Oncman 6'13

Oncology Business Management Volume 2 Number 2 6.13

Measuring Quality Cancer Care p.5 Mining the Pipeline: Leading Investigational Products and Areas of Unmet Need p.8 Cost Versus Quality in Different Sites of Cancer Care p.11

insights into oncology business practice

Published in collaboration with

Performance Metrics in Oncology

table of Contents

Volume 2 Number 2 6.13

Oncology Business Management Feature

Performance Metrics in Oncology

By Thomas R. Barr, MBA

2

5

Measuring Quality Cancer Care

8

Mining the Pipeline:

By Robert Gamble

Leading Investigational Products and Areas of Unmet Need

By Stephanie Hawthorne, PhD

11

Cost Versus Quality in Different Sites of Cancer Care

By Zachary Hartman

Advisory Board

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Patrick Wayne Cobb, MD Hematology-Oncology Centers of the Northern Rockies Billings, MT

Adam I. Riker, MD Cancer Services Ochsner Cancer Institute New Orleans, LA

Jeffery C. Ward, MD Oncologist Puget Sound Cancer Centers Edmonds, WA

Jeffrey D. Dunn, PharmD, MBA Formulary and Contract Manager Select Health Murray, UT

Richard J. Rosenbluth, MD John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

H. Jack West, MD Thoracic Oncology Program Swedish Cancer Institute Seattle, WA

Gary Lyman, MD, MPH, FRCP(Edin) Duke University Medical Center Durham, NC

Lee Schwartzberg, MD The West Clinic Memphis, TN

David B. Wilson, RPh Oncology Pharmacy Manager Oncology Pharmacy Residency Director St. Luke’s Mountain States Tumor Institute Boise, ID

Interested in contributing to Oncology Business Management?

If you’d like to submit an article for consideration in an upcoming issue, please e-mail Devera Pine at dpine@onclive.com.

Oncology Business Management

from the publisher

Integrated Delivery Networks and the Future of Cancer Care

The Gold Standard in Physician-Led Education

This month we take a closer look at two key issues in cancer care: How to measure the quality of care, and balancing cost versus quality. On page 2, “Performance Metrics in Oncology,” by Thomas R. Barr, MBA, argues that the presence of specific, essential clinical information as structured data in the clinical database is necessary for oncology care management. “Measuring Quality Cancer Care,” by Robert Gamble, on page 5, notes that healthcare, particularly cancer care, seems to be the last industry to define, measure, benchmark, and promote quality, value, and positive outcomes. On page 11, an article from Oncology Business Review, “Cost Versus Quality in Different Sites of Cancer Care,” by Zachary Hartman, concludes that consolidation of practices is contributing to rising costs of cancer care without producing gains in quality of care. Also from Oncology Business Review is a look, on page 8, at leading investigational products in oncology and areas of unmet need.

We hope that you enjoy this issue and look forward to your comments.

Please contact our editorial staff at dpine@onclive.com.

—Jack Lepping VICE President, Oncology

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Performance Metrics in Oncology

By Thomas R. Barr, MBA

In 2011, the Medicare Electronic Health Record (EHR) Incentive Program began paying physicians and hospitals for the measurement and reporting of performance metrics through the utilization of certified electronic medical record (EMR) software. This epic program began in earnest the irrevocable shift in the provision of healthcare from an individual craft-based art to a structured, evidence-based system. The EHR Incentive Program has three specific phases that progressively build from data capture and reporting, through clinical process refinement, to the final goal of achieving measurably improved healthcare outcomes.1 Currently, we are in the first phase of this transition, and in oncology, trends are emerging about what metrics are important to three key groups—patients, payers, and providers.

Each seeks improvements to quality and lower—or at least stable—costs for cancer care. The broad utilization of EMR technology has, for the first time in history, enabled systematic measures of care delivery on a broad scale.

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While management of clinical care using modern information technology is important to providers and payers of oncology care, it is critical to those of us who have a cancer diagnosis in our family or in our future— and that is just about everyone. Providers must participate in the move to active measurement of clinical variables or become obsolete. They must also integrate reporting and measurement of important process measures into routine clinical management. Payers have a critical role in promoting this technology adoption. They are positioned to promote payment methodologies that support and reward clinical measurement. Without such support, innovative practices suffer economically as they push toward rational care. We all should expect basic quality process measures that are indicative of good clinical management of cancer care for our families and

Oncology Business Management

Figure 1. Survey Data Showing Who Is Entering Information Into the EMR

ourselves. Successful payers and providers will encourage patients to seek care where these quality indicators are available and exemplary.

