofabout ASP plus 4%. Oncology prac-tices and hospital centers incurdirect drug handling costs between12% and 27% over the cost to pur-chase a drug. The margin over ASPis used partially to offset handlingand inventory costs, but obviouslynot fully.To the extent that the joint com-

mittee may decide to enact reduc-tions on the ASP plus 6% model, itwill put oncologists (who pay the

lowest commercially available mar-ket rates for oncology drugs as a classof trade) in the position of payingmore for drugs for treatment ofMedicare patients than they receivein reimbursement.There are some who believe that

the consequences of such a policyshift will encourage physicians tostop acquiring drugs on their own

and either obtain drugs from anexternal specialty pharmacy or shiftthe affected Medicare patients to thehospital setting, where they will stillhave access to the drugs and thusthere is no harm nor foul to theMedicare program. This belief isbeing promulgated actively as part ofthe discussion of op tions for thejoint committee.The reality is that there are like-

ly to be significant cost in creases ifsuch a policy is enacted—the exactopposite of the savings that areintended. There are no specialtypharmacy programs now in place oravailable as an alternative (such aprogram was tried and proved to bea complete failure for both pro -viders and specialty pharmacyorganizations). Putting aside the question of

access for a moment (which itselfcannot be ignored due to the muchlower capacity in the hospital outpa-tient setting, which would be over-whelmed by a sudden large shift inMedicare patients from physiciantreatment sites), the hospital outpa-tient setting is likely to incur costsfor treatment that could run as muchas twice the cost of treatment in aphysician office setting. Hospitalreimbursement structures are quitedifferent from reimbursement struc-tures for physician practices, andinvolve higher facility and overheadcosts not found in the physicianoffice.Because Medicare has not tradi-

tionally done a good job of correlat-ing whether or not a policy changein the physician office (Part B) set-ting has affected hospital setting(Part A) costs, that question proba-bly has not been considered by thosecontemplating reducing oncologydrug reimbursements. The oncologycommunity, however, should bringsuch discussions to the forefront ofthe debt reduction debate.

November 2011…Continued from the cover

Oncology services and costs could beaffected significantlyand adversely forMedicare patients andproviders if certaintypes of cuts happen,either driven by the jointcommittee or by theautomated mandatoryuniversal cuts.


Advocacy

Impact of MakingOncology PracticesFinancially VulnerableShould the joint committee pro-

pose policy recommendations thatmake oncology practices too vulner-able financially, the repercussionsmay be a massive exodus of privateoncology practices from the commu-nity into employed hospital arrange-ments. Again, there are those (par-ticularly within the congressionaland Medicare infrastructures) whobe lieve this would be a good shift,with improvements in care coordi-nation and oversight. There are, however, significant

adverse repercussions from such ashift, which are well recognized bythe private insurance industry thatclosely tracks their inpatient andoutpatient costs. Hospital-based careis recognized widely in the privateinsurance industry as costing more(as described) than care provided inprivate physician offices. Congress

and Medicare tend to look at costs ofhealthcare in silos of Part A and PartB, and thus lose sight of how changesin one infrastructure can pushMedicare beneficiaries into anotherhigher-cost infrastructure and ulti-mately increase costs rather thanachieve expected reductions. Privatehealth insurance is watching theactivities of the joint committeeclosely. If physicians choose tobecome hospital employees becauseof Medicare policies, the privateinsurance companies also will beaffected because physicians would beunlikely to become employed just fortheir Medicare populations, but forall their patients.

Short Window forEngagementThe joint committee will make its

recommendations by November 23.If it does not act, automatic across-the-board reductions will be trig-gered. Unfortunately, oncology is a

specialty that was already poorlyserved by the actions of Congressregarding Medicare in 2003 and2007. Despite the business and reali-ty logic of the situation, there is ahigh likelihood that, by November,the nation will move much closer to a hospital-employed model forhealthcare. Even though the rest ofthe nation seems to understand thatthis move is likely to cost signifi-cantly more than the current model,Congress and Medicare do not.There are only a few weeks beforethat date to communicate what suchchanges may bring, intended orunintended. l

Dawn Holcombe is President of DGHConsulting, which provides consultingand speaking services to practices, phar-ma, and payers in strategy develop-ment, MD/payer negotiations and rela-tionships, and oncology managementand pathways.

Implementing SolutionsTo address the flaws in the process-

es, the practice developed a central-ized team of preregistration liaisons(PRLs) to complete accurate andtimely preregistrations for all newpatients. After a patient is scheduledat any location (most new patientappointments are scheduled by thepatient’s referring office), a PRL con-tacts the patient within 48 hours toobtain his or her address, phone num-ber, emergency contacts, insuranceinformation, and other pertinentdemographics. While on the phone,the PRL answers any questions re -garding the upcoming visit, such asdirections to the clinic or informationabout the provider or practice.The PRL then contacts the insur-

ance company to verify benefits,

including deductibles, copays, andcoinsurance. This information isscanned into the practice manage-

ment system for access by the site ofservice. After the treatment hasbeen ordered, the process is pickedup by the clinic’s financial counselor,who educates the patient about hisor her potential liability and identi-fies payment assistance if needed.

With the development of this newteam and processes, the preregistra-tion defect rate ultimately decreasedfrom 52% to 2%, which the practicecontinues to maintain today. Byidentifying an opportunity for im -provement, defining quality from thecustomer’s perspective, collectingdata, and targeting root causes, prac-tices can make improvements totheir previsit processes that willdecrease costs, increase revenue, andmaintain patient satisfaction. l

At Kansas City Cancer Center/TheUni versity of Kansas Cancer Center,Sarah W. Rock, MSOD, focuses on per-formance and quality improvementefforts, and Deb Gregory is director ofpatient financial services.

Improving Previsit…Continued from page 12

Practices can makeimprovements to theirprevisit processes thatwill decrease costsand increase revenue.

Data Management

Hospital-based cancer centersand service lines face toughcompetitive pressures from

other practices and hospitals com-peting for market share, reputation,referrals, and managed care con-tracts. For hospital-based programs,competition also can arise internally,as other service lines and businessunits compete with oncology forinvestments and resources at a timewhen hospital margins are shrinking.To formulate and make the best

possible judgments in strategic plan-ning, business development, andrevenue cycle management, oncolo-gy managers must maximize thepower of the data available to them.The problem has been that existingtools were inadequate for the uniquechallenges of cancer service lines. AtMassey Cancer Center of VirginiaCommonwealth University we havefound that the typical data systemsmade available to hospital adminis-trators were not adequate for thecomplexity of the cancer serviceline. Simple “cube”-based financialtools were not able to capture themany clinics, units, and ancillaryservices that are used by cancerpatients and providers. Many tools were too focused on

inpatient care, when in oncology atleast 50% of charges were driven byambulatory chemotherapy, radiation,surgery, and imaging. Standard toolsalso were unable to deliver disease-focused output so that each cancertype (eg, breast, colorectal, lung)could be analyzed separately. Nor werethey able to capture the entire treat-ment course from diagnosis, throughcancer-directed treatments, and in -clude palliative and end-of-life care.

