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MAY 2010 VOL 1 NO 1

www.ValueBasedCancer.com

New Tools Arriving to Measure and Manage Chemotherapy Care Business, clinical concerns now connected in value-focused approach

By Daniel Denvir Baltimore, MD—A long-held business truism is that “if you can’t measure it, you can’t manage it.” The application of this belief to the oncology setting was demonstrated at a session of the Association of Community Cancer Centers’ (ACCC) 36th Annual National Meeting. Kimberly Bergstrom, PharmD, chief clinical officer for McKesson Specialty Care Solutions, told attendees of the growing importance of developing and using standardized chemotherapy treatment regimens, and of the tools that

can benchmark performance and foster compliance with treatment guidelines.

Public and private payers are moving to control exploding healthcare costs, Dr Bergstrom told attendees, and because increased cost control was inevitable, it is in providers’ interest to get a seat at the table.

“It is an important topic, because this is one of those things, if we don’t get a handle on it, it’s going to happen to us,” she said. “People and groups and organizations are going to start dictating how we provide cancer care, and we can’t let that happen.”

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Value-Based Cancer Care will be at the ASCO Annual Meeting, June 4-8, in Chicago.

NCCN Roundtable: Clinical and Economic Issues Impacting Cancer Care Delivery “Collision course” in sight

By Audrey Andrews Hollywood, FL—Clinical practice guidelines issued by the National Comprehensive Cancer Network (NCCN) are followed by conscientious oncologists in their everyday practice, but they are developed based on clinical efficacy and without regard to costs. At a roundtable held during the NCCN’s 15th Annual Conference, moderator Clifford Goodman, PhD, Senior Vice President at The Lewin Group, predicted, “The appropriate use of evidence-based guidelines is on a collision course with the financial nonsustainability of the healthcare system.”

Dr Goodman alluded to a level of frustration that has never been higher in cancer care. “Too many patients are still dying young. We need innovations and a cure,” he said.

But the inadequacy of current treatments for cancer is no longer the main problem. Equally challenging, he suggested, is finding a means to pay for the ever-costlier care that threatens to bankrupt the healthcare system.

As society struggles to find solutions, “the ground is shaking beneath us,” Dr Goodman commented.

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Please visit us at booth 18121

SEER-Medicare Database Analysis Confirms Expensive Prostate Breast Cancer Survival Improves, Cancers Gaining Supremacy Photo by © ASCO/Todd Buchanan 2009

Thanks to New Therapies

By Colin Gittens Barcelona—Survival for patients with metastatic breast cancer has improved dramatically in the last 20 years, especially in the subgroup of patients with HER2-positive tumors, according to research presented at the 7th European

Breast Cancer Conference (EBCC7).

This improvement, the researchers suggest, is due to increased use of anthracyclines and the rise of targeted therapies.

“There is no doubt that trastuzumab (Herceptin), which targets the HER2 gene, is the most important Continued on page 27

But cost-effectiveness of this move remains to be determined

By Rosemary Frei, MSc San Francisco, CA—The popularity of minimally invasive radical prostatectomy (MIRP), intensity-modulated radiation therapy (IMRT), and of brachytherapy combined with IMRT for prostate cancer started to take off after 2002, a new database analysis has confirmed.

At the American Society of Clinical Oncology’s 2010 Genitourinary Cancers Symposium, Paul L. Nguyen, MD, presented the results of his team’s analysis of data from the Surveillance, Epidemiology and End Results (SEER)-Medicare database.

Dr Nguyen, director of Prostate Brachytherapy, Dana-Farber/Brigham

The 2010 Genitourinary Cancers Symposium: Progress in Multidisciplinary Management was held March 5-7 in San Francisco. All sessions emphasized a multidisciplinary approach to care; a number of them brought out the cost and value issues associated with caring for genitourinary cancers. and Women’s Hospital, Harvard Medical School, Boston, and his coinvestigators found MIRP jumped from 1.5% of radical prostatectomies (RPs) in 2002 to 28.7% in 2005. They also found that IMRT soared from 8.7% of external radiation treatments for prostate cancer to 81.7%. In addiContinued on page 24

©2010 Engage Healthcare Communications, LLC

ALOXI provides powerful CINV prevention that can’t be ignored. ®

Proven chemotherapy-induced nausea and vomiting (CINV) prevention in a single IV dose.

• Powerful CINV prevention in the first 24 hours and up to 5 days following moderately emetogenic chemotherapy1,2 • Powerful acute CINV prevention following highly emetogenic chemotherapy3 • Can be used in multiple-day chemotherapy regimens4* * The restriction on repeated dosing of ALOXI within a 7-day interval was removed from the label.5

Indication ALOXI® (palonosetron HCl) injection 0.25 mg is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.

Important Safety Information • ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components • Most commonly reported adverse reactions in chemotherapy-induced nausea and vomiting include headache (9%) and constipation (5%) Please see the following brief summary of Full Prescribing Information.

References: 1. Gralla R, et al. Ann Oncol. 2003;14:1570-1577. 2. Eisenberg P, et al. Cancer. 2003;98:2473-2482. 3. Aapro MS, et al. Ann Oncol. 2006;17:1441-1449.

4. ALOXI® (palonosetron HCl) injection full prescribing information. 5. Data on file. Eisai Inc., Woodcliff Lake, NJ.

STARTS STRONG. LASTS LONG.

ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license.

Distributed and marketed by Eisai Inc. © 2010 Eisai Inc. All rights reserved. Printed in USA. ALO00034 04/10

FDA upDAtes

Oncology-related updates from the US Food and Drug Administration Cellular Immunotherapy Approved in Advanced Prostate Cancer The FDA approved Provenge (sipuleucel-T), a new therapy for certain men with advanced prostate cancer ALOXI® (palonosetron HCl) injection BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Chemotherapy-Induced Nausea and Vomiting ALOXI is indicated for: • Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses • Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat courses DOSAGE AND ADMINISTRATION Recommended Dosing Chemotherapy-Induced Nausea and Vomiting Dosage for Adults - a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy.

Instructions for I.V. Administration ALOXI is supplied ready for intravenous injection.

ALOXI should not be mixed with other drugs. Flush the infusion line with normal saline before and after administration of ALOXI. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.

CONTRAINDICATIONS ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [see Adverse Reactions (6) in full prescribing information ] WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT 3 receptor antagonists.

ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates reported in practice.

In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron.

Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).

Table 1: Adverse Reactions from ChemotherapyInduced Nausea and Vomiting Studies ≥ 2% in any Treatment Group ALOXI Ondansetron Dolasetron Event 0.25 mg 32 mg I.V. 100 mg I.V. (N=410) (N=633) (N=194) Headache 60 (9%) 34 (8%) 32 (16%) Constipation 29 (5%) 8 (2%) 12 (6%) Diarrhea 8 (1%) 7 (2%) 4 (2%) Dizziness 8 (1%) 9 (2%) 4 (2%) Fatigue 3 (< 1%) 4 (1%) 4 (2%) Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%) Insomnia 1 (< 1%) 3 (1%) 3 (2%) In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a postoperative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study.

In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy: Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear.

Dermatological: < 1%: allergic dermatitis, rash.

Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.

Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence.

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that uses the patient’s own immune system to fight the disease. Provenge is indicated for the treatment of asymptomatic or minimally symptomatic prostate cancer that has spread General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome.

Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy.

Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.

Musculoskeletal: < 1%: arthralgia.

Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia.

Psychiatric: 1%: anxiety, < 1%: euphoric mood.

Urinary System: < 1%: urinary retention.

Vascular: < 1%: vein discoloration, vein distention.

Postmarketing Experience The following adverse reactions have been identified during postapproval use of ALOXI. 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 drug exposure.

Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience of ALOXI 0.25 mg in the prevention of chemotherapy-induced nausea and vomiting.

DRUG INTERACTIONS Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low.

Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone.

In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not significantly altered (AUC: no change, Cmax: 15% increase).

A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no significant pharmacokinetic interaction.

In controlled clinical trials, ALOXI injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents.

Palonosetron did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models.

USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category B Teratology studies have been performed in rats at oral doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) and rabbits at oral doses up to 60 mg/ kg/day (3789 times the recommended human intravenous dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed.

Labor and Delivery Palonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown.

Nursing Mothers It is not known whether palonosetron 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 and the potential for tumorigenicity shown for palonosetron in the rat carcinogenicity study, 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.

to other parts of the body and is resistant to standard hormone treatment.

The majority of adverse reactions with Provenge were mild or moderate in severity. (April 29, 2010) Pediatric Use Safety and effectiveness in patients below the age of 18 years have not been established.

Geriatric Use Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out. No dose adjustment or special monitoring are required for geriatric patients.

Of the 1520 adult patients in ALOXI PONV clinical studies, 73 (5%) were ≥65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded. No differences in efficacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, ALOXI efficacy in geriatric patients has not been adequately evaluated.

Renal Impairment Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure increased by approximately 28% in severe renal impairment relative to healthy subjects.

Dosage adjustment is not necessary in patients with any degree of renal impairment.

Hepatic Impairment Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment.

Race Intravenous palonosetron pharmacokinetics was characterized in twenty-four healthy Japanese subjects over the dose range of 3 – 90 mcg/kg. Total body clearance was 25% higher in Japanese subjects compared to Whites, however, no dose adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been adequately characterized.

OVERDOSAGE There is no known antidote to ALOXI. Overdose should be managed with supportive care.

Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fixed dose) as part of a dose ranging study. This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed.

Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose. A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.

PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.2) in full prescribing information Instructions for Patients • Patients should be advised to report to their physician all of their medical conditions, any pain, redness, or swelling in and around the infusion site [see Adverse Reactions (6) in full prescribing information].

• Patients should be instructed to read the patient insert.

Rx Only Mfd by OSO Biopharmaceuticals, LLC, Albuquerque, NM, USA or Pierre Fabre, Médicament Production, Idron, Aquitaine, France and Helsinn Birex Pharmaceuticals, Dublin, Ireland.

ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license.

Distributed and marketed by Eisai Inc., Woodcliff Lake, NJ 07677. © 2009 Eisai Inc. All rights reserved. Printed in USA. AL449 08/09

Tarceva Receives New Indication The FDA approved erlotinib (Tarceva) tablets for maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy. This approval is erlotinib’s second indication in locally advanced or metastatic NSCLC. Erlotinib was originally approved in November 2004 for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen.

(April 16, 2010) Pancreatic Product Approved The FDA approved Pancreaze Delayed Release Capsules, a pancreatic enzyme product used to improve food digestion in patients whose bodies do not produce enough pancreatic enzymes. This includes people who have conditions such as cystic fibrosis, chronic pancreatitis, pancreatic tumors, or removal of all or a part of the pancreas. (April 12, 2010) An Extended Shortage of Mustargen The FDA has been informed by Lundbeck Inc, the sole worldwide manufacturer of Mustargen (mechlorethamine HCl for injection), that an extended supply shortage of this drug is in the offing.

A limited supply of Mustargen is expected to be available starting in mid-to-late April, and will be distributed by Lundbeck Inc to meet current patient needs, with priority given to sites with patients currently receiving Mustargen. Once this limited supply is exhausted, a shortage is anticipated until early 2011. Given the expected shortage, alternative treatment plans should be made for new patients to avoid interruption to a Mustargen treatment program. (April 9, 2010) OxyContin Reformulated The FDA approved a new formulation of the controlled-release drug OxyContin that is designed to discourage misuse and abuse of the medication. The reworked capsule is intended to prevent the medication from being cut, broken, chewed, crushed, or dissolved to release medication more quickly. The drug’s manufacturer, Purdue Pharma, LP, will be required to conduct a postmarket study to evaluate the effectiveness of the new formulation in lessening abuse, as well as a risk evaluation and mitigation strategy. (April 5, 2010)

www.ValueBasedCancer.com

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tABle oF coNteNts Publisher Nicholas Englezos nick@engagehc.com 732-992-1884 Associate Publisher Maurice Nogueira maurice@engagehc.com 732-992-1895

May 2010 A Letter to Our Readers Value Propositions VBCC Perspective Evidence-based Medicine: A First Step on the Path to Value/Arlene A. Forastiere, MD

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Directors, Client Services John Hennessy john@greenhillhc.com 732-992-1886 Phil Pawelko phil@greenhillhc.com 732-992-1887 Cristopher Pires cris@greenhillhc.com 732-992-1896 Editorial Director Dalia Buffery dalia@AHDBonline.com 732-992-1889 Managing Editor Colin Gittens colin@engagehc.com 732-992-1536 Senior Production Manager Robyn Jacobs

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Coverage from the Association of Community Cancer Centers 36th Annual National Meeting 8 Pennsylvania Practice Drives Value in Pilot Program 9 Foreign Cancer Care Offers a Mirror to Our Own 10 Radiation and Reimbursement Concerns Dog Diagnostic Imaging 11 Get Ready for Comparative Effectiveness Research Community Cancer Centers Face Economy’s Impact

13 VBCC Perspective Traditional Managed Care Tools Just Don’t Work in Oncology/Peter G. Ellis, MD, and Kathy Lokay

Business Manager Blanche Marchitto Mission Statement Value-Based Cancer Care provides a forum for payers, providers, and the entire oncology team to consider the cost-value issues particular to cancer treatments.

This unique focus is achieved through news coverage from major hematology/oncology meetings and the cancer literature, supplemented with commentaries and perspectives from those involved in evaluating therapies, treating patients, and paying for care.

Coverage from the Hematology/Oncology Pharmacists Association 6th Annual Meeting 14 Healthcare Reform Through the Eyes of Joseph S. Bailes, MD 15 Oncology Pharmacy Reimbursement Issues in 2010

Contact Information: For subscription and reprint information please contact: circulation@valuebasedcare.com Telephone: 732-992-1538 Fax: 732-992-1881

16 VBCC Perspective

Permission requests to reprint all or part of any article published in this magazine should be addressed to PERMISSIONS DEPARTMENT. Fax: 732-992-1881.

Address all editorial correspondence to: editor@valuebasedcare.com Telephone: 732-992-1536 Fax: 732-992-1881 Value-Based Cancer Care, ISSN 2153-4888 (print); ISSN 2153-4896 (online), is published 6 times a year by Engage Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205A, Monroe Township, NJ 08831. Copyright © 2010 by Engage Healthcare Communications, LLC. All rights reserved.

Value-Based Cancer Care is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher.

Printed in the United States of America.

The ideas and opinions expressed in Value-Based Cancer Care do not necessarily reflect those of the editorial board, the editors, or the publisher.

Publication of an advertisement or other product mentioned in Value-Based Cancer Care should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the editors nor 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 mentioned in this publication.

Compendia: Powerful Tools, Wrong Job?/ Lynn Nishida, RPh

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Coverage from the National Comprehensive Cancer Network 15th Annual Conference 20 The NCCN Task Force on Specialty Pharmacy Issues Preliminary Report 21 Reimbursement for Expensive Cancer Therapies: The Role of Cost-effectiveness Analysis Coverage from the 2010 Genitourinary Cancers Symposium 24 Researcher Graphically Illustrating Which Treatments Are Best for Prostate Cancer 25 Better Diagnostic Accuracy Through More Testing?

Not Necessarily When It Comes to Bladder Cancer Researchers Probe Concurrent Timing of ADT Use Drop and Medicare Reimbursement Policy Change Other Research from the 2010 Genitourinary Cancers Symposium Coverage from the 7th European Breast Cancer Conference 27 Radical Treatment Not Best Course for BRCA Mutations Collaboration Needed to Maximize Tamoxifen’s Benefit 28 Existing Test May Have New Use in Anthracycline Targeting Protein Offers Expanded Predictive Significance in Early Breast Cancer

29 For Dying Patients, Emergency Care Is Less 30

VBCC editorial Board

Than Ideal New Colorectal Cancer Therapies Foster New Discussions on the Value of Medications

Bruce A. Cutter, MD, MMM Cancer Care Northwest Spokane, WA

Lynn Nishida, RPh Regence Blue Cross Blue Shield of Oregon Portland, OR

Peter G. Ellis, MD University of Pittsburgh School of Medicine and UPMC Cancer Centers Pittsburgh, PA

Lee Newcomer, MD, MHA UnitedHealthcare Minnetonka, MN

Arlene A. Forastiere, MD ITA Partners Philadelphia, PA

Ed Pezalla, MD, MPH Aetna Pharmacy Management Hartford, CT

Tracy Gosselin, RN, MSN Duke University Medical Center Durham, NC

Denise K. Pierce DK Pierce & Associates Zionsville, IN

Scott Gottlieb, MD Mount Sinai Medical Center and the American Enterprise Institute New York, NY

Jatin J. Shah, MD M. D. Anderson Cancer Center Houston, TX

VALUE-BASED CANCER CARE

Jayson Slotnik, JD Foley Hoag Washington, DC Brian K. Solow, MD, FAAFP PrescriptionSolutions San Diego, CA G. Rhys Williams, ScD, MS Amgen Thousand Oaks, CA Winston Wong, PharmD CareFirst BlueCross BlueShield Baltimore, MD Yu-Ning Wong, MD, MSCE Fox Chase Cancer Center Philadelphia, PA

Value-Based Cancer Care is the official publication of the Association for Value-Based Cancer Care

POSTMASTER: CORRESPONDENCE REGARDING SUBSCRIPTIONS OR CHANGE OF ADDRESS should be directed to CIRCULATION DIRECTOR, Value-Based Cancer Care, 241 Forsgate Drive, Suite 205A, Monroe Township, NJ 08831. Fax: 732-992-1881. YEARLY SUBSCRIPTION RATES: One year: $99.00 USD; Two years: $149.00 USD; Three years: $199.00 USD.

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Save the date for our first annual meeting, Tuesday, October 12, 2010, in St. Louis, Missouri

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FRoM the puBlisheRs

A letter to our Readers

W

elcome to this, the first issue of Value-Based Cancer Care! What sort of publication is this, why have we decided to create it, and what can you expect to see as you review this and future issues?

The title expresses it clearly and succinctly. This publication will focus relentlessly on matters of value in cancer through news reporting, feature writing, and commentary from clinicians, payers, and policymakers. Many publications already cover policy, pharmacoeconomics, and/or clinical medicine as part of their editorial focus, so how is Value-Based Cancer Care different?

Value is often defined by the equation value = quality / cost, and in this era of steadily increasing costs—of medications, of new technologies, and of health insurance premiums—a careful and consistent look at the benefits of new therapies and their costs is, we believe, helpful to all stakeholders.

With the cost of bringing a new medication to the market now past the $1-billion mark, it is not surprising that drug therapies cost more than ever before. And with many cancer medications being developed for particular subsets of patients, or being found efficacious only in smaller, genotypically similar groups, the day of the universally applicable cancer drug may well be over.

In addition, the results offered by some of these drugs, often measured in weeks or months of additional life, have led some to raise an issue previously unspeakable when it came to medical treatment—is it worth it?

That difficult question, and more general conversations involving access, costs, and outcomes are what Value-Based Cancer Care will address by drawing together coverage of medicine, policy, economics, business practice, and regulatory matters. Comparative effectiveness research, which addresses value in a very basic way and that will become more familiar as healthcare reform kicks in, will also be covered in this publication. And the real-world implications and application of these developments will be considered in analytical, insightful perspectives provided by our editorial board.

That editorial board reflects the diversity of our readership, with members drawn from the spectrum of cancer care payers, purchasers, policymakers, and providers. Our panel of experts possesses a broad background in clinical medicine, benefit design, law, pharmacy, and practice management, allowing for the topical analysis from a number of perspectives that will be a cornerstone of the publication. We will continue to grow this board as the publication matures, but please look at the facing page to see our present roster of experts.

This first issue contains coverage from a number of recent meetings at which the economics of cancer care were addressed; clearly this is a topic on the minds of many right now. We envision Value-Based Cancer Care as a place where timely coverage and discussion of such important topics will occur regularly, and where all parties in today’s cancer care will find not just news but insight.

We hope this is the case for you, and we welcome your thoughts on this publication.

Colin Gittens, Managing Editor

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VAlue pRopositioNs Cost Creeps into Cancer Treatment Considerations

Imaging Gone Wild

Findings from a representative national survey of 1379 US oncologists (787 of whom responded) indicate that the rising cost of cancer therapies has become a factor in treatment deliberations. The percentages indicate the oncologists surveyed who “strongly or somewhat agreed” with the following statements.

