Initial Trends in the Use of the 21-Gene Recurrence Score Assay for Patients With Breast Cancer in the Medicare Population, 2005-2009.

IMPORTANCE: In 2006, the Centers for Medicare & Medicaid Services approved coverage for the use of the 21-gene recurrence score (RS) assay in women with early-stage, estrogen receptor-positive, node-negative breast cancers to help guide recommendations for adjuvant chemotherapy. Use of the assay in community settings has not been previously examined in a nationally representative sample of patients. OBJECTIVE: To examine trends in the use of the RS assay in routine clinical practice in a nationally representative sample of women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study of Medicare beneficiaries diagnosed with incident breast cancer between 2005 and 2009, as recorded in a Surveillance, Epidemiology, and End Results data set with linked Medicare claims through 2010. MAIN OUTCOMES AND MEASURES: Demographic and clinical variables associated with the use of the assay. RESULTS: A total of 70,802 patients met the study criteria. Use of the RS assay increased from 1.1% in 2005 to 10.1% in 2009 (P < .001). The majority of tests (60.9%) occurred in patients with National Comprehensive Cancer Network-defined intermediate-risk disease (ie, estrogen receptor-positive, node-negative tumors >1 cm). Most patients with other than intermediate-risk disease had borderline indications for testing, including T1b (47.5%) or N1 (26.8%) disease. Testing was associated with younger age, fewer comorbid conditions, higher-grade disease, and being married. Among patients younger than 70 years with intermediate-risk disease, testing rates increased from 7.7% in 2005 to 38.8% in 2009 (P < .001). In multivariable analysis, testing was modestly higher in Northeast than in Western registries (odds ratio, 1.83; 95% CI, 1.49-2.26) but was otherwise not associated with region, local census tract demographic characteristics, black race, location in an urban area, or tumor histologic characteristics. CONCLUSIONS AND RELEVANCE: The RS assay was adopted quickly in clinical practice after the Medicare coverage decision in 2006, and use appears to be consistent with guidelines and equitable across geographic and racial groups. Factors influencing adoption of the assay and its impact on adjuvant chemotherapy use in clinical practice remain important areas of study.

Management of chemotherapy-induced neutropenia: measuring quality, cost, and value.

Treatment-associated neutropenia continues to represent the most common dose-limiting toxicity of cancer chemotherapy. It often leads to fever and infection, prompting hospitalization and occasionally resulting in serious morbidity, and even mortality, despite modern broad-spectrum antibiotic treatment and supportive care. Neutropenia and its complications may also lead to chemotherapy dose reductions, treatment delays, or early treatment termination, compromising disease control and the potential for cure. NCCN Clinical Practice Guidelines in Oncology recommend administration of primary prophylaxis with a myeloid growth factor in patients receiving regimens associated with a high risk for febrile neutropenia, and consideration of prophylaxis in patients receiving lower-risk regimens who have other risk factors that might place them at higher risk for febrile neutropenia. Although these agents have been shown to be effective and safe in numerous randomized controlled trials, they are expensive and contribute significantly to increasing health care costs. Regulatory agencies and guideline organizations do not currently address the issue of cost. However, with the relentless increase in health care use and current efforts to reform health care, it has become increasingly important to assess both the cost and the net benefit of interventions related to an episode of care in order to compare the overall value of therapeutic options. This article defines and discusses the intersection of quality, costs, and value in the context of prophylactic myeloid growth factor use in patients with cancer receiving myelosuppressive chemotherapy.

The impact of specialty pharmaceuticals as drivers of health care costs.

The pharmaceutical industry is shifting its focus from blockbuster small molecules to specialty pharmaceuticals. Specialty pharmaceuticals are novel drugs and biologic agents that require special handling and ongoing monitoring, are administered by injection or infusion, and are sold in the marketplace by a small number of distributors. They are frequently identified by having a cost to payers and patients of $600 or more per treatment. The total costs of the new agents are likely to have a substantial impact on overall health care costs and on patients during the next decade, unless steps are taken to align competing interests. We examine the economic and policy issues related to specialty pharmaceuticals, taking care to consider the impact on patients. We assess the role of cost-sharing provisions, legislation that is promoting realignment within the market, the role of biosimilars in price competition, and the potential for novel drug development paradigms to help bend the cost curve. The economic aspects of this analysis highlight the need for a far-reaching discussion of potential novel approaches to innovation pathways in our quest for both affordability and new technology.

