The US Supreme Court’s decision to uphold the Affordable Care Act but allow states to decide whether to expand Medicaid

 has raised a question in many states: Where political leaders have been opposed or split on President Obama’s healthcare reforms, is it smart or foolish to cover more people?

While Republicans oppose healthcare reform more often than Democrats, having a Republican in the state house has not always doomed Medicaid expansion. Arizona Governor Jan Brewer, who famously wagged her finger at Obama on an airport tarmac, nonetheless stared down legislators in her own party until they added 300,000 people to the rolls. For New Jersey’s Chris Christie, having a Democratic legislature made Medicaid expansion easier. However, neither Arizona nor New Jersey set up a state-run exchange to enroll people in health plans.

But in other states, philosophical opposition to expanding a government program and concerns about long-term costs forced full-blown rejection of Medicaid Expansion or, in the case of places like Arkansas, Iowa, and Pennsylvania, attempts at hybrid plans. Waivers would allow states to craft their own versions of Medicaid, most with elements of privatization and one, in Pennsylvania, that would require, for the first time, that most new recipients look for work.

On Friday, September 27, Arkansas Governor Mike Beebe received a phone call from US Health and Human Services Secretary Kathleen Sebelius that his state would be the first granted a waiver to pursue a so-called “private option,” which will allow state residents to use Medicaid dollars to subsidize coverage obtained through private insurance. Up to six states may pursue some form of Arkansas’ plan with two, Iowa and Pennsylvania, filing waiver requests.

Beebe, a Democrat, said the waiver would allow about 218,000 Arkansans to receive private coverage. “Our actions have drawn positive attention from across the country, and now we will focus on getting this insurance to the Arkansans who need it to lead healthier, more productive lives,” he said in a statement.

The Arkansas, Iowa, and Pennsylvania plans all feature free-market aspects to the expansion of coverage—a unique “hybrid” strategy palatable to Republican or conservative Democratic legislators in their own states, and perhaps to conservative lawmakers elsewhere who have resisted expanding any government program.

 Indeed, at the recent Medicare-Medicaid conference sponsored by America’s Health Insurance Plans, Daniel Crippen, executive director of the National Governors Association, said absent the willingness of the Centers for Medicare & Medicaid Services (CMS) to approve hybrid plans, he did not foresee additional Medicaid expansion until after the 2016 election cycle. “If there’s more flexibility, the sooner the expansion will occur,” he said.

		Table. Key Provisions of the Arkansas, Iowa, and Pennsylvania Waiver Applications

					Use of Private Health Plans for Newly Eligible?

					All newly eligible benificiaries up to 138% of FPL

					All new eligible beneficiaries between 101% and 138% FPL

					All newly eligible beneficiaries up to 138%of FOPL

					Same as existing state law for those at 100%-138% of FPL; waived for others

					Limited to nonemergency use of ED services (starting year 2)

					Auto-assignment for beneficiaries who do not choose from at least 2 “Silver” level Marketplace plans

					Financial penalties for low adherence to medical regimen and regular check-ups

					Beneficiary work status to be reviewed to determine eligibility

		ED indicates emergency department; FPL, federal poverty level.

Pennsylvania will evaluate the program within 2 years to determine if savings outpace its costs. If it is found to cost the state more, it will discontinue the program.

Based on a sliding scale; premiums can be waived based on beneficiary participation in health improvement activities.

			Musumeci M. Medicaid expansion through premium assistance: key issues for beneficiaries in Arkansas’ section 1115 demonstration waiver proposal: issue brief. Kaiser Commission on Medicaid and the Uninsured. July 2013. http:// kff.org/medicaid/issue-brief/medicaid-expansion-through-premium-assistance-key-issues-for-beneficiaries-in-arkansassection- 1115-demonstration-waiver-proposal/). Accessed September 20, 2013.

			Musumeci M. Medicaid expansion through premium assistance: Arkansas and Iowa’s Section 1115 Demonstration Waiver applications compared. Kaiser Commission on Medicaid and the Uninsured. http://kff.org/health-reform/fact-sheet/ medicaid-expansion-through-premium-assistance-arkansas-and-iowas-section-1115-demonstration-waiver-applicationscompared/. Published September 18, 2013. Accessed September 20, 2013.

			Henderson OK. Branstad signs Iowa’s response to Medicaid expansion. Radio Iowa, June 20, 2013. www.radioiowa. com/2013/06/20/branstad-signs-iowas-response-to-medicaid-expansion-audio/. Accessed September 20, 2013.

			Worden A. Corbett plan: accept Medicaid funding, add requirements. Philadelphia Inquirer September 17, 2013. www.philly.com/philly/news/20130917_Corbett_plan__Accept_Medicaid_funding__add_requirements. html#ZH21WehqGdFJTyg2.99. Accessed September 25, 2013.

			Worden A, Couloumbis A, Brubaker H. Gov. Corbett to propose big changes to Pennsylvania Medicaid. Kaiser Health News, September 15, 2013. www.kaiserhealthnews.org/Stories/2013/September/15/Pennsylvania-Medicaid-Gov-Tom- Corbett.aspx. Accessed September 20, 2013.

			Healthy Pennsylvania: Reforming Medicaid. Pennsylvania Department of Public Welfare. www.dpw.state.pa.us/ucmprd/ groups/webcontent/documents/document/p_035843.pdf. Accessed September 25, 2013.