and the promise that being measured offers improvement. To be scientifically sound, there must be substantial, explicit evidence with validity, reliability, and sufficient specificity to patient factors to be clinically Discussion useful. Feasibility requires an explicit definition of the Three visions of performance metrics in oncology were numerator and denominator needed for the measure presented at the Cancer Center Business Summit held from data that are available at low cost and with low October 11-12, 2012, in Fort Worth, Texas. The theme of administrative burden. Today, the fact is that payment the conference was transitioning to value-based oncoldrives process measurement, and most systematic ogy, and most of the program content, including the data are about billing, not about medical care. The EHR full program that is summarized in this article, is availIncentive Program, coupled with many providers and able online.2 While the three perspectives are different, payers seeking a departure from fee for service, are factors driving oncology data feasibility toward important, there were consistent themes throughout. All speakers scientifically sound measurements. endorsed the use of available data, keeping metrics The presence of specific, essential clinical information simple, delivering measurements to the care providers as structured data in the clinical database is necessary who can affect the numerator, and showing these profor oncology care management. These data support viders how they compare with peers. The speakers all understand that current payment methodology does not pathway and guideline adherence, reduce treatment variability, take advantage of emerging companion treatsupport process optimization, yet view that as a transiment diagnostics, and promote cost savings through tional barrier that will not persist. the avoidance of valueless care. In oncology, six basic I presented the three criteria that are generally acelements are needed to enable such measurement. For cepted for choosing clinical performance measures.3 To every patient, we need to have structured data in the be successful, measures must be important, scientifielectronic medical record for stage, intent of therapy, cally sound, and feasible. Importance is measured by toxicity, disease status, patient status, and line of therthe relevance of the measure to patients and providers, apy. When there is substantial data density for these six Figure 2. Sample Process Metric Presented to Physicians process measures, the foundation is in place to begin to measure clinical outcomes across large populations of patients, and then in real time, see what is working.

So how do we get from low density, as presently observed in oncology EMR data, to

Cover Story high density on these process measures? Figure 1 shows data from an Oncology Metrics survey performed in 2009 and reveals that physicians directly enter most of these data as part of their clinical management activity.

There is ample evidence that peer review does alter physician behavior. Oncologists who received feedback about the amount of chemotherapy that they were giving at the end of life decreased from 50% of patients to 20% of patients in only 6 months.4 Structured clinical data offer the opportunity to show individuals how they compare with named physicians in their own practice.

Additionally, this lets the physician know that others see his score too (Figure 2).

Deb Hood, vice president of the national oncology service line of Catholic Health Initiatives (CHI), spoke about the experience of her institution in beginning to establish what she called value-based care metrics.

While there are five dimensions to their hospital per-

Thomas R. Barr, MBA

The presence of specific, essential clinical information as structured data in the clinical database is necessary for oncology care management.

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Cover Story

Figure 4. Hierarchy of Metrics and the Organizational Sponsors Transitioning to Value-Based Oncology: Strategies to Survive and Thrive

spective, she emphasized improvement in quality and reduction of cost. Although there are many quality metrics in oncology, CHI has decided to focus on data that are readily available and easy to audit. The best data source for them is registry data, as they are extracted in real time and encompass more that 30,000 new cases each year. From these data, they have created “dashboards” for breast cancer, exception reporting for chemotherapy and radiation therapy, readmission tracking for all oncology patients, and pharmaceutical expense tracking. To leverage these reports to create measurable improvement in care, they are presenting comparative measures at the institutional level with color coding to promote easy understanding. Green signifies compliance, yellow is nearly in range, and red is out of compliance standard. A sample of such a report card is shown in Figure 3.

Wes Chapman, president and CEO of PCD Partners, provided an overview of the application of ISO 9001 and Lean Six Sigma in two large-scale projects.5,6 Noting that outcome metrics are only viable in the context of a uniform process, and understanding that healthcare provision is not at all a uniform process, useful metrics are limited to process metrics (Figure 4).

To adequately measure processes in large systems, the integration of documents and data into a single system is necessary. Chapman said that this novel func-

Metrics/Quality & Process Change Process Metrics: • Measure compliance • Almost all metrics are process metrics Outcome Metrics: • Only viable in context of uniform processes

tionality could be created in a cloud-based relational database but noted that these two types of information are not standardized. This shortcoming limits the ability of process measurement to provide compelling information about problems addressed and determine if improvements are realized. To achieve process control and improvement, it is necessary to define the process and train process operators, collect process performance data, and then audit process for compliance. None of

Figure 3. Service Line Dashboard From Catholic Health Initiatives

this functionality is present in large-scale systems today and this is a limiting reality to the application of tested process management technology that is used in the manufacturing environment. To no small degree, this fractioning of healthcare is part of the payment methodology. Fee for service provides incentives for more process steps and leads to variable endpoints, uncoordinated care, and undocumented outcomes. When healthcare delivery and payment more closely resemble typical manufacturing environments, characterized by a drive to reduce process steps and maximize value, then the tools from that sector will become applicable.  References 1. EHR incentive programs. Centers for Medicare & Medicaid Services website. www.cms.gov/Regulations-and-Guidance/Legislation/ EHRIncentivePrograms/index.html. Accessed May 22, 2013.

2. Cancer Center Business Summit website. www.cancerbusinesssummit. com/program.htm. Accessed May 22, 2013.

3. Center for Health Policy Studies, Harvard School of Public Health, Center for Quality of Care Research and Education. Understanding and choosing clinical performance measures for quality improvement: development of typology: final report. Rockville, MD: Agency for Healthcare Research and Quality; 1995.

4. Blayney DW, McNiff K, Hanauer D, et al. Implementation of quality practice initiative at a university comprehensive cancer center. J Clin Oncol. 2009;27(23):3802-3807.