Biosimilars: a cure to the U.S. health care cost conundrum?

As the cost of healthcare continues to rise and patents on biologics near expiration, biosimilars are gaining visibility as a mechanism for cost reduction. Yet, the introduction of biosimilars into the U.S. market will be complex, due to the related complexity of production, research requirements, and regulatory uncertainty. The purpose of this paper is to frame the relevant issues in order to provide context for stakeholders. It is particularly crucial that clinicians understand the scientific, regulatory, legislative and economic considerations involved in order to ensure that the path to approval is consistent with their needs and that appropriate utilization occurs, once approved.

Comparative effectiveness research: moving medical oncology forward.

Comparative effectiveness research (CER) is critically needed in medical oncology to improve the care being delivered to oncology patients. As medical oncologists are forced to rely on insufficient data as a part of daily treatment decision making, and as the cancer treatment landscape evolves quickly relative to other areas of medicine, CER is particularly pressing in our field. Continued reliance on randomized clinical trials is a part of the solution, but it cannot be the sole answer. As new and richer data sources become available addressing quality of life, resource utilization, and other critical elements, the implementation of CER will advance. Its true power will lie in linkages to "learning health systems" and real-time application to the day-to-day practice of medicine.

The economics of new drugs: can we afford to make progress in a common disease?

The concept of personalized medicine is beginning to come to fruition, but the cost of drug development is untenable today. To identify new initiatives that would support a more sustainable business model, the economics of drug development are analyzed, including the cost of drug development, cost of capital, target market size, returns to innovators at the product and firm levels, and, finally, product pricing. We argue that a quick fix is not available. Instead, a rethinking of the entire pharmaceutical development process is needed from the way that clinical trials are conducted, to the role of biomarkers in segmenting markets, to the use of grant support, and conditional approval to decrease the cost of capital. In aggregate, the opportunities abound.

The ethics of health information technology in oncology: emerging isssues from both local and global perspectives.

Health information technology (HIT) is ever-increasing in complexity and has incrementally become a fundamental part of our everyday clinical lives. As HIT becomes more complex and commonplace, so do the questions it raises about stewardship and usage of data, along with the ethics of these applications. With the development of rapid-learning systems, such as ASCO's CancerLinQ, careful thought about the ethics and applications of these technologies is necessary. This article uses the principles-based framework of modern bioethics to examine evolving ethical issues that arise in the context of HIT and also discusses HIT's application in reducing cancer care disparities in the developing world. We recognize that this topic is quite broad, so here we provide an overview of the issues, rather than any definitive conclusions about a particular "correct path." Our hope is to stimulate discussion about this important topic, which will increasingly need to be addressed in the oncology community.

Pharmacoeconomics of the myeloid growth factors: a critical and systematic review.

BACKGROUND: The pharmacoeconomics of the myeloid growth factors (MGFs) is an important topic that has received substantial attention in recent years. The use of the MGFs as primary prophylaxis to prevent febrile neutropenia (FN) has grown considerably over the past decade and professional guidelines regarding their use have broadened the settings in which these agents are indicated. Recent data also suggest a potential role for them in reducing infection-related and all-cause mortality. The cost and effectiveness of these agents will continue to gain visibility as companies pursue approval for biosimilar agents in the US, similar to their recent approval in Europe. OBJECTIVES: The objective of this paper is to review the available pharmacoeconomic literature on the MGFs, which is particularly timely in light of the recent passage of healthcare reform and the increasing focus on cost control. The cost of treating cancer in the US is rising faster than the already rapid increase in overall medical expenditure. The clinical utility and cost effectiveness of supportive care measures in oncology must therefore be weighed carefully. This review focuses on the use of different formulations of MGFs for primary and secondary prophylaxis of chemotherapy-induced neutropenia. METHODS: A MEDLINE search was performed to find studies that became available since the prior review of this topic was published in Pharmacoeconomics in 2003. RESULTS: Acceptable cost-minimization estimates for primary prophylaxis with the MGFs in patients receiving cancer chemotherapy have been provided by several studies in the US. Of the commonly used agents in the US, pegfilgrastim appears to be superior to the currently recommended dose and schedule of filgrastim in terms of cost minimization, and primary prophylaxis appears to be less costly than secondary prophylaxis. However, the cost benefits of primary prophylaxis in Europe are not as pronounced as in the US, due to the lower costs of medical care. Data continue to emerge suggesting a decreased risk of early mortality from averted infections as well as the possibility of a disease-specific mortality benefit through maintaining the relative dose intensity of chemotherapy with MGF support. CONCLUSION: This evidence will prove valuable in assessing the overall cost effectiveness and cost utility of the MGFs in patients receiving cancer chemotherapy.