Patient out-of-pocket drug costs currently influenced treatment recommendations More use of cost-effectiveness data for coverage and payment decisions is needed More government research on comparative effectiveness is needed Cost of new drugs in next 5 years will influence my treatment recommendations Every US patient should have access to effective treatment regardless of cost Patients should have access to effective medicines only if they provide “good value for money” Costs of new cancer drugs currently influence my treatment recommendations

84% 80% 79% 73% 67% 58% 56%

On the question of who should determine the value of a medication, 60% responded “physicians,” while 57% responded “nonprofit.” Only 37% thought that patients should address this question.

Data adapted from Cancer Therapy Costs Influence Treatment: A National Survey of Oncologists (Health Affairs. January 2010;29[1]:196-202).

Early Melanoma Diagnosis, Treatment Offers Fiscal Protection The clinical benefit of catching any cancer at an earlier stage is well known, but now evidence of what this earlier diagnosis and treatment would mean in terms of costs is also emerging. Writing in the March 2010 issue of the Archives of Dermatology (2010;146[3]:249-256), a team of researchers from Emory University report on their study of persons ≥65 years of age with late-stage melanoma. The average monthly, per-patient melanoma charges were $2194 during the initial 4 months of treatment; dropped to $902 during the interim phase; but increased to $3933 during the terminal 6 months of treatment. The authors concluded from the data that if all patients were diagnosed and treated in stage 0 or I, the annual direct costs in those ≥65 years of age would be between $99 million and $161 million, or 40% to 65% of the current costs of $249 million.

“The US population is aging rapidly,” explained principal investigator Suephy C. Chen, MD, MS, in a press release announcing the findings.

“Routine screening of these individuals to diagnose melanoma before it reaches an advanced stage will not only impact the physical outcome, but could also vastly reduce the financial burden of the disease.”

Consumerism and Cancer A San Diego–based company has announced the release of an outpatient testing kit that may detect 18 types of cancer. The test, called You Test You, provides results in 10 days, costs $149, and is, according to the press release announcing the test, “a convenient and low-cost way to periodically test for indication of cancer.”

The test is ordered online, and that form is reviewed by a You Test You doctor, who then writes a prescription allowing the patient to then visit a local laboratory to have a blood sample drawn. The test evaluates certain proteins in the blood that are frequently associated with most cancers, according to Robert Gans, the CEO of the manufacturer, GenWay Biotech, Inc. A home sample collection kit will be available in the first part of 2010.

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“How have we evolved to ordering the most expensive imaging technique first for these patients, only to be followed frequently by a far less costly ultrasound examination to clarify the CT [computed tomography] findings? Ultrasound is the established modality of choice to evaluate the female pelvis, so why do patients with pelvic masses or pain get a CT scan? In my opinion, doing a CT scan first for female patients with lower abdominal pain is dangerous and wasteful, a drain of much-needed healthcare dollars.”

Beryl Benacerraf, MD, a clinical professor of radiology and obstetrics and gynecology at Harvard Medical School, and editor-in-chief of the Journal of Ultrasound in Medicine, discusses the evaluation of acute female pelvic and lower abdominal conditions in an editorial in the March 2010 issue.

Putting the Brakes on Inappropriate Treatments Physicians can say no—nicely—to patient requests for a particular medication without jeopardizing the physician–patient relationship, indicates a report in the Archives of Internal Medicine (2010;170[4]:381-388).

“Medications prescribed at the behest of patients may not always represent physicians’ first choice of treatment, particularly if the requests are commercially motivated, as for example, by direct-to-consumer advertising,” the authors write in setting the context of the study. Nevertheless, physicians worry that denials of these requests could lead to lower patient satisfaction.

The authors conducted a randomized trial using trained patients who requested antidepressants of primary care physicians while complaining of feeling tired and also either wrist or back pain.

Improving Payment for Cancer Trial Participants Although Medicare patients participating in cancer clinical trials are covered for clinical-trial–related medical costs by federal law, non-Medicare patients are not protected by this law and must rely on individual state insurance mandates, which can lead to financial, ethical, and scientific inequity.

In a study published online in the Journal of the National Cancer Institute on March 2, Patrick L. Taylor, JD, of the Children’s Hospital, Boston, and Harvard Medical School reviewed the mandates for requirements to assure trials’ scientific and ethical soundness, whom these covered and omitted, their scope, and the coverage for participants’ research-related injuries in addition to routine care costs. Mr Taylor found that only 25 states had enacted legislation concerning coverage of cancer clinical trial costs. About half of them required coverage of only certain kinds of trials, under certain conditions, and very few required publication of results.

Medication Compliance? There’s a Pill for That The next generation of medications may allow doctors to know whether their patients have actually taken the medication prescribed, thanks to continued developments in nanotechnology.

Engineering researchers from the University of Florida in Gainesville have created a prototype pill capsule that includes a tiny microchip and a digestible antenna. The microchip is the size of a period, while the antenna is made from silver nanoparticles embossed in lines on the exterior of the pill.

The delivery system is intended to bolster compliance in clinical drug trials, say the authors. For now, the pill has been tested only in human models and cadavers. According to Eric Buffkin, president of the firm developing the commercial application of the pill, the technology would add $0.25 to $0.50 to the cost of a dose, and should be ready for the marketplace in 2 years.

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Evidence-based Medicine: A First Step on the Path to Value

By Arlene A. Forastiere, MD established standard chemotherapy regimen, supportive care drug, or a clinical trial. The potential risks and benefits of the particular treatment are quantifiable from published data.

This is the first step in improving quality, and physician registries and payer databases are analyzing this information in retrospective and prospective fashion.

Although it seems intuitive that practicing evidence-based medicine will reduce ineffective prescribing (ie, overdosing, underdosing, and Continued on page 23

T

he 2007 annual meeting summary of the Institute of Medicine (IOM) succinctly highlighted the issue of variability in care. “Studies repeatedly show marked variability in what healthcare providers actually do in a given situation. [By following evidence-based practice], there is an untapped potential to reduce healthcare costs and improve quality.”1 In the 2001 IOM report Crossing the Quality Chasm: A New Health System for the 21st Century, one of the 10 axioms for the redesign of our healthcare system called for evidence-based decision making. “Patients should receive care based on the best available scientific knowledge. Care should not vary illogically from clinician to clinician or from place to place.”2

In oncology, we have an opportunity to test the hypothesis that reducing variability in patient care improves quality & lowers cost Today in oncology, we have an opportunity to test the hypothesis that reducing variability in patient care (eg, by adherence to guidelines) improves quality and lowers cost.

Oncology is perfectly positioned for this, owing to the regularly updated practice guidelines documenting the strength of the evidence that underpin the recommendations. These include guidelines from the National Cancer Institute/Physicians Data Query, American Society of Clinical Oncology, National Comprehensive Cancer Network, and others. Evidence-based medicine benefits all 3 constituents in cancer care and brings the payer and provider into alignment for the right reasons. The physician has a credible basis for the treatment options and recommendations in discussions with the patient; the patient can feel confident that the treatment he or she has decided upon is the best for them; and the health plan is paying for medically necessary and appropriate care, whether an Arlene A. Forastiere, MD, is senior vice president, Medical Affairs, at ITA Partners, Inc, Philadelphia, Pa and an editorial board member of Value-Based Cancer Care.

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UNITED IN PURPOSE WE’LL FIGHT AS ONE. UNTIL CANCER IS GONE.

In one way or another, cancer touches everybody. That’s why US Oncology is bringing physicians, patients and insurers together. Using evidence-based medicine and a data-driven approach, we are helping more people get the best cancer care while ensuring that scarce healthcare resources are used wisely.

To learn more about how US Oncology is transforming cancer care, visit usoncology.com

Copyright © 2010 US Oncology, Inc. All rights reserved.

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New Tools Arriving to Measure Care...

Cost Increases, Cost Management According to Dr Bergstrom, the last decade has seen a shift by payers in their approach to managing spending for oncology drugs. Up until the early 2000s, there was little in the way of medical policy guidance and preauthorization. In the early to middle part of that decade, preauthorization and guidance was applied to select high-value and high-risk products.

From the mid-2000s on, medical policy has increasingly been based on care guidelines and pathways, and this evolution has led to increasingly complex administrative requirements and data needs on the parts of both payers and providers.

Health plans are taking a number of long- and short-term approaches to managing costs, she said. The plans “have a huge interest in reducing your drug margin to save them money,” said Dr Bergstrom. “They want to move [physicians] away from their dependence on the drug margin and move to more service-based fees.

They want to separate the oncology income from drug sales.”

But many payers, said Dr Bergstrom, are currently reducing costs on their own terms, and cutting into providers’ bottom lines.

“This really provides us with a great dilemma,” she said. “Decreased revenue, increased administrative burden, and costs. Payers are managing specialized care aggressively. And they’re using 2 key tools that they know best: they’re reducing your fee schedules and they’re requiring prior authorization.”

But reduced costs don’t have to mean reduced care. According to Dr Bergstrom, cost control and standardization of effective treatment regimens should go hand in hand.

“They are creating payment policies that actually reward clinical performance,” she said. “A lot of that has to do with the focus on standardized

Table Sources of Free Cancer Clinical Guidelines National Guideline Clearinghouse (www.guideline.gov) National Comprehensive Cancer Network (www.nccn.org) ASCO Guidelines (www.asco.org) Cancer Care Ontario (www.cancercare.on.ca) McKesson Guidelines (www.onmarkservices.com)

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treatment guidelines and rewards for achieving certain clinical measures.”

From Onerous to Opportunity Dr Bergstrom argued that increased payer scrutiny creates an opportunity for caregivers to examine practice efficiency, to present community-based oncology as a cost-efficient means of care delivery, and to explore a wider use of data-based performance.

Standardized chemotherapy regimens increase practice efficiency, reduce errors, simplify billing, and make it easier to measure outcomes of care, Dr Bergstrom suggested. And from the payer’s perspective, improved care consistency and predictability of costs is appealing, as is the ability to prove quality and value to plan sponsors and patients.

There are a number of free clinical tools that can help with benchmarking and standardization (Table). In addition, limiting the number of chemotherapy regimens via an electronic medical record and standardizing prechemotherapy medications, supportive care drugs, and antineoplastic dosing are helpful means of standardizing care, Dr Bergstrom suggested.

Other analytical tools provide the

Continued from cover

ability to track and manage costs, reimbursement, and profitability.

With today’s narrow financial margins, Dr Bergstrom noted, making physicians aware that a particular chemotherapy regimen is “underwater” (ie, more expensive than the reimbursement given for it) in real time is essential. She recommended that practices regularly check their standardized regimens against the

sation is essential in today’s environment, Dr Bergstrom emphasized. “If you can get your physicians together and talk about how to focus your approach to care for certain diagnoses, and really narrow the choices of regimen, you will improve quality across the team,” she said. “Because all of a sudden instead of every physician doing a slightly different version of CHOP or FOLFOX…

“Payers are managing specialized care aggressively. And they’re using 2 key tools that they know best: they’re reducing your fee schedules and they’re requiring prior authorization.”

—Kimberly Bergstrom, PharmD

quarterly changed Medicare fee schedule to ensure continued profitability. Some of these chemotherapy management tools include ION Protocol Analyzer (www. iononline.com), McKesson’s Onmark Regimen Profiler (www.onmark services.com), and P4 PBIS eobONE (www.p4healthcare.com).

Having a clinical and cost conver-

everyone’s going to be singing from the same songbook. The nurses aren’t confused. Everyone is standardized.

Your billers know what to bill: it’s the same thing over and over again.”

“Payers need consistency of care,” concluded Dr Bergstrom. “If they can predict what the costs of cancer care are, they will be able to set their premiums better.” ■

Pennsylvania Practice Drives Value in Pilot Program

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ick Leasure, MD, of Berks Hematology-Oncology Associates in Reading, Pa, described an effort at his 7-person hematology/oncology practice to understand utilization patterns, standardize care, foster guideline adherence, and demonstrate value to payers. The practice focused specifically on breast and colon cancer, as these are commonly handled in the community setting, and they used Onmark’s Regimen Profiler for this pilot program.

The practice began the program by establishing benchmarks for existing care. During 9 months of measurement in 2007 and 2008, they documented 52 chemotherapy regimens for colon cancer and 147 regimens for breast cancer at their practice. They also measured compliance with National Comprehensive Cancer Network (NCCN) guidelines for care of these cancers (Table) and the costs associated with the regimens.

Rather than any top-down management edicts, the standardization experience process involved physician champions who worked to tailor the

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care pathways to fit practice preferences, including selected regimens.

These care pathways were then presented to subspecialty chairs, then to the group as part of incorporation into the electronic medical record (EMR).

“It wasn’t hard to get buy-in when you showed the physicians the statistics.”

—Nick Leasure, MD The program succeeded both in limiting the number of regimens used and in reducing costs. In 6 months, the number of adjuvant regimens for

colon cancer dropped from 4 to 3, and costs dropped from $53,966 to $39,285 from baseline to poststandardization.

Adjuvant treatment for breast cancer saw a reduction to 7 chemotherapy regimens (from 23 at the outset), while the number of regimens used for firstline metastatic breast cancer dropped to 5 from 23.

“With some discussion we were able to pare down the number of regimens pretty quickly and effectively,” said Dr Leasure, adding “the EMR carrot has been very effective” in guiding the use of particular regimens.

“The concern whenever you speak about regimen standardization is the loss of physician autonomy,”

Table Berks Hematology-Oncology Associates Compliance with NCCN Pathways Colon Cancer Adjuvant treatment First-line metastatic treatment Breast Cancer Adjuvant treatment First-line metastatic treatment

At Baseline

Following Program

76% 91%

100% 100%

78% 52%

96% 88%

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Foreign Cancer Care Offers a Mirror to Our Own

By Colin Gittens Baltimore, MD—In light of ongoing discussions on healthcare and its reform in the United States, an examination of how care is financed and delivered in other parts of the world could provide a useful contrast for our own national deliberations. That was the premise behind a session at the Association of Community Cancer Centers’ (ACCC) 36th Annual National Meeting titled “Treating Cancer in Foreign Healthcare Systems,” which offered an insightful look into the financing and the value systems that undergird the healthcare systems in France, Germany, Italy, the United Kingdom (UK), and other nations around the world.

The panel discussion, moderated

by Cliff Goodman, PhD, of the Lewin Group of Falls Church, Va, began with a discussion of how healthcare is financed in other countries. As with those countries, “The way this country’s healthcare financing system is set up trickles down and has a lot of other effects in the way choices are made in cancer care,” said Dr Goodman.

Anne-Pierre Pickaert, MSc, of Kantar Health, described the social

acknowledged Dr Leasure. “That we decide to use a certain number of regimens, that you’re being told how to prescribe and what to prescribe. I think that although that’s a concern, just the opposite is the case...in our practice.”

Although physicians have found the standardization process helpful, Leasure said that if physicians are not part of the decision making from square one, there could be resistance to change. Ultimately, “it wasn’t hard to get buy-in when you showed the physicians the statistics,” he said.

Clinical effectiveness remains Dr Leasure’s top priority, but the value of a program such as Regimen Profiler is that it can help break a tie between 2 clinically equivalent treatments, he noted. Most importantly, the data allows the practice to demonstrate value to payers. The practice is meeting with a payer soon, hoping to smooth the coming transition away from fee-for-service. Regimen Profiler is just one tool Berks has used as part of a larger effort to standardize regimens. ■

construct of healthcare financing in Western Europe. Germany has a social contribution system; Italy, Spain, and the UK have a tax-based system. In France, there “are no hurdles to access” for care, she noted; coverage is universal and publicly funded.

they order or how long they give them. That actually helps to get that part of the pressure off their backs.”

Evaluating New Innovation With new, costly cancer medications entering the market, a look at how other nations evaluate these

“Because most oncologists in Canada feel that…they are stewards of a set of resources, they have a long history of healthy skepticism about the value of new drugs.”

—Carol Sawka, MD, FRCPC

Harris W. Dalrymple, PhD, MML, of the UK-based contract research firm PPD, indicated that Eastern Europe also has a federally funded system of healthcare, but generally speaking, that coverage is capped.

“One of the consequences of that capping is that once the funds for treatment are exhausted, the treatment options are exhausted as well,” he noted. “That has implications for access to some of the newer, more expensive cancer therapies.”

In Canada, said Carol Sawka, MD, FRCPC, of Cancer Care Ontario, a mix of provincial and federal taxes support the financing of public healthcare, but responsibility for actually organizing and delivering care is assigned at the provincial level. “The overall principles that govern healthcare are determined by the Canada Health Act (CHA), something that Canadians hold very dear,” Dr Sawka related.

These principles emphasize that Canadian healthcare should be universally accessible, portable, comprehensive, and that the system should be publicly administered, she outlined. Under this system, Canada spends 10% of its gross domestic product on healthcare, compared with 16% in the United States. The public system pays for hospitals, physicians, and many drugs, but is also supplemented by private insurance that can cover items not provided by the public plan, such as certain drugs.

In addition, “Oncologists have nothing to do with buying and selling drugs” in Canada, Dr Sawka pointed out, so “they don’t have a financial stake in terms of the type of drugs

drugs and make coverage decisions offered contrasts to the US system. In France, Ms Pickaert noted, access to the new medicines is fairly good; for those in clinical trials, early-access programs ensure the patient continued access to the drug they are receiving. The other 4 countries (Italy, Spain, Germany, and the UK) have “compassionate use” programs, as well as temporary protocols that allow drug use for unapproved indications.

But this access does come at a cost, and as Ms Pickaert related, and with their budgetary impact, the French government is trying to restrict these programs. “French oncologists don’t know how much their drugs cost. They’ve got no clue,” said Ms Pickaert.

Increasingly in Eastern and Western Europe and Japan, said Dr Dalrymple, a risk-sharing approach to new oncology drugs is being used.

With this approach, drugs are given for a certain number of cycles or for a limited period of time, and then an evaluation of efficacy is made. If the drug is considered efficacious, treatment continues and reimbursement is made by the central authority to the manufacturer, with no financial liability assigned to the patient. Two situations may financially burden the patient, however. One is conditional access, wherein a patient who has previously failed a treatment is given access to a new agent, or where a drug has been approved but is not yet available in the centralized healthcare system.

In Canada, drug manufacturers first must get a certificate of compli-

ance from the federal government indicating that its drug is safe and effective, and pricing is controlled.

But whether a drug is included on a publicly funded formulary is a provincial decision guided by a panel of cancer clinicians who evaluate new drugs. “Cost-effectiveness is a part of every deliberation,” Dr Sawka pointed out, “and it’s always ‘how costeffective is this drug in relation to a more standard approach?’” For manufacturers, the evidentiary bar can shift, since “every province has its own way of doing [these evaluations].” So, for example, in Ontario, Avastin (Bevacizumab) for colon cancer is covered for everybody, while Avastin for breast cancer wasn’t even forwarded to the formulary, as the evidence was not seen as compelling enough, she said.

For the evaluating panel, there are clear nos and yeses, but “many, many drugs are in the middle,” said Dr Sawka. “Because most oncologists in Canada feel that…they are stewards of a set of resources, they have a long history of healthy skepticism about the value of new drugs. Yes, they’d like to use them if they’re effective, but they want to make sure they’re adding value.”

Values Influence Value Decisions Dr Sawka suggested that the Canadian mindset reflected a pragmatic attitude toward healthcare—on the physician side, a cultural adherence to evidence-based guidelines and population-based medicine; on the patient side, a recognition that “the public purse can’t pay for every single drug, unless it provides significant value.” This recognition of limits continues with fixed amounts allotted to hospitals to cover cancer patient care and to radiation centers for each new case.

In other parts of the world, Dr Dalrymple echoed, centralized healthcare with fixed budgets are the norm, so it is common to have a fixed number of oncologists, a limited number of care settings, and limited amounts of medical equipment. Countries have instituted top-down efforts to try and contain costs by moving treatment to the outpatient setting, but in some countries, notably the Middle East and Eastern Europe, there is also a patient mindset that emphasizes restraint when accessing healthcare.

As Dr Dalrymple put it, these patients think, “Don’t bother the doctor unless it’s really, really bad.”

In the UK, government-imposed Continued on page 10

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Radiation and Reimbursement Concerns Dog Diagnostic Imaging

By Daniel Denvir Baltimore, MD—Although major technological advances continue in the diagnostic imaging arena, heightened concern over radiation overdoses, steep prices for equipment, and questions about whether the new technologies will be reimbursed pose challenges for the field.