5. Bloomberg highlights Vermont cancer pilot; PCD partners plays key HIT role. PCD Systems website. http://pcdsys.com/bloomberghighlights-vermont-cancer-pilot/. Published August 24, 2012.

Accessed May 22, 2013.

6. Decreasing complexity, improving care quality, and reducing cost in oncology. http://pcdsys.com/care-quality-in-oncology/. PCD Systems website. Published July 5, 2012. Accessed May 22, 2013.

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Oncology Business Management

Feature

Measuring Quality Cancer Care

By Robert Gamble

Two of my favorite activities are running and salt-water fishing. Both are very precise and numbers-oriented activities. Running is about time, pace, distance, calorie burn rates, and heart rate zones, among other factors. When talking with runners, it does not take long for the conversation to come around to the essential questions: “What is your PR (personal record) for a half (or full) marathon?” or “What is your average weekly miles?” Both of these questions reflect standard benchmarks of the level of accomplishment in the sport.

Fishing, or as we say in the South, “fishin’,” has its own set of standards. Before we graduate to the point of hoping the fish do not bother us, we are watchful of length, weight, creel limit, and also making sure the catch falls within season. Measurement is serious business, to the point that the fishing industry has its own “Golden Rule”—an official calibrated tool to measure the length of a fish. Woe to the person who is

caught with a fish under or over the size requirements.

The fisherman strives to have the best answer to the routine question, “Did you catch anything?” If that is answered in the affirmative, the next question will hopefully be answered with a boast: “Any size?”

Both of these activities have finite and very specific criteria of what is considered “good” or “excellent.” Why is it we struggle with the similar concepts in healthcare, and particularly cancer care? It is interesting that healthcare accounted for 15.2% of GDP in 2008.1 Fishing (even when included in the category of agriculture, hunting, forestry, and fishing) is only 1.1% of GDP.2 The running industry is not even high enough to score a 1/100 of a percent. If healthcare consumes so much of our world, why is it then that we focus so little attention on the specifics of quality or value or outcomes in healthcare?

Defining Quality, Value, and Outcome Measures The lack of attention in systematically measuring quality and value in cancer care became particularly obvious when working with the Oncology Medical Home (OMH) Steering Committee on its objective of defining 16 quality, value, and outcome measures for cancer care.

Robert Gamble

The lack of attention in systematically measuring quality and value in cancer care became particularly obvious when working with the Oncology Medical Home (OMH) Steering Committee on its objective of defining 16 quality, value, and outcome measures for cancer care.

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Feature

This cross-section and balanced approach to defining key determinants to patient care, resource utilization, survivorship, and end-of-life care may prove challenging, but its time is past due. For example, as an outdoor enthusiast, my hope is that I will be called home while running, fishing, or simply walking on a trail. For a cancer patient, the hope is that he or she may leave this earth among family or friends and surrounded by a known and friendly environment—peacefully and quietly. Dying at home would seem to be the choice for all, if we had a choice. And there is no better indicator of the quality of life, at end of life, than the place of death.

However, it seems that the national death registry does not record a “place” of death. The standard death certificate includes the following choices for place of death: “Hospital inpatient, ER/Outpatient or DOA; Nursing home, Residence or Other (Specify).” It would seem that it would be beneficial to include these data in the national death registry and to recognize same as a quality and value indicator for all of healthcare, not just cancer care. This seems to be an easy fix.

And somewhat related is the entire discussion surrounding end-of-life care conversations. Patients and families need open and honest dialogue regarding their current status, their wishes, and how their wishes are to be carried out. This goes beyond the simple question of asking patients if they are ready to meet their maker.

One of several programs that attempt to remedy this issue is the “5 Wishes” program.3 This program asks 5 probing questions regarding assigning decision makers, medical treatment preferences, preferred comfort levels, preferences on interactions with others, and last wishes. This program provides specific guidance on how to conduct these conversations. Dr John Sprandio (Pennsylvania) and Dr John Fox (Michigan) have indicated that when these discussions occur, and at the right time, patients have made decisions to discontinue aggressive cancer treatment. The end result is more

Perhaps we need to revise this notion of “precertification” and insert the patient’s medical home provider as the “Mother may I” authority before these services are rendered.

—Robert Gamble

comfortable end-of-life care. Although some patients (or family members) may resist these discussions, they should be required for any healthcare team charged with managing any terminal disease. When done properly, the door is left open for miracles, but the patient and family are able to make informed decisions regarding care. Electronic medical record vendors will need to enhance their data capture fields from a simple “Advanced directive on file – Y or N” to a more detailed and comprehensive approach to this question if we are to raise the bar in care and compassion. There should be similar guidelines for the specifics of care plans and cancer survivorship plans.

Another milestone by the Community Oncology Alliance (COA) OMH Steering Committee was the endorsement that all cancer care providers should calculate their own 5-year survival rates for breast, colon, and lung cancers. This is completely logical and is a measurement whose time has come. As a former manager of a cancer center, I often wondered what I would say when asked for our own 5-year survival rate for stage 3 breast cancer.

It would seem to be a logical and reasonable question but one that currently has no answer—at least not for an individual cancer center. “Survival” rates, when they are the only measure, are not necessarily a good indication of quality, particularly if a patient is being kept alive through artificial means and against the wishes of the patient or family. But, when combined with other standards and educational requirements, this information can be very helpful to patients and their families in planning and in the celebration of significant milestones.