Conflict of interest disclosure in off-label oncology clinical trials.

PURPOSE: We sought to determine the prevalence, reliability, and predictors of conflict of interest (COI) and funding disclosure statements for studies of anticancer targeted therapies conducted in the off-label prescribing setting. METHODS: As a part of a federally funded systematic review, manuscripts were included in the analysis if they were used to support one of 19 indications for cancer targeted therapies that were off-label but reimbursable according to compendia published in 2006 or before. Studies were categorized according to trial design, trial results, average impact factor of journals, and presence of COI and funding disclosure statements. RESULTS: Among the 69 included studies, prevalence of COI and funding disclosures was low, at 33% and 58% respectively; time trends showed some improvement between 2002 to 2007, but only 60% of studies had disclosures by 2007. Predictors of COI disclosure were publication in high-impact-factor journals (P < .001), large study sample size (P = .001), enrollment exclusively in the United States (P = .04), and study of the targeted therapy in combination with other agents as opposed to the study drug alone (P = .03). CONCLUSION: Disclosure of potential sources of bias in COI and funding statements in studies of off-label indications for anticancer targeted therapies was low and did not increase substantially over time.

Delivering affordable cancer care in high-income countries.

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

Biosimilars: are they ready for primetime in the United States?

The introduction of alternative versions of biologic products, also known as biosimilars, into the United States market has been gaining increasing visibility as patents for many agents are nearing expiration. Unlike generics, which are regulated under the Hatch-Waxman legislation passed in 1984, the approval process for biosimilars in the United States has not been defined. In 2004, the European Union established a regulatory pathway for these agents, and the FDA is now following suit. The economic implications are large, with $66.9 billion spent on the top 20 biologics in 2009. Of the top 10 biologics, 6 are routinely used in oncology. As the regulatory requirements are debated, several critical issues must be resolved. The most obvious is that the agents must be shown to be comparable to the original biologic they intend to replace. Knowledge of pharmacokinetic parameters alone will not be adequate, but the amount of clinical data required by the FDA remains unclear. The regulations will define the ease with which a biosimilar can be brought to market, and the associated costs of trials will influence the ultimate price of the medications. Balancing the needs of the relevant stakeholders is critical to ensure patient safety while controlling costs, improving access, and encouraging innovation. This is not an easy balance to strike.

Informatics in action: lessons learned in comparative effectiveness research.

Comparative effectiveness research (CER) is meant to provide evidence about the relative risks and benefits of different treatment options. It is gaining visibility as a tool to address the evidence gaps that clinicians struggle with every day; however, CER is particularly challenging in oncology as there is great variability in how individuals respond to interventions, and a wide range of drugs and procedures are available. In order to overcome these obstacles and conduct reliable CER studies, it is critical to create a robust data infrastructure to support it.The Center for Medical Technology Policy held its first annual CER Summit in November 2010, with a particular focus on oncology. A number of critical informatics themes emerged including the need for consistent data standards, registry reform, tools to assist trial accrual, and data to integrate into value deliberations. Addressing the data issues highlighted in this report will provide a significant opportunity to improve the health of our medical system.