Lack of expansion translates directly into lack of coverage. In June, researchers estimated that if 14 states opted out of Medicaid expansion, as allowed by the 2012 Supreme Court ruling, 3.6 million fewer people would be insured than if all of the states participated. These states would lose out on $8.4 billion in federal transfer payments. Furthermore, uncompensated care could cost these states another $1 billion by 2016.

 In most instances, the states’ healthcare industries have been arguing loudly in favor of Medicaid expansion, based on the forecasts for greater revenues resulting from larger populations having coverage and seeking care. This has been putting state governments at odds with major local and regional businesses in largely Republican areas, an uncomfortable position for businessfriendly elected officials.

If Pennsylvania’s waiver is approved by CMS, it would be the 26th state to expand Medicaid, and it could provide other hesitant state governors a usable pathway to not only cover more people but also to accept federal assistance to take part in the program.

The common element of the hybrid plans is to use the health insurance exchange to increase coverage of the newly insured. Technically, this is not an expansion of Medicaid, though each state would use federal Medicaid dollars to provide subsidies to state residents who would, in turn, use the subsidies to purchase private insurance on the exchanges (now called “the marketplace”). This is also referred to as a “premium assistance” model.

This approach does not necessarily mean that lowincome residents would obtain benefits equal to what they would have received in the traditional Medicaid program. This may be a key objection by critics and CMS alike. To address this gap, CMS would require the states to provide “wraparound coverage,” which would ensure that members have the same level of benefit as any Medicaid beneficiary. This includes paying for any plan cost-sharing requirements above and beyond Medicaid’s own out-of-pocket limits.

 In addition, CMS will require that new beneficiaries have a choice of at least two qualified health plans in the marketplace before the agency will approve any section 1115 waiver request.

Arkansas’ plan tightens its eligibility requirements for its state Medicaid program, leaving a greater share of the newly insured population to seek a plan on the exchange (income thresholds would be ratcheted down to a mere 17% of the federal poverty level, covering those with incomes up to 138% of that benchmark). Arkansas will require those entering the program to use the marketplace to choose a health plan for coverage. If this were voluntary, a section 1115 waiver would not be necessary.

Sandra Cook, consumer assistance specialist for the Arkansas Insurance Department, described the private option as a “win-win” while appearing at Diabetes Innovation 2013, a conference sponsored in Washington, DC, by the Joslin Diabetes Center of Harvard. “Insurers have guaranteed payment for 250,000 lives in Arkansas,” she said, noting it will be at an insurance rate, not the Medicaid rate. This expansion of coverage into areas where the working poor live will encourage young doctors to locate in rural areas, she said, because they will be able to make a living. Private coverage, Cook said, doesn’t carry the “stigma” that some feel when they are on public assistance programs.

Pennsylvania seeks to address Medicaid expansion of the previously uninsured on many levels, including the use of premium assistance and private insurance plans, but notably, Governor Tom Corbett has added a provision onto the state’s section 1115 waiver request: that coverage is contingent on a beneficiary’s actively seeking a job. This may prove to be the most controversial part of Pennsylvania’s application.

Sharon Ward, executive director of the Pennsylvania Budget and Policy Center, issued a white paper September 27 that stated, “Federal law and policy prohibit premiums in the Medicaid program for anyone under 100% of the (federal poverty level) and the conditioning of health care coverage on job search and training requirements. The Corbett administration will be applying for a waiver to suspend those provisions of the law. Where CMS comes down on these issues remains to be seen.”

Additionally, Corbett is seeking to keep children in the state Children’s Health Insurance Program, and out of the general Medicaid program, as directed by the ACA.

 It is not known whether these provisions may be deal-breakers for CMS.

Articles

The US Supreme Court's decision to uphold the Affordable Care Act but allow states to decide whether to expand Medicaid has raised a question in many states: Where political leaders have been opposed or split on President Obama's healthcare reforms, is it smart or foolish to cover more people?


Medicaid Expansion Plans Provide Novel Approaches for Healthcare Coverage

The federal sequester trims Medicare payments for cancer patients receiving chemotherapy in doctors’ offices in an effort to save the government money. Instead, it will end up costing more in the long run, according to the president of the American Society of Clinical Oncology (ASCO).

ASCO President Clifford A. Hudis, MD, said most community-based oncology practices that operate under the “buy-and-bill” system, in which providers purchase chemotherapy drugs for onsite treatment and then bill Medicare, cannot afford to absorb the cuts imposed under the Budget Control Act of 2011, popularly known as the “sequester.”

, these providers have been forced to refer patients seeking certain chemotherapy treatments to hospitals, where reimbursements— and costs to Medicare&mdash;are greater. It is not yet known how much this practice is costing the federal government.

“This is one of the true disappointments of the whole sequester—it’s converting lower total costs associated with physician office care into higher costs incurred at the hospital-based setting,” Hudis said. “It’s going to significantly increase the cost of delivering the same care while making it frequently less convenient.”

“It’s quite an amazing paradox,” he said.

Since the financial sequester took effect in April, medical providers, patients, and health plan administrators have worked to adjust to both immediate and long-term implications. The picture in cancer care has many aspects: There are effects on patients undergoing care, and there are effects on research into new treatments for future patients.

While other areas of the federal government sustained deeper cuts by the Budget Control Act, Medicare payment cuts were limited to 2% (

). This applies to payments to Medicare Advantage plans and providers while also affecting physicians who purchase part B medications, administer them onsite, and seek reimbursement from Medicare (referred to as “buy-and-bill”). A 2% cut may not sound like much, but it is having alarming effects.