The Cancer AnalyticsSolutionIn response, we created the Massey

Data Analysis System that extractsthe hospital’s and providers’ claimsdata, and reconstitutes them in aneasy-to-analyze structured query lan-guage–based system. Categories ofICD-9-CM codes are stored in refer-ence tables for easy application in anygiven analysis, for example, giving usthe ability to analyze each type ofleukemia and lymphoma separately,or to combine them all into a singlecategory of hematopoietic diseases. Each modality of care is categorized

into a handful of key types. Auto -mated programs do the bulk of theextraction, categorization, and “pre -digestion” of data, allowing our ana-lytic resources to be devoted to pro-

ducing useful output for clinical, oper -ational, and financial im provements.The flexibility and power of this

system has been invaluable. We havebeen able to turn one program with-in our cancer center from an annualloss of $1 million or worse, to a sus-tained positive net margin. We havedeveloped and implemented strate-gic plans that are organized arounddisease-specific centers of excellence.We have combined cancer registry

Improving Oncology Service LineManagement Using Cancer Analytics to Your AdvantageBy Brian Cassel, PhD; Lisa Shickle, MS

Q:Do you have the tools youneed to evaluate the costs andrevenues of each of your major pro-grams/centers across modalities ofcare from screening and diagnosisthrough all forms of treatment?

A:If not, explore options to accessand analyze these data in waysthat meet your specific needs. Most hos-pitals have a decision-support departmentthat would be a good first contact.

Q:Do you have the tools youneed to develop and imple-ment disease-focused strategic plansand business development initiatives?

A:If not, you need to identify a can-cer data analyst who can bringfamiliarity and expertise regarding cancerand its treatments to assist you in yourplanning efforts.

Q:Do you have the tools you needto answer new questions flexiblyas they arise, regarding all aspects ofyour cancer patients’ use of services?

A:Cancer treatments continually areevolving; and cancer programsadapt to keep pace with scientific develop-ments, regulatory changes, and organiza-tional shifts. Make sure your system canadapt accordingly.

Making Analytics Work for YouKey Questions and Action Steps


Brian Cassel, PhD Lisa Shickle, MS


Data Management

Case Study

From informal discussions in2004 to a ribbon cutting in2008, Dana-Farber Cancer

Institute (DFCI) and New Ham pshireOncology-Hematology (NHOH)embarked on an odyssey to provideworld-class cancer care in Lon -donderry, New Hampshire (Sidebar),according to Denis B. Hammond,MD, chief medical oncologist atNHOH, who detailed “why and how”a multisite, single-specialty adulthematology and oncology independ-ent practice affiliated with an aca-demic cancer center at the 2011annual meeting of the AmericanSociety of Clinical Oncology.

Why“We were facing the first serious

competition in our history, and wewere also facing the same increasedeconomic pressures all of us havebeen facing in the United States,”said Hammond. To help determinethe best collaboration strategy,

NHOH’s leaders posed themselvesquestions, as stated by Hammond:• Would a closer relationship withanother institution support ourmission?

• Are the values of this other insti-tution consistent with our own?

• Have we had successful interac-tions with this institution in thepast?

• Is there an alignment of our stra -tegic goals?Their answers aligned well with

DFCI. As a Cancer and LeukemiaGroup B affiliate with a strong com-mitment to research, NHOH be -lieved that working with DFCI couldimprove the quality and scope of services it could provide patients,explained Ham mond. Next, theyneeded to pursue building a successfulrelationship.

HowInformal discussion began in

2004, exploring the possibility of a

closer relationship between NHOHand DFCI. In January 2005, accord-ing to Hammond, they signed a“memorandum of understanding,”which detailed the affiliation andthe lack of a financial relationship.From this, the 2 groups developedprograms, which included “openingselective DFCI trials at NHOH, ajoint psychosocial research project,genetics clinics at some of our pri-vate practices, and a communityeducation program called ‘Let’s Talk’that featured physicians both fromNHOH and DFCI,” he said.Also that year, Elliott Hospital

expanded its services from Man -chester to Londonderry. This chal-lenge offered an opportunity forshared clinical space and programs atthis campus, said Hammond. InDecember 2006, NHOH signed a“letter of intent” to explore an agree-ment with DFCI, which would seizethis opportunity and set up a sharedfinancial relationship.

Dana-Farber/New Hampshire Oncology-HematologyAligning an Academic Cancer Center and a Community Oncology Practice By Dawn Lagrosa

2004

Begin informal discussions

2005

Sign Memorandum ofUnderstandingdetailed the affiliationand that there was NOfinancial relationship

Elliott Hospital expandsto Londonderry; buildsmedical campus

2006

Sign Letter of Intentdetailed formal plan toexplore agreement forshared clinical space andprograms at Londonderrysite; designated sharedfinancial relationship

Conduct feasibilityanalysis of various alignment strategies

Decide to pursue providerservices agreement

2007

Expand clinical servicesat existing sites

2008

Dana-Farber CancerInstitute signs lease forclinic space atLondonderry

Sign long-term providerservices agreement atLondonderry

Dana-Farber/NewHampshire Oncology-Hematology providesservices at Londonderry

Provider Services Agreement Time Line

I ONCOLOGY PRACTICE MANAGEMENT I October 2011 I Special Edition22

Case Study

Case Study


To go from intent to agreement,the 2 groups needed to determinewhat would work best. This feasibil-ity analysis, said Hammond, asked:• Where would the patients comefrom?

• How many patients would welikely see?

• What were the reimbursementissues?

• What were the regulatory issues?• Could this relationship be struc-tured so as not to alienate refer-ring physicians?

• What type of financial relation-ship would be most profitablefor both NHOH and DFCI?

• What model of care would workbest: an NHOH office withDFCI affiliation (the statusquo); a provider services agree-ment; a joint venture; NHOHas a wholly owned entity ofFarber?

The entities decided upon aprovider services agreement. “NHOHphysicians would join the DFCI staff.[NHOH] would provide professionalmedical and support staff services.The administration of the unitwould be carried out by DFCI, withthe advisory function of an NHOHphysician. There would be joint gov-ernance, and there would be a steer-ing committee,” shared Hammond.“The basics of the provider servicesrelationship would be that DFCIwould rent the clinical space fromElliott Hospital and equip the unitaccording to DFCI standards. Thestaff would perform functions in

accordance with DFCI policy andprocedures. Neither party wouldtake any action that would harm theother. And the clinic would utilizeDFCI’s electronic medical recordand computerized physician order-entry system.”

After DFCI signed the lease forclinic space at the Londonderrycampus, DFCI and NHOH formal-ized their alignment by signing along-term provider services agree-ment for that location.

OutcomesNow a new entity, Dana-Farber/

New Hampshire Oncology-Hematology(DF/NHOH) has enhanced its servic-es. To date, it has opened genetic,survivorship, and second-opinionclinics; developed joint tumorboards for multiple disease sites;opened DFCI trials in NewHampshire; and begun continuingmedical education and communityeducation programs, Hammondextolled. The group also has added

staff: a full-time social worker (1FTE), a nutrition counselor (0.4FTE), and a chaplain (0.25 FTE).“Patient satisfaction has been

high and clinic growth has contin-ued through this present year [June2011]. Additionally, there is now afully staffed radiation oncology uniton site, and it is a group throughwhich we have had a long relation-ship,” he said.To conclude his presentation,

Hammond shared how the affilia-tion has fared in the 2 years since theagreement was signed. Measuringnew patients/consults per year, estab-lished patients per quarter, and infu-sions, DF/NHOH analyzed their pro-jected versus actual numbers. For thefirst year, 2009, projected amountsmirrored the actual, he said; for thesecond year, 2010, the actuals weresignificantly lower than what wasprojected.He offered this analysis of why the

projections were off: “The projectionswere based primarily on the existingdemographics of each of the entitiesinvolved in the project and did nottake into account the subtractionthat would happen when the 2 enti-ties joined. In addition, the projec-tions did not account for the increasein competition in the clinic’s catch-ment area. The projections also didnot account for the fact that openingthis clinic would alienate some of ourreferring physicians. And the projec-tions did not account for the fact thatsome patients just wanted to godowntown for their care.” l

“Patient satisfaction hasbeen high and clinicgrowth has continuedthrough this presentyear [June 2011].”