Overutilization of Hospital Services One of the more elusive measures but one that has great significance in the value department is the use, or overuse, of hospital services. Some patients and healthcare providers are quick to utilize these expensive inpatient, outpatient, or emergency department (ED) resources over a less expensive setting such as the exam or procedure room of their medical home.

Governmental and commercial payers all agree that the overuse of these resources represents a significant expense and an opportunity to realize savings in time and dollars to the payer and patient. The challenge with curbing this misuse of resources is that the person who should know of these encounters, the patient’s medical home physician, does not always know when they occur. The hospital staff will be the first to know, the patient’s payer may be the second to know, but the person who should know first, the patient’s physician, may never know if or when this event occurs. Some commercial insurance companies are providing financial incentives to curb unnecessary ED visits or hospitalizations. This is why the COA OMH Steering Committee has endorsed this measure. Perhaps we need to revise this notion of “precertification” and insert the patient’s medical home provider as the “Mother may I” authority before these services are rendered. This procedural change would allow the patient’s main care team to intervene with, hopefully, a more efficient solution, and it would also assist in nurturing the relationship between the patient and his or her medical home physician.

Only then will we be able to measure and benchmark the utilization of these valuable resources and reward those care teams that use them appropriately.

Applying Our Own “Golden Rule” Other industries seem to have a head start on defining quality statements. Healthcare, and particularly cancer care, seems to be the last industry to define, measure, benchmark, and promote quality, value, and positive outcomes. Perhaps it is because we have been busy taking care of others that we have not been able to focus on such a mammoth undertaking. Now may be the time to apply our own “Golden Rule” to measuring quality and value in cancer care. After all, and as I am sometimes reminded, there is more to life than running and fishing.  References 1. Health care in the United States. http://en.wikipedia.org/wiki/ Health_care_in_the_United_States. Accessed May 22, 2013.

2. OECD. StatExtracts. http://stats.oecd.org/Index. aspx?DatasetCode=SNA_TABLE1. Accessed May 22, 2013.

3. Aging with Dignity website. www.agingwithdignity.org/fivewishes.php. Accessed May 22, 2013.

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Oncology Business Management

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Mining the Pipeline: Leading Investigational Products and Areas of Unmet Need

By Stephanie Hawthorne, PhD

00

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>2

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-7

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pipeline agents

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Figure 2. Agents in Pivotal Trials, by Market Size these multiple trials initiated before definitively established activity in patients.

It’s worthwhile to note that these pipeline 30 compounds are nearly equally being developed by “Big Pharma” and “Small Biotechs,” with only a handful in development by Mid23 size/Emerging Pharma or as a collabora16 tive effort. However, pipeline agents with multiple pivotal trials ongoing are heavily 12 10 weighted toward those in development by 4 Big Pharma or as part of a collaborative effort. Conversely, those agents with a single pivotal trial ongoing, trend toward those in development by smaller biotechs; this potentially reflects limited resources for R&D, especially considering that the mechanisms number of eligible patients of action of two-thirds of these agents have In our analysis, over one-half of oncology pipeline Source: Kantar Health agents possess novel mechanisms of action (MOA) and the potential to support development in multiple indications. are vying to be first-in-class. Perhaps not surprisingly, Interestingly, the majority of the indications in which subsets of larger tumor types, such as Met+ NSCLC the vast majority of these agents currently seeking first these 69 agents are being developed target rather or NRAS mutant melanoma. However, despite the market entry are only being evaluated in one pivotal small indications in terms of patient population size. As oncology community’s growing focus on personalized study (Figure 1). One-quarter of these pipeline agents Figure 2 shows, 60% of the ongoing pivotal trials are medicine, only 22% of pipeline agents currently in are, however, being studied in multiple phase III trials being conducted in indications with a target population pivotal trials are being developed in a biomarker-de(predominantly targeting multiple tumor types), with of less than 12,500 patients.1 fined patient population. Two-thirds of ongoing pivotal This is in contrast to a decade studies with pipeline agents are being conducted in indications with relatively low unmet need (Figure 3). ago, when most agents in Figure 1. Number of Trials Each Agent is Participating In Of course, all cancer indications have rather high pivotal development were 50 unmet need compared to non-oncology indications due targeting the largest patient 50 to the life-threatening nature of the disease; however, populations, such as breast among the numerous cancer indications, the level of cancer, non-small cell lung 40 need may vary considerably. cancer (NSCLC), and colorec30 Through extensive analysis based on a combination tal cancer (CRC). of product and indication attributes, Kantar Health has Some of the smaller 20 12 evaluated and rated these 69 pipeline agents to identify indications represent tumors 5 10 those with the greatest likelihood of clinical impact in in which the incidence of 1 1 the next three years. Our analysis identified the Top 10 the disease overall is rather 0 One Two Three Four Five pipeline agents with the greatest potential for impact small, such as acute lymTrial Trials Trials Trials Trials on the oncology market (Table 1). phocytic leukemia (ALL) and Pivotal Trials Ongoing Separately, five pipeline agents have emerged as soft tissue sarcoma, whereas Source: Kantar Health having significant “breakthrough” potential, based others represent biomarker Oncology continues to be a significant focus of development in the pharmaceutical market. The field is crowded, despite the fact that the agents in development target a broad range of tumor types. Kantar Health has profiled 69 pipeline agents that are in pivotal clinical development, in addition to the vast number of pivotal trials ongoing as part of lifecycle management (LCM) for launched oncology products. Here, we take a sneak peek focused on some of the late-stage drugs in development in the oncology pipeline.