		Figure. Estimated Impact of Sequestration on Medicare Spending for FY 2013

		Reprinted from the Kaiser Family Foundation

The already-slight margins on office-based infusible products means that oncology practices are making extremely difficult decisions regarding whether to continue providing infused chemotherapy to their patients. For some, the choice involves whether to continue treating these patients or lose money on their medications. “If we treated the patients receiving the most expensive drugs, we’d be out of business in 6 months to a year,” according to Jeff Vacirca, chief executive of North Shore Hematology Oncology Associates in New York.

, “The drugs we’re going to lose money on, we’re not going to administer right now,” noting that Medicare beneficiaries comprised more than half of his practice.

The result, according to Hudis and other clinicians, is that patients are being directed to hospitals or clinics to receive the treatments, with the result being greater expense to Medicare. A study by Milliman, the actuarial consulting firm, estimates that chemotherapy given in a hospital costs on average $6500 more annually than chemotherapy provided in a community-based location.

Furthermore, the question arises as to whether hospitals can handle the increased load: In 2011, Milliman found that 33% of patients were receiving their chemotherapy in a hospital setting. This may actually be exacerbating a trend toward administering chemotherapy in hospital-based outpatient centers. A study of fee-for-service Medicare data found that this shift has been continuing since the implementation of average sales price (ASP) pricing. Preliminary results from a study by the Moran Company revealed that in 2005, fully 87% were receiving chemotherapy in physician offices compared with just 13% in hospital settings.

William T. McGivney, PhD, principal of McGivney Global Advisors, stated, “Sometimes, federal government policies are ‘misdirected.’ The sequestration cuts in reimbursement for oncologic drugs and biologics (therapeutic and supportive care) fall into a new category of ‘undirected misdirection.’” McGivney, the former CEO of the National Comprehensive Cancer Network (NCCN), added, “Gaps in current federal reimbursement levels for oncologic agents have been amplified by the sequestration cuts, and this, in turn, has exacerbated an already difficult situation into one that jeopardizes patient access.”

When clinics and physicians purchase chemotherapies for administration at their facilities, they had been receiving reimbursement of the ASP of the agent plus 6%. According to ASCO, the sequestration has reduced this reimbursement effectively to ASP plus 4.3%. This change is enough to erase their small margins and put their practices into the red, especially when purchasing expensive infusible products. This is driving oncologists and their practice administrators to advise patients that they are no longer providing chemotherapy at their offices.

A survey of 500 oncologists by ASCO revealed that close to one-half were “no longer able to continue caring for Medicare patients unless they had supplemental insurance.”

 The survey, completed in May 2013, also specified that 50% of practices were reportedly sending their Medicare patients who need chemotherapy to hospital outpatient infusion centers (

). A total of 14% reported that they no longer accept Medicare patients. Hudis pointed out that the results of this survey should be interpreted with caution, as it was voluntary in nature (ie, selection bias may be an issue). The results of a separate survey of 326 practices by the Community Oncology Alliance do support ASCO’s findings, however. In addition, one-fifth of practices reported that they have reduced administrative staff, and two-fifths expected that they would do so should the cuts remain in effect through mid-summer. Interestingly, 14% of practices surveyed indicated that they are now considering renewed discussions with hospitals to form closer relationships, including being acquired by them.

		Table. Key Results of ASCO’s Survey: Early Effects of the Sequester on Oncology Practices

					25% no longer participate in clinical research

					74% now have difficulty paying for chemotherapy medications

					80% indicate that the sequestration has affected their practice

					50% send their Medicare patients elsewhere for chemotherapy

					14% have stopped accepting Medicare patients

					22% will close satellite or outreach clinics

					27% will no longer accept patients covered by Medicare Advantage plans

		Source: ASCO sequestration impact survey: One month out, sequestration affecting care of Medicare cancer patients. American Society of Clinical Oncology, May 9, 2013 (www.asco.org/press-center/asco-sequestration-impact-survey-one-month-out-sequestration-affecting-care-medicare). Accessed June 14, 2013.

Intensive clinical research continues to be a force behind advances in cancer treatment. Sequestration seems to be affecting oncology clinical research at the national and local level.

As part of sequestration, the National Institutes of Health (NIH) took a 4.7% hit to its operating budget, including clinical research trial grants. Since NIH is a major source of funding for drug trials, this will certainly result in fewer cancer drug therapy investigations over time, and possibly, slower delivery of oncology medications to the FDA for drug approval.

Patients participating in active clinical trials may be especially hard hit in less-populated areas. In areas with few cancer treatment centers, there may be no option for those patients if their treatment center decides to turn away patients—any facility participating in a clinical trial must be individually approved. That patient may be forced to go across state lines to continue in the trial at an approved facility.

In clinical trials, the chemotherapy under investigation is usually provided to the patient free of charge, but this may not be the case with supportive or ancillary therapies for their care.

From a practical view, Hudis believes that less will seem different at the community level than meets the eye. “The community is so dedicated to doing clinical trials, and frankly has a history of doing clinical trials even when they represented a financial loss,” Hudis explained, “that most patients are likely to keep getting their care in studies that are ongoing. So the impact of this could arguably not be fully appreciated for many months to years—new trials are not started, and the old trials that close aren’t replaced.”

It is expected that the next federal fiscal budget will address the current across-the-board cuts, retaining much of the savings obtained through the sequestration. The situation compelled some legislators to take immediate action.