–Denis B. Hammond, MD

and claims data to analyze utilizationpatterns and financial outcomes atthe patient level by disease type andstage. And we have used this systemto develop the financial metrics forour palliative care program. l

Brian Cassel, PhD, and Lisa Shickle,MS, are analysts with Massey CancerCenter of Virginia CommonwealthUniversity, and senior consultants withData Blueprint, a data managementand IT consulting firm that empowers

organizations to gain more value fromdata systems and provides analytic solu-tions for oncology program decisionmaking. Dr Cassel can be reached [email protected]. Ms Shickle can bereached at [email protected].

Improving Oncology Service…Continued from page 21


Reimbursement

The deadlinefor going livewith the Inter -

national Class ifica-t ion of Diseases (ICD),10th edition is Oct -ober 1, 2013, and theCenters for Medicare& Medi caid Servicesrepeatedly has attest-ed this as a firm

deadline with no extensions, de -lays, or grace periods. After thedeadline for transition, providerswill not be able to use the clinicalmodification (CM) of the 9th edi-tion, that is, the ICD-9-CM codes.The implication being: If you aren’tlive with ICD-10-CM, you won’tget paid. When we hear ICD-10 in the

United States, it usually refers to thenation’s latest clinical modificationof the ICD, which was developed to support reimbursement coding,called ICD-10-CM. The ICD-10procedural coding system, designat-ed as PCS, will replace codes in vol-ume 3 of ICD-9-CM in the UnitedStates. The Current ProceduralTermin ology code set will remainun changed for physician services.So what’s the difference between

ICD-9 and ICD-10? The big changehas been the increase in the level ofdetail that will be reported usingICD-10 codes. Within ICD-9, thereare about 13,500 valid codes com-pared with more than 68,000 codesin ICD-10. ICD-9-CM has a maxi-mum of 5 code elements, whereasthe new codes have up to 7 alphanu-meric digits.The transition from ICD-9 to ICD-

10 has the potential to impact allareas of how a practice operates. Ofparticular importance are 3 areas that

every practice manager should con-sider in developing a transition plan.

1Scrutinize vendors. Are they upto speed? Many vendors supportrevenue cycle management for med-ical practices. The good ones will be well on their way to complet-ing internal testing of a change toVersion 5010 of the Electronic DataTransactions protocol. The deadlinefor making the transition to this newprotocol is well in advance of thedeadline for ICD-10 implementa-tion at January 1, 2012. It is impor-tant to understand a vendor’sprogress toward completing thistransition and to develop a jointplan for implementing the change inyour practice that allows ample timefor addressing challenges that mayarise during the rollout.

2Evaluate your coding solution. Isit the right solution for the future?With the increased complexity ofthe code structure of ICD-10 com-pared with ICD-9 and the underly-ing need for increased knowledge ofmedical terminology and anatomy, itis important to evaluate if your cod-ing capabilities will meet your re -quirements in the ICD-10 world.Considerations about optimizing cli-nicians’ time with patients and theamount of training required for theentire practice workforce, coupledwith the increasing availability ofremote coding as a business solution,provide medical practices with manynew drivers in selecting a codingsolution. Key considerations that can be

used in evaluating current versusproposed coding solutions includethe amount of time to code a chart,the accuracy of the codes, and cost

(both the actual cost plus the oppor-tunity cost associated with delayedreimbursement). Even if your cur-rent coding solution will be adequatefor your expected future needs, a“plan B” should be considered toprovide additional coding capabilityduring the period of the transitionfrom ICD-9 to ICD-10.

3Train everybody. The implica-tions of the transition will impactevery facet of a practice. For this rea-son, everybody needs training. Thelevel of training will range from gen-eral awareness training on what isinvolved in the transition and yourpractice’s plans for change all theway through detailed coder trainingon how to apply the new code set.Training everybody to the appropri-ate level will ensure that this is apractice-wide initiative with all staffequally invested in the success of theICD-10 implementation.

The looming transition to ICD-10will require changes in how yourpractice operates. Now is the idealtime to evaluate the current solutionsused for revenue cycle managementin light of the new business require-ments of operating in the ICD-10environment. Critical considerationshould be given to evaluating yourvendor’s capability to grow with youand support you, the applicability ofyour current coding solution for thefuture, and the need for trainingacross the entire practice. l

Richard Vander Burg, RN, BSN, issenior vice president and director ofhealthcare services at DOMA Tech -nologies, a software-as-a-service con-sulting firm.

Getting from ICD-9 to ICD-103 Things Every Practice Manager Should Consider By Richard Vander Burg, RN, BSN

Wellness-Based Healthcare: Economic Incentives and Benefit Design


■ VELCADE+MP (n=344)■ MP (n=338)

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INDICATIONS:

VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma. VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

CONTRAINDICATIONS:

VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.

WARNINGS AND PRECAUTIONS:

VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE.

Pregnancy Category D: Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.

Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require change in the dose and schedule of VELCADE. Following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with ≥Grade 2 peripheral neuropathy in the relapsed multiple myeloma study. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 13%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics.

Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the VELCADE and dexamethasone groups, respectively. The incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the VELCADE and dexamethasone groups, 5% and 4%, respectively. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.

Pulmonary Disorders: There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. In a clinical trial, the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicin and VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease. In the event of new or worsening cardiopulmonary symptoms, a prompt comprehensive diagnostic evaluation should be conducted.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing RPLS, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing RPLS is not known.

Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration.

Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia was related to pretreatment platelet count. In the relapsed multiple myeloma study, the incidence of significant bleeding events (≥Grade 3) was similar on both the VELCADE (4%) and dexamethasone (5%) arms. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. The incidence of febrile neutropenia was <1%.

Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of VELCADE. There is limited re-challenge information in these patients.

Patients with Hepatic Impairment: VELCADE is metabolized by liver enzymes. VELCADE exposure is increased in patients with moderate or severe hepatic impairment. These patients should be treated with VELCADE at reduced starting doses and closely monitored for toxicities.

ADVERSE EVENT DATA:

Safety data from phase 2 and 3 studies of single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the phase 3, VELCADE plus DOXIL® [doxorubicin HCI liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness); (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated); (39%), thrombocytopenia and appetite decreased (including anorexia); (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo); (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

In the phase 3 VELCADE + melphalan and prednisone study, the safety profile of VELCADE in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events in this study (VELCADE+melphalan/prednisone vs melphalan/prednisone) were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).

DRUG INTERACTIONS:

Co-administration of ketoconazole, a potent CYP3A inhibitor, increased the exposure of bortezomib. Therefore, patients should be closely monitored when given bortezomib in combination with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). Co-administration of melphalan-prednisone increased the exposure of bortezomib. However, this increase is unlikely to be clinically relevant. Co-administration of omeprazole, a potent inhibitor of CYP2C19, had no effect on the exposure of bortezomib. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy.

USE IN SPECIFIC POPULATIONS:

Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VELCADE, 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: The safety and effectiveness of VELCADE in children has not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, the drug should be administered after the dialysis procedure. For information concerning dosing of melphalan in patients with renal impairment, see manufacturer’s prescribing information.

Patients with Hepatic Impairment: The exposure of VELCADE is increased in patients with moderate and severe hepatic impairment. Starting dose should be reduced in those patients.

Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.

Please see full Prescribing Information for VELCADE at www.VELCADE.com

Brief Summary

VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright © 2011, Millennium Pharmaceuticals, Inc.All rights reserved. Printed in USA V-11-0041 04/11

1:23 PM

Physician Wealth Management


Although mem bers of the can-cer care team will sacrificetheir time and energy for the

care of their patients, all too often itis done to the detriment of them-selves and their families, especiallyin the areas of personal financialplanning. This article focuses onprotecting your most valuable asset—your ability to earn an income.