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Oncology Business Management

Figure 3. Agents in Pivotal Trials, by Unmet Need 51

26 14 5

60% of the ongoing pivotal trials are being conducted in indications with a target population of less than 12,500 patients. primarily on the merits of their clinical data and independent of target indication attributes. We believe these five agents have the potential to dramatically improve efficacy outcomes and may transform the standard of care in their target indications.

1. Dabrafenib + Trametinib <10 (Low Need)

10-19

20-29

30+ (High Need)

unmet need score Source: Kantar Health The level of unmet needs was calculated based on the number of existing treatment options in the target indication (with fewer treatment options correlating with higher need), the rate of treatment (with high non-treatment rates correlating with higher need), and efficacy outcomes achieved with current options (with short survival times correlating with higher need). High overall scores for the sum of these three attributes were considered to be a high unmet need, whereas low overall scores were considered to be a low unmet need.

Table 1. Pipeline Agents with the Greatest Potential Impact in Oncology Drug in Development

Manufacturer

Indications

Afatinib

Boehringer Ingelheim

Breast, NSCLC, head and neck

Radium-223

Algeta/Bayer

Prostate

Astuprotimut-r

GlaxoSmithKline

Melanoma, NSCLC

Dabrafenib + Trametinib

GlaxoSmithKline

Melanoma

Ibrutinib

Pharmacyclics/ Johnson & Johnson

Chronic lymphocytic leukemia, mantle cell leukemia

Nivolumab

Bristol-Myers Squibb

Melanoma, NSCLC, renal cell carcinoma

Onartuzumab

Genentech/Roche

Gastric, NSCLC

Ramucirumab

Eli Lilly

Breast, colorectal, gastric, hepatoceullular carcinoma, NSCLC

Palbociclib

Pfizer

Breast

Rivantinib

ArQule/ Daiichi Sankyo

Hepatocellular carcinoma

Attributes that were scored included mechanistic innovation, strength of prior published data, target indication population size, and level of competition. For more in-depth information on Kantar Health’s scoring methodology, please e-mail info@kantarhealth.com.

For metastatic melanoma, 2011 was a transformative year with the approval of Yervoy (Bristol-Myers Squibb) and Zelboraf (Genentech/Roche). GlaxoSmithKline is developing the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib as challengers to Zelboraf’s foothold as the new standard of care in patients with the BRAF mutation. As monotherapies, neither dabrafenib nor trametinib raises eyebrows.

In combination, however, they may be a force to be reckoned with.

In randomized phase II data reported at the 2012 European Society for Medical Oncology (ESMO) annual meeting (Long, Abstract LBA27), the combination significantly prolonged progression-free survival (PFS) compared with dabrafenib alone (9.4 months vs 5.8 months; HR = 0.39; P<0.0001) while also reducing the incidence of key toxicities associated with this class of agents. These data are currently being explored in two phase III trials, evaluating the combination of dabrafenib plus trametinib in first-line metastatic melanoma, and in the adjuvant setting for patients with stage III disease.

FDA approval of each agent as a monotherapy is expected in 2013, but Kantar Health anticipates that the National Comprehensive Cancer Network (NCCN) will recommend use of the combination regimen based on the highly positive randomized phase II data, giving this combination a near-term impact on the melanoma market. With the poor prognosis of patients with BRAF-mutant melanoma, the strong phase II data that nearly doubles the PFS for these patients, and the biologic potential to

expand into other indications, this combination can be viewed as a regimen with breakthrough potential.

2. Ibrutinib The Bruton’s tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor pathway, making ibrutinib a novel mechanistic approach to the treatment of B-cell malignancies. Ibrutinib has demonstrated robust activity in heavily pretreated chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Interestingly, ibrutinib activity does not seem to be dependent upon prior therapies or poor-risk features that typically produce varied results with other treatments. As a single agent, it produced response rates in 68% of treatment-naïve patients and in 71% of relapsed/refractory and high-risk patients with CLL (Byrd, Abstract 189, ASH 2012).

Furthermore, ibrutinib is amazingly well tolerated, with very few serious adverse events. The lack of significant toxicity opens the door for it to be combined with current standards of care. Capitalizing on the early efficacy signals, Pharmacyclics and Johnson & Johnson are pursuing multiple pivotal trials of ibrutinib in relapsed/ refractory CLL and MCL. With robust clinical activity and a favorable safety profile, ibrutinib makes Kantar Health’s list of potential breakthrough agents to watch.

3. Idelalisib The PI3K pathway undoubtedly represents one of the hottest drug targets in oncology. Idelalisib is the most advanced of the isoform-specific PI3K inhibitors, and it made a big splash when its clinical data was first reported at ASH 2011, showing a high response rate and PFS achieved in heavily pretreated CLL and nonHodgkin’s lymphoma (NHL) (Coutre, Abstract 6631, ASCO 2011; de Vos, Abstract 2699, ASH 2011).