Marilyn B. Tavenner, CMS administrator, responded to a request by more than 100 legislators to avoid chemotherapy reimbursement cuts, replying on June 3, “The Department of Health and Human Services assessed whether the law allows discretion to administer the sequestration reductions in a manner that is different from the across the board approach that has been used to implement it. We do not believe that we have the authority under the Budget Control Act of 2011 to exempt Medicare payment for Part B drugs.”

Since CMS does not believe that it has the authority under the Budget Control Act to decide where cuts can be avoided, congressional intervention will be necessary to effect a change in the law. A bill introduced by US Rep. Renee Ellmers (RNC) has received bipartisan support in the House, capturing 101 co-sponsors by late July. The legislation, the Cancer Patient Protection Act of 2013 (HR 1416), would exempt chemotherapy from the 2% cut in payment. It has been referred to the House Budget Subcommittee on Health.

, Ellmers said, “What’s needed is momentum and public awareness. Many members were waiting to hear from CMS before they would agree to a legislative fix. Now that CMS has responded and said they will not act, members of Congress know the ball is in their court.” Ellmers continued, “Furthermore, support for this bill has been enhanced by evidence from oncologists across the country that they are sending patients to the more expensive hospital setting because of CMS’s application of the cuts.”

She has seen negative effects in her own district, spurring her to act. “I have heard from numerous oncologists and cancer centers throughout the second district of North Carolina,” she stated. “They have reported that, already facing small profit margins, their centers are concerned that CMS’s application of these cuts will put them out of business.

“I have also heard from the Blood & Cancer Clinic in Fayetteville, North Carolina. They have had to send several patients to the local hospital. This is unfortunate because most of the patients have received several treatments in their office already, but are now suddenly forced to transfer to the hospital. Their patients are very frustrated. Most of them are sick and would benefit from staying with their clinic,” according to Ellmers.

This would be a welcome change in attitude, based on ASCO’s initial meetings on Capitol Hill. Hudis stated, “The last time we actually spoke with representatives and senators about the impact of the sequester, we pointedly highlighted the exemption that they carved out for the air traffic controllers and the FAA. Our arguments, though, seemed to fall on relatively deaf ears.”

“The near-term probability of relief, legislative or regulatory, seems modest,” McGivney told 

. “Thus, providers likely will have to deal with staying afloat as the delivery/payment system remains awash in cuts, mandates, and change.”

			Kliff S. Cancer clinics are turning away thousands of Medicare patients: blame the sequester. 

			Fitch K, Pyenson B. Site of Service Cost Differences for Medicare Patients Receiving Chemotherapy. Milliman Inc. October 19, 2011 (http://publications. milliman.com/publications/health-published/pdfs/ site-of-service-cost-differences.pdf). Accessed June 12, 2013.

			Results of Analyses for Chemotherapy Administration Utilization and Chemotherapy Drug Utilization, 2005- 2011 for Medicare Fee-for-Service Beneficiaries. The Moran Company, 2013; unpublished data.

			ASCO sequestration impact survey: one month out, sequestration affecting care of Medicare cancer patients. American Society of Clinical Oncology, May 9, 2013 (www.asco.org/press-center/asco-sequestration- impact-survey-one-month-out-sequestration-affecting- care-medicare). Accessed June 14, 2013.

			Fact sheet: Impact of sequestration on the National Institutes of Health. National Institutes of Health (http://www.nih.gov/news/health/jun2013/nih-03. htm). Published 2013. Accessed June 16, 2013.

			Tavenner M. Letter to the Honorable Pete Sessions. Centers for Medicare & Medicaid Services, June 3, 2013.

			Bill Summary & Status, 113th Congress (2013 - 2014), H.R.1416. The Library of Congress, June 24, 2013 (http://thomas.loc.gov/cgi-bin/bdquery/ z?d113:h.r.01416:). Accessed June 24, 2013.

The federal sequester trims Medicare payments for cancer patients receiving chemotherapy in doctors' offices in an effort to save the government money. Instead, it will end up costing more in the long run, according to the president of ASCO.

Sequester Cuts to Cancer Care May Cost Taxpayers More in the End

	Today’s healthcare controversies often lead to explosive debates. Few discussions in healthcare can be as incendiary as those concerning the care provided at the end of life. Addressing the real systemic problems seen during a patient’s last weeks is complicated by (1) erroneous, dire characterizations of health reform legislation resulting in “death panels”; (2) the latest evidence of the great health expenditures in the last weeks of life; and (3) questions about care quality in patients with terminal illness.

	The philosophy of “keeping hope alive” despite the almost certain likelihood of near-term mortality fuels efforts to continue to try new active treatments right up until the end. On a population-wide basis, fiscal concerns and clinical facts show that this way of thinking cannot be supported for long.

	The last year of life is associated with high health expenditures in the United States, and the costs are increasingly focused on patients’ last few months. According to a 2002 landmark study, the last month of life accounts for fully one-third of the health resources expended during the final 12 months.

	In another investigation of 230,000 Medicare patients who died as a result of congestive heart failure from 2000 to 2007, researchers found that the rate of hospitalization in the last 6 months of life was approximately 80%.

 In their study, published in 2011 in the Annals of Internal Medicine, 50% of the patients spent time in the hospital’s intensive care unit (ICU), and mean length of stay in the ICU increased as the study progressed. By 2007, ICU stays for these terminal patients reached nearly 5 days. This translated to an average cost per patient of $36,000 (in 2007).