So said Jason Launders, MSc, a medical physicist and expert on computed tomography (CT) at the ECRI Institute in Plymouth Meeting, Pa. He presented an overview of the state of diagnostic imaging at a session of the Association of Community Cancer Centers’ (ACCC) 36th Annual National Meeting.

As diagnostic imaging technology has evolved, so too has the thinking about its place in patient care. “As we move more and more into chronic disease management, diagnostic imaging is really becoming part of the whole continuum of care,” he said, including screening, initial diagnosis, initial treatment strategy, therapy guidance, and subsequent treatment strategy.

But this expansion of the role of digital imaging over the past decades has necessarily led to cost increases.

So how we’re paying for imaging “needs to be rethought,” Mr Launders said, because “as we all know, it’s unsustainable.”

Clinical and Cost Concerns Lawsuits filed against Cedars-Sinai Medical Center and General Electric (GE) allege dangerous radiation overdoses of patients undergoing CT scans. “A class action lawsuit really changes everyone’s perspective,” pointed out Mr Launders. “This is huge, almost like a turning point in diagnostic radiology, because I don’t think there has been a major legal case before on too high a dose.”

GE, Siemens, Toshiba, and Philips are all marketing equipment that lowers dosage by 50%—but at $500000, the equipment is expensive. “This is an area of some concern, because most patients are going to be denied the low-dose technology,” Mr Launders argued.

“Slices really aren’t the question,” said Mr Launders. “The real question today is how low can you get that dose?”

In addition to radiation-lowering technological developments, there have been a number of advances in CT scanning, including dual-energy technology, which streamline the identification of distinct anatomy. But

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CT also faces growing concerns, with payers pushing back on reimbursement because of cost.

tients must be seen more quickly, in 5- or 10-minute time slots. And although digital mammography is

“I think the days of film are going to be over. The high price of digital mammography has to come down; otherwise screening mammography could be under threat. It’s just going to become too expensive.”

—Jason Launders, MSc

According to Mr Launders, the high cost of CT means the equipment will increasingly only be available at larger providers. “I can see that most of the advanced CT is only going to be available in major centers in years to come because the cost of the technology— we’re now talking $2.5 million for a top-of-the-range CT scanner.”

Another major change that continues to sweep the diagnostic imaging community is the growth of digital devices. “Sixty percent of all mammography units in this country are now digital,” said Mr Launders. “The digital mammography vendors are saying that basically the market [for nondigital equipment] has disappeared. Very few devices are being sold. Maybe that will start Pushing the price down below the half million mark, which is where they’re at now.”

Mr Launders said that although reimbursement for full field digital mammography is now higher, pa-

only of proven benefit to a subset of women, it will nonetheless displace the less costly film.

“You can’t provide digital mammography and screen field mammography in a workload,” he argued.

“You can’t say beforehand, ‘You don’t meet the criteria for digital, therefore we’re going to use film.’ I think the days of film are going to be over. The high price of digital mammography has to come down; otherwise screening mammography could be under threat. It’s just going to become too expensive.”

Tomosynthesis is another developing mammography technology (not yet approved by the US Food and Drug Administration) that raises many of the same issues. Tomosynthesis provides a lower radiation dose, and is especially adept at seeing through overlying anatomy. “We’re talking about a DVD worth of data per patient to be stored almost

forever, every year,” Mr Launders remarked. “The problem is there’s no reimbursement specific to it.” Clinical trials are ongoing; Mr Launders ventured that “I think tomosynthesis will be the future of mammography, because it will leave normal mammography in the shadows.”

Mammogram interpretation may be improved by computer-aided detection (CAD), and the technology is making rapid inroads, despite spotty reimbursements. “I think CAD will become invisible in the workplace,” said Mr Launders. “It will be built into the workstations [and] it will be such a time saver for any radiologist.”

Positron emission tomography (PET) has also been bolstered by the addition of time-of-flight information.

Time of flight dramatically shortens the time necessary for a PET scan, lowering its price—but is itself still very expensive. Nevertheless, Mr Launders suggested that “despite the high cost of the equipment, in a few years—or very soon—PET will be so useful in so many cases, especially in oncology, that when you can afford to add a PET scanner, you will add time of flight.” In addition, he noted that hybrid imaging “is on the rise,” including PET/CT and single photon emission computed tomography/CT. Magnetic resonance/PET has also generated interest, but is still in very early stages of development.

Technological innovation is moving ahead, but Mr Launders emphasized that both reimbursement and radiation dosing will likely be coming down in the future. ■

Foreign Cancer Care... Continued from page 9 restrictions on financing for cancer care led to involvement by that country’s supreme court. Patients were electing to pay privately for treatment for their cancer, Dr Dalrymple explained, and the government interpreted this as the patients exempting themselves from the National Health Service as far as their cancer treatment was concerned, an interpretation that was later overturned by the courts. He also cited a study that found that because of the refusal of the National Institute for Health and Clinical Excellence (NICE) to approve a number of drugs for a range of rare cancers, 20000 deaths had occurred in the UK in the last 3 years.

Unlike these countries, France and Germany do not seem to recognize that there are limits to healthcare resources, said Ms Pickaert, and people from other countries, especially

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the UK, travel to here to access care more quickly, albeit paying the cost out of pocket.

Beyond these big-picture issues of access and affordability, efforts to study utilization, outcomes, and cost in a way that will positively impact patient care are now being undertaken.

Dr Sawka profiled a study in Ontario that assessed emergency department use by cancer patients in the last 4 weeks of life and chemotherapy in the last 2 weeks of life. This sort of review is intended to “drive the discussion— what should happen, what constitutes good practice?” she commented.

In closing, the panel considered what lessons each country’s healthcare system might offer to the others.

America, Dr Sawka indicated, provides a lesson in entrepreneurial spirit. “What we could use in Canada is

the competitive driver for innovation.

Having a single-payer system is a blessing and a curse.” Innovations such as pay for performance and electronic records systems have originated in the United States and come to Canada. “The creativity that you see in the US healthcare system comes from competition,” she said.

Both Dr Dalrymple and Ms Pickaert emphasized their countries’ treasuring of universal access for all.

Ultimately, the whole debate revolves around what kind of social contract the people want, said Ms Pickaert.

In Europe, there is acceptance of the notion that “I will pay for others, and when I get sick, they will pay for me.” The organizing principles of American healthcare, she indicated, are difficult for Europeans to understand. ■

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Get Ready for Comparative Effectiveness Research

By Daniel Denvir Baltimore, MD—Comparative effectiveness research (CER) is at the forefront of new cost-control efforts, according to experts speaking at a panel discussion at the Association of Community Cancer Centers’ (ACCC) 36th Annual National Meeting.

Unlike traditional drug evaluations conducted by the US Food and Drug Administration, CER aims to evaluate the clinical and cost-effectiveness of treatments through head-to-head trials. And although CER promises important new clinical insights, no one doubts that rising healthcare costs are forcing payers and providers alike to think about driving value.

“Although you keep hearing this isn’t about money, I don’t think anyone believes that for 1 second,” said Al B. Benson III, MD, and incoming president of the ACCC. “It’s all about money. It’s going to affect our pocketbooks in many ways. We’re all going to see reimbursement based on supplying data.”

Exploding healthcare costs and the new healthcare law have focused increased attention on CER. The Recovery Act of 2009 dedicated $1.1 billion to CER, and the healthcare reform law creates a Patient-Centered Outcomes Research Institute to coordinate federal CER support, seeded with hundreds of millions of dollars in new funding.

“The purpose for setting it up...was to create an independent entity that would be separate from government pressure and have a sustained funding source,” Jeff Allen, PhD, executive director of Friends of Cancer Research, told Value-Based Cancer Care.

Advocates say the funds are just a start. In a recent perspective, Jerry Avorn, MD, wrote that, “at 1/20 of 1% of our $2-trillion annual healthcare expenditure, the CER funding amounts to a fraction of what any corporation would spend to find out whether it was getting its money’s worth from its purchases” (N Engl J Med. 2009;360[19]:1927-1929).

Given the intensely partisan environment in Washington, CER has become a political football of sorts: Republicans have charged that CER will lead to rationed care; and pharmaceutical companies and device makers eager to get their products to market are nervous about lost profits.

In an attempt to placate critics, the stimulus law included a provision ostensibly limiting the role CER could play in reimbursement, but the clause

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is more politics than substance: Dr Allen said that the Centers for Medicare & Medicaid Services will likely treat CER data the same way they treat any research in evaluating cost and clinical effectiveness.

Others worry that CER will undermine patient-based medicine, and some advocates worry it could gloss over differences among subpopulations. At the session, Dr Allen worried that the paltry information provided by the current model is a more significant concern, and said that CER should enhance the identifications of subset variations. Consumer advocate groups such as the Consumers Union have backed CER. Problems and Priorities A recent analysis of medication comparative effectiveness studies found that the majority of the studies examined did not compare drugs to currently available therapies, and that many simply measured drugs against a placebo (JAMA. 2010;303[10]:951958). The authors blame the pharmaceutical industry for skewing research toward bringing new drugs to market. They also found that nonprofit foundations or the government funded most comparative effectiveness studies, so it seems likely that public funding will drive CER in the future.

In addition to funding, government is providing guidance on how CER

should be pursued. In June 2009, the Institute of Medicine released 100 top priorities for CER, including 6 in the fields of oncology and hematology.

These include comparing the effectiveness of genetic and biomarker testing for preventing and treating cancer; effectiveness of management strategies for localized prostate cancer; effectiveness of ductal carcinoma in situ management strategies; and the use of diagnostic imaging, an issue that has been in the news a lot and was on the mind of Dr Benson.

“We talk in oncology organizations a great deal about drug reimbursement,” Dr Benson noted. “Well, that pales when you look at imaging. And we in oncology order a lot of tests.

We make a lot of money for our radiology department. And unfortunately, when you look at the literature, there’s very little guidance with how to use imaging.”

Beyond the politics of the situation, one of the biggest challenges will be the collection of data. “We do have to generate evidence,” said H. Kim Lyerly, MD. “One of the challenges, though, is cost.” Since hospitals already collect much of this data, electronic health records would not be necessary—but they would be a big help in making data collection more affordable.

“What we would hope is that this would be one component of practic-

“Although you keep hearing this isn’t about money, I don’t think anyone believes that for 1 second.” —Al B. Benson III, MD ing evidence-based medicine,” said Dr Benson.

There is no shortage of methodological questions to work out, including how to ensure that outliers are identified. And once that CER data gets generated, it will have to percolate down into the day-to-day of clinical practice.

“Getting new research findings into the hands of doctors and patients is easier said than done,” said Dr Allen. “Some estimate that it takes upwards of a decade to implement a new research finding into routine clinical practice.” ■

Community Cancer Centers Face Economy’s Impact

By Colin Gittens Baltimore, MD—The preliminary results of a 2009 survey on cancer care trends among community hospital cancer centers indicates the growing impact of the recession, with data showing a greater inability of patients to pay for cancer care and a freezing of plans to purchase new equipment.

The Internet survey collected data from 84 Association of Community Cancer Centers (ACCC) members in September and October 2009 and was presented at the group’s 36th Annual National Meeting by Lee Blansett, MBA, of Kantar Health. The majority of respondents (73%) were community hospital comprehensive or community hospital cancer programs, and most provided both in- and outpatient services.

“We are facing an environment where we’re going to have to be able to do more with less,” Mr Blansett acknowledged in outlining the rea-

sons for the survey. Determining benchmarks in the business aspects of cancer care may be a helpful starting point for changing practice and retaining profitability, he indicated.

Community oncology practices are definitely feeling the pinch, with 58% of respondents acknowledging an impact to their practice from the recession, and in that group, reports of decreased patient volume (52%), an inability of patients to pay out-ofpocket costs (59%), and an impact of these financial difficulties influencing a patient’s choice of treatment (50%).

In addition, more patients are being referred to hospitals for chemotherapy (rising to 18% in 2009 from 11% in 2007).

As a result, hospitals also report a financial impact, with 88% of respondents indicating that patients need assistance with copays or coinsurance, prescription drug expenses (87%), and even transportation costs (78%). Survey data also indicated a shift in patient

mix—a decrease in patients with commercial insurance and a rise in under- or uninsured patients, further contributing to hospital cancer programs’ woes.

Nevertheless, because hospital programs have a more diversified revenue stream and are less dependent on drugs as the major source of profits, they may be better positioned to ride out the recession, Mr Blansett noted.

Given the state of the economy, survey findings regarding capital upgrades for 2010 were perhaps not surprising. Linear accelerators, ultrasound machines, computed tomography (CT) scanners, magnetic resonance imaging machines, and positron emission tomography (PET) are essential components in diagnosing and treating cancers, but for now, cancer centers appear ready to stand pat with the equipment currently on hand. Most dramatically, no PET or PET/CT machines were budgeted for 2009, and planned purchases of all types of equipment were dramatically lower. ■

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Evolution in

1 OF A SERIES PART

Oncology Practice Management

™

Oncology Pharmacy Delivers Value and Quality to Health Plans

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s health plans grapple with the rapidly rising cost of oncology medications and a “buy and bill” system that does not work for physicians or for the plans, they are seeking new strategies for providing these life-saving drugs to their members and for freeing up oncology and hematology practices to focus solely on caring for patients, not managing a pharmacy.

One company has stepped up to fill the void and provide the solutions that health plans need. New York– based OncoMed, The Oncology Pharmacy, is a leading pharmaceutical services company that specializes solely in oncology pharmaceuticals and has established itself as a key partner to health plans.

Blue Cross Blue Shield of Massachusetts has contracted with OncoMed to provide all oncology medications— oral, injected, and infused—to the plan members’ physicians. The plan has made OncoMed’s services optional, so that physicians who want to continue to “buy and bill” oncology drugs can do so.

greatly reduces waste,” said OncoMed CEO Burt Zweigenhaft. “At over $1000 per dose, neither health plans nor our healthcare system can afford to operate in a way that does not take every necessary step to reduce wasted medication.”

OncoMed, founded in 2004, is licensed to provide oncology prescriptions in all 50 states to patients covered by Medicare, Medicaid, and private health plans. “It’s a field that is constantly evolving, with research driving changes in oncology day by day,” said Kevin Askari, RPh, president and chief clinical pharmacist of OncoMed. “Our goal is to act as a virtual oncology pharmacy within the practice, and also be used as a pharmacological resource and experienced knowledge center in the oncologist’s office.”

The arsenal of oncology pharmaceuticals and biotechnology targeted drugs has grown dramatically in recent years. As recently as the 1970s, there were no biologics and few drug choices and cancer frontline treatments were mainly surgery and radia-

“At over a thousand dollars per dose, neither health plans nor our healthcare system can afford to operate in a way that does not take every necessary step to reduce wasted medication.”

—Burt Zweigenhaft OncoMed CEO

In response to a surge in demand for its services, OncoMed recently opened its newest facility in New England to provide high-level oncology pharmacy services in that region, and the company has announced plans to open 4 additional new facilities this year in Arizona; Buffalo, New York; Florida; and Illinois.

“What we offer to health plans is the confidence that comes from using a dedicated oncology pharmacy partner that prepares medications according to the highest quality standards and delivers them using a process that

tion. Many of the first chemotherapy drugs, novel at the time, are obsolete today as stand-alone drugs (although some remain effective in combination with the new targeted biotechnology drugs used in protocols).

“Given the expanding complexity of therapies and protocols, we saw there was a need for an oncology pharmacy,” said Mr Askari. “We wanted to be involved in an evolving, dynamic field. Every day, even now, you get bombarded with new information.

The treatment that was the best thing yesterday may not work today.”

Pharmacists filling orders at the OncoMed facility.

Amid this complexity, Mr Askari said his emphasis remains on safety and quality. As an example, he said, “we hire only pharmacists who meet our own rigorous oncology pharmacy experience standards, who are then shadowed under close supervision for 6 months before they work on the dispensing front.”

OncoMed’s oncology pharmacists are at the heart of the prescription intake process, supervising all dispensing activities. All compounding and mixing is conducted in a USP 797compliant clean room environment.

Each dose and measure goes through a 6-point quality check process done by oncology pharmacists or pharmacy technicians to ensure safety and accuracy. OncoMed goes an extra step to ensure that all of its pharmaceuticals are purchased under a publicly disclosed “Drug Pedigree Program” that specifically allows only direct documented purchases from the prime manufacturers to ensure 100% drug efficacy and inventory safety.

“Having an oncology pharmacist review and process each order ensures that all prescription regimens are routinely evaluated against the rapidly emerging standards in care, such as the National Comprehensive Cancer Network (NCCN) guidelines,” Mr Askari said. “This enables OncoMed’s pharmacists to alert physician practices to contra-indicated drugs or treatment complications in advance of therapy.”

Events such as a prescription for contra-indicated pharmaceuticals do happen and one such event occurred recently when OncoMed pharmacists received a prescription for Avastin (bevacizumab) and Erbitux (cetuximab) to treat the same patient with previously untreated metastatic colorectal cancer. In this instance the oncology pharmacist called the physician and alerted them to the very recent study that found the combination of Avastin and Erbitux, when administered alongside chemotherapy, worsens colorectal cancer outcomes among patients with previously untreated, metastatic colorectal cancer and results in shorter progression-free survival and worse quality of life. The improved patient care that results from interactions like these also generates better business outcomes for health plans.

OncoMed CEO Burt Zweigenhaft describes the company’s overall goals and vision this way: “We have established ourselves as a trusted member of the cancer care community for delivering ‘just-in-time treatment day’ oncology pharmaceuticals and care management services. We’ve done this by studying the marketplace, listening to physician practices, and providing market-proven solutions to the challenges that our 600 current oncology practice providers face in the cancer care environment today.”

“We are recognized for our rigorous clinical standards in preparing and Continued on page 13

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delivering complex pharmaceutical regimens,” Mr Zweigenhaft said. “The evolving role of the oncology pharmacist is to be a cohort of the doctor’s office. This is done by assisting with critical clinical thinking during the regimen selection process. Perhaps most important, we also maximize the clinical yield of these expensive drugs through eliminating drug waste by compounding the patient-specific orders and then delivering them in treatment day doses.”

Kevin Askari, RPh President and Chief Clinical Pharmacist OncoMed

The challenges health plans are facing today in the area of oncology medication include: • heavy administrative costs to review and authorize requested treatments • new studies and standards in care, resulting in more drug combinations and protocols • dramatically increasing medication cost • lack of consistency in clinical standards for drug preparation because physician practices all operate differently, and • oncology and hematology practices that are not accredited by the Pharmacy Compounding Accreditation Board.

With Medicare’s shift to marketbased reimbursement schedules, the economic downside of “buy and bill” has become more apparent to physician practices.

“Physicians should be focused on caring for their patients and their complex disease,” said Mr Zweigenhaft.

“They should not have to worry about running a pharmacy and the tasks of

acquiring and maintaining an inventory of medications, the drug authorization burdens, collection of copayments and drug reimbursement, and the risk of bad debt.” Mr Zweigenhaft went on to say that “we see new challenges appearing as more state pharmacy boards seek to control enforcement of drug preparation sites using USP 797 and PCAB certifications.”

The validation of the OncoMed Oncology Pharmacy model is evidenced by the positive results that OncoMed has generated for health OncoMed oncology pharmacists at work in the clean room. plans that have used the company to provide oncology medications, such as Blue support the oncology pharmacy Cross Blue Shield of Massachusetts. model can provide for health plans’ Perhaps the greatest value that members, who face the supreme chalOncoMed delivers, however, is the lenge of defeating their cancer. ■

For more information or to request a presentation, call OncoMed at 1-877-662-6633 or go to www.oncomed.net

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Traditional Managed Care Tools Just Don’t Work in Oncology

By Peter G. Ellis, MD, and Kathy Lokay

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s payers focus on the rising cancer care spend, they are turning to tools previously applied to other diseases. Each seems to have potential, but upon closer review, these have fundamental shortcomings when used for cancer.

Disease management. Payers pay to have nurses in national call centers reach out telephonically to patients to help avoid hospitalizations. It is a labor-intensive model, often perceived by physicians as redundant at best and conflicting at worst with direct patient care. Return on investment in cancer care has proven elusive due to the high number of confounding variables.