In CLL, idelalisib in combination with rituximab (Rituxan; Genentech/Roche) and/or bendamustine (Treanda; Teva) produced response rates in the range of 78% to 87% in patients who had received a median of three prior therapies, which is impressive activity compared with historical standards in this setting. Further follow-up of these studies continues to support the hype. Although it’s not without toxicity, the observed toxicities don’t overlap with those associated with current standards of care in CLL and NHL, leaving open the possibility for idelalisib to be combined with existing regimens.

Following its 2011 acquisition of Calistoga, Gilead has charged ahead with the development of idelalisib, initiating four phase III trials in relapsed/refractory CLL and indolent NHL. In CLL, idelalisib will com6.13 9

pete strongly with ibrutinib, as they are both being developed in nearly identical clinical studies, so the commercial success of each agent will depend in part on the success of the other. Although limited data are available on idelalisib, the strong clinical efficacy that has been observed, coupled with the promise of PI3K inhibition gives this agent breakthrough potential.

4. Nivolumab One of the hottest topics at the 2012 American Society of Clinical Oncology (ASCO) annual meeting was the role of PD-1 in suppression of antitumor immunity, most notably captured in the results of a large first-in-human phase I trial of nivolumab (Bristol-Myers Squibb). These data have been discussed at length previously, but the short story is that nivolumab demonstrated impressive activity, with durable objective responses observed in several solid tumors. The level of activity was so exciting, based largely on the fact that they were achieved with a single-agent immunotherapeutic in patients with heavily pretreated disease.

Preliminary data also suggest that PD-L1 expression may serve as a biomarker to select patients for response to nivolumab, which could further increase its efficacy in a selected population. On top of these efficacy outcomes, nivolumab impressed with its rather tolerable safety profile. From this single (albeit large) phase I trial, Bristol-Myers Squibb plowed ahead, initiating five phase III trials in three tumor types (melanoma, NSCLC, and renal cell carcinoma—the three indications with strongest efficacy signals in phase I). Such a quick move from phase I to phase III is not always advised, but it has been successful for several other agents in recent years (eg, Xalkori [Pfizer] in ALK+ NSCLC).

The strong phase I data, good safety profile, broad

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applicability across multiple tumors, and the possibility for a predictive biomarker all contribute to nivolumab’s potential breakthrough status.

5. Palbociclib (PD-0332991) PD-0332991 (palbociclib; Pfizer) wowed the audience at the 2012 San Antonio Breast Cancer Symposium (SABCS) annual meeting with its Kaplan-Meier curve for PFS in a randomized phase II trial of letrozole with or without PD-0332991 as first-line therapy for ER+ metastatic breast cancer. At the median, the addition of PD-0332991 increased PFS by 18.6 months, with an overall 63% reduction in the risk of progression or death (Finn, Abstract S1-6, SABCS 2012).

The drug was associated with significant hematologic toxicity, which appeared all the more significant when considered in the space of hormone therapy for breast cancer that has very few serious adverse events. While this high level of toxicity might have raised concerns, the ability to manage these toxicities through supportive care measures keeps the excitement level for this agent from being downgraded.

As a CDK 4/6 inhibitor, it will be first-in-class if it hits the market, although inhibitors of other CDKs are also in late-stage development (eg, dinaciclib [Merck] is a CDK-1/2/5/9 inhibitor being studied in CLL).

Although currently in pivotal development only for metastatic breast cancer, the eventual development of this regimen in earlier-stage breast cancer can be foreseen, and Pfizer is also investigating the drug in a number of other solid tumors. With broad applicability and stunning phase II data, PD-0332991 has the ability to be a breakthrough agent in the treatment of cancer.

These five agents are just the tip of the iceberg. The

oncology pipeline continues to grow, and the number of novel MOAs in development offer significant promise toward improving outcomes in a variety of indications.

The past couple of years have seen some significant breakthroughs in cancer management, and the next few years have great potential to similarly transform care and outcomes.  Reference 1. Kantar Health, CancerMPact® Patient Metrics, U.S., www.Kantarhealth.com. Accessed March 25, 2013

About the Contributor Stephanie Hawthorne, PhD, is Director, Clinical and Scientific Assessment at Kantar Health.

Kantar Health is a leading global healthcare advisory firm and trusted advisor to the world’s largest pharmaceutical, biotech, and medical device and diagnostic companies. It combines evidence-based research capabilities with deep scientific, therapeutic and clinical knowledge, commercial development know-how, and marketing expertise to help clients launch products and differentiate their brands in the marketplace.

Kantar Health’s oncology-related offers include the CancerMPact® Future Trends and Insights module, which explores potential changes in treatment practices in the U.S., Western Europe, and Japan based on a critical evaluation of recently published clinical data, regulatory advances/ setbacks, and ongoing clinical trials.

If you would like us to act as catalysts for you, contact us at www. kantarhealth.com/contactus.