	Complicating the issue is the variance in most healthcare costs from one geographic location to another. The same is true with end-of-life care. In 2008, the Dartmouth College group led by John Wennberg, MD,

 revealed that in patients with serious chronic diseases (including cancer) treated at one of 3000 hospitals, costs per patient in the last 2 years of life ranged from $53,432 (Mayo Clinic) to $105,000 (New York University Medical Center). Compared with lower-cost centers, the higher-cost institutions were associated with longer hospital stays, greater ICU use, more doctor and specialist visits, and greater use of other hospital-provided services. The researchers could find no difference in patient outcomes among the centers studied. They speculated that medical centers that received capitated payments or paid their physicians on a salary basis may be less likely to order unnecessary (or nonbeneficial) tests and procedures at the end of life.

	Another study found that in-hospital end-of-life care was 65% greater in Los Angeles than in San Diego, and this was principally related to the more aggressive care observed in the Los Angeles institutions.

 The researchers found that “San Diego residents are significantly more likely to die with the assistance of hospice services and less likely to spend time in hospitals and intensive care units during the last 2 years of life.”

	Palliative Care, Hospice Care, and the End of Life

	In patients with advanced metastatic disease, palliative therapy may be the only remaining option: Relieve the symptoms, ease the pain, and provide the best supportive care possible, with “the goal of improving quality of life for both the patient and the family,” said Diane Meier, MD, professor of geriatrics and palliative medicine at the Mount Sinai School of Medicine in New York City.

	Palliative care is provided by a team of doctors, nurses, and other specialists who work with a patient’s other doctors to provide an extra layer of support. Dr Meier told Evidence-Based Oncology, “Palliative care is appropriate at any stage in a serious illness and can be provided together with curative treatment.” The Sidebar below provides some of the key recommendations from the American College of Physicians, which are backed by solid evidence.

	The demand for palliative care has increased significantly, according to a 2012 national poll. The surveyors found that 71% believe that “It is more important to enhance the quality of life for seriously ill patients, even if it means a shorter life.”

	Ample evidence exists that hospice care plays a highly cost-effective role in end-of-life care. It seems that payers agree: “Commercial and government payers reimburse palliative care as in any other physician or advanced practice nurse services. For patients who are clearly dying, hospice is the most appropriate model of palliative care. It is covered by virtually all payers in the United States,” said Dr Meier.

		Sidebar. Keys to Palliative End-of-Life Care in Cancer

Patients with advanced, terminal cancer should be:

				Regularly evaluated for pain, dyspnea, and depression

				Prescribed treatments proven to be effective in managing pain; these include nonsteroidal antiinflammatory drugs, opioids, and bisphosphonates (which may be effective in relieving bone pain in patients with metastatic breast cancer or advanced myeloma)

				Given treatments to effectively manage their dyspnea (eg, opioids in patients with unrelieved dyspnea and oxygen for short-term relief of hypoxemia)

				Prescribed treatments to treat depression (in patients with cancer, this may include tricyclic antidepressants, selective serotonin reuptake inhibitors, or psychosocial intervention)

				Counseled to complete advance care planning, including advance directives, to address specific issues such as tube feeding, or continuation or discontinuation of chemotherapy

: Data from Qaseem A, Snow V, Shekelle P, et al. Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;148(2):141-146.

	Although few would dispute the cost-effectiveness of palliative care, perhaps the most challenging issue is convincing providers, patients, and their families to avail themselves of hospice services earlier in the course of serious disease. Patients eligible for hospice services are generally considered to have a life expectancy of 6 months or less. Why don’t more people use hospice services? Dr Meier responded, “The greatest challenge is the statutory requirement for patients to give up insurance coverage for life-prolonging/disease-modifying treatment once they elect hospice. This is a very difficult decision for patients, families, and oncologists.” She added, “Because palliative care services can be delivered at the same time as active cancer treatment, there is no need to choose between approaches—it is sometimes easier for the team to address achievable goals of care earlier in the disease course, and this influences the understanding of and acceptability of hospice for many patients and families.”

	The physician has a great deal of influence in the patient/family’s decision to use hospice services. “The decision to enter hospice is a deeply personal one for both the patient and his or her family,” according to Val Halamandaris, president of the National Association for Home Care and Hospice (NAHC). “The factors that lead to the decision will vary on a case-by-case basis.

	Physicians play a pivotal role in hospice—they are frequently the most knowledgeable about a patient’s condition and prognosis, and are frequently the source of education about and referral to hospice for care.” He added that generally, an individual will choose hospice “when he or she comes to believe that hospice will afford them a better quality of life, and a higher level of participation in their lives, for the remainder of their days.”

	Roughly 82% of all hospice services are provided at home, not in hospice facilities, according to the NAHC.

 The concept of hospice, first introduced in 1972 in Connecticut,

 is not one of care based only in a separate facility, but of comprehensive palliative services that can be given anywhere.

		Table. Distribution of Hospice by Primary Payment Source, 2008

Data from NHCPO Facts and Figures: Hospice Care in America. National Hospice and Palliative Care Organization, October 2009.

	Medicare accounts for the lion’s share of financing for hospice services (

), and therefore, the vast majority of providers seek Medicare certification. The NAHC estimates that in January 2010, 3407 hospices were Medicare-certified, with 66% of these being free-standing facilities, 17% being home health agency—based, 15% being hospital-based, and less than 1% based in skilled nursing facilities. Of total Medicare expenditures, hospice care accounts for roughly 3%. In terms of Medicaid, the Center for Medicare & Medicaid Services does not mandate hospice benefits, but as of 2010, Oklahoma and New Hampshire were the only state programs to specifically exclude it.