Most importantly, reductions in side effects and hospitalizations are better achieved through evidence-based treatments and supportive care combined with accountability and financial incentives to physicians for manPeter G. Ellis, MD, is an editorial board member of Value-Based Cancer Care and a clinical associate professor of medicine, University of Pittsburgh School of Medicine and chief medical officer, Via Oncology, Pittsburgh.

Kathy Lokay is president, Via Oncology.

aging the entire continuum of care.

Utilization management (UM) imposes prior authorization as an external control on patient care. Oncologists have to obtain approval before initiating a treatment plan. With the complexity of cancer diagnoses and potential toxicities, it is difficult to secondguess cancer treatment decisions from outside the process of direct patient

ering and incentivizing physicians to adopt evidence-based best practices.

Pharmacy benefit management (PBM), including specialty pharmacy, has long been utilized to drive down pharmaceutical costs by enforcing use of generics over brands through formularies or tiered pricing along with negotiating volume discounts with pharmaceutical companies. This can

Reductions in side effects and hospitalizations are better achieved through evidence-based treatments and supportive care combined with accountability and financial incentives to physicians.

—Peter G. Ellis, MD care. Oncologists’ therapy decisions are rarely outside national guidelines, and therefore cannot and should not be denied. Thus, UM adds a costly, cumbersome administrative process that is likely to have minimal impact on patient treatment. Moreover, UM imposes compliance costs on practices and offers physicians no incentive to narrow the variability of care or prioritize cost-effectiveness. Far greater savings could be achieved by empow-

work for high-volume drugs, such as statins for lowering cholesterol. But it is not applicable in cancer care. For oral oncology drugs, most of the spending is on single-source drugs whose price cannot be negotiated with pharma based on market share or volume targets.

Managing injectable or infusional agents through PBM mail order is problematic due to 3 factors. First, with oncology reimbursement on the

basis of Healthcare Common Procedure Coding System codes, all versions of a multisource drug, such as paclitaxel, are reimbursed by insurers at the same rate, whether the drug is the branded or generic version, which leaves no advantage to managing drug selection. Second, the waste associated with drop shipments of injectable or infusional drugs is high due to the frequent changes in cancer treatment plans. Drugs are shipped as patient-specific prescriptions and cannot be used for any other patient or returned to the mail order pharmacy. Finally, until the reimbursement system for oncology changes, the revenues associated with drugs are the vital financial engine to keeping community-based oncology care viable.

Benefit design. Coinsurance can be tiered by drug or increased in general by putting cancer drugs under pharmacy benefit plans instead of treating them as a medical benefit. In addition to possibly being an unfair burden on cancer patients, since the vast majority of cancer therapies are extremely expensive, this tactic is likely to fail because patients lack the expertise to Continued on page 23

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Healthcare Reform Through the Eyes of Joseph S. Bailes, MD ASCO government liaison foresees changes for oncology

By Caroline Helwick New Orleans, LA—The Patient Protection and Affordable Care Act, ie, “healthcare reform,” was recently passed, but oncologists and those who pay for their services are still wondering what’s in store for them. In a keynote address delivered at the annual conference of the Hematology/Oncology Pharmacy Association (HOPA), Joseph S. Bailes, MD, chairman of the Government Relations Council and past-president of the American Society of Clinical Oncology (ASCO), enlightened attendees.

“This horse has left the barn and they tied an awful lot to it,” Dr Bailes said of the bill. “We will all be engaged in this, whether we like it or not.”

The main principles of reform— fairness and stability—were never in dispute, he said. “This is what the American people and physicians alike want.”

Nor are the general components of the legislation arguable: access to high-quality cancer care regardless of gender, race, ethnicity, or income; coverage, consistent with evidence-based medicine and reflective of the important role of clinical trials in cancer care; and reimbursement that reflects both the full scope of medically necessary services and fair payments that are stable from year to year.

But there have been disagreements as to how to achieve these principles, and now, how to implement change.

Joseph S. Bailes, MD

will be more important than they have been previously,” he predicted.

Payers may see the emergence of a new entity that will help design Medicare payment policy, sort of a “MedPAC on steroids,” Dr Bailes commented.

MedPAC was established in 1997 as an independent advisory committee to

Medicare does not adequately recognize and cover the labor-intensive services required to coordinate cancer patients’ care with other providers and social services.

A Closer Look at Medicare Payment Policy By way of background on Medicare policy development, Dr Bailes noted that “Congress is in charge” and many members want to “micromanage” Medicare. The Centers for Medicare & Medicaid Services (CMS) interprets Congress’ directions, he said, “and going forward this is going to be incredibly important to us and the patients we care for.”

A number of other entities will also be involved in interpreting the bill and making coverage decisions, including state legislations. “These

advise Congress, based on concerns that Congress lacks the political will to make controversial payment decisions. Some have proposed an Independent Payment Advisory Board that will have additional authority to cut payment rates, he said. Supported by the Obama administration, this board would provide recommendations outside of Medicare.

Healthcare Reform Goals, Current “Trends” The concept of the healthcare reform bill is to cover the 35 million uninsured Americans and stabilize

coverage for the currently insured, to make changes in the healthcare delivery system that will promote efficiencies and quality, and to slow the increasing costs of healthcare.

“If fully implemented, this bill contains $140 billion in savings the first 10 years and over $1 trillion the second 10 years,” Dr Bailes noted.

The components of reform will be paid for through individual and employer mandates; taxes on high incomes, employer health insurance benefits that exceed certain levels, and the pharmaceutical industry; US Food and Drug Administration–approved biosimilar pathways; productivity adjustments; Medicare provider cuts; a medical device tax; and multiple other provisions.

He emphasized that one-third of the cost of the healthcare reform act will be funded through reductions in the growth of Medicare spending.

Several “trends” in improving access and quality will be debated and refined as the reform movement evolves. There are movements to promote access to quality care and “value,” address disparities in care, develop and use performance measures, obtain and use data to promote best practices, promote the use of

evidence-based medicine, and address the lack of coordination among providers.

Specific to cost-control, he also named these trends: • reduction in Medicare payment levels • limits on annual updates to payment rates • an attempt to “bend the cost curve” toward more efficient care • promote or require more efficient care • shift resources away from specialists toward primary care providers • react to services or regions with significant growth in utilization • identify practices as fraudulent or wasteful.

Registries will be promoted because they provide “a real-world view of the effectiveness of various drugs and devices,” he said. They are viewed as an important means of determining effects on smaller subpopulations and addressing disparities in care.

CMS is naming specific registries as useful tools for reporting performance measures to the federal government, and using registry data for some newly covered items and services, ie, coverage with evidence development, or “CED,” he said.

“This is incredibly important. I urge you to pay attention to how this is formulated and who is included in these registries,” he said, “and to be vigilant against unintended consequences [of the use of the data].”

Issues Facing the Oncology Community in 2010 and Beyond “Cancer is viewed in Washington as an area that needs greater efficiency,” said Dr Bailes, who described what the oncology community can expect to face with regard to coverage issues.

Coordination of care will be promoted, but Medicare does not adequately recognize and cover the labor-intensive services required to coordinate cancer patients’ care with other providers and social services, he pointed out.

Medicare also does not adequately cover treatment planning and educational services, but demonstration projects are targeting this area. Other innovative pilots include the medical home, accountable care organizations, bundled hospital and postacute care plans, and programs to reduce hospital readmissions. These pilot projects will be combined under a new CMS Center on Payment Innovation.

Medicare no longer covers consultation codes, although the codes exist Continued on page 15

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Oncology Pharmacy Reimbursement Issues in 2010

By Caroline Helwick New Orleans, LA—As reimbursement for services continues to decline, oncology pharmacists must be proactive and develop a strategy to minimize losses, said Steven L. D’Amato, RPh, a clinical pharmacy specialist with the Maine Center for Cancer Medicine, Scarborough, Me, at a presentation at the annual meeting of the Hematology/Oncology Pharmacy Association (HOPA).

“The landscape for oncology reimbursement presents challenges for clinicians and payers. Reimbursement for services is declining in both the hospital and private sectors as administrative burdens are increasing,” Mr D’Amato said. “These days we need to maximize efficiencies to make sure we get every dollar coming to us.”

2010 Billing and Coding Changes Consultation code changes took effect January 1, 2010, and as Mr D’Amato noted, “billing and coding changes occur from year to year. If you don’t keep up, this can affect your bottom line.” The Centers for Medicare & Medicaid Services (CMS) eliminated the use of all consultation codes for various places of service except for telehealth consultation Gcodes. In place of the consultation codes, CMS increased the relative value units (RVUs) for new and established office visits, increased the work RVUs for initial hospital and initial nursing facility visits, and incorporated the increased use of these visits into the practice expense and malpractice calculations, he said. The proposed RVU cut of 6% for oncology will affect the bottom line, with reim-

bursement cut by 1% in 2010 and the 6% cut phased in over 4 years.

A change in the sustainable growth rate has again been delayed, but when eventually implemented “it will mean a huge financial loss for private practices,” Mr D’Amato predicted, estimating a 25% reduction in payment for chemotherapy administration.

Regarding drug payments, CMS will no longer exempt 5-HT3 antiemetic products from standard packaging methodology. Drugs costing less than $65 per day are not reimbursed separately, while those costing more than $65 will continue to be paid separately. Separately billed drugs are reimbursed at average sales price + 4%.

It Contracts with Payers It Pays to Get Involved Pharmacist involvement in the financial side of oncology is becoming increasingly important, Mr D’Amato told attendees. Institutions have contracting teams to identify issues pertinent to new or renewing contracts, and pharmacists should participate in these discussions.

Private payers are looking to control costs and spending through the use of specialty pharmacies, preauthorizations, and other mechanisms.

In addition, payer requirements may slow patients’ access to care since treatments cannot begin until authorizations are received, and there is the additional administrative burden of managing denials. Pharmacists can weigh in on these issues, he said.

E-Prescribing Incentive Program Participation in the Physician Quality Reporting Initiative (PQRI) is not a

Healthcare Reform... for potential use by other payers.

Regarding compendia, Medicare contractors are using documentation requirements as a barrier to coverage for off-label drugs, he observed.

Clinical trials for patients with serious or life-threatening diseases—cancer being one—will be covered in terms of routine costs; however, Medicare does not cover the labor-intensive services associated with identifying and enrolling patients, he added.

Confronting the Reimbursement Issues The “framework” of reimbursement contains 4 key pieces: physician services, chemotherapy administra-

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Table Financial Considerations for Contracting with MCOs Know the current reimbursement landscape Compare contracts Develop cost-effective formularies Develop or incorporate clinical pathways that consider cost-effectiveness Participate in contracting and carve-outs that can benefit both payer and provider Implement effective precertification processes that reduce or eliminate risk prerequisite for joining the electronic e-Prescribing Incentive Program in 2010. “The program requirements have been simplified, with a minimum of just 25 encounters for patients you have e-prescribed and for whom you utilized the G8443 code,” he said. CMS has expanded the reporting mechanism to be claimsbased, registry-based, and electronic medical records-based.

“With the 2% PQRI incentive and 2% e-prescribing incentive, providers have the opportunity for a 4% increase in Medicare reimbursement,” he noted. By 2010, CMS will begin penalizing professionals who are not e-prescribers, reducing payments by 1%, then by 1.5% in 2013 and by 2% in 2014.

Managed Care Organizations Medical oncology has become a new priority for managed care organizations (MCOs), based on the rise in cancer and cost of care. In 2008, new cancer cases numbered 1.437 million. Caring for these patients totaled $89 billion in direct costs in 2007 and $219.2 billion overall, once secondary costs and comorbidities were considered.

MCOs also are concerned about the cost of novel and new agents, especially oral oncolytics, and the evolving paradigm of cancer as a chronic

disease. Other challenges for MCOs are the changing reimbursement model and new mandates to measure quality and performance.

“When you contract with MCOs, be creative,” he told oncology pharmacists. “For example, for anti-emesis you could agree to use the less expensive agent but asked to be paid more to offset what you would make instead on the more expensive agent.

There are many opportunities to enhance reimbursement and reduce costs within MCOs (Table).”

Unfortunately, the future will be rife with other worries, Mr D’Amato predicted. There will be issues related to random audits from payers, for which pharmacists receive no payment; the Recovery Audit Contractor Program, which aims to identify potential overpayments and underpayments made to providers and are required in all states; coding compliance by physicians; the rise in underinsured and uninsured patients who need assistance in accessing care; the demand for Risk Evaluation and Mitigation Strategies; budget and staffing shortages; and competition by specialty pharmacies.

“As a profession,” Mr D’Amato concluded, “we have a lot to deal with outside of patient care.” ■

and can be implemented by Congress without further action. It was established under the Medicare Modernization Act of 2003, but its initial implementation was plagued by low interest from vendors and low enrollment by physicians, and it was eventually terminated.

“But some members of Congress feel wedded to this program,” he said. “CAP is not dead. There is much interest in revitalizing this. You will see this return as an innovative, efficient way to handle injectable drugs.”

Other issues to be tangled with are average sales price + 6%, prompt pay discounts, reductions in the malpractice component of payment, shift in

clinical practice toward oral agents, the impact of Medicare’s decision to discontinue payment under consultation codes, the potential costs inflicted by Medicare audits, and the potential for payment to be tied to performance measures and to the use of electronic medical records.

In closing, Dr Bailes assured the assembled oncology pharmacists that there will be many opportunities to be part of positive changes. “There are opportunities here in oncology,” he emphasized. “As we move forward, it is important for us to be at these tables for discussion, so that our patients are represented and cared for by professionals who understand them.” ■

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tion, drug costs, and the potential movement away from fee-for-service to bundled payment models.

A number of factors will affect reimbursement, Dr Bailes said. He foresees practice expense reductions, especially for chemotherapy administration codes, due in large part to CMS’ use of flawed Physician Practice Information Survey data.

Additionally, the costs of doing business are rising faster than annual updates (sustained growth rates, Medicare economic index, etc).

The Competitive Acquisition Program (CAP) for Medicare Part B drugs and biologics, as an alternative to buy-and-bill, was refined in 2009

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Compendia: Powerful Tools, Wrong Job

By Lynn Nishida, RPh tions that were considered “off-label” at the time of the analysis, the researchers found great disparities in compendia listings and the evidence cited to support the recommenda-

tions. Additionally, there were different lag times in the way that the 6 compendia identified, processed, and updated information.

Among the reasons identified by

the AHRQ to explain this variability were that the compendia were unable to keep up with evolving science; used inconsistent methods to critically appraise scientific studies and

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t the most basic level, compendia are drug information resources intended to aid clinicians in making “informed treatment decisions, especially in difficult and complex cases.”1 They were not intended for use in determining reimbursement of medications for the public and private healthcare insurance sectors. Nevertheless, this responsibility was assigned by the Centers for Medicare & Medicaid Services (CMS) in a 1993 law that requires Medicare plans to use 1 of 4 national compendia to determine coverage and pay for “off-label uses of anticancer drugs for Medicare beneficiaries.”2 Although determining coverage for off-label use of anticancer drugs was the CMS’s primary intent with this law, the importance of CMS’s decision may be magnified if health plans and private payers follow the agency’s guidance and adopt similar practices across both the public and private sectors. Even as some plans embrace compendia as the starting point in expediting coverage determinations for anticancer drugs, those opposed would argue that as “stewards of the healthcare dollar” these fall short of good science and that we should invest the resources to do better. Since the passage of this law, questions as to the feasibility and financial impact of this policy have arisen, which I’ll review briefly here.

Variability Among Compendia The 4 national compendia recognized by CMS include the NCCN Drugs & Biologics Compendium3; DRUGDEX, published by Thomson Micromedex4; Clinical Pharmacology5; and American Hospital Formulary Service Drug Information (AHFSDI).6 An analysis of these compendia (plus 2 others) conducted by the Agency for Healthcare Research and Quality (AHRQ) sought to determine whether the compendia adhered to stated methods concerning evidence-based medicine and whether they provided comprehensive, research-based, and timely information for off-label prescribing of anticancer drugs.7,8 Of 14 anticancer drug/condition combina-

Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED. IF PATIENTS REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN, THEY SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE. Acute respiratory distress syndrome (ARDS) has been reported. Evaluate patients who develop fever, lung infiltrates, or respiratory distress for ARDS. If patient is diagnosed with ARDS, discontinue and/or withhold Neulasta® until resolution.

Allergic reactions to Neulasta®, manifesting as anaphylaxis, angioedema, or urticaria have been reported. The majority of these reactions occurred upon initial exposure. However, in rare cases, allergic reactions, including anaphylaxis, recurred within days after discontinuing anti-allergic treatment.

Severe sickle cell crises have been associated with the use of Neulasta® in patients with sickle cell disorders. Only physicians qualified by specialized training or experience in the treatment of patients with sickle cell disorders should prescribe Neulasta® for such patients.

Lynn Nishida, RPh is director, Clinical Pharmacy Services at Regence BlueCross BlueShield of Oregon, Portland, and an editorial board member of Value-Based Cancer Care.

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VBCC peRspectiVe report levels of evidence; varied in the level of evidence considered to support medically accepted uses; lacked transparent decision-making or systematic ways for including scientific information; and did not always disclose financial ties to pharmaceutical industry and potential conflicts of interest.

In addition to methodological variables with each compendium, there are operational concerns and an unknown cost impact. Health plans are required to follow CMS guidance in applying compendia for Medicare beneficiaries, but they may be reluctant to use this approach in the private sector without due diligence assessing

the ongoing reliability and conflicts in evidence. Although health plans want to prevent the creation of a double standard, some plans will opt for creating separate coverage policies for their commercial plans.

Using utilization data from our own plan, we looked at the potential impact in applying different compen-

dia for coverage decisions and estimated a corresponding cost impact.

We selected 5 cancer medications (trastuzumab, bortezomib, lapatinib, dasatinib, and nilotinib) and compared the National Comprehensive Cancer Network (NCCN) and DRUGDEX compendia for differences Continued on page 18

Help reduce the risk of infection in patients receiving moderate-risk* chemotherapy regimens

Act before febrile neutropenia strikes Potential consequences of febrile neutropenia may be serious and can impact patient care First- and every-cycle Neulasta® achieved: ■ 94% reduction in febrile neutropenia (17% placebo vs 1% Neulasta®; P < 0.001).1,2 ■ 93% reduction in febrile neutropenia–related hospitalization (14% placebo vs 1% Neulasta®; P < 0.001).1,2 ■ 80% reduction in febrile neutropenia–related IV anti-infective use (10% placebo vs 2% Neulasta®; P < 0.001).1,2

Neulasta® should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy. The use of Neulasta® has not been studied in patients receiving chemotherapy associated with delayed myelosuppression (eg, nitrosoureas, mitomycin C).

In a placebo-controlled trial, bone pain occurred at a higher incidence in patients treated with Neulasta®, as compared to placebo-treated patients. The most common adverse events reported in either placebo- or active-controlled trials were consistent with the underlying cancer diagnosis and its treatment with chemotherapy, with the exception of bone pain.

Please see brief summary of Neulasta® Prescribing Information on the adjacent page. *Regimens associated with ≥ 17% risk of febrile neutropenia.

© 2010 Amgen. All rights reserved.

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Compendia: Powerful Tools, Wrong Job... in their listings of “medically accepted” off-label uses for these medications and what the differences would be in terms of coverage determinations and estimated net cost avoidance

(in dollars) with the different compendia if applied to real-world claims.

Our findings echoed those of the AHRQ study, with variability for medically accepted off-label uses and

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in the quality and type of evidence that could be used to support the listing. In dollar terms, identifying uses that were not considered medically acceptable provided an estimated

References: 1. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 2. Neulasta® (pegfilgrastim) Prescribing Information. Thousand Oaks, Calif: Amgen.

BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

CONTRAINDICATIONS Neulasta is contraindicated in patients with known hypersensitivity to E coli-derived proteins‚ pegfilgrastim‚ Filgrastim, or any other component of the product.

WARNINGS General The safety and efficacy of Neulasta for peripheral blood progenitor cell (PBPC) mobilization has not been evaluated in adequate and well-controlled studies.

Neulasta should not be used for PBPC mobilization.