Disability InsuranceDisability insurance can be pur-

chased on an individual or groupbasis. Group insurance usually is pro-vided by an employer or purchasedindividually from a sponsoring asso-ciation. Although initially low incost, group policies have several lim-itations. They can be canceled (bythe association or insurance compa-ny), rates increase as you grow older,and premiums are subject to adjust-ments based on the claims experi-ence of the group. In addition, groupand association contracts often con-tain restrictive definitions of disabil-ity as well as less generous contractprovisions.First, find out what long-term dis-

ability (LTD) benefits, if any, areavailable or provided to you by youremployer. You will need the answersto the following questions:• What percent of your income iscovered? Is only your base sal-ary covered or is commission,bonus, and overtime incomealso included?

• What is the maximum monthlybenefit?

• How long must you be disabledbefore benefits become payable?

• How long are benefits payable?• Are you contributing to the costof the coverage or is it paid forentirely by your employer?

• Would benefits paid to you betaxable or income tax–free toyou upon receipt? Do you have achoice?

• Is the plan mandatory or volun-tary?

• What is the name of the insur-ance carrier that underwritesthe coverage?

Disability Insurance LimitsInsurance companies don’t want

you to earn a higher income whenyou are disabled compared withwhen you were working. For this rea-son, most insurance companies willlimit the amount of disability insur-ance available.Ideally, you would like to have

60% of your earned income replacedon an income tax–free basis in theevent of your disability. When youhave group insurance in place, how-ever, this will limit the amount ofindividual coverage available toyou—even if you were willing to payfor a larger amount of coverage. Forthis reason, when shopping for anindividual disability insurance poli-cy, it is best to provide your agentwith a copy of your group LTD plan,the specifics as to how your salary iscomprised, your job title, as well asduties. You should also let him or herknow if you have any health issues orare taking any prescription medica-tions. They then will go to the mar-ketplace to present you with theoptions available so you can make awell-informed, educated decisionbased on your budget and individualneeds and goals.

The Cost of DisabilityInsurancePremium rates are based on several

factors, including the insured’s age,

gender, monthly ben-efit be ing purchased,and the optional riders selected. Theyounger you are whenthe purchase is made,the lower the cost ofthe insurance. There -fore, you should pur-chase a policy as earlyin your career as pos-sible to lock in lower premium rates.Rates for women are substantially

higher and their policies generallycost 50% to 60% more than thosefor men. Fortunately, many disabilityinsurance carriers offer a “multilife”discount when several employeesworking for the same hospital orpractice purchase individual policiesat the same time. Whereas these pro-grams typically produce a savings of10% to 15% for men, this strategyallows female physicians to save upto 60% on the cost of their disabilityinsurance. Another option is tosecure a discount as a result of a pro-fessional association in which youare a member or are eligible to join.

SummaryProtecting one’s income in the

event of a disability is one of the coreelements of financial planning. Mynext article will describe what fea-tures should be included in your pol-icy and how to choose the companyand policy to best meet your needs. l

Lawrence B. Keller, CLU, ChFC,CFP®, is the founder of PhysicianFinancial Services, a firm specializing inincome protection and wealth accumu-lation strategies for physicians. He canbe reached at 516-677-6211 or [email protected].

Disability Insurance Planning Protecting Your Ability to Earn an Income

(

w

O

2 9

With Lawrence B. Keller, CLU, ChFC, CFP®


Patient and Provider Access

This has provento be a diffi-cult year for

reimbursement forcommunity cancercare providers. Al -though there aremany hurdles to ap -propriate reimburse-ment, 3 issues arehanging fire in Con -

gress this year. The sustainablegrowth rate (SGR) formula remainsunfixed. Drug manufacturers’ prompt-pay discount is still calculated in theaverage sales price (ASP) for physi-cian reimbursement. And most re -

cently, select members of Congress areconsidering across-the-board cuts ofup to 2% in Medicare reimbursement.

1The SGR formula. This funda-mentally flawed formula linksreimbursement rates to increases inthe gross domestic product (GDP).Because spending on physician serv-ices has grown faster than increasesin GDP, the formula has called forcuts in reimbursement each year formost of the past decade. In 2012,the SGR formula calls for nearly a30% cut to physician reimburse-ment. Each year, Congress haspassed a “doc fix,” pushing thosecuts down the road. Once again, a

similar “fix” is expected by year’send. However, these continual last-minute “fixes” make future plan-ning and investment difficult forpractices that cannot know when,or if, another short-term fix is going to happen. The Association of Community Cancer Centers(ACCC) continues to work withthe Centers for Medicare &Medicaid Services (CMS) andCongress to ensure physicians donot see these significant cuts.

2The prompt-pay discount in -cluded in the calculation of ASP.ACCC is fighting to remove thesecustomary prompt-pay discounts,which are extended by manufactur-ers to distributors, from the manufac-turers’ calculation of the ASP forPart B drugs and biologicals. Thesediscounts typically are not passed onto the physician purchasing theproduct. ACCC supports S.733 andHR.905, 2 pieces of companion leg-islation that would remove theprompt-pay discount from the ASPcalculation, aligning Medicare re-imbursement methodology withMedicaid methodology. Medicaidmethodology excludes these dis-counts from the calculation of aver-age manufacturers price (AMP),ensuring fair and accurate reimburse-ment for physicians and clinics.Thanks in part to the hard work ofACCC members, the bills are gain-ing bipartisan support in both theHouse and Senate.

3Congress considering cuts inMedicare reimbursement. Mosturgently, Congress recently finalizedthe members of the bicameral, bipar-tisan debt reduction “super” commit-tee, which was created by the debt-

ceiling compromise signed into lawby President Obama in August. Thisjoint committee has until Thanks -giving to find at least $1.5 trillion indeficit savings over 10 years for anup-or-down vote in both chambersby Christmas 2011.This is of concern to all cancer

care providers because Medicarereimbursement is looking at signifi-cant cuts. President Obama has beenvery clear that when he envisionscuts to Medicare, he does not seechanges in coverage for beneficiar-ies, he sees provider-side cuts. Itappears that the committee is lookingat provider-side cuts as well—some-where in the range of a 2% reduction.And these cuts will be in addition toprojected cuts of almost 30% result-ing from the SGR formula.

Although these hurdles are signif-icant, ACCC will continue to workuntil they are overcome. For exam-ple, ACCC has worked with con -gressional offices, held Hill Dayevents for its members, sponsoredcongressional briefings on issuesaffecting its membership, and sub-mitted comments to CMS on therecent Hospital Outpatient Pro -spective Payment System andMedicare Physician Fee Schedule2012 proposed rules. ACCC will address these issues

in greater detail at ACCC’s 28thNational Oncology Conference inSeattle, October 19-22, 2011. Formore information visit: www.accc-cancer.org/meetings/meetingsNOC2011.asp. l

Sydney Abbott, JD, is policy coordina-tor for the Association of CommunityCancer Centers.

Hurdles to Appropriate ReimbursementThe SGR, Prompt-Pay Discounts, and Cuts in Medicare Reimbursement By Sydney Abbott, JD

It appears that thecommittee is lookingat provider-side cutsas well—somewhere inthe range of a 2%reduction.

Brought to you by the Association of Community Cancer Centers

The Oncology Publication That Looks Out for Your Bottom LineQuestions? Contact our Editor, Dawn Lagrosa: [email protected]

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Invites You to Submit Your Practice Management Solution

Oncology Practice Management™

is seeking articles detailinginnovative solutions to today’s business challenges.