	Interestingly, patients with cancer comprise a much smaller proportion of patients receiving facility-based hospice services (10%) than those receiving hospice services in the community (42%).

 According to the Medicare Payment Advisory Commission, the percentage of patients with cancer utilizing any hospice services is increasing each year.

	The aging of the baby boom generation will touch end-of-life care in a big way, Mr Halamandaris believes. “We will see much greater demand from the aging population for hospice and palliative care, for not only cancer, but a variety of diagnoses.” He told Evidence-Based Oncology, “In the coming years, hospices will continue to expand their scope of services so that they are not only providing care at the very end of life, but are engaged earlier on in the terminal disease process.”

	No doubt, more focus will be placed on the completion of advance directives (eg, to forgo extraordinary measures when hope for longer life expectancy with an acceptable quality is vanishing). This may avoid tube feeding, mechanical ventilation, and other life-sustaining measures when the body begins the last phase of life. Mr Halamandaris added, “We are already seeing the beginnings of a very public debate about individual self-determination and making advance decisions about how we—as individuals&mdash;want to be cared for toward the end of our lives. Hospices and palliative care organizations will have an important role in educating the public about the options available to them.”

	In any case, policy makers will need to engage the public much better than in the past. David Nash, MD, MBA, dean, Jefferson School of Population Health, Philadelphia, thinks “It will become more apparent that our spending is untenable and the trade-offs will become painful. Only then,” he believes, “will the public regard the end-of-life discussion as routine and commonplace.”

 Mr Mehr reports receiving payment for involvement in the preparation of this article.

 Concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.	

			Emanuel EJ, Ash A, Yu W, et al. Managed care, hospice use, site of death, and medical expenditures in the last year of life. 

			Unroe KT, Greiner MA, Hernandez AF, et al. Resource use in the last 6 months of life among Medicare beneficiaries with heart failure, 2000-2007. 

			Wennberg JE, Fisher ES, Goodman DC, Skinner JS. Tracking the course of patients with severe chronic illness: The Dartmouth Atlas of Health Care 2008. 

			Kaplan RM: Variation between end-of-life health care costs in Los Angeles and San Diego: why are they so different? 

			Living well at the end of life: a national conversation. The Regence Foundation. 

http://syndication.nationaljournal.com/events/NJ_Events_Website/Regence_NationalSurvey_Toplinedata.pdf

. Published 2011. Accessed July 12, 2012.

			Hospice Facts and Stats. National Association for Home Care and Hospice. 

http://www.nahc.org/facts/HospiceStats10.pdf

. Published November 2010. Accessed July 12, 2012.

			Medicare Payment Advisory Commission, Report to the Congress: Medicare Payment Policy. Published March 2009.

The last year of life is associated with high health expenditures in the United States, and the costs are increasingly focused on patients' last few months.

How Can We Get Better Value in End-of-Life Care?

 Melanoma is one of the most frequent cancers; more than 2 million Americans are treated for skin cancer annually. However, in its earlier stages, it can be easily cured by removal of the skin lesion.

 “Melanoma is on the surface of the skin, and therefore easily visible to patients, doctors, and other health professionals without the use of x-rays or invasive procedures,” said Lynn M. Schuchter, MD, professor of Medicine, University of Pennsylvania School of Medicine, Philadelphia. “Therefore, early detection is highly feasible. Most melanomas are cured with surgery because the melanoma is detected at an early stage of disease before melanoma cells have the potential to metastasize.” Schuchter explained, “Once melanoma metastasizes to distant sites, it is highly resistant to therapy.” Melanoma caused an estimated 8700 deaths in 2010.1

	Chemotherapy for advanced disease has yielded poor 5-year survivals for patients with metastatic disease—16% of those with metastatic melanoma survive 5 years post-diagnosis.

 Dacarbazine has long been the only drug approved by the FDA for treating metastatic melanoma, and it is often ineffective.

 In other words, the prognosis for patients whose melanoma has spread is generally poor, and very few therapies existed before 2011 that could make more than a marginal difference. Only recently have investigational products emerged that, alone or in combination, seem to yield positive responses in some patients.

	Taking Advantage of the Body’s Immune Response

	Melanoma is one of the few cancers that triggers the body’s immune response naturally.

 The problem is that the response is easily overwhelmed by the malignancy. Ipilimumab, which was approved by the FDA in March 2011, works by spurring the body’s immune system to attack the tumor. The melanoma pipeline comprises several examples of investigational agents that seek to enhance the immune response, including therapeutic vaccines.

 The therapeutic vaccine that is perhaps furthest along the pipeline is OncoVEXGM-CSF, which is customized to the patient by using his/ her own tumor antigens. This viral vaccine invades both healthy cells and melanoma cells, but it does not harm the healthy cells, only replicating within the malignant cells, according to the manufacturer, BioVex, which was acquired by Amgen in March 2011.

 The virus produces granulocyte-macrophage colony-stimulating factor (GM-CSF), which gathers dendritic cells, causing the rupture of the tumor cell. This releases GM-CSF and tumor-cell peptides into the local area. The dendritic cells collect the tumor-cell peptides, allowing the immune system to recognize and attack them.