This article was originally published online on Oncology Business Review, OBR Green. http://oncbiz.com/obrgreen

Oncology Business Management

Cost Versus Quality in Different Sites of Cancer Care

By Zachary Hartman

Debate in Favor of Oncology Practice Consolidation An argument could be made that the changes in Medicare reimbursement due to implementation of the Medicare Modernization Act of 2003 that revised the reimbursement methodology to ASP +6% is the major driver of today’s practice consolidation. According to the 2012 National Benchmarking Survey, that reimbursement modification is seen as an increased difficulty for community practices in maintaining operational margins, a phenomenon colloquially referred to as “the squeeze.”2 Many community cancer care sites have also found this reimbursement model to be insufficient to stay in business. Further complicating matters, the Patient Protection and Affordable Care Act (ACA) fails to address the issues connected to the sustainable growth rate, which calculates Medicare’s formula for determining annual updates to physician reimbursements for

Figure 1. Trends in Costs and Revenue from 2005-2011 services. The ACA’s Independent Payment Advisory Board has yet 5,500,000  Total Medical Revenue to be implemented, and there are  Total Operating Costs still many unknown consequences 5,000,000 R 2 = 0.8596

p Medical and Surgical Supplies (cost of drugs) providers will have to face.

4,500,000 Arguments in favor of practice R 2 = 0.8703 4,000,000 consolidation are many. For start3,500,000 ers, a large hospital typically has 3,000,000 access to a larger variety of re2,500,000 R 2 = 0.4533 sources than a private practice can 2,000,000 afford to invest in, such as psychological and financial counseling not 1,500,000 2005 2006 2007 2008 2009 2010 2011 2012 directly related to oncology care.

By offering more services, a hospiSource: Barr TR, Towle EL. J Oncol Pract. 2012 ;8(5):292-297. tal setting has more opportunities to create cost-savings through efficiency than a community practice.

Although some may argue that these additional Hospitals, being more centrally run as a business services drive up the cost of treatment, the practice have more resources and wherewithal to figure out of cost-shifting allows hospitals to ride out economic what works to improve efficiency, and then implement storms for short periods of time without major changes. An oncologist running a private practice may labor-force upheavals or service cuts. Cost-shifting have neither the time nor the drive to do the same. towards higher prices for treatments therefore grants It’s of paramount importance, though, that changes a measure of financial stability to the hospital. The are made to labor structures, since this expenditure is negative is that cost-shifting can also become a neamong the fastest-growing in all of cancer care, and cessity because hospitals, being nonprofit organizaoperating costs are climbing faster than revenues tions, are required to maintain a certain amount of (Figure 1).2 A hospital is better-positioned to absorb charity work to earn tax benefits. This practice does these rising labor costs than a private practice. not improve quality, per se, but it can become an efSize confers another important benefit to hospitals: fective “rainy day” strategy for many hospitals. leverage. The lowering tide of reimbursement by payers Charity work itself points to another benefit of consoli- like Medicare can be mitigated by hospitals because dation: wider access to healthcare for the poor. Private the threat of losing a large client base may allow paypractices can either accept or refer patients at their ment negotiations to open up considerably. A hospital discretion, leaving hospitals to absorb the high costs of can use this leverage to earn a more favorable payment treating uninsured and unhealthier patients requiring plan to cover rising costs. more extensive care. Approximately 24% of all cancer Consolidation is also an important investment treatment occurs exclusively in the hospital outpatient vehicle for hospitals. Initially, they may lose money setting, meaning hospitals are likely not handling a by hiring more doctors while absorbing practices.4 majority of the “ideal” patients for treatment.3 A higher However, hospitals may reap significant rewards and remain competitive as accountable care organizations rate of comorbidity in patients treated at hospitals may (ACOs) are formed as per provisions outlined in the account for, and justify, higher treatment costs overall.

Amount ($)

Over the past decade, more oncology providers have shifted toward consolidation of practices to remain viable. In fact, in the last 4 years, 524 private practices have entered into agreements with or have been acquired by hospitals.1 As a result of private practices closing, an increasing amount of oncology patient care has migrated toward the outpatient hospital setting. But, is this phenomenon a positive or a negative for healthcare on the whole?

Data from recently published white papers and surveys suggest that consolidation of practices may provide significant financial stability for providers, but it may also be contributing to the ever-rising costs to the cancer care industry without tangible gains in quality of care.

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ACA. Although the future impact of ACOs is not yet fully understood, Michael Kolodziej, MD, National Medical Director for Oncology Strategies at Aetna, told us that the ACA was implemented with the intention of driving toward more integrated, seamless Michael Kolodziej, MD care. “ACOs,” he said, “are going to change the game of oncology care. It is just not yet known exactly how this will take place.”

Kolodziej remains optimistic. To him, consolidation is a transitory state that will force both community and hospital-based providers to improve infrastructure and efficiency. With consolidation, hospitals are better positioning themselves by bringing in new talent, and strengthening their internal referral base and servicing more patients.4 “The more forward-thinking hospitals are already considering how to change to decrease the cost and improve the quality of care.”