Hot topics include:• Technology implementation

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www.OncPracticeManagement.com/manuscripts

OPMASize1011

DOXIL®(doxorubicin HCl liposome injection) for intravenous infusionBRIEF SUMMARY. Please see Full Prescribing Information.

INDICATIONS AND USAGE: Ovarian Cancer: DOXIL (doxorubicin HCl liposome injection) is indicated for thetreatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-basedchemotherapy. AIDS-Related Kaposi’s Sarcoma: DOXIL is indicated for the treatment of AIDS-relatedKaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.Multiple Myeloma: DOXIL in combination with bortezomib is indicated for the treatment of patients withmultiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

CONTRAINDICATIONS: DOXIL (doxorubicin HCl liposome injection) is contraindicated in patients whohave a history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or thecomponents of DOXIL [see Warnings and Precautions]. DOXIL is contraindicated in nursing mothers [seeFull Prescribing Information].

WARNINGS AND PRECAUTIONS: Cardiac Toxicity: Special attention must be given to the risk ofmyocardial damage from cumulative doses of doxorubicin HCl. Acute left ventricular failure may occurwith doxorubicin, particularly in patients who have received a total cumulative dosage of doxorubicinexceeding the currently recommended limit of 550 mg/m2. Lower (400 mg/m2) doses appear to cause heartfailure in patients who have received radiotherapy to the mediastinal area or concomitant therapy withother potentially cardiotoxic agents such as cyclophosphamide. Prior use of other anthracyclines oranthracenodiones should be included in calculations of total cumulative dosage. Congestive heart failureor cardiomyopathy may be encountered after discontinuation of anthracycline therapy. Patients with ahistory of cardiovascular disease should be administered DOXIL only when the potential benefit oftreatment outweighs the risk. Cardiac function should be carefully monitored in patients treated withDOXIL. The most definitive test for anthracycline myocardial injury is endomyocardial biopsy. Othermethods, such as echocardiography or multigated radionuclide scans, have been used to monitor cardiacfunction during anthracycline therapy. Any of these methods should be employed to monitor potentialcardiac toxicity in patients treated with DOXIL. If these test results indicate possible cardiac injuryassociated with DOXIL therapy, the benefit of continued therapy must be carefully weighed against therisk of myocardial injury. In a clinical study in patients with advanced breast cancer, 250 patients receivedDOXIL at starting dose of 50 mg/m2 every 4 weeks. At all cumulative anthracycline doses between 450-500 mg/m2, or between 500–550 mg/m2, the risk of cardiac toxicity for patients treated with DOXIL was11%. In this study, cardiotoxicity was defined as a decrease of >20% from baseline if the resting leftventricular ejection fraction (LVEF) remained in the normal range, or a decrease of >10% if the resting LVEFbecame abnormal (less than the institutional lower limit of normal). The data on left ventricular ejectionfraction (LVEF) defined cardiotoxicity and congestive heart failure (CHF) are in the table below.

Table 1: Number of Patients With Advanced Breast CancerDOXIL (n=250)

Patients who Developed Cardiotoxicity 10(LVEF Defined)

Cardiotoxicity (With Signs & Symptoms of CHF) 0Cardiotoxicity (no Signs & Symptoms of CHF) 10

Patients With Signs and Symptoms of CHF Only 2

In the randomized multiple myeloma study, the incidence of heart failure events (ventricular dysfunction,cardiac failure, right ventricular failure, congestive cardiac failure, chronic cardiac failure, acute pulmonaryedema and pulmonary edema) was similar in the DOXIL+bortezomib group and the bortezomib monotherapygroup, 3% in each group. LVEF decrease was defined as an absolute decrease of 15% over baseline or a

5% decrease below the institutional lower limit of normal. Based on this definition, 25 patients in thebortezomib arm (8%) and 42 patients in the DOXIL+bortezomib arm (13%) experienced a reduction in LVEF.

Infusion Reactions: Acute infusion-related reactions were reported in 7.1% of patients treated withDOXIL in the randomized ovarian cancer study. These reactions were characterized by one or more ofthe following symptoms: flushing, shortness of breath, facial swelling, headache, chills, chest pain, backpain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope,bronchospasm, asthma, apnea, and hypotension. In most patients, these reactions resolve over thecourse of several hours to a day once the infusion is terminated. In some patients, the reaction resolvedwhen the rate of infusion was slowed. In this study, two patients treated with DOXIL (0.8%) discontinueddue to infusion-related reactions. In clinical studies, six patients with AIDS-related Kaposi’s sarcoma(0.9%) and 13 (1.7%) solid tumor patients discontinued DOXIL therapy because of infusion-relatedreactions. Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactionshave been reported. Medications to treat such reactions, as well as emergency equipment, should beavailable for immediate use. The majority of infusion-related events occurred during the first infusion.Similar reactions have not been reported with conventional doxorubicin and they presumably representa reaction to the DOXIL liposomes or one of its surface components. The initial rate of infusion should be1 mg/min to help minimize the risk of infusion reactions [see Full Prescribing Information].

Myelosuppression: Because of the potential for bone marrow suppression, careful hematologicmonitoring is required during use of DOXIL, including white blood cell, neutrophil, platelet counts, andHgb/Hct. With the recommended dosage schedule, leukopenia is usually transient. Hematologic toxicitymay require dose reduction or delay or suspension of DOXIL therapy. Persistent severe myelosuppressionmay result in superinfection, neutropenic fever, or hemorrhage. Development of sepsis in the setting ofneutropenia has resulted in discontinuation of treatment and, in rare cases, death. DOXIL may potentiatethe toxicity of other anticancer therapies. In particular, hematologic toxicity may be more severe whenDOXIL is administered in combination with other agents that cause bone marrow suppression. In patientswith relapsed ovarian cancer, myelosuppression was generally moderate and reversible. In the threesingle-arm studies, anemia was the most common hematologic adverse reaction (52.6%), followed byleukopenia (WBC <4,000 mm3; 42.2%), thrombocytopenia (24.2%), and neutropenia (ANC <1,000; 19.0%). Inthe randomized study, anemia was the most common hematologic adverse reaction (40.2%), followed byleukopenia (WBC <4,000 mm3; 36.8%), neutropenia (ANC <1,000; 35.1%), and thrombocytopenia (13.0%)[see Adverse Reactions]. In patients with relapsed ovarian cancer, 4.6% received G-CSF (or GM-CSF) tosupport their blood counts [see Full Prescribing Information]. For patients with AIDS-related Kaposi’ssarcoma who often present with baseline myelosuppression due to such factors as their HIV disease orconcomitant medications, myelosuppression appears to be the dose-limiting adverse reaction at therecommended dose of 20 mg/m2 [see Adverse Reactions]. Leukopenia is the most common adversereaction experienced in this population; anemia and thrombocytopenia can also be expected. Sepsisoccurred in 5% of patients; for 0.7% of patients the event was considered possibly or probably related toDOXIL. Eleven patients (1.6%) discontinued study because of bone marrow suppression or neutropenia.Table 10 presents data on myelosuppression in patients with multiple myeloma receiving DOXIL andbortezomib in combination [see Adverse Reactions].

Hand-Foot Syndrome (HFS): In the randomized ovarian cancer study, 50.6% of patients treated with DOXILat 50 mg/m2 every 4 weeks experienced HFS (developed palmar-plantar skin eruptions characterized byswelling, pain, erythema and, for some patients, desquamation of the skin on the hands and the feet), with23.8% of the patients reporting HFS Grade 3 or 4 events. Ten subjects (4.2%) discontinued treatment dueto HFS or other skin toxicity. HFS toxicity grades are described in Dosage and Administration section [seeFull Prescribing Information]. Among 705 patients with AIDS-related Kaposi’s sarcoma treated with DOXILat 20 mg/m2 every 2 weeks, 24 (3.4%) developed HFS, with 3 (0.9%) discontinuing. In the randomizedmultiple myeloma study, 19% of patients treated with DOXIL at 30 mg/m2 every three weeks experiencedHFS. HFS was generally observed after 2 or 3 cycles of treatment but may occur earlier. In most patientsthe reaction is mild and resolves in one to two weeks so that prolonged delay of therapy need not occur.However, dose modification may be required to manage HFS [see Full Prescribing Information]. Thereaction can be severe and debilitating in some patients and may require discontinuation of treatment.