	In 2009, phase II testing of the vaccine in 50 patients with metastatic melanoma revealed overall survival at 2 years of 52%, and an objective response rate of 26% (stable disease rate of 20%).

 Phase III testing is currently under way, and this OPTiM trial is expected to be completed in June 2012 (ClinicalTrials.gov, NCT00769704). The OPTiM trial compares the vaccine with the use of GM-CSF administered subcutaneously in patients with stage III (b-c) and stage IV (M1a-c) disease.

 (vitespen). Not all autologous vaccinebased therapies entering phase III trials have met with success. This vaccine (formerly known as Oncophage), which is developed using gp96 and other peptides from the patient’s own tumor, was found to not improve survival in patients with stage IV melanoma compared with any other choice of therapy. In this phase III trial, only patients with better prognostic characteristics who were injected with vitespen seemed to improve.

 In the case of MVax, from Avax Technologies, the phase II clinical trial results were encouraging, yet the phase III study was halted in 2010, not for safety reasons or poor outcomes, but because of a lack of capital. It is unclear as to when or if this phase III trial may be continued, or if an interim analysis of the study results will take place as planned.

	Most melanomas are cured with surgery...[but] once melanoma metastasizes to distant sites, it is highly resistant to therapy. ”

	Similarly, in 2005, CancerVax Corp halted its phase III trial of the vaccine Canavaxinin for latestage melanoma, not because of safety reasons, but because it had not shown any benefit over placebo.

	Schuchter commented that, “Current approaches to vaccine development are still a major challenge. Unless there is a whole new approach to melanoma vaccines, I am not optimistic about the future of vaccines for patients with melanoma."

 A plasmid that contains the genetic sequences for HLA-B7 and β2-microglobulin, Allovectin-7 is a receptor that activates T cells to provoke an immune response.

 This immunomodulator can be injected directly into the tumor lesion, which may help T-cell recognition of the malignancy and trigger attacks on these specific tumor cells.9 In phase II studies, Allovectin-7 injection in patients with recurrent or refractory advanced melanoma produced a 12% response rate, with a median duration of response of 13.8 months.

 The phase III AIMM trial was begun in 2007 and compares Allovectin-7 with dacarbazine or temozolomide in patients who had not been previously treated with chemotherapy (Clinical- Trials.gov, NCT00395070). This trial is scheduled for completion in the third quarter of 2012.

 GSK2132231A is a recombinant fusion protein with potential immunostimulatory and antineoplastic properties that is derived from the melanoma antigen MAGE-3 and protein D from Hemophilus influenzae (it is also referred to as a MAGE-3 AS02B by the manufacturer). No clinical trial data using this agent have yet been made public, but a phase III trial called DERMA is ongoing to examine the use of GSK2132231A as adjuvant therapy for patients with resected melanoma (ClinicalTrials.gov, NCT00796445). Thirteen hundred patients will be enrolled, and the study is expected to be completed in December 2016.

 This product, a fully human IgG2 monoclonal antibody targeted to CTLA-4, like ipilimumab, may summarize the key learning of research on melanoma to date: The shotgun approach to drug development in metastatic melanoma works poorly. In a previous phase III trial, tremelimumab failed to demonstrate a significant improvement in overall survival compared with temozolomide or dacarbazine in a cohort of patients without prior systemic treatment for their metastatic melanoma.

 However, Pfizer came to an agreement with Switzerland’s Debiopharm to revive plans for a clinical trial of tremelimumab in patients with a biomarker indicating it would most likely be effective. Under this arrangement, Debiopharm would be responsible for funding and running the phase III trial (not yet under way).

 In October 2011, Pfizer granted global rights to the product to MedImmune, a subsidiary of AstraZeneca, for development of this product for other indications.

 Approved in March 2011 for use in nonresectable or metastatic (untreated) melanoma, its manufacturer, Bristol-Myers Squibb (BMS), is conducting additional trials to determine if ipilimumab is also effective in untreated metastatic disease when combined with dacarbazine (ClinicalTrials.gov, NCT00324155) and if it is effective as adjuvant therapy in patients with high-risk stage III disease (ClinicalTrials. gov, NCT00636168). Randomized phase II data have demonstrated 65% 1-year survival and 23% 3-year survival for the ipilimumab dacarbazine combination in patients with chemotherapynaïve advanced disease.

	Ipilimumab is a fully human monoclonal antibody targeted to CTLA-4, a molecule known to negatively regulate the immune system.

 By inhibiting CTLA-4, ipilimumab can enhance the immune system’s T-cell response to tumor cells. In its pivotal 3-arm trial, another BMS agent, gp100 peptide vaccine, which was dubbed MDX- 1379, was used as the active control, despite the fact that no standard of care exists for this patient population. Patients were randomized to receive ipilimumab and gp100, gp100 and placebo, or ipilimumab and placebo. Compared with the median overall survival (OS) of the gp100 arm (6.4 mo), both ipilimumab-containing arms produced significant improvements, with a median OS of 10.0 months in the combination therapy arm (

 <.001) and 10.1 months in the monotherapy arm (

 =.003). In addition to these promising data, ipilimumab is also in phase III testing as an addition to dacarbazine chemotherapy for patients with untreated advanced melanoma (ClinicalTrials.gov, NCT00324155). Clinical trials have identified potential toxic liver effects.

	There is no evidence that BMS is proceeding with the developmental program for MDX-1379.