Splenic Rupture SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED FOLLOWING THE ADMINISTRATION OF NEULASTA AND ITS PARENT COMPOUND, FILGRASTIM. PATIENTS RECEIVING NEULASTA WHO REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE. Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) has been reported in patients receiving Neulasta, and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving Neulasta who develop fever, lung infiltrates, or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, Neulasta should be discontinued and/or withheld until resolution of ARDS and patients should receive appropriate medical management for this condition.

Allergic Reactions Allergic reactions to Neulasta, including anaphylaxis, skin rash, urticaria, and erythema/flushing have been reported in postmarketing experience. The majority of reported events occurred upon initial exposure. In some cases, symptoms recurred with rechallenge, suggesting a causal relationship. In rare cases, allergic reactions including anaphylaxis, recurred within days after initial anti-allergic treatment was discontinued. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Neulasta should be permanently discontinued in patients with serious allergic reactions.

Sickle Cell Disorders Severe sickle cell crises have been associated with the use of Neulasta in patients with sickle cell disorders. Severe sickle cell crises, in some cases resulting in death, have also been associated with Filgrastim, the parent compound of pegfilgrastim. Only physicians qualified by specialized training or experience in the treatment of patients with sickle cell disorders should prescribe Neulasta for such patients, and only after careful consideration of the potential risks and benefits.

PRECAUTIONS General Use With Chemotherapy and/or Radiation Therapy Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy (see DOSAGE AND ADMINISTRATION) because of the potential for an increase in sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.

The use of Neulasta has not been studied in patients receiving chemotherapy associated with delayed myelosuppression (eg, nitrosoureas, mitomycin C).

The administration of Neulasta concomitantly with 5-fluorouracil or other antimetabolites has not been evaluated in patients. Administration of pegfilgrastim at 0, 1, and 3 days before 5-fluorouracil resulted in increased mortality in mice; administration of pegfilgrastim 24 hours after 5-fluorouracil did not adversely affect survival.

The use of Neulasta has not been studied in patients receiving radiation therapy.

Potential Effect on Malignant Cells Pegfilgrastim is a growth factor that primarily stimulates neutrophils and neutrophil precursors; however, the G-CSF receptor through which pegfilgrastim and Filgrastim act has been found on tumor cell lines, including some myeloid, T-lymphoid, lung, head and neck, and bladder tumor cell lines. The possibility that pegfilgrastim can act as a growth factor for any tumor type cannot be excluded. Use of Neulasta in myeloid malignancies and myelodysplasia (MDS) has not been studied. In a randomized study comparing the effects of the parent compound of Neulasta, Filgrastim, to placebo in patients undergoing remission induction and consolidation chemotherapy for acute myeloid leukemia, important differences in remission rate between the two arms were excluded. Disease-free survival and overall survival were comparable; however, the study was not designed to detect important differences in these endpoints.* Information for Patients Patients should be informed of the possible side effects of Neulasta and be instructed to report them to the prescribing physician. Patients should be informed of the signs and symptoms of allergic drug reactions and be advised of appropriate actions. Patients should be counseled on the importance of compliance with their Neulasta treatment, including regular monitoring of blood counts.

If it is determined that a patient or caregiver can safely and effectively administer Neulasta (pegfilgrastim) at home, appropriate instruction on the proper use of Neulasta (pegfilgrastim) should be provided for patients and their caregivers, including careful review of the “Information for Patients and Caregivers” insert.

Patients and caregivers should be cautioned against the reuse of needles, syringes, or drug product, and be thoroughly instructed in their proper disposal.

A puncture-resistant container for the disposal of used syringes and needles should be available.

Laboratory Monitoring To assess a patient’s hematologic status and ability to tolerate myelosuppressive chemotherapy, a complete blood count and platelet count should be obtained before chemotherapy is administered. Regular monitoring of hematocrit value and platelet count is recommended.

Drug Interaction No formal drug interaction studies between Neulasta and other drugs have been performed. Drugs such as lithium may potentiate the release of neutrophils;

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patients receiving lithium and Neulasta should have more frequent monitoring of neutrophil counts.

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Carcinogenesis, Mutagenesis, and Impairment of Fertility No mutagenesis studies were conducted with pegfilgrastim. The carcinogenic potential of pegfilgrastim has not been evaluated in long-term animal studies.

In a toxicity study of 6 months duration in rats given once weekly subcutaneous injections of up to 1000 mcg/kg of pegfilgrastim (approximately 23-fold higher than the recommended human dose), no precancerous or cancerous lesions were noted.

When administered once weekly via subcutaneous injections to male and female rats at doses up to 1000 mcg/kg prior to, and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected.

Pregnancy Category C Pegfilgrastim has been shown to have adverse effects in pregnant rabbits when administered subcutaneously every other day during gestation at doses as low as 50 mcg/kg/dose (approximately 4-fold higher than the recommended human dose). Decreased maternal food consumption, accompanied by a decreased maternal body weight gain and decreased fetal body weights were observed at 50 to 1000 mcg/kg/dose. Pegfilgrastim doses of 200 and 250 mcg/kg/dose resulted in an increased incidence of abortions. Increased post-implantation loss due to early resorptions was observed at doses of 200 to 1000 mcg/kg/dose, and decreased numbers of live rabbit fetuses were observed at pegfilgrastim doses of 200 to 1000 mcg/kg/dose, given every other day.

Subcutaneous injections of pegfilgrastim of up to 1000 mcg/kg/dose every other day during the period of organogenesis in rats were not associated with an embryotoxic or fetotoxic outcome. However, an increased incidence (compared to historical controls) of wavy ribs was observed in rat fetuses at 1000 mcg/kg/dose every other day. Very low levels (< 0.5%) of pegfilgrastim crossed the placenta when administered subcutaneously to pregnant rats every other day during gestation.

Once weekly subcutaneous injections of pegfilgrastim to female rats from day 6 of gestation through day 18 of lactation at doses up to 1000 mcg/kg/dose did not result in any adverse maternal effects. There were no deleterious effects on the growth and development of the offspring and no adverse effects were found upon assessment of fertility indices.

There are no adequate and well-controlled studies in pregnant women. Neulasta should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers It is not known whether pegfilgrastim is excreted in human milk. Because many drugs are excreted in human milk‚ caution should be exercised when Neulasta is administered to a nursing woman.

Pediatric Use The safety and pharmacokinetics of Neulasta were studied in 37 pediatric patients with sarcoma. The mean (± Standard Deviation) systemic exposure (AUC0-inf) of Neulasta after subcutaneous administration at 100 mcg/kg was 22.0 (±13.1) mcg·hr/mL in the 6–11 years age group (n = 10), 29.3 (±23.2) mcg·hr/mL in the 12–21 years age group (n = 13) and 47.9 (±22.5) mcg·hr/mL in the youngest age group (0–5 years, n = 11).

The terminal elimination half-lives of the corresponding age groups were 20.2 (±11.3) hours, 21.2 (±16.0) hours and 30.1 (±38.2) hours, respectively. The most common adverse reaction was bone pain.

The 6 mg fixed dose single-use syringe formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg.

Geriatric Use Of the 932 patients with cancer who received Neulasta in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

ADVERSE REACTIONS (See WARNINGS, Splenic Rupture, Acute Respiratory Distress Syndrome (ARDS), Allergic Reactions, and Sickle Cell Disorders.)

Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Neulasta cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to Neulasta use and for approximating rates.

The data described below reflect exposure to Neulasta in 932 patients.

Neulasta was studied in placebo- and active-controlled trials (n = 467, and n = 465, respectively). The population encompassed an age range of 21 to 88 years. Ninety-two percent of patients were female. The ethnicity of the patients was as follows: 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian.

Patients with solid tumors (breast [n = 823], lung and thoracic tumors [n = 53]) or lymphoma (n = 56) received Neulasta after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

In the placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta-treated patients as compared to placebo-treated patients. The incidence of other commonly reported adverse events were similar in the Neulasta- and placebo-treated patients, and were consistent with the underlying cancer diagnosis and its treatment with chemotherapy. The data in Table 1 reflect those adverse events occurring in at least 10% of patients treated with Neulasta in the placebo-controlled study.

Table 1. Adverse Events Occurring in ≥ 10%a of Patients in the Placebo-Controlled Study Event Alopecia Bone Painb Diarrhea Pyrexia (not including febrile neutropenia) Myalgia Headache Arthralgia Vomiting Asthenia Peripheral Edema Constipation

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Neulasta (n = 467) 48% 31% 29%

Placebo (n = 461) 47% 26% 28%

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21% 16% 16% 13% 13% 12% 10%

18% 14% 13% 11% 11% 10% 6%

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Events occurring in ≥ 10% of Neulasta-treated patients and at a higher incidence as compared to placebo-treated patients Bone pain is limited to the specified adverse event term “bone pain”

a

b

In the active controlled studies, common adverse events occurred at similar rates and severities in both treatment arms (Neulasta, n = 465; Filgrastim, n = 331).

These adverse experiences occurred at rates between 72% and 15% and included: nausea, fatigue, alopecia, diarrhea, vomiting, constipation, fever, anorexia, skeletal pain, headache, taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalized weakness, peripheral edema, dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever.

Bone Pain The analysis of bone pain described below is based on a composite analysis using multiple, related, adverse event terms.

In the placebo-controlled study, the incidence of bone pain was 57% in Neulasta-treated patients compared to 50% in placebo-treated patients.

Bone pain was generally reported to be of mild-to-moderate severity.

Among patients experiencing bone pain, approximately 37% of Neulasta- and 31% of placebo-treated patients utilized non-narcotic analgesics and 10% of Neulasta- and 9% of placebo-treated patients utilized narcotic analgesics.

In the active-controlled studies, the use of non-narcotic and narcotic analgesics in association with bone pain was similar between Neulasta- and Filgrastim treated patients. No patient withdrew from study due to bone pain.

Laboratory Abnormalities In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with nonmyeloid malignancies receiving Neulasta. Leukocytosis was not associated with any adverse effects.

Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

Cytopenias resulting from a neutralizing antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against pegfilgrastim may cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia. This has not been observed in clinical studies of Neulasta.

Postmarketing Experience The following adverse reactions have been identified during postapproval of Neulasta. 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 drug exposure.

• splenic rupture (see WARNINGS: Splenic Rupture) • acute respiratory distress syndrome (ARDS) (see WARNINGS: Acute Respiratory Distress Syndrome) • allergic reactions (including anaphylaxis, skin rash, urticaria, erythema/flushing) (see WARNINGS: Allergic Reactions) • sickle cell crisis (see WARNINGS: Sickle Cell Disorders) • injection site pain • Sweet’s syndrome (acute febrile dermatosis) OVERDOSAGE The maximum amount of Neulasta that can be safely administered in single or multiple doses has not been determined. Single subcutaneous doses of 300 mcg/kg have been administered to 8 healthy volunteers and 3 patients with non-small cell lung cancer without serious adverse effects. These patients experienced a mean maximum ANC of 55 x 109/L, with a corresponding mean maximum WBC of 67 x 109/L. The absolute maximum ANC observed was 96 x 109/L with a corresponding absolute maximum WBC observed of 120 x 109/L. The duration of leukocytosis ranged from 6 to 13 days. Leukapheresis should be considered in the management of symptomatic individuals.

DOSAGE AND ADMINISTRATION The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy (see PRECAUTIONS).

The 6 mg fixed-dose formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg.

No dosing adjustment is necessary for renal dysfunction.

Neulasta should be visually inspected for discoloration and particulate matter before administration. Neulasta should not be administered if discoloration or particulates are observed.

Rx Only This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 4,810,643; 4,999,291; 5,582,823; 5,580,755, as well as other patents or patents pending.

REFERENCE *Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebocontrolled, phase III study of Filgrastim in remission induction and consolidation therapy for adults with de novo Acute Myeloid Leukemia.

Blood. 1997;90:4710-4718. v.10 Issue Date: 11/2008

Manufactured by: Amgen Manufacturing, Limited, a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 © 2002–2009 Amgen Inc. All rights reserved.

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overall cost avoidance of just under $1 million annually.

What’s Practical and Feasible It is impractical and duplicative for health plans to consult all 4 compendia in rendering coverage determinations for anticancer drugs under Medicare, so most plans select 1 or 2 compendia as their informational resource. Furthermore, subscriptions are costly, depending on the compendia selected and number of users having access, with annual fees ranging from $500 to $22000.

As for the matter of plans applying compendia across both public and private sectors for coverage determinations, it will take time for a consistent method that assures patient access to the best treatment options to emerge.

In an ideal world, we would look at the appropriate use of every medication, but that’s just not practical. Instead we need to focus on the drugs with the greatest safety signals and/or are most expensive. It is best to catch these anticancer drugs right out of the gate, building on evidence, rather than trying to plow through hundreds of trials later on. New anticancer drugs that come to market have top-dollar price tags of up to $100000 a year, so it makes sense to focus on these from the outset.

As for compendia, these are only one means by which health plans can understand how prescribers and the expert community plan to use these drugs and determine their relative place among treatment options.

However, we can’t stop there—we need to perform due diligence in looking at the underlying science, balancing cost, access, quality of care, and outcomes to put the patient first. ■ References 1. Butcher L. CMS’s use of compendia drawing criticism. Oncol Times. 2009;31(7):39-41.

2. Medicare Benefit Policy Manual. 50.4.5. Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen (Rev. 96, Issued: 10-24-08, Effective: 06-05-08 NCCN/06-10-08 Thomson Micromedex/07-02-08 Clinical Pharmacology, Implementation: 11-25-08.) US Dept of Health and Human Services publication 100-02.

3. National Comprehensive Cancer Network. NCCN Drugs & Biologics Compendium. www.nccn.org.

Accessed September 1, 2009.

4. Thomson Micromedex Healthcare Series. www.thomsonhc.com. Accessed Sept. 1, 2009.

5. Elsevier Gold Standard: Clinical Pharmacology. www.clinicalpharmacology.com. Accessed Sept. 1, 2009.

6. American Society of Health-System Pharmacists. www. ahfsdruginformation.com. Accessed Sept. 1, 2009.

7. Abernethy AP, Raman G, Balk EM, et al. Systematic review: reliability of compendia methods for off-label oncology indications. Ann Intern Med. 2009;150 (5): 336-343.

8. Abernathy AP et al. Compendia for coverage of off-label uses of drugs and biologics in an anticancer chemotherapeutic regimen. Final Report. Rockville, Md: Agency for Healthcare Research and Quality; May 2007. www.cms.hhs.gov/determinationprocess/ downloads/id46TA.pdf. Accessed April 26, 2010.

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NCCN Roundtable: Clinical and Economic Issues...

The conflict between optimal cancer care and today’s economic environment was the issue tackled in a lively discussion. Panelists included physicians, patient advocates, third-party payers, and industry representatives.

Do Practice Guidelines Really Guide Practice?

Representatives from Aetna Inc and UnitedHealthcare said their companies use the NCCN guidelines to inform both clinical care and coverage decisions. Both payers cover all treatments given a category 2B or higher recommendation by the NCCN. “It is extraordinarily rare that treatment is denied by Aetna in a lifethreatening illness,” said James D. Cross, MD, National Head of Medical

“It is extraordinarily rare that treatment is denied by Aetna in a life-threatening illness.”

—James D. Cross, MD Policy and Program Administration for Aetna. Adherence to evidencebased practice guidelines can also have an effect on the overall cost of treatment, according to Dr Cross, who described a recent report from Aetna that showed overall care to be 35% less expensive when treatment guidelines were followed.

“We encourage the use of evidencebased guidelines. In my mind that is the commonality that brings patients, physicians, and insurers together,” he said.

Lee Newcomer, MD, MHA, Senior Vice President of Oncology Services at UnitedHealthcare, said his company gauges its physicians’ compliance with the guidelines. The data are not used “to judge physicians, but for quality improvement,” one aim of which is to “close gaps in care,” he said.

Physicians on the panel, however, bristled somewhat at the use of the guidelines as a measurement of best practices. Joseph S. Bailes, MD, Chair of the Government Relations Council of the American Society of Clinical Oncology (ASCO), said that the UnitedHealthcare project “is not necessarily well received” by ASCO members.

“What is good care, or not good care, is not always determined by guidelines,” he maintained.

The other oncologist on the panel, Al Benson, MD, Professor of Medicine at the Robert H. Lurie

Comprehensive Cancer Center at Northwestern University, Chicago, agreed that the guidelines should not be “prescriptive,” as not every recommendation is suitable for every patient. “A 100% concordance cannot be expected,” he pointed out. He called the NCCN guidelines the most “well structured and user-friendly” among hundreds of others, as they allow the entire medical system to have immediate access to evidencebased recommendations.

The NCCN guidelines are certainly useful to the National Patient Advocate Foundation, said Nancy Davenport-Ennis, cancer survivor and President and CEO of the organization. Her case managers have used the guidelines daily to win more than 500 000 preauthorizations and appeals for patients. In addition, guidelines serve as reassurance to patients that they are receiving the recommended care they deserve, she said.

After the Guidelines: Then What?

After patients have received the various interventions listed in the NCCN guidelines, they may desire further treatment. Without evidence to guide these choices, “isn’t this when you begin experimenting with expensive therapies that may do more harm than good?” Dr Goodman asked the panelists.

“In my area, colorectal cancer, this is an increasing problem as we improve survivorship,” Dr Benson acknowledged. “A clinical trial is often the appropriate choice, but unfortunately, there are challenges in finding and enrolling individuals in trials.”

Ms Davenport-Ennis looks to “courageous” oncologists to find

interventions that might control the patient’s disease without inflicting harm, she said.

But this did not sit well with Dr Cross of Aetna, who said physicians must not just “take things off the shelf when there are no known solutions” but should work harder to get patients into trials. Dr Bailes noted that clinical trials would be a more viable option for more patients if they were universally covered by all thirdparty payers.

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mia and lymphoma. “The end-of-life costs you keep hearing about turned out to be primarily associated with hospitalization for complications of disease,” he reported. “We did not see a sudden surge in chemotherapy at the end.”

But when anticancer treatment is desired at the end of life, expenditures can appear irrational, he added.

The cost of chemotherapy for advanced lung cancer patients has been found to add $60000 to cost of

“Costs aside, let’s not expose patients to harm with little chance of benefit. We know patients will have toxicities, yet we have no confidence that they will get better.”

—Lee Newcomer, MD, MHA Dr Benson reminded the panel that best supportive care is often the most appropriate choice for these patients and is integrated into the guidelines.

He acknowledged that “it takes some work for people to grasp that there are limitations to what we can do for them.”

Expense of Cancer Care at the End of Life Cancer care at the end of life is usually assumed to be inordinately expensive, but a study by UnitedHealthcare did not substantiate this, according to Dr Newcomer.

“We busted that myth,” he said, as the UnitedHealthcare study found that from disease recurrence until death “expenditures remained constant” in all malignancies but leuke-

How to Contain Costs, Before It’s Too Late Lee Newcomer, MD, MHA: “We have to spend less on healthcare and eliminate components that do not add value. We need a World War II mentality, where we all sacrifice to make the system work. Otherwise, we are going to be forced to allocate funds as a result of financial collapse.”

Douglas Lind, MD: “We need research that will produce pharmacoeconomic data to justify the value of current and future drugs and technologies.”

Al Benson, MD: “The best hope for controlling costs is to encourage a system where patients get the right care at the right time.”

Jason Slotnik, Esq: “I would encourage models where someone in the center coordinates patient care.”

Nancy Davenport-Ennis: “Have patients talk with their physicians in a way in which both parties are comfortable. Consumers will ask sound questions and will participate in making wise decisions regarding cost.”

James Cross, MD: “The problem of cost-containment must be solved by all stakeholders working together, and that is just what we are having trouble doing.”

care, while rendering just 10 extra days of survival, he said.

Avoiding aggressive treatment at the end of life may not only reduce costs but may improve quality of life, Dr Newcomer suggested. “Costs aside, let’s not expose patients to harm with little chance of benefit. We know patients will have toxicities, yet we have no confidence that they will get better,” he pointed out.

Is Innovation Being Sacrificed?

Concerns over costs are now contaminating the most sacrosanct of areas—drug development, said 2 panelists who work in that field.

Douglas Lind, MD, a managing partner in the venture-capital firm GBP Capital, said investors are now greatly interested in the likelihood of compounds being covered, once approved. “Companies used to innovate without concerns about cost but the table has turned,” he said. “The first question is not whether a phase 1 or 2 clinical trial will be positive, and not even if a product will become FDA-approved, but whether it will be reimbursed.