Radiation Recall Reaction: Recall reaction has occurred with DOXIL administration after radiotherapy.

Fetal Mortality: Pregnancy Category D: DOXIL can cause fetal harm when administered to a pregnantwoman. There are no adequate and well-controlled studies in pregnant women. If DOXIL is to be usedduring pregnancy, or if the patient becomes pregnant during therapy, the patient should be apprised ofthe potential hazard to the fetus. If pregnancy occurs in the first few months following treatment withDOXIL, the prolonged half-life of the drug must be considered. Women of childbearing potential shouldbe advised to avoid pregnancy during treatment with Doxil. [see Full Prescribing Information].

Toxicity Potentiation: The doxorubicin in DOXIL may potentiate the toxicity of other anticancer therapies.Exacerbation of cyclophosphamide-induced hemorrhagic cystitis and enhancement of the hepatotoxicityof 6-mercaptopurine have been reported with the conventional formulation of doxorubicin HCl. Radiation-induced toxicity to the myocardium, mucosae, skin, and liver have been reported to be increased by theadministration of doxorubicin HCl.

Monitoring: Laboratory Tests: Complete blood counts, including platelet counts, should be obtainedfrequently and at a minimum prior to each dose of DOXIL [see Warnings and Precautions].

ADVERSE REACTIONS: Overall Adverse Reactions Profile: The following adverse reactions are discussedin more detail in other sections of the labeling. • Cardiac Toxicity [see Warnings and Precautions] • Infusionreactions [see Warnings and Precautions] • Myelosuppression [see Warnings and Precautions] • Hand-Foot syndrome [see Warnings and Precautions]

The most common adverse reactions observed with DOXIL are asthenia, fatigue, fever, nausea, stomatitis,vomiting, diarrhea, constipation, anorexia, hand-foot syndrome, rash and neutropenia, thrombocytopeniaand anemia. The most common serious adverse reactions observed with DOXIL are described in SectionAdverse Reactions in Clinical Trials. The safety data described below reflect exposure to DOXIL in 1310patients including: 239 patients with ovarian cancer, 753 patients with AIDS-related Kaposi’s sarcoma and318 patients with multiple myeloma.

Adverse Reactions in Clinical Trials: Because clinical trials are conducted under widely varyingconditions, the adverse reaction rates observed cannot be directly compared to rates on other clinicaltrials and may not reflect the rates observed in clinical practice. The following tables present adversereactions from clinical trials of DOXIL in ovarian cancer, AIDS-Related Kaposi’s sarcoma, and multiplemyeloma.

Patients With Ovarian Cancer: The safety data described below are from 239 patients with ovariancancer treated with DOXIL (doxorubicin HCl liposome injection) at 50 mg/m2 once every 4 weeks for aminimum of 4 courses in a randomized, multicenter, open-label study. In this study, patients receivedDOXIL for a median number of 98.0 days (range 1-785 days). The population studied was 27-87 years ofage, 91% Caucasian, 6% Black and 3% Hispanic and other. Table 2 presents the hematologic adversereactions from the randomized study of DOXIL compared to topotecan.

Table 2: Ovarian Cancer Randomized Study Hematology Data Reported in Patients With Ovarian CancerDOXIL Topotecan

Patients Patients(n = 239) (n = 235)

Neutropenia500 - <1000/mm3 19 (7.9%) 33 (14.0%)<500/mm3 10 (4.2%) 146 (62.1%)

Anemia6.5 - <8 g/dL 13 (5.4%) 59 (25.1%)<6.5 g/dL 1 (0.4%) 10 (4.3%)

Thrombocytopenia10,000 - <50,000/mm3 3 (1.3%) 40 (17.0%)<10,000/mm3 0 (0.0%) 40 (17.0%)

Table 3 presents a comparative profile of the non-hematologic adverse reactions from the randomizedstudy of DOXIL compared to topotecan.

WARNING: INFUSION REACTIONS, MYELOSUPPRESSION, CARDIOTOXICITY, LIVER IMPAIRMENT,ACCIDENTAL SUBSTITUTION1. The use of DOXIL (doxorubicin HCl liposome injection) may lead to cardiac toxicity. Myocardialdamage may lead to congestive heart failure and may occur as the total cumulative dose of doxorubicinHCl approaches 550 mg/m2. In a clinical study in patients with advanced breast cancer, 250 patients received DOXIL at a starting dose of 50 mg/m2 every 4 weeks. At all cumulativeanthracycline doses between 450-500 mg/m2 or between 500-550 mg/m2, the risk of cardiac toxicity forpatients treated with DOXIL was 11%. Prior use of other anthracyclines or anthracenediones should beincluded in calculations of total cumulative dosage. Cardiac toxicity may also occur at lowercumulative doses in patients with prior mediastinal irradiation or who are receiving concurrentcyclophosphamide therapy [see Warnings and Precautions]. 2. Acute infusion-related reactionsincluding, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, backpain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patientstreated with DOXIL. In most patients, these reactions resolve over the course of several hours to aday once the infusion is terminated. In some patients, the reaction has resolved with slowing of theinfusion rate. Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusionreactions have been reported. Medications to treat such reactions, as well as emergency equipment,should be available for immediate use. DOXIL should be administered at an initial rate of 1 mg/minto minimize the risk of infusion reactions [see Warnings and Precautions]. 3. Severemyelosuppression may occur [see Warnings and Precautions]. 4. Dosage should be reduced inpatients with impaired hepatic function [see Full Prescribing Information]. 5. Accidental substitutionof DOXIL for doxorubicin HCl has resulted in severe side effects. DOXIL should not be substituted fordoxorubicin HCl on a mg per mg basis [see Full Prescribing Information].

3:28 PM

Table 3: Ovarian Cancer Randomized StudyNon-Hematologic DOXIL (%) treated Topotecan (%) treatedAdverse Reaction 10% or Greater (n = 239) (n =235)

All Grades All Grades grades 3-4 grades 3-4

Body as a WholeAsthenia 40.2 7.1 51.5 8.1Fever 21.3 0.8 30.6 5.5Mucous Membrane 14.2 3.8 3.4 0DisorderBack Pain 11.7 1.7 10.2 0.9Infection 11.7 2.1 6.4 0.9Headache 10.5 0.8 14.9 0

DigestiveNausea 46.0 5.4 63.0 8.1Stomatitis 41.4 8.3 15.3 0.4Vomiting 32.6 7.9 43.8 9.8Diarrhea 20.9 2.5 34.9 4.2Anorexia 20.1 2.5 21.7 1.3Dyspepsia 12.1 0.8 14.0 0

Nervous Dizziness 4.2 0 10.2 0

RespiratoryPharyngitis 15.9 0 17.9 0.4Dyspnea 15.1 4.1 23.4 4.3Cough increased 9.6 0 11.5 0

Skin and AppendagesHand-foot syndrome 50.6 23.8 0.9 0Rash 28.5 4.2 12.3 0.4Alopecia 19.2 N/A 52.3 N/A