	Much research in metastatic melanoma has involved testing of agents on specific melanoma cell targets or biomarkers. The targeted medication that has received the most attention, vemurafenib, was approved along with its companion diagnostic test in August 2011 to treat patients with metastatic (late-stage) or unresected (inoperable) melanoma in patients whose tumors express the BRAF gene’s V600E mutation, a driver of tumor growth. Other targets include c-kit, MEK, and Bcl-2 inhibitors. However, successful targeting is difficult, as demonstrated by Genta, which in May 2011 terminated its phase III trial and development program for the Bcl-2 inhibitor oblimersen (genasense) for the treatment of melanoma.

 On the other hand, GlaxoSmithKline’s GSK2118436, a BRAF inhibitor, has entered phase III testing (the first phase III study is scheduled to be completed in June 2012), which if successful in clinical trials won’t reach the market for some time (2014 at the earliest).

 Another targeted agent, GSK1120212, is an inhibitor of the MEK1 and MEK2 (MEK1/2) enzymes, preventing Raf-dependent MEK phosphorylation, resulting in antitumor effects in early-stage trials.

 This GlaxoSmithKline product is the subject of multiple clinical trials for different oncology indications. For melanoma, it is being tested in an open-label, randomized Phase III study comparing GSK1120212 with chemotherapy (either dacarbazine or paclitaxel) in up to 297 patients with stage IIIc or stage IV malignant cutaneous melanoma (all having a 

 mutation—positive tumor). This trial is not scheduled for completion until September 2012 (ClinicalTrials.gov, NCT01245062).

 Developed by Plexxicon and Roche, this BRAF V600E inhibitor seems to be effective

— in some cases, dramatically effective&mdash;for patients with this mutation, although its effects seem to wane after a period of time.

	In previous studies, vemurafenib had induced response rates of 50% and more in patients with metastatic melanoma who have the 

 mutation. In the phase III BRIM3 study, this oral agent (960 mg bid) was compared with intravenous dacarbazine (1000 mg/m2 of body surface area) every 3 weeks as monotherapy in 675 previously untreated patients with stage IIIC or IV melanoma.

	After 6 months of treatment, vemurafenib demonstrated an OS of 84% compared with 64% in the dacarbazine group. In the interim analysis for OS and final analysis for progession-free survival (PFS), vemurafenib demonstrated a 63% relative reduction in risk of death from melanoma compared with dacarbazine. Response rates were 48% for vemurafenib and 5% for dacarbazine (

 <.001). In addition, the risk of the composite endpoint, death, or disease progression was 74% lower in the vemurafenib group (

	However, this agent is not without significant side effects. Thirty-eight percent of the study population taking vemurafenib required dose adjustments to alleviate side effects such as photosensitivity skin reactions, arthralgia, and fatigue.

	Although this study did not report long-term follow-up, there is anecdotal evidence that patients who benefit from vemurafenib may not experience a recurrence for 7 months to 2 years or more.

	With the recent progress in treating metastatic melanoma using targeted therapies like ipilimumab and vemurafenib, might combination approaches of these 2 agents be next in line for clinical trials? Samjiv S. Agarwala, MD, at St. Luke’s Cancer Center in Bethlehem, Pennsylvania, said, “Combination therapy would be an interesting research approach given the differences between ipilimumab (low response rate, prolonged duration) and vemurafenib (high response rate, possibly less durable).” Agarwala pointed out, however, that “Future trials with other agents in combination should address specific biomarkers.”

	A study to test this combination of vemurafenib and ipilimumab is listed on ClinicalTrials.gov but is not currently under way. Additionally, it is expected that the use of vemurafenib will be tested in coming years in a phase IIII study as adjunctive therapy in patients with metastatic melanoma.

	There are few positive data to report on conventional chemotherapeutic agents in the treatment of metastatic melanoma. One agent in development, tasisulam, has run into safety problems in phase III testing.

 Tasisulam is an acyl-sulfonamide compound that induces apoptosis through the mitochondrial-mediated cell death pathway. In phase II trials, 47% of patients taking tasisulam experienced some level of disease control, and a 2.6-month PFS (median) as second-line treatment of patients with unresectable or metastatic melanoma.

 This was not a controlled trial. In December 2010, the SUMMIT-1 phase III registration trial of tasisulam versus paclitaxel stopped recruiting patients with metastatic melanoma because of 12 patient deaths that were potentially associated with the medication.

	There is no further word from the manufacturer (Eli Lilly) whether dosing will be changed for continued enrollment or whether the trial has been discontinued permanently.

	Although the late-stage pipeline for melanoma seems bustling, most of the interest is occurring around ipilimumab and vemurafenib, which have been approved for their initial indications.

	The success of these 2 agents in treating metastatic melanoma may encourage more drug development activity for targeted therapy, according to Agarwala. “I believe it will spur more drug development, as we are still a long way off from curing patients and the encouraging results seen so far have at least opened the door to even more effective drugs in the future,” he remarked. “I believe the results with vemurafenib and ipilimumab are proof of principal trials that show these approaches are effective. Now let’s move that up a notch and find drugs or combinations with even greater efficacy.”

		Table. Drug Pipeline for Melanoma Products.

					Tyrosine kinase inhibitor/ c-kit inhibitor

					Metastatic melanoma in treatment-naïve patients

					In combination with low-dose interleukin-2 in patients with stage IV melanoma

					Raf kinase inhibitor/ vascular endothelial growth factor receptor inhibitor

Melanoma is one of the most frequent cancers; more than 2 million Americans are treated for skin cancer annually.

Stanton R. Mehr

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