“If our investors cannot predict what will happen down the road in terms of a drug being cost-neutral or cost-saving, then they think ‘why bother?’ For the first time this is the central question,” he said, adding that this question actually begins on the industry level. “They are equally asking this question.”

Considerations about reimbursement are not intended to suppress innovation but to direct it, and this is Continued on page 20

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The NCCN Task Force on Specialty Pharmacy Issues Preliminary Report

By Audrey Andrews Hollywood, FL—As specialty pharmacy (SP) expands rapidly into oncology, there is a need to better define its role. This was the aim of the National Comprehensive Cancer Network (NCCN) Task Force on Specialty Pharmacy, whose chair presented the group’s preliminary report at the 15th Annual NCCN Conference.

“There is a vibrant specialty pharmacy industry, and the impact in cancer care is expanding,” said Rowena N. Schwartz, PharmD, of Johns Hopkins Hospital in Baltimore, Maryland.

Much of the interest in SP comes from the evolving role of oral antineoplastic agents. Of the 400 new antineoplastic agents in the pipeline, 25% are planned as oral drugs, and already spending on oral agents has more than doubled since 2002 (Weingart SN, et al. J Natl Compr Canc Netw. 2008;6[suppl 3]:S1-14).

Specialty pharmacists may prove to

be a valuable source of information on using these new medications safely, effectively, and economically, according to Dr Schwartz.

The Task Force explored aspects of SP that are unique to oncology and presented recommendations for joining SP and oncology. In particular, the Task Force addressed the mechanisms and potential benefits of SP as a distribution channel for oncology therapeutics. It identified opportunities as well for disease state management, cost of care, clinical research, and safety.

“The Task Force wanted to demonstrate there are opportunities to optimize cancer care by partnering with specialty pharmacy,” she said. “We wanted to show how specialty pharmacy is cost saving and offers value to third-party payers.”

Defining Specialty Pharmacy The Task Force defined SP as a pharmacy service model designed to fill the perceived gaps in pharmaceutical care associated with traditional

community pharmacy practices. In oncology, the scope of the practice includes the oral antineoplastic agents and supportive care medications, such as erythropoiesis-stimulating agents.

Health maintenance and management of comorbidities is also part of SP.

“We wanted to show how specialty pharmacy is cost saving and offers value to third-party payers.”

—Rowena N. Schwartz, PharmD

The current operational models include limited-distribution medications, infusion services, mail order, and distribution of medication via the community pharmacy network.

SP serves as a “hub” between prescribers, the drug manufacturer, and the patient, Dr Schwartz explained. Within this “hub” is a

NCCN Roundtable: Clinical and Economic Issues... a positive concept, he maintained.

“Reimbursement is where the rubber should meet the road.”

Financial Crises Already at Hand For patients already dealing with cancer, the crisis is occurring now. For many, medical insurance is simply unaffordable, Dr Newcomer emphasized. “In 1970, if you were a minimum wage worker in California you could buy a healthcare plan for your family of 4 for 15% of your income. In 2007, that same plan would cost you 102% of your income,” he noted.

“And we are about 4 years away from telling that same story about a middle class worker. We are spending far more on medical care than the economy can sustain.”

The National Patient Advocacy Foundation has witnessed an 87% increase in the number of families filing for bankruptcy as a result of nonreimbursed medical expenses, according to Ms Davenport-Ennis.

This parallels the findings from a 2009 study showing that nearly twothirds of all bankruptcies are due to medical-related debt and that most debtors have health insurers (Himmelstein DU, et al. Am J Med. 2009; 122:741-746). This represented a rise

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of 50% over 2001 medical-related bankruptcies, the authors reported.

“Be aware that the American consumer is bellying up to the bar to try to pay for healthcare and is slipping into bankruptcy,” she told attendees.

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Advances in Patient Care “Patients are increasingly expected to share more of the cost burden of the oral antineoplastics,” she observed.

There are high copays, tiered coverage, and the infamous “doughnut hole,” as well as hidden costs, such as changes in medication that lead to Continued on page 21

Continued from page 19

Jason Slotnik, Esq, an attorney with the Washington, DC–based legal firm Foley Hoag, who represents pharmaceutical and biotech companies, noted that regardless of public perception, economic hardships are being felt by

“The first question is not whether a phase 1 or 2 clinical trial will be positive, and not even if a product will become FDA-approved, but whether it will be reimbursed.”

—Douglas Lind, MD

Dr Newcomer took exception with this notion. “Are we living in the same country?” he responded. “I can’t think of any FDA-approved drug that we don’t pay for. If the drug has FDA approval, the patient can recover the cost,” he maintained.

Ms Davenport-Ennis pointed out that the problem is not necessarily with insurance reimbursement, but the high copayments the insured now face. “And while UnitedHealthcare may be generous in covering costs,” she added, “not all insurance companies are alike.”

patient/provider registry, verification of insurance coverage, and monitoring of treatment adherence and side effects. SP can also be involved in outcomes assessment, which is a growing need in the current environment.

industry. Built into the emerging payment model, he said, must be a means for industry to recoup its expenditures for drug development that are only becoming greater as a result of new demands.

“Doing health economics studies to demonstrate cost-effectiveness for a new drug, for example, adds another $200 million to the cost of bringing a drug to market,” he pointed out.

Ms Davenport-Ennis put the different perspectives together to conclude that reining in healthcare costs will be the responsibility of all stakeholders,

including employers who “make arbitrary decisions about coverage” and a government system that imposes regulatory burdens within the clinical trials system. “All this drives up cost,” she stressed, “and reduces the opportunity for the patient to obtain innovative care.”

Patients can and should be part of the discussion about their cost of care.

“They can participate in making wise decisions,” she insisted.

Dr Newcomer agreed that patients need to better appreciate the consequences of the current payment model. “From diagnosis to death from breast cancer, our company spends an average of $160,000 per patient,” he noted. “Would the conversation change if the patient were not spending someone else’s money?

If we said, ‘Do with this money as you wish’?”

Such conversations might be more likely to have their intended effect, Dr Lind added, if they are not postponed until the end of life when patients and their families are desperate and emotional.

“We are all complicit in this upward spiral,” Dr Goodman concluded, “and we are stuck with a collision course.” ■

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Reimbursement for Expensive Cancer Therapies: The Role of Cost-effectiveness Analysis

By Gary C. Yee, PharmD, FCCP, BCOP

D

ue to changes in the US Food and Drug Administration (FDA) approval process for cancer drugs, many new cancer drugs have been approved over the past 10 to 15 years. Although the availability of these new drugs has improved survival for many cancer patients, there is increasing concern over the cost of these agents.1 The global oncology market is predicted to increase 12% to 15% each year, from $48 billion in 2008 to $75 billion to $80 billion in 2012.2 About 70% of all sales of cancer drugs in North America and the European Union are of agents introduced in the past 10 years.

Although purchasers and payers have always been concerned about healthcare costs, recently concerns

have been raised by providers (ie, hospitals and oncologists) and patients. In an effort to control the utilization of expensive specialty drugs, many insurers have added a fourth tier to their pharmacy benefit plans.3 In contrast to the modest copayments required for other tiers, the fourth tier usually requires that patients pay a percentage of the drug cost (ie, coinsurance). Coinsurance payments, which generally range from 20% to 33% of the drug cost, can sometimes exceed $10 000 each year. Elderly patients with Medicare coverage who receive their chemotherapy in the clinic setting are subject to similar coinsurance payments. As a result, many patients cannot afford the coinsurance payments.4 With declining reimbursement, private oncology offices and hospital-based clinics are

Specialty Pharmacy... medication wastage. “Specialty pharmacy offers cost-friendly strategies to reduce costs to the patient,” according to Dr Schwartz.

SP also enhances medication safety by increasing product familiarity, availability, and access, and providing individualized monitoring, data tracking, and hazardous waste disposal.

Additionally, patients in clinical trials can have timely drug access, coordination of care (ie, dose modification), and coordination of information through SP, the Task Force pointed out.

But coordination of cancer care is perhaps the most important concern of SP. “We need to find out how specialty pharmacy can impact positively on cancer care,” Dr Schwartz said, “and not fragment care or confuse patients about the care they receive.”

Optimal care coordination will include not only authorization and drug distribution but also patient education, treatment monitoring, and disease management. This expanded responsibility for pharmacy highlights the need for team collaboration and a change in mindset about the role of pharmacy. The specialty pharmacist’s unique training can be an asset to patients and oncologists alike, she pointed out.

“One of the great things about specialty pharmacy is you are often working with pharmacists who are very knowledgeable about the products they are dealing with and there-

caught in the middle, and many now require up-front payment before chemotherapy administration.5 In a recent survey, 23% of oncologists responded that costs influenced their treatment decisions, and 16% said that they omit discussion of very expensive treatments when they know that cost would place a great strain on patient resources.6 In this review, a recently published cost-effectiveness analysis will be used to illustrate how these types of analyses may be used by policymakers to make reimbursement decisions concerning cancer drugs.

Case Study: Sunitinib for First-line Treatment of Metastatic Renal Cell Carcinoma Sunitinib malate (Sutent) is a recently approved, orally administered

Continued from page 20

fore have a lot of information for patients and their families,” Dr Schwartz explained.

One area left unaddressed by the Task Force, however, included drug costs and economic concerns. The group maintains that these issues are too broad and complex to be considered under its mission. However, the

group did recommend that an alternative financial model for pharmacy reimbursement be designed—one that will “get away from selling a product to providing services of value,” Dr Schwartz explained, and that inefficiencies associated with increased cost be identified and eliminated. ■

Preliminary Recommendations by the NCCN Task Force on Specialty Pharmacy • Specialty pharmacy personnel should be “trained” in oncology.

• Optimal coordination of care for patients and their families should be the priority.

• Communication among all members of the oncology team involved in drug therapy decision-making should be standardized, using a common language.

• Strategies should be created to assure coordination of care for patients treated in multiple healthcare settings.

• Health information technology systems (ie, electronic health records) should be developed and used to foster collaborative care.

• Shared-data needs (ie, for integration of case management, insurance coverage, clinical information and outcomes) should be identified and national standards established.

• Standards and requirements for care coordination and medication safety should be developed.

• Operational processes that support frequent changes of treatment should be established (eg, allowing dispensing of smaller amounts of medication at one time).

• Regulations should be implemented for dispensing and handling of oral chemotherapy.

• The use of “brown bagging” (ie, purchases made at one place but administered in another) for chemotherapy, antineoplastic agents, and supportive care medications should be eliminated.

small molecule with antitumor activity against renal cell carcinoma, gastrointestinal stromal tumors, and other solid tumors. The annual cost of sunitinib in the United States is $50000 to $60000. A recently published, large, multicenter, randomized, phase 3 trial showed that sunitinib was superior to interferon alfa in patients with previously untreated metastatic renal cell carcinoma.7 Sunitinib-treated patients had a significantly higher objective response rate (31% vs 6%, P <. 001) and longer median progression-free survival (11 vs 5 months, P < .001) than those treated with interferon alfa. In a recent update of that trial, patients in the sunitinib group had longer median overall survival than those in the interferon alfa group (26.4 vs 21.8 months), although the difference was of borderline significance (P = .051).8 Based on the results of that phase 3 trial, a Pfizer-supported cost-effectiveness analysis was conducted, and the results of that analysis were recently published.9 A Markov model was developed to evaluate the costeffectiveness and cost utility of sunitinib (as compared with interferon alfa or interleukin-2) in a hypothetical cohort of 1000 patients with metastatic renal cell carcinoma receiving firstline treatment of sunitinib. The analysis was done from a US societal perspective. Model parameters were obtained from trial results, published literature, government sources, and expert opinion. A 10-year time horizon was assumed to represent a lifetime horizon, because the model predicted that less than 1% of patients would still be alive at 10 years.

Utilities were derived from qualityof-life data collected with the EuroQoL (EQ-5D) instrument in clinical trials. Only direct medical costs were included.

Sunitinib was more effective and more costly than interferon alfa. Both sunitinib and interferon alfa dominated interleukin-2 (ie, more effective and less costly). The incremental costeffectiveness or cost-utility ratio of sunitinib versus interferon alfa was $18 611 per progression-free year gained, $67215 per life-year gained, or $52593 per quality-adjusted lifeyear (QALY) gained (2006 US dollars; costs and outcomes discounted at 5%). A probabilistic sensitivity analysis showed that the model was most sensitive to utility values during treatment, sunitinib cost, and the cost Continued on page 22

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Reimbursement for Expensive Cancer Therapies... of best supportive care.

The authors concluded that sunitinib is a cost-effective alternative to interferon alfa as first-line treatment for metastatic renal cell carcinoma because the cost-effectiveness (or costutility) ratios were in the range of values that society (in the United States) is willing to pay for health benefits.

NICE Declines Drugs for Metastatic Renal Cell Carcinoma In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE), a government agency, advises the National Health Service (NHS) on coverage for medicines and technologies.10 Details on its appraisal process are available online on the NICE web site (www.nice.org.uk). NICE usually hires an academic group to prepare its appraisals, which include an economic evaluation that estimates the incremental cost-effectiveness (or cost-utility) ratio of the new drug. These appraisals can sometimes take 2 to 3 years after a drug has been approved.

The NHS then considers these analyses when it makes decisions concerning reimbursement for that new drug or technology.

In August 2008, NICE issued draft guidance that rejected the use of 4 drugs, including sunitinib, for metastatic renal cell carcinoma.11 Although the report concluded that the 4 drugs were effective, NICE rejected them because its analysis showed that they were “not costeffective use of NHS resources” based on its usual threshold of £30,000 per QALY (Table). It is interesting to note that estimates of the cost-effectiveness ratios of the 4 drugs from the manufacturers differed considerably from the estimates from the independent academic group hired by NICE. The estimated cost-utility ratio for sunitinib in the setting of first-line treatment in the Pfizer model submitted to NICE was about 25% lower than the value reported in the study published

by Remák and associates,9 which is about the same as the difference in sunitinib cost between the United States and Britain. That decision angered patients and physicians, because the drugs are widely available in other European countries.

Furthermore, British patients were angered by the NHS guidelines, which state that they would lose all of their NHS benefits if they decided to pay for the cancer drugs with their personal funds. In response to this outcry, the British government announced in November 2008 that it

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would not withdraw NHS benefits from patients who choose to pay outof-pocket for cancer drugs and issued new guidelines to NICE that encourage greater flexibility when NICE appraises high-cost drugs for patients with rare and serious conditions.

Some reports indicate that NICE will increase the threshold to as high as £80 000 per QALY for these selected drugs. In a final ruling announced March 25, 2009, NICE recommends sunitinib for the first-line treatment of renal cancer.

Role of Cost-effectiveness Analysis in Reimbursement Decisions In the United States, the single largest payer of healthcare for cancer patients is the Centers for Medicare & Medicaid Services. The long-standing Medicare policy is to not consider cost-effectiveness analyses in its reimbursement decisions.12 Private insurers also have been reluctant to formally consider cost-effectiveness analyses in its reimbursement decisions.

Decision makers have been reluctant to consider cost-effectiveness analyses in reimbursement decisions.

Although cancer drugs usually have been viewed as “off limits” for utilization management strategies, the high cost of these agents has prompted private insurers to apply these strategies to cancer drugs.13,14 Some insurers are limiting the use of these agents to FDA-approved indications, which can be problematic because cancer drugs are often used for “off-label” indications and because some drugs are approved based on limited evidence. Others are applying step-therapy protocols to cancer drugs, which require that patients fail 1 or more less expensive options before they are eligible to receive the more expensive agent.

One innovative approach is a “payfor-performance” strategy, which means that the manufacturer agrees to lower the price of its drug by providing a rebate if the drug fails to perform.15,16 Several manufacturers have already agreed to that strategy in Britain, and at least 1 large private insurer in the United States is exploring it.

Many policy experts support an expanded role of cost-effectiveness analyses in determining reimburse-

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Continued from page 21

Table Cost-effectiveness of Targeted Agents for Renal Cell Carcinoma Base-case ICER (Cost [£] per QALY) Treatment Comparator NICE Manufacturer First-line treatment, suitable for immunotherapy Sunitinib IFN 71462 28546 Bevacizumab plus IFN IFN 171301 74978 First-line treatment, poor prognosis Temsirolimus IFN 94385 55814 Second-line treatment Sorafenib BSC 102498 90630 BSC indicates best supportive care; ICER, incremental cost-effectiveness ratio; IFN, interferon; NICE, National Institute for Health and Clinical Excellence; QALY, quality-adjusted life-year.

Adapted with permission from Coon JT, Hoyle M, Green C, et al; Peninsula Technology Assessment Group. Bevacizumab, sorafenib tosylate, sunitinib, and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation. Exeter, UK: Peninsula Medical School; May 2008.

ment decisions, including the creation of a new federally funded, independent entity (modeled after NICE) to produce comparative effectiveness and cost-effectiveness information.1,12,17-19 Some argue that payers already make these comparisons, either implicitly or explicitly. Creation of such a formal entity was recently predicted to yield savings of $368 billion to the healthcare system over the next 10 years.19 Although cost-effectiveness analyses can be useful to decision makers, healthcare professionals and the public are skeptical of the use of these types of information and are uncomfortable with efforts to allocate resources based on the economic value of a person’s life.20 Ideally, the public (ie, society) should determine how societal resources are allocated.

Private employers, however, are major purchasers of healthcare in the United States. The outcry in Britain over NICE’s decision concerning drugs to treat renal cell carcinoma suggests that the public views cancer drugs differently from other drugs. In response, NICE has adjusted its costeffectiveness threshold for certain cancer drugs. Similarly, some experts suggest Americans do not want to consider cost when making decisions concerning new cancer treatments.20 Summary The rising cost of cancer drugs is of concern to society, particularly patients with cancer, who often cannot afford the newer agents. Although decision makers have been reluctant to consider cost-effectiveness analyses in reimbursement decisions, there is increasing support for an expanded role of these types of analyses, including the creation of a new federally funded entity to produce these analyses. As illustrated by the experiences in Britain, however, application of

cost-effectiveness analyses to reimbursement decisions for cancer drugs can be controversial because of the societal burden of cancer. ■ A version of this article originally appeared in The Oncology Nurse March/April 2009.

References 1. Sinha G. Expensive cancer drugs with modest benefit ignite debate over solutions. J Natl Cancer Inst.

2008;100:1347-1349.

2. Gavel SJ. The oncology pipeline: maturing, competitive, and growing? Oncology Business Review.

September 2008. www.imshealth.com/imshealth/ Global/Content/Web%20Article/The_Oncology_ Pipeline3.pdf. Accessed February 6, 2009.

3. Kolata G. Co-payments soar for drugs with high prices. The New York Times. April 14, 2008.

4. Kolata G, Pollack A. Costly cancer drug offers hope, but also a dilemma. The New York Times. July 6, 2008.

5. Chase M. Pricey drugs put squeeze on doctors. The Wall Street Journal. July 8, 2008.

6. Schrag D, Hanger M. Medical oncologists’ views on communicating with patients about chemotherapy costs: a pilot survey. J Clin Oncol. 2007;25:233-237.

7. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2008;356:115-124.

8. Figlin RA, Hutson TE, Tomczak P, et al. Overall survival with sunitinib versus interferon-alfa as first-line treatment of metastatic renal cell carcinoma [abstract].

J Clin Oncol. 2008;26(suppl). Abstract 5024.

9. Remák E, Charbonneau C, Négrier S, et al.

Economic evaluation of sunitinib malate for the firstline treatment of metastatic renal cell carcinoma. J Clin Oncol. 2008;26:3995-4000.

10. Steinbrook R. Saying no isn’t NICE—travails of Britain’s National Institute for Health and Clinical Excellence. N Engl J Med. 2008;359:1977-1981.

11. Harris G. British balance benefit vs. cost of latest drugs. The New York Times. December 2, 2008.

12. Neumann PJ, Rosen AB, Weinstein MC. Medicare and cost-effectiveness analysis. N Engl J Med. 2005;353:1516-1522.

13. Anand G. As costs rise, new medicines face pushback. The Wall Street Journal. September 18, 2007.

14. Chase M. Payers aim to rein in specialty-drug spending. The Wall Street Journal. March 20, 2008.

15. Pollack A. Pricing pills by the results. The New York Times. July 14, 2007.

16. Garber AM, McClellan MB. Satisfaction guaranteed—“payment by results” for biologic agents. N Engl J Med. 2007;357:1575-1577.