The following additional adverse reactions (not in table) were observed in patients with ovarian cancerwith doses administered every four weeks. Incidence 1% to 10%: Cardiovascular: vasodilation, tachycardia, deep thrombo phlebitis, hypotension,cardiac arrest. Digestive: oral moniliasis, mouth ulceration, esophagitis, dysphagia, rectal bleeding, ileus.Hemic and Lymphatic: ecchymosis. Metabolic and Nutritional: dehydration, weight loss,hyperbilirubinemia, hypokalemia, hypercalcemia, hyponatremia. Nervous: somnolence, dizziness,depression. Respiratory: rhinitis, pneumonia, sinusitis, epistaxis. Skin and Appendages: pruritus, skindiscoloration, vesiculobullous rash, maculopapular rash, exfoliative dermatitis, herpes zoster, dry skin,herpes simplex, fungal dermatitis, furunculosis, acne. Special Senses: conjunctivitis, taste perversion,dry eyes. Urinary: urinary tract infection, hematuria, vaginal moniliasis.Patients With AIDS-Related Kaposi’s Sarcoma: The safety data below is based on the experiencereported in 753 patients with AIDS-related Kaposi’s sarcoma enrolled in four studies. The median age ofthe population was 38.7 years (range 24-70 years), which was 99% male, 1% female, 88% Caucasian, 6%Hispanic, 4% Black, and 2% Asian/other/unknown. The majority of patients were treated with 20 mg/m2

of DOXIL every two to three weeks. The median time on study was 127 days and ranged from 1 to 811days. The median cumulative dose was 120 mg/m2 and ranged from 3.3 to 798.6 mg/m2. Twenty-sixpatients (3.0%) received cumulative doses of greater than 450 mg/m2. Of these 753 patients, 61.2% wereconsidered poor risk for KS tumor burden, 91.5% poor for immune system, and 46.9% for systemic illness;36.2% were poor risk for all three categories. Patients’ median CD4 count was 21.0 cells/mm3, with 50.8%of patients having less than 50 cells/mm3. The mean absolute neutrophil count at study entry wasapproximately 3,000 cells/mm3. Patients received a variety of potentially myelotoxic drugs in combinationwith DOXIL. Of the 693 patients with concomitant medication information, 58.7% were on one or moreantiretroviral medications; 34.9% patients were on zidovudine (AZT), 20.8% on didanosine (ddI), 16.5% onzalcitabine (ddC), and 9.5% on stavudine (D4T). A total of 85.1% patients were on PCP prophylaxis, most(54.4%) on sulfamethoxazole/trimethoprim. Eighty-five percent of patients were receiving antifungalmedications, primarily fluconazole (75.8%). Seventy-two percent of patients were receiving antivirals,56.3% acyclovir, 29% ganciclovir, and 16% foscarnet. In addition, 47.8% patients received colony-stimulating factors (sargramostim/filgrastim) sometime during their course of treatment. Adversereactions led to discontinuation of treatment in 5% of patients with AIDS related Kaposi’s sarcoma. Thosethat did so included bone marrow suppression, cardiac adverse reactions, infusion-related reactions,toxoplasmosis, HFS, pneumonia, cough/dyspnea, fatigue, optic neuritis, progression of a non-KS tumor,allergy to penicillin, and unspecified reasons.Table 4: Hematology Data Reported in Patients With AIDS-Related Kaposi’s Sarcoma

Patients With Total PatientsRefractory or Intolerant With

AIDS-Related AIDS-RelatedKaposi’s Sarcoma Kaposi’s Sarcoma

(n = 74) (n = 720)Neutropenia

1000/mm3 34 (45.9%) 352 (48.9%)500/mm3 8 (10.8%) 96 (13.3%)

Anemia10 g/dL 43 (58.1%) 399 (55.4%)8 g/dL 12 (16.2%) 131 (18.2%)

Thrombocytopenia150,000/mm3 45 (60.8%) 439 (60.9%)25,000/mm3 1 (1.4%) 30 (4.2%)

Table 5: Probably and Possibly Drug-Related Non-Hematologic Adverse Reactions Reported in 5%of Patients With AIDS-Related Kaposi’s Sarcoma

Adverse Patients With Total PatientsReactions Refractory or Intolerant With

AIDS-Related AIDS-RelatedKaposi’s Sarcoma Kaposi’s Sarcoma

(n = 77) (n = 705)Nausea 14 (18.2%) 119 (16.9%)Asthenia 5 (6.5%) 70 (9.9%)Fever 6 (7.8%) 64 (9.1%)Alopecia 7 (9.1%) 63 (8.9%)Alkaline Phosphatase 1 (1.3%) 55 (7.8%)Increase Vomiting 6 (7.8%) 55 (7.8%)Diarrhea 4 (5.2%) 55 (7.8%)Stomatitis 4 (5.2%) 48 (6.8%)Oral Moniliasis 1 (1.3%) 39 (5.5%)

The following additional (not in table) adverse reactions were observed in patients with AIDS-relatedKaposi’s sarcoma. Incidence 1% to 5%: Body as a Whole: headache, back pain, infection, allergicreaction, chills. Cardiovascular: chest pain, hypotension, tachycardia. Cutaneous: herpes simplex, rash,itching. Digestive: mouth ulceration, anorexia, dysphagia. Metabolic and Nutritional: SGPT increase,weight loss, hyperbilirubinemia. Other: dyspnea, pneumonia, dizziness, somnolence. Incidence Less Than 1%: Body As A Whole: sepsis, moniliasis, cryptococcosis. Cardiovascular: thrombophlebitis,cardiomyopathy, palpitation, bundle branch block, congestive heart failure, heart arrest, thrombosis,ventricular arrhythmia. Digestive: hepatitis. Metabolic and Nutritional Disorders: dehydration.Respiratory: cough increase, pharyngitis. Skin and Appendages: maculopapular rash, herpes zoster.Special Senses: taste perversion, conjunctivitis.Patients With Multiple Myeloma: The safety data below are from 318 patients treated with DOXIL (30 mg/m2 as a 1-hr i.v. infusion) administered on day 4 following bortezomib (1.3 mg/m2 i.v. bolus on days1, 4, 8 and 11) every three weeks, in a randomized, open-label, multicenter study. In this study, patients inthe DOXIL + bortezomib combination group were treated for a median number of 138 days (range 21-410days). The population was 28-85 years of age, 58% male, 42% female, 90% Caucasian, 6% Black, and 4%Asian and other. Table 6 lists adverse reactions reported in 10% or more of patients treated with DOXIL incombination with bortezomib for multiple myeloma. Table 6: Frequency of treatment emergent adverse reactions reported in 10% patients treated for

multiple myeloma with DOXIL in combination with bortezomib, by Severity, Body System, and MedDRA Terminology.

Adverse DOXIL + bortezomib BortezomibReaction (n=318) (n=318)

Any Grade Grade Any Grade Grade(%) 3 4 (%) 3 4

Blood and lymphatic system disordersNeutropenia 36 22 10 22 11 5Thrombocytopenia 33 11 13 28 9 8Anemia 25 7 2 21 8 2General disorders and administration site conditionsFatigue 36 6 1 28 3 0Pyrexia 31 1 0 22 1 0Asthenia 22 6 0 18 4 0Gastrointestinal disordersNausea 48 3 0 40 1 0Diarrhea 46 7 0 39 5 0Vomiting 32 4 0 22 1 0Constipation 31 1 0 31 1 0

Abdominal pain 11 1 0 8 1 0Infections and infestationsHerpes zoster 11 2 0 9 2 0Herpes simplex 10 0 0 6 1 0InvestigationsWeight decreased 12 0 0 4 0 0Metabolism and Nutritional disorders

Nervous system disorders

Neuralgia 17 3 0 20 4 1

Respiratory, thoracic and mediastinal disordersCough 18 0 0 12 0 0Skin and subcutaneous tissue disordersRash** 22 1 0 18 1 0

*Peripheral neuropathy includes the following adverse reactions: peripheral sensory neuropathy,neuropathy peripheral, polyneuropathy, peripheral motor neuropathy, and neuropathy NOS.