Debate Against Oncology Practice Consolidation Managing the cost of healthcare is important to payers and the economy at large, since healthcare spending is a large portion of our gross domestic product.5 In a recently published AmerisourceBergen white paper, it is suggested that one problem with the consolidation of practices is that while the quality of care is not significantly better,6 it is more expensive. Supporting this evidence is an Avalere Health report from a study it conducted, which found an average increase of 24% in costs associated with chemotherapeutic care in the outpatient hospital setting compared with community practices.7 Another analysis by Milliman, Inc. demonstrated that the average annual cost of chemotherapy covered

by Medicare from 2006 through 2009 was $47,500 for privately owned practices, while similar services performed in the outpatient hospital setting incurred a cost of $54,000 on average.3 As discussed in the “Value of Community Oncology Site of Care Cost Analysis,” rising costs in the hospital outpatient setting have not translated to better patient outcome.6 A retrospective analysis as part of The Synthesis Project reported that hospital consolidation reduces quality of care at the same time that it increases costs.8 Even if both consolidated hospitals and community practices are meeting similar standards of care and improving outcomes for oncology patients, innovation in the form of clinical trials is carried out primarily by community practices.9 Consolidation may

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result in stunted development of new generations of cancer therapeutics.

Consolidation may also place undue burden on the supply of doctors. In years past, the end goal of an oncologist’s education was to open a business of his or her own. For many, the idea of working in a hospital and losing autonomy and career potential may be enough of a disincentive to prevent him or her from entering the oncology care field entirely.

A generational shift of priorities may mitigate this problem, however, as many young doctors are willing to sacrifice some amount of career development in favor of the financial stability that is afforded by working for a hospital.4

Considering Perspective Despite the advantages conferred by hospitals absorbing private practices, continued consolidation is not likely to yield good returns for many reasons. Private practices have traditionally been important delivery vehicles of quality treatment and screening to regions that make little economic sense to service, such as rural areas. The closure of these practices makes getting access to treatments more difficult in this case, necessitating longer trips for diagnosis and treatment.

This difficulty could lead to higher-risk populations allowing a malignant disease to progress beyond a stage where treatment is economical or effective. Community oncology also provides convenient, personalized care in large and small cities alike.

Private practices also present an important cost balance against rising of costs by creating competition.

The greater power wielded by hospitals in terms of payer negotiation can present a double-edged sword. Reimbursements can reach out-of-control levels, resulting in a greater burden on payers that is transferred to the consumer in the forms of higher premiums and taxes.

Cautionary tales of unchecked competitive positioning can be told about the California and Massachusetts markets.10,11 For example, in California consolidation has created some markets where a single “must-have” hospital can negotiate massively-inflated reimbursements.8 “Must-have” hospitals, by definition, have market leverage over health plans that cannot plausibly threaten to exclude them. Importantly, “must-have” providers’ strong negotiating position is not necessarily derived from size, but rather by factors not typically part of antitrust analysis. That is, they are “must-have” for reasons other than large market share.

So the question remains: Is consolidation working?

The answer most likely depends on perspective. Oncology practices consolidating may weather uncertain economic and legislative times, but they also lose their autonomy. The challenges of running a successful

oncology practice are many, and may be better handled

by MBAs than MDs. Improvements in efficiency can be more easily translated into big gains within a larger system such as a hospital. Unfortunately, those savings have not been realized, since it still costs markedly more to treat cancer in the hospital outpatient setting compared with the community practice. From the payer and consumer perspective, consolidation has yet to provide significant benefit. Access is decreased (especially in rural areas); costs are elevated; and patient outcome is not enhanced. These problems must be engaged in order to help control the burgeoning cost of healthcare in the United States, and the trend of consolidation does not appear to be slowing any time soon. references 1. Community Oncology Practice Impact Report, April 4, 2012.

2. Barr TR, Towle EL. Oncology practice trends from the national practice benchmark. J Oncol Pract. 2012;8(5):292-7.

3. Finch K, Pyenson B. Site of Service Cost Differences for Medicare Patients Receiving Chemotherapy. Prepared by Milliman, Inc. October 2011.

4. Kocher R, Sahni NR. Hospitals’ race to employ physicians--the logic behind a money-losing proposition. N Engl J Med. 2011 12;364(19):1790-1793.

5. Roehr B. US spent $2.7 trillion on healthcare in 2011, but growth remains steady. BMJ. 2013 10;346:f199.

6. The Value of Community Oncology Site of Care Cost Analysis. http://www.ourcommunitycounts.org/assets/SiteofCareWhitePaper.pdf. Accessed May 22, 2013.

7. Total Cost of Cancer Care by Site of Service: Physician Office vs Outpatient Hospital. March 2012. Prepared by Avalere Health, LLC. 8. Vogt WB, Town R, Williams CH. How has hospital consolidation affected the price and quality of hospital care? Synth Proj Res Synth Rep. 2006 (9); pii: 15231.

9. Blayney DW. Commentary: six years of trends in oncology practice data. J Oncol Pract. 2011 Sep;7(5):291-3.

10. Berenson RA, Ginsburg PB, Kemper N. Unchecked provider clout in California foreshadows challenges to health reform. Health Aff (Millwood). 2010;29(4):699-705.

11. Office of Attorney General Martha Coakley. Examination of Health Care Cost Trends and Cost Drivers. June 22, 2011.

This article was originally published online on Oncology Business Review, OBR Green. http://oncbiz.com/obrgreen

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