17. Emanuel EJ, Fuchs VR, Garber AM. Essential elements of a technology and outcomes assessment initiative. JAMA. 2007;298:1323-1325.

18. American College of Physicians. Information on cost effectiveness: an essential product of a national comparative effectiveness program. Ann Intern Med. 2008;148:956-961.

19. Davis K. Slowing the growth of health care costs— learning from international experience. N Engl J Med. 2008;359:1751-1755.

20. Berenson A. Pinning down the money’s value of a person’s life. The New York Times. June 11, 2007.

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Traditional Managed Care Tools... evaluate the value of comparable but not identical therapies. Even more difficult is the untenable choice for patients to decline treatment they cannot afford.

use of therapeutics in second-line therapy and beyond. And it will not drive the application of personalized medicine to distinguish patients who benefit from targeted therapies from those who only experience toxicities

Continued from page 13 and cost.

If managed care tools are not the answer, what is the way forward?

Pathways are the medically appropriate, sensible, and sustainable strategy to address the unnecessary variability

and uneven quality in cancer treatment and thereby improve quality, decrease potential toxicities and side effects, and moderate costs. Pathways will actually improve the value of cancer care from the inside out. ■

Until the reimbursement system for oncology changes, the revenues associated with drugs are the vital financial engine to keeping communitybased oncology care viable.

Manipulating drug reimbursement schedules. Payers are exploring equalizing the financial incentives to oncologists between higher cost single-source agents and lower cost multisource agents. This approach does make sense in that it removes the financial disincentive for oncologists to use an equally efficacious multisource drug where it might be appropriate. But, taken by itself, this tactic does not go far enough in defining optimal and least toxic care for patients that will drive better outcomes and present fewer complications. It will not address appropriate

with new enhanced online services There is A place you can go for user-friendly online tools and reimbursement forms… …where your coverage questions can be Answered

Evidence-based Medicine... Continued from page 7 unsubstantiated therapies), in cancer there is often more than one treatment regimen with demonstrated antitumor efficacy for a given tumor type, histology, stage of disease, and treatment intent. How should we prioritize these therapies and select among them? A next challenge to achieve better care at lower cost is to define the components of value (such as potential for prolonging life or cure, side effects [both acute and long-term complications], cost, patient experience, etc) and to devise appropriate weighting of the components. With more than 750 therapeutic agents in the development pipeline for cancer alone, systems-based decision-support at the moment of clinical prescribing that aligns proper prescribing with appropriate reimbursement is now needed to assist therapeutic decision-making in community practice. ■ References 1. Institute of Medicine. Evidence-Based Medicine and the Changing Nature of Health Care: 2007 IOM Annual Meeting Summary. Washington, DC: National Academies Press; 2008.

2. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academies Press; 2001.

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GeNitouRiNARy cANceRs syMposiuM

Researcher Graphically Illustrating Which Treatments Are Best for Prostate Cancer examined intermediate-risk PCa (Figure). “PCRSG” stands for Prostate Cancer Results Study Group, which is the 25-member panel. Each symbol indicates an individual study; the

By Rosemary Frei, MSc San Francisco, CA—The expression “a picture is worth a thousand words” is certainly true when it comes to figures from a new literature review of prostate cancer (PCa) treatments.

In a presentation at the American Society of Clinical Oncology’s 2010 Genitourinary Cancers Symposium, Peter Grimm, DO, showed that brachytherapy is more effective than surgery or electron beam radiation therapy (EBRT) in preventing progression in low- and intermediaterisk PCa. Dr Grimm, executive director of the Prostate Cancer Treatment Center, Seattle, Wash, helped put together a panel of 25 radiation oncologists, brachytherapists, urologists, and medical oncologists from North America and Europe. They developed and then applied a set of strict inclusion criteria to 603 PCa treatment-related articles published since 2000. Dr Grimm then marked on graphs the rate of progression-free survival from each of the 51 articles that met all the criteria.

The results show that, for most patients with low- or intermediate-risk PCa, brachytherapy provides better outcomes than either surgery or EBRT. The average prostate-specific antigen (PSA) progression-free survival rate from the low-risk PCa studies was 98% for brachytherapy, 92% for surgery, and 80% for EBRT. Moreover, this sequence of effectiveness remained when Dr Grimm widened the inclusion criteria to take in low-risk PCa studies that had a median follow-up of ≥40 months or enrolled <100 patients, and when he

The results show that, for most patients with low- or intermediaterisk PCa, brachytherapy provides better outcomes than either surgery or EBRT. —Peter Grimm, DO

shapes of the symbols represent the types of treatments, and the large circles represent the range of results from all of the studies of each treatment modality. (A full list of the studies referenced in this figure is available from the author—contact peter@grimm.com.)

“Dr Grimm’s work synthesizes and summarizes the best retrospective data available regarding the relative strengths and weaknesses of all the available treatment options for prostate cancer…he did not ‘cherry pick’ articles from the literature,” commented Mark Scholz, MD, medical director, Prostate Oncology Specialists, Marina del Ray, Calif, and clinical assistant professor, Department of Medical Oncology, University of Southern California, Los Angeles. “It is a significant accomplishment, because there presently are no prospective comparisons and nor are there likely to be any in the future.”

The PCRSG criteria were: • patients stratified into pretreat-

Figure Intermediate-risk PCRSG Criteria

%

% PSA Progression Free

100

Brachy

90 80

EBRT

70 60

Surgery

EBRT EBRT && Seeds Seeds Brachy

Surgery EBRT CRYO HIFU Protons Protons HDR HDR

50 40 1

2

3

4

5

6

7

8

9 10 11 12 13 14 15

" Years 2

4

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ment, low-, intermediate- or highrisk groups, according to the D’Amico, Zelefsky, or National Comprehensive Cancer Network criteria;

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• biochemical relapse-free survival used as the standard end point— defined based on either the American Society of Therapeutic Radiology and Oncology or the Phoenix criteria, and including PSA <0.2 ng/mL; • no postsurgery pathological staging—clinical staging only;

• EBRT with ≥72 Gy, including intensity modulated radiation therapy and conformal radiation therapy; • published in a peer-reviewed journal; • ≥100 patients if focused on low- or intermediate-risk disease; • ≥50 patients if focused on high-risk disease; and, • minimum median follow-up of 5 years.

Only 13% of the brachytherapy articles, 7% of the radical prostatectomy articles, and 0% of the high-intensity– focused ultrasound articles met all of these criteria.

Dr Grimm has not yet completed the analyses for the high-risk PCa studies.

“What I hope this kind of data does is also highlight the lack of uniformity of reporting,” concluded Dr Grimm. “We hope to move the field towards journal editors saying, ‘If you want your studies to be comparable to other work in the literature, they will have to meet these basic criteria.” ■

SEER-Medicare Database Analysis Confirms...

Continued from cover

tion, brachytherapy was combined with IMRT in only 8.5% of brachytherapy treatments in 2002, but in 31.1% in 2005.

Danil Makarov, MD, Robert Wood Johnson Foundation Clinical Scholar, Yale University School of Medicine, New Haven, Conn, commented that the investigators’ study is broadly relevant.

“It’s one thing to come to these conclusions about patients that have private insurance or can afford to pay for these expensive procedures out of their own pockets. But since these are Medicare data they are very relevant to public policy because this is government-funded; we’re all paying for it,” he said.

Dr Nguyen also performed a univariate regression analysis that revealed factors significantly associated with having the latest technology.

They include being highly educated, having a high income, living in the Northeast or West, having a highgrade or clinical T1 tumor, and being Asian. Being an African American or Hispanic was associated with having an open RP rather than MIRP. And, perhaps surprisingly, being either an African American or white was asso-

“So for MIRP, for example, there are still not enough data to define exactly what the benefits are over RP, or what the downsides are.”

—Paul L. Nguyen, MD

ciated with having 3D-CRT rather than IMRT. Dr Nguyen noted that comparative effectiveness research into these more expensive therapies has yet to be conducted.

“So for MIRP, for example, there are still not enough data to define exactly what the benefits are over RP, or what the downsides are,” he told ValueBased Cancer Care. ■

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Better Diagnostic Accuracy Through More Testing? Not Necessarily When It Comes to Bladder Cancer

By Rosemary Frei, MSc San Francisco, CA—A new study challenges the notion that more testing leads to greater accuracy in detection of non–muscle-invasive bladder cancer (NMIBC).

Results presented at the ASCO 2010 Genitourinary Cancers Symposium indicate that cystoscopy alone costs $7692 per tumor detected and has a low false-positive rate. Adding cytology, nuclear matrix protein 22 (NMP22), fluorescence in situ hybridization (FISH), or NMP22 plus FISH increases the cost significantly without a concomitant improvement in accuracy.

Ashish Kamat, MD, associate professor of Urology and director of the Oncology Fellowship Urologic Program, M. D. Anderson Cancer Center, Houston, Tx, and his colleagues conducted a study of 200 NMIBC patients.

At enrollment, the subjects underwent cystoscopy along with each of the above-mentioned tests. The investigators detected cancer in 13 patients at enrollment and another 12 at follow-up within 6 months.

The cost per tumor detected was $7692 for cystoscopy alone, $11100 for cystoscopy plus NMP22 BladderChek, $19 111 for cystoscopy plus FISH Urovysion testing, $10 300 for

Researchers Probe Concurrent Timing of ADT Use Drop and Medicare Reimbursement Policy Change

By Rosemary Frei, MSc San Francisco, CA—By mining the Surveillance, Epidemiology and End Results-Medicare Database, researchers have documented a significant decline in nonevidence-based use of androgen deprivation therapy (ADT) for prostate cancer between 2003 and 2005. This coincides with a significant drop in Medicare reimbursement in 2004 for the form of ADT known as a gonadotropin-releasing hormone agonist.

In the database there were 54925 men with prostate cancer newly diagnosed between 2003 and 2005, 43.2% of whom used ADT. The rate of evidence-based ADT use among those 43.2% remained roughly steady at around 80% over that period. “Nonevidence-based use of androgen deprivation therapy fell from 38.7% in 2003, to 30.7% in 2004, and to 25.7% in 2005.”

The investigators created a modified Poisson regression analysis model that confirmed nonevidencebased ADT use dropped: there was a 0.72 odds ratio of use in 2005 compared with 2003.

They presented the results at the ASCO 2010 Genitourinary Cancers Symposium.

The question remains, however, what the main driver of the drop was.

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Lead researcher Vahakn Shahinian, MD, MS, assistant professor of medicine, University of Michigan School of Medicine, Ann Arbor, and his coinvestigators seem to believe it was the change in reimbursement. But David Penson, MD, MPH, professor of urologic surgery and director, Vanderbilt Center for Surgical Quality and Outcome Research, Institute for Medicine and Public Health, Vanderbilt University, Nashville, Tenn, thinks it may be more complicated than that.

“Nonevidence-based use of androgen deprivation therapy fell from 38.7% in 2003, to 30.7% in 2004, and to 25.7% in 2005.”

—Vahakn Shahinian, MD, MS

He points out that around the same time, several papers were published— including one with Dr Shahinian as the lead author (N Engl J Med. 2005; 352[2]:154-156)—that documented significant adverse events from ADTs. “It is likely that this also played an important role in changes in ADT patterns of care in the first decade of the 21st century,” Dr Penson concluded, when discussing the study with Value-Based Cancer Care. ■

“The costs associated with the markers as well as the extra invasive procedures required for false-positive tests did not improve detection of invasive tumors.”

—Ashish Kamat, MD

cystoscopy plus cystology, and $9600 for cystoscopy plus NMP22 followed by selective FISH use.

Taking into account the tumors detected at first follow-up, and assuming that the markers detected tumors prior to clinical visibility, the tumor detection rate for each strategy was 52%, 56%, 72%, 60%, and 56%, respectively.

“It is important to note that even though the markers could improve detection of tumors, the costs associated with the markers as well as the extra invasive procedures required for false-positive tests did not improve detection of invasive tumors,” Dr Kamat told Value-Based Cancer Care, in an interview conducted after the conference. ■

Other Research from the 2010 Genitourinary Cancers Symposium The Shifting Role of Biopsy in Renal Cell Cancer A study of patients undergoing biopsy for renal cell cancer (RCC) over a 10-year period indicates that the role of biopsy has changed over time, with the procedure now being used more frequently to assess the suitability of elderly patients for targeted therapies.

The United Kingdom–based team of researchers examined pathology and radiology databases to assess the indications, outcomes, and final pathology of patients undergoing biopsy for RCC. For the 255 patients undergoing the procedure, the median age was 67 (range 22-90 years) with 41% aged 70 or over. Of 193 biopsies (76%) confirmed RCC, 33 (13%) an alternative malignancy, 14 (6%) were benign, and 15 (6%) were inconclusive and not repeated. The commonest reason for biopsy was to establish diagnosis and histological subtype in metastatic disease, followed by a previous or concurrent malignancy, and then clinical uncertainty over diagnosis.

Biopsies in metastatic disease increased significantly over the years studied, (P ≤ .05), while the numbers of biopsies in patients with another malignancy (most commonly a primary lung tumor [P = .899] or indeterminate lesions [P = .421]) have not changed significantly. Only 33 significantly younger patients (13%) underwent nephrectomy following their biopsy.

Renal biopsy is now no longer simply for diagnostic dilemmas with renal masses, the authors conclude, saying that the procedure now has a major role as a confirmatory investigation prior to treatment.

The Effects of Targeted Therapy in Metastatic Renal Cell Carcinoma A study of primary tumor response to the present generation of targeted therapies finds a disappointing response rate among patients with metastatic renal cell carcinoma, with few patients achieving a partial response as defined by RECIST criteria. This finding may have an important impact on the design of clinical trials, the authors say.

The researchers, from the University of Texas M. D. Anderson Cancer Center, Houston, identified patients with primary tumor and metastatic disease who received targeted therapies (among them sunitinib, bevacizumab, bevacizumab + gemcitabine, erlotinib, bevacizumab + erlotinib, bevacizumab + sunitinib, temsirolimus, and sorafenib) at initial treatment. Imaging was used to evaluate the change in tumor size from baseline to after treatment.

There was an overall median decrease of 6% in primary tumor size among the 151 patients, and the authors noted no difference in primary tumor response rates based on MSKCC criteria or histology.

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Breast Cancer Survival Improves... reason for the improved survival in this group of patients, and use of the chemotherapy drugs known as anthracyclines also contributed,” said lead author Marie Sundquist, from the Department of Surgery, County Hospital, Kalmar, Sweden, in a press release announcing the findings.

The study is a retrospective analysis of follow-up data of metastatic breast cancer patients who were diagnosed in Kalmar County since 1985, and this continuity is a strength of the study. “We have studied a consecutive population in a defined geographical area for a continuous period of 25 years,” noted Dr Sundquist.

The researchers collected patient and tumor data from patient records and the tumor registry, and survival curves were generated in 5-year intervals by tumor grade. Separate analyses were performed for patients with ER/PR-positive and HER2-positive tumors; there were 557 patients in the entire study population.

Median survival for the complete study population increased from 10 to 22 months, respectively, in the first and last 5-year period. For patients with grade 3 tumors, the most aggressive type of breast cancer (n = 288), the median survival time increased from 10 months in the 1985-1990 time period to 17 months for the 2000-2004 period. The percentage of patients with grade 3 tumors surviving more than 3 years improved from 14% to 34%. For patients with grade 2 tumors, the median survival was 17 and 27 months, respectively, in those same time frames. Survival for patients with grade 1 tumors did not change over time.

Better Targeting, But at a Cost In looking at the HER2-positive subset, 40 patients treated before 2000 had a median survival of 14 months, and the same number diagnosed in the year 2000 or later survived for 21 months. And this improved survival

Continued from cover

is largely due to new therapies, Dr Sundquist noted.

“In the group of HER2-positive patients that had the most aggressive type of breast cancer (grade 3), 45% of those patients that received trastuzumab had survived more than 3 years and 30% more than 5 years,” she said.

“These new targeted therapies will, at least in the beginning after their development, be very costly for healthcare systems.”

—Marie Sundquist In a follow-up interview, Dr Sundquist noted that HER2 testing is routine in Sweden in all invasive breast tumors. “In our hospital, we introduced this routine in 1996,” she said.

Even with better targeting of therapy, metastatic disease presents a complex decision-making process for

patients and physicians. “Patients whose breast tumors have spread outside of the breast and armpit areas are essentially incurable. However, some patients live even decades with a good quality of life despite an initially widespread tumor burden, while others fail to respond to any therapy,” Dr Sundquist noted. “To explore and try to understand these mechanisms would make it easier to tailor the treatment for each individual patient.”

But tailored treatments will not come cheap. “These new targeted therapies will, at least in the beginning after their development, be very costly for healthcare systems,” Dr Sundquist said. “When the public health insurance authorities decide which costs to cover, it is important that they realize the cost-benefit ratio.” Despite these costs, these drugs “will make it possible for many women to lead almost normal lives, work, and contribute to society for an increased number of years,” she concluded. ■

Radical Treatment Not Best Course for BRCA Mutations Barcelona—For women with the BRCA1 or 2 genetic mutation that predisposes them to breast cancer, the option to undergo prophylactic mastectomy of the other, noncancerous breast following their initial breast cancer treatment does not improve disease-free survival or overall survival, said researchers at the EBCC7 meeting.

Annette Heemskerk-Gerritsen, a PhD student in the Department of Medical Oncology, Erasmus Medical Centre, Rotterdam, the Netherlands, described a study that looked at the efficacy of risk-reducing mastectomy (RRM) in 390 patients with the BRCA1/2 genetic mutation who already had cancer in 1 breast. One hundred thirty-eight underwent RRM and the balance continued with regu-

lar surveillance; there were no observed differences in age at diagnosis, hormone-receptor status, and adjuvant systemic treatment between the 2 groups. There were greater numbers of patients undergoing adjuvant chemotherapy and riskreducing salpingo-oophorectomy in the RRM group.

The regular surveillance group experienced 54 patients who developed metastatic disease during 2033 person-years of observation (PYO), as opposed to 18 patients during 642 PYO in the RRM group. Regarding overall survival, 56 women in the nonRRM group died (in 2164 PYO), and 16 in the RRM group (in 682 PYO).

According to background information provided in the press release

announcing these findings, women who carry the mutated BRCA1/2 gene have a risk of between 55% and 85% of developing cancer in their lifetime, and those who do develop it have to make difficult decisions about their treatment, often opting for the most radical therapy in the belief that they will have a better chance of overcoming their disease. Until now there has been little data on the longer-term effects of such treatments on these patients.

“RRM obviously reduces the incidence of breast cancer in the other breast to zero,” said Ms HeemskerkGerritsen, but “we found that there was very little difference in diseasefree and overall survival between the 2 groups.”

As to next steps and how this information might eventually be used in patient care, Ms HeemskerkGerritsen remarked, “We intend to follow up this study by identifying a set of prognostic factors related to survival in breast cancer patients with a BRCA1 or BRCA2 mutation. In this way, we hope to be able to identify a subgroup of patients who may benefit from RRM. In the meantime, we hope that our findings will provide additional information to improve the counseling of breast cancer patients considering risk-reducing mastectomy, by emphasizing that the gain that may be obtained by this radical surgery is mainly in respect of reducing the risk of contralateral breast cancer.” ■

Collaboration Needed to Maximize Tamoxifen’s Benefit Barcelona—An effort to monitor and modify prescription drug use in breast cancer patients prescribed tamoxifen can help prevent the polypharmacy that lessens tamoxifen’s effectiveness.

Drugs including bupropion, fluoxetine, and paroxetine can inhibit the action of the CYP2D6 enzyme, which is crucial to the metabolism of tamoxifen for breast cancer. Sean Hopkins,

BSc, RPEBC, a clinical pharmacy specialist in breast cancer at the Ottawa Hospital Regional Cancer Centre, Ottawa, Canada, described an effort at his institution to investigate how many patients taking hormonal therapy for breast cancer were also being prescribed CYP2D6 inhibitors. He presented his findings at EBCC7.

Mr Hopkins began by extracting drug claim data from the Ottawa

Hospital Breast Cancer Disease Site Group clinical database, including any patients on tamoxifen, aromatase inhibitor (AI) therapy, or CYP2D6 inhibitors. Of 531 claims eligible for this analysis, 463 (87%) of these patients received 1 of the prescribed hormonal therapies while 68 (13%) were not on hormonal therapy but did receive the CYP2D6 medications.