**Rash includes the following adverse reactions: rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic, exfoliative rash, and rash generalized.

Post Marketing Experience: The following additional adverse reactions have been identified during postapproval use of DOXIL. Because these reactions are reported voluntarily from a population of uncertain size,it is not always possible to reliably estimate their frequency or establish a causal relationship to drugexposure. Musculoskeletal and Connective Tissue Disorders: rare cases of muscle spasms. Respiratory,Thoracic and Mediastinal Disorders: rare cases of pulmonary embolism (in some cases fatal). Hematologicdisorders: Secondary acute myelogenous leukemia with and without fatal outcome has been reported inpatients whose treatment included DOXIL. Skin and subcutaneous tissue disorders: rare cases of erythemamultiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.DRUG INTERACTIONS: No formal drug interaction studies have been conducted with DOXIL. DOXIL mayinteract with drugs known to interact with the conventional formulation of doxorubicin HCl.USE IN SPECIFIC POPULATIONS: Pediatric Use: The safety and effectiveness of DOXIL in pediatricpatients have not been established.Geriatric Use: Of the patients treated with DOXIL in the randomized ovarian cancer study, 34.7% (n=83)were 65 years of age or older while 7.9% (n=19) were 75 years of age or older. Of the 318 patients treatedwith DOXIL in combination with bortezomib for multiple myeloma, 37% were 65 years of age or older and8% were 75 years of age or older. No overall differences in safety or efficacy were observed betweenthese patients and younger patients.OVERDOSAGE: Acute overdosage with doxorubicin HCl causes increases in mucositis, leucopenia, andthrombocytopenia. Treatment of acute overdosage consists of treatment of the severelymyelosuppressed patient with hospitalization, antibiotics, platelet and granulocyte transfusions, andsymptomatic treatment of mucositis.

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STEALTH® and DOXIL® are registered trademarks of ALZA Corporation.

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DOXIL® C.A.R.E.S. Complements the Efforts of the Healthcare Team With:� Treatment follow-up

— Regularly scheduled telephone calls from oncology nurses to review lifestyle tips to help manage potential side effects of DOXIL® therapy such as hand-foot syndrome and stomatitis

� Patient education materials

Distributed by: Centocor Ortho Biotech Products, L.P., Horsham, Pennsylvania 19044-3607 © Centocor Ortho Biotech Products, L.P. 2010 9/10 08D10019B

For your patients receiving or about to start treatment with DOXIL® for recurrent ovarian cancer or relapsed/refractory multiple myeloma…

INDICATIONS� DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease

has progressed or recurred after platinum-based chemotherapy� DOXIL® in combination with VELCADE® (bortezomib) is indicated for the treatment of

patients with multiple myeloma who have not previously received VELCADE and have received at least one prior therapy

IMPORTANT SAFETY INFORMATIONBOXED WARNINGSCardiotoxicity, infusion reaction, myelosuppression, liver impairment, substitution � The use of DOXIL® may lead to cardiac toxicity. Myocardial damage may lead

to congestive heart failure and may occur as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2

— Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dose

— Cardiac toxicity may also occur at lower cumulative doses (400 mg/m2) in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy

� Acute infusion-related reactions including, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patients treated with DOXIL®. In most patients, these reactions have resolved within several hours to a day once the infusion is terminated. In some patients, reactions resolved with slowing of the infusion rate

— Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have occurred. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use

— The initial rate of infusion should be 1 mg/min to minimize the risk of infusion reactions

� Severe myelosuppression may occur� DOXIL® dosage should be reduced in patients with impaired hepatic function� Accidental substitution has resulted in severe side effects. Do not substitute

for doxorubicin HCl on a mg per mg basis

CONTRAINDICATIONS� Patients with a history of hypersensitivity reactions to a conventional doxorubicin

formulation or the components of DOXIL®

� Nursing mothers

ADDITIONAL SAFETY INFORMATION� Cardiac function should be carefully monitored — Congestive heart failure or cardiomyopathy may occur after discontinuation of

anthracycline therapy — For patients with a history of cardiovascular disease, or if the results of cardiac

monitoring indicate possible cardiac injury, the benefit of therapy must be weighed against the risk of myocardial injury

— In the randomized multiple myeloma study, 25 patients (8%) in the VELCADE arm and 42 patients (13%) in the DOXIL® plus VELCADE arm experienced left ventricular ejection fraction decrease (defined as absolute decrease 15% over baseline or a

5% decrease below institutional lower limit of normal)

� Myelosuppression may occur; frequently monitor complete blood count (including platelet count), at least prior to each dose of DOXIL®

— In patients with recurrent ovarian cancer, hematologic toxicity (based on platelet count or absolute neutrophil count) may require dose reduction or delay in administration of DOXIL®

— In patients with multiple myeloma, hematologic toxicity (based on platelet count, absolute neutrophil count, hemoglobin level, or neutropenia with fever) may require dose reduction, delay in administration, or suspension of DOXIL® and/or VELCADE

— Persistent severe myelosuppression may result in superinfection, neutropenic fever, or hemorrhage

— Sepsis occurring during neutropenia has resulted in discontinuation of treatment and in rare cases of death

� DOXIL® may potentiate the toxicity of other anticancer therapies, especially hematologic toxicities, when used in combination with other therapies that suppress bone marrow

� Hand-foot syndrome (HFS) may occur during therapy with DOXIL®

— Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL® may be required

— HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier• The reaction was mild in most patients, resolving in 1 to 2 weeks• The reaction can be severe and debilitating in some patients, resulting in

discontinuation of therapy� DOXIL® is an irritant, not a vesicant; use precautions to avoid extravasation� DOXIL® can cause fetal harm when used during pregnancy� Recall reaction has occurred with DOXIL® administration after radiotherapy� DOXIL® may interact with drugs known to interact with the conventional formulation

of doxorubicin HCl� In patients with recurrent ovarian cancer, the most common all-grade adverse reactions

(ARs) 20% (DOXIL® vs topotecan, respectively) included: asthenia (40% vs 51%), fever (21% vs 31%), nausea (46% vs 63%), stomatitis (41% vs 15%), vomiting (33% vs 44%), diarrhea (21% vs 35%), anorexia (20% vs 22%), dyspnea (15% vs 23%), HFS (51% vs 1%), and rash (29% vs 12%)

— In addition, 19% vs 52.3% reported alopecia (all grades) — Grade 3/4 hematologic ARs reported in 5% (DOXIL® vs topotecan, respectively)

were neutropenia (12% vs 76%) and anemia (6% vs 29%)� In patients with multiple myeloma, the most common all-grade ARs 20% (DOXIL®

plus VELCADE vs VELCADE, respectively) included: neutropenia (36% vs 22%), thrombocytopenia (33% vs 28%), anemia (25% vs 21%), fatigue (36% vs 28%), pyrexia (31% vs 22%), asthenia (22% vs 18%), nausea (48% vs 40%), diarrhea (46% vs 39%), vomiting (32% vs 22%), constipation (31% vs 31%), mucositis/stomatitis (20% vs 5%), peripheral neuropathy (42% vs 45%), neuralgia (17% vs 20%), and rash (22% vs 18%)

— In addition, 19% vs <1% reported HFS

Please see brief summary of Prescribing Information, including Boxed WARNINGS, on adjacent pages.

VELCADE is a registered trademark of Millennium Pharmaceuticals, Inc.

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