Seven patients (4.5%) receiving

tamoxifen and 16 patients (5%) receiving an AI were concurrently on a strong CYP2D6 inhibitor. Moderate enzyme inhibitors were given to 1 patient (0.6%) on tamoxifen and 6 patients (1.9%) receiving an AI. Weak CYP2D6 inhibitors were given to 24 patients (16.5%) on tamoxifen and 40 patients (12.4%) on an AI. Unlike a “straight” retrospective study, however, this one allowed Continued on page 28

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Existing Test May Have New Use in Anthracycline Targeting Barcelona—A meta-analysis of 4 large breast cancer trials reveals that a particular chromosome abnormality is a highly significant indicator that a patient’s breast cancer will respond to anthracycline therapy, announced an international team of researchers at the EBCC7 meeting.

According to the lead author on the current study, John Bartlett, PhD, professor of molecular pathology at the University of Edinburgh, United Kingdom, evidence on whether the HER2 and TOP2A genes could provide accurate indication of tumor response to anthracyclines is conflicting. Earlier research by Dr Bartlett did show that duplication of chromosome 17 alpha satellite (CEP17) predicted sensitivity to anthracyclines. The present retrospective meta-analysis of nearly 3000 patients attempted to sort out this conflicting evidence.

The test used to assess patient genetic sequences, fluorescent in situ hybridization or FISH, is carried out routinely in breast cancer patients; it is used to test for the HER2 gene to see whether the woman might

benefit from the drug trastuzumab (Herceptin). Because CEP17 is on the same chromosome as the HER2 and TOP2A genes, the assessment for CEP17 could be easily carried out in the same FISH analysis as for HER2, said Dr Bartlett. In the present study, Dr Bartlett’s lab conducted the FISH analysis on samples from the original trials.

Overall, CEP17 duplication was detected in 27.5% of tumors and was associated with poorer overall survival (OS) and recurrence-free survival (RFS). Patients with this genetic abnormality who were treated with anthracyclines were approximately two-thirds more likely to survive (OS = 63%) and to survive without a recurrence of cancer (RFS = 67%) than those who did not receive anthracyclines.

In a press release announcing the findings, Dr Bartlett stated that “our finding that patients whose tumors have the CEP17 abnormality are more likely to respond to anthracyclines is entirely novel.” This genetic abnormality, the authors conclude, may represent a clinically useful biomark-

Collaboration Needed... intervention on the part of Mr Hopkins. He noted in a press release announcing the findings, “We have been able to take action as soon as we have discovered that a patient is taking interacting medication(s) by contacting the prescribing doctor in order to get them to switch to a different medication with no deleterious effect on tamoxifen metabolism.”

Communication Is Key “We have known for a while that patients with a deficiency in CYP2D6 activity did not derive the full benefit from tamoxifen because they cannot metabolize it to endoxifen, its active metabolite,” said Mr Hopkins.

For these patients, having the knowledge to be able to plan effectively in advance is important, as it can take many weeks to wean patients off CYP2D6 inhibitors, and this may affect their breast cancer therapy. The findings reinforce the need for good communication between all healthcare providers in order to eliminate the risk of reducing the efficacy of prescribed therapy, Mr Hopkins indicated.

“Patients can receive care from many different healthcare professionals—oncologists, other specialists, family doctors, etc—and they can

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receive medications from multiple pharmacies,” he continued. “If there is insufficient information transfer between the individuals who care for a patient, the risks of drug interactions increase, and this can affect the quality and efficacy of care being given.”

“If there is insufficient information transfer between the individuals who care for a patient, the risks of drug interactions increase.”

—Sean Hopkins, BSc, RPEBC In addition to communication, another means to better care could be greater openness among those providing and paying for care, Mr Hopkins said. “I believe that we need to have policies in place to require healthcare providers and their agencies, including private insurance companies, to provide better access to information for healthcare professionals involved in patient care. If these organizations try to protect their information in an unreasonable manner, it can seriously impact care and outcomes for patients.” ■

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er for selection of patients likely to benefit from anthracycline-containing chemotherapies.

In addition to helping better target chemotherapy, the discovery may open the way for biochemists to research the mechanisms involved in CEP17 and to design new drugs to target these pathways.

He cautioned that these findings need to be validated, saying “whilst the finding is of high evidence level, we need to confirm its applicability in an era where taxanes are a key component of treatment choice.”

Nevertheless, they suggest that “only those patients with CEP17 tumors should receive anthracyclines, thereby enabling other patients who do not have the CEP17 abnormality to avoid a toxic treatment that will not be effective.” ■

“Whilst the finding is of high evidence level, we need to confirm its applicability in an era where taxanes are a key component of treatment choice.”

—John Bartlett, PhD

Protein Offers Expanded Predictive Significance in Early Breast Cancer Barcelona—A protein previously thought to exist only in a limited number of tumors in fact exists across all breast cancer subtypes, a finding that can help predict the tumor’s response to chemotherapy and guide treatment decisions.

These results are from a study, led by first author Gunter von Minckwitz, MD, of the German Breast Group Forschungs GmbH, Neu-Isenburg, Germany, which looked at the protein polyadenosine diphosphate [ADP]ribose polymerase (PARP), its expression in various hormone and HER2 receptor subtypes of early breast cancer, and its predictive value for pathological complete response. With PARP inhibited, cell death occurs, meaning that chemotherapy can be targeted precisely at cancer cells, while leaving normal, healthy cells relatively untouched. The research team examined tissue from 582 patients who received neoadjuvant chemotherapy, staining the samples immunohistochemically for PARP, ER, PgR, and HER2 expression. PARP expression was scored as low, medium, or high.

High expression was found in 19.9% of 286 HR+/HER2- tumors, 20.2% of 129 HR+/HER2+ tumors, 36.0% of 50 HR-/HER2+ tumors, and 35.6% of 101 HR-/HER2- tumors. Patients with high PARP expression showed a pathological complete response rate of 25.7% compared to 18.8% and 6.1% in patients with medium or low expression (P < .001).

“The relationship to total response

was remarkable,” Professor von Minckwitz said in a press release announcing the findings. “Tumors with a high level of PARP expression had a total response in 26% of cases, whereas those tumors which did not express PARP had a total response in only 9%. Additionally, we found that the presence of PARP can provide more accurate prognostic information than the grade of differentiation or degree of abnormality of tumors. We believe that this is the first study to describe a broad expression of PARP in untreated breast tumors together with a correlation of sensitivity to chemotherapy.”

The authors conclude that because PARP expression can be detected by immunohistochemistry in all subtypes of early breast cancers and it predicts pathological complete response to neoadjuvant taxane anthracycline– based chemotherapy, clinical investigation of PARP inhibitors should not be limited to triple-negative tumors alone.

However, the question of whether immunohistochemical detection of PARP is the best method of predicting PARP inhibitor efficacy remains, the scientists said. “We need more prospective trials to be sure that there is no better way of making sure that the right people are getting the right therapy,” said Professor von Minckwitz.

“However, it would be fair to say that we believe that we may be on the verge of a major change in the way breast cancer is treated.” ■

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For Dying Patients, Emergency Care Is Less than Ideal

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Canadian study examining the reasons why a patient with cancer will visit the emergency department near the end of life points out shortcomings in current care delivery systems and suggests a greater role for more effective palliative care, say the authors.

The study, a retrospective examination of data from the Ontario Cancer Registry, identified all patients who died of cancer between 2002 and 2005 using ICD-9 codes and examined how often and why they visited the emergency department. The authors, led

by Lisa Barbera, MD, MPA, recorded this usage in the final 6 months and final 2 weeks of life.

In this 4-year period in Ontario, 91 561 patients died of cancer and were included in the analysis. In the last 6 months of life, 76759 patients made 194017 visits to the emergency department; during the last 2 weeks of life, 31076 patients made 36600 visits. The top 10 reasons in each time period are listed in the Table.

Given the reasons for these visits, the authors argue that “with comprehensive and coordinated palliative care, individual patients could be managed in clinics, at home, and in palliative care units or residential hospices without the need for a visit to the emergency department. A highquality palliative care team would reasonably be expected to be able to address symptoms such as pain, dyspnea, nausea and vomiting, constipation, malaise, and fatigue.”

But building that high-quality team is not easy. Deborah Dudgeon, MD, the provincial head of Palliative Care for Cancer Care Ontario and a coauthor on the paper, detailed some of those obstacles in a follow-up e-mail interview. Geography (with pockets of expert palliative care scattered across the province and inaccessible

to more remote regions), the palliative care education of physicians and nurses providing primary care, a lack of physician home visits, and limited home care resources are all factors working against good home-based palliative care.

The Ontario government has worked to address these shortcomings by providing significant funding ($115.5 million US over 3 years) to an end-of-life care strategy beginning in 2005. The funding was directed at enhancing home care services, strengthening volunteer hospice services, funding residential hospices, and planning and integrating local services through regional networks. Dr Dudgeon’s own organization, Cancer Care Ontario, has developed a palliative care program whose strategy includes developing, implementing, and disseminating evidence-based guidelines and standards; the development of a care model for the delivery of palliative cancer care; supporting regional physician leaders; implementing common assessment tools including the Edmonton Symptom Assessment System and Palliative Performance Scale; and developing and measuring quality indicators. Because there is a delay in getting date of death data, the results of these measures (including emergency department visits, length of stay, and place of death) should be evaluable when that data becomes available, Dr Dudgeon indicated.

Systemic Differences, Similar Problems Eduardo Bruera, MD, F.T. McGraw chair in the treatment of cancer and medical director, Supportive Care Center at M. D. Anderson Cancer Center, noted some of these same issues when discussing the study with Value-Based Cancer Care. Some

Table Top ranked reasons for visits to the emergency department by cancer patients in the last 6 months and 2 weeks of life.

Reason Frequency, n (%) Reason Frequency, n (%) Last 6 months Last 2 weeks Abdominal pain 9224 (4.75) Lung cancer 3242 (8.86) Lung cancer 8741 (4.51) Dyspnea 1844 (5.04) Pneumonia 6924 (3.57) Pneumonia 1832 (5.01) Dyspnea 6171 (3.18) Abdominal pain 1126 (3.08) Malaise & fatigue 4972 (2.56) Malaise & fatigue 1084 (2.96) Chest pain 4463 (2.30) Palliative care 1042 (2.85) Pleural effusion 3667 (1.89) Dehydration 944 (2.58) Nausea or vomiting 3525 (1.82) Pleural effusion 717 (1.96) Anemia 3513 (1.81) Altered consciousness 689 (1.88) Back pain 3460 (1.78) Pancreatic cancer 585 (1.60) Adapted from Barbera L, et al. Why do patients with cancer visit the emergency department near the end of life? CMAJ. 2010;182(6):563-568.

areas of Canada have excellent home care and community-based programs, he indicated, while others are not as good, so the lack of regionally analyzed data is a shortcoming.

Differences in the basic organization of the Canadian system are also an issue, he said.

family want to continue receiving cancer treatment, Dr Bruera explained, they will delay access to hospice or the oncologist will delay referral to hospice until the cancer treatment has been completed. And with the rise of targeted therapies, which are generally better tolerated

“We need to remember that even Medicare patients in the United States still pay a substantial proportion of their cost of emergency and inpatient care. In Canada, the cost is pretty well zero.”

—Eduardo Bruera, MD

“The healthcare system in Canada is dramatically different from that in the United States,” Dr Bruera emphasized. “Patients can go to the emergency center and be admitted without any fear of a financial consequence from doing it. We need to remember that even Medicare patients in the United States still pay a substantial proportion of their cost of emergency and inpatient care. In Canada, the cost is pretty well zero.”

This may have pushed the number of patients availing themselves of the emergency department higher, he suggested.

Nevertheless, “overwhelmingly this is an excellent study…truly a population-based study,” he enthused.

Because of the structure of the Canadian healthcare system, there are no biases due to age or insurance type, Dr Bruera pointed out, and “that’s what makes it dramatically useful for us to understand [the] experience of cancer patients.”

The structure of the US healthcare system introduces its own impediments to good palliative care, Dr Bruera suggested. First among them is the conception of palliative care itself by hospitals and cancer centers.

Too often, palliative care is initiated too late in the trajectory of illness.

By “limiting palliative care programs to the inpatient [setting], the catastrophic event that brought the patient to the emergency room and gotten them admitted has already occurred,” he argued.

A second barrier involves paying for treatment. The Medicare hospice benefit is currently structured so that patients who enter into hospice care are not eligible for continued cancer treatment. So if the patient and the

than traditional chemotherapies, treatment can continue longer into the course of illness.

“At this point, it’s an either/or system, in which a patient enters the Medicare hospice benefit, and therefore exits the traditional reimbursement system in the United States,” he said.

Dr Bruera foresees “great opportunities to develop palliative care programs in acute care facilities, in teaching hospitals, and in cancer centers that operate according to the existing reimbursement mechanisms,” suggesting that these centers can do an outstanding job in providing in- and outpatients with integrated cancer treatment and supportive and palliative care. Data from the Canadian study may serve to foster the development of palliative care programs in the acute care setting, Dr Bruera argued.

It will also be essential to develop a real integration of hospice care with acute care, rather than making it one or the other, Dr Bruera emphasized.

“This would allow patients who are interested to access hospice care at home a little bit earlier, while they are still receiving cancer treatment,” he pointed out. “Accessing both systems might allow patients to avoid unnecessary emergency room [visits] and hospitalizations. While this looks like a more expensive [way to go], it might… prove to be beneficial financially.”

M. D. Anderson has taken this integrated care approach for almost 11 years, Dr Bruera stated, and he pointed out that a number of other centers around the nation, including the cancer center in San Diego and the Cleveland Clinic, have also incorporated this approach.

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New Colorectal Cancer Therapies Foster New Discussions on the Value of Medications

By Colin Gittens

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ew chemotherapies for metastatic colon cancer have improved life expectancy, but at a significant cost, say the authors of a study that explores the value of medications including bevacizumab (Avastin, Genentech), capecitabine (Xeloda, Roche Laboratories), cetuximab (Erbitux, Bristol-Myers Squibb), irinotecan hydrochloride (Camptosar, Pfizer, Inc), and oxaliplatin (Eloxatin, Sanofi-Aventis LLC).

The team of researchers, from Emory University in Atlanta, constructed a sample of patients aged 66 and older who were diagnosed with stage IV colorectal cancer between 1995 and 2005 and were treated initially with chemotherapy. The sample was broken down into 5 groups by diagnosis date, and those dates were organized by time periods coinciding with the introduction of these new drugs. The researchers calculated actual survival and projected survival rates from short-term survival data, and calculated lifetime medical costs, breaking these costs down by the phase of care (ie, initial costs, ongoing costs, and end-of-life costs).

The final patient sample contained 12 473 members, of whom 4665 (37.4%) were given chemotherapy within 6 months of diagnosis. Among the patients receiving chemotherapy, median survival time increased by 4.5 months, and costs in the 2 years following diagnosis increased by $17 800. Survival increased steadily during the course of the study, with 19.1% of patients in the last time period surviving at 3 years postdiagnosis, compared with 11.7% in the first time period. The projected life expectancy and lifetime costs, respectively, were 6.8 months and $37 100 for those receiving chemotherapy. The implied

cost-effectiveness ratio was $66 200 per life-year gained; after discounting and controlling for variables, the incremental cost per quality-adjusted life-year was $99100.

Dr Howard noted, “but some of the new chemo drugs are really pushing the envelope. While it is unlikely that a payer would completely deny coverage for a new, effective chemo drug,

A Potential for Collaborative Research Yu-Ning Wong, MD, MSCE, an assistant professor at Fox Chase Cancer and adjunct senior fellow at the Leonard Davis Institute of Health Economics at the University of Pennsylvania, both in Philadelphia, PA, echoed the importance of this “bigger picture” perspective.

“We should consider value when making any decision, whether it’s a consumer product or a medication,” she argued. “What is important, however, is to consider the value of an expensive cancer medication in its clinical setting, not just its price. Does it increase the cure rate so that more patients live their lives without

cancer? Or does it just extend life by a few months? In addition, certain drugs may become more ‘valuable’ if we are able to better identify the patients who are most likely to benefit from them.”

In Dr Wong’s eyes, this study is important “because it supports clinical trial experience that we are improving the life expectancy of patients with metastatic colorectal cancer. It’s important to demonstrate this improvement in ‘real world’ patients, not just clinical trial patients.” The study also shows how quickly new drugs have been adopted in clinical practice, she pointed out.

Dr Wong, who is an editorial board member for Value-Based Cancer Care, also cautioned that because the study period ended in 2005, the cost of more recently treated patients is unknowable. In addition, “We don’t have data on the patients who originally had localized disease but developed metastatic disease.”

Nevertheless, the study suggests new areas of potential cooperation, Dr Wong concluded.

“Payers should realize that medical oncology is a rapidly evolving field.

New drugs are being introduced and tested in a variety of tumor types across a variety of clinical settings.

Clearly, this is an important opportunity for clinicians to work with insurers to determine which treatments are appropriate to cover and which should involve more scrutiny,” she said. But “it would be helpful to have more claims data available, like this Medicare database, so we can see how patients are treated in the real world.

This is an important opportunity for the insurance industry to pair with academia to do these studies.”

The study appeared in the Archives of Internal Medicine (2010;170[6]:537542. Epub 2010 Mar 16). ■

what the Canadian paper shows— patients with extremely complex interventions coming back to the emergency department and getting admitted.”

As the authors of the Canadian study emphasize, “Patients who are failing at home are unlikely to need to visit the emergency department.

Instead, these patients require either additional support to remain at home or direct transfer to a palliative care

unit or residential hospice.”

Dr Bruera built on this notion, arguing that for care in the community to be successful over time, it is important to pay attention to care transitions.

“We need to simplify a lot of the interventions that [are] being administered as part of the acute care of the patient.”

Home care, Dr Bruera emphasized, puts an enormous burden on the patient’s family. “We can keep very simple treatments in the community.” ■

“Traditionally payers haven’t considered cost-effectiveness when deciding whether to cover new drugs, but some of the new chemo drugs are really pushing the envelope.”

—David H. Howard, PhD The authors note that other studies modeling cost-effectiveness of colorectal cancer therapies have found similar or larger cost-effectiveness ratios, but that the $37100 increase in lifetime costs for patients treated with new chemotherapeutic agents is less than the figures often quoted in the media or journal commentaries.

These new agents, the authors conclude, “have been singled out as examples of high-cost/low-value medical care” that would “receive close scrutiny if Medicare and other payers were to consider cost-effectiveness in coverage decisions.

“Continuation of Medicare’s openended coverage policy for new chemotherapeutic agents and other expensive technologies will prove difficult to sustain as costs for the program continue to rise,” they warn.

In a follow-up e-mail interview, lead author David H. Howard, PhD, summed up 2 main messages from the paper. First, “the new drugs for colorectal cancer aren’t ‘too bad’ in terms of cost-effectiveness” and second, “the drugs are not as costly as initially advertised.” Their cost-effectiveness can change, however, if the drugs are used for other tumor types, he pointed out.

“Traditionally payers haven’t considered cost-effectiveness when deciding whether to cover new drugs,”

I think they will start to scrutinize use of these costly drugs much more carefully and try to limit their use.”

In discussing the larger issues raised by the study, Dr Howard put forth the following: “Should Medicare continue to cover effective drugs without regard to cost, even if they are cost-effective? The federal debt is such a big problem [and] we can’t afford business as usual. And we must face the tradeoff that if we spend money on new chemo drugs, we are going to have less for education, roads, bridges, and other priorities.”

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Care Setting Makes Psychic, Financial Difference The question of where care is provided also raises the matter of value. If the intention is to keep patients receiving very complex therapy as is given in the acute care facility, but to transition those people to the community, then there’s a high risk of failure and enormous distress for the patient and the family, Dr Bruera stated. A thirdparty payer may want the patient in

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the community, Dr Bruera said, but it may not take into consideration the enormous physical and emotional burden they are putting on that patient’s relatives in the process of doing that. This creates a major ethical dilemma for caregivers.

“What is the advantage of having that person with this extremely complex therapy staying at home?” Dr Bruera wondered. “If we transfer care to the community, then we would see

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