Bradford R. Hirsch

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

Characteristics of Oncology Clinical Trials: Insights From a Systematic Analysis of ClinicalTrials.gov

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.

Capecitabine in the management of colorectal cancer

IMPORTANCE Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement. OBJECTIVE To perform a comprehensive analysis of the national oncology clinical research portfolio. DESIGN All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. RESULTS Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America. CONCLUSIONS AND RELEVANCE There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.

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

5-Fluorouracil has been a mainstay in the treatment of colorectal cancer for nearly five decades; however, the use of oral formulations of the medication has been gaining increasing traction since capecitabine was approved for use in adjuvant settings by the US Food and Drug Administration in 2005. The use of capecitabine has since spread to a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer and the neoadjuvant treatment of rectal cancer. In light of increasing utilization, it is critical that clinicians have a firm understanding of the literature supporting capecitabine across various settings as well as the attributes of the drug, such as its dosing recommendations, side-effect profile, and use in the elderly. The purpose of this review is to synthesize the literature in a fashion that can be used to help guide decisions. In a setting of increasing focus on cost, the pharmacoeconomic literature is also briefly reviewed.

The Impact Of Specialty Pharmaceuticals As Drivers Of Health Care Costs

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.

Clinical Trial Participants With Metastatic Renal Cell Carcinoma Differ From Patients Treated in Real-World Practice

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

Real-World Outcomes in Metastatic Renal Cell Carcinoma: Insights From a Joint Community-Academic Registry

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.

Pharmacoeconomics of the Myeloid Growth Factors

PURPOSE Although narrow eligibility criteria improve the internal validity of clinical trials, they may result in differences between study populations and real-world patients, threatening generalizability. Therefore, we evaluated whether patients treated for metastatic renal cell cancer (mRCC) in routine clinical practice are similar to those enrolled onto clinical trials. PATIENTS AND METHODS In this cohort study, we compared baseline characteristics of patients with mRCC in phase III clinical trials of new targeted therapies and those in a retrospective registry composed of academic (Duke) and community (ACORN Network) practices. RESULTS A total of 438 registry patients received sunitinib, sorafenib, temsirolimus, or pazopanib (most commonly used agents) in first-line treatment. Registry patients receiving tyrosine kinase inhibitors (sunitinib, sorafenib, or pazopanib) were more likely to have poor-risk disease by Memorial Sloan Kettering Cancer Center criteria (poor, 7.4% v 2.9%; P < .001; favorable, 30.1% v 43.8%; P < .001) and to have impaired performance status (Eastern Cooperative Oncology Group > 1, 11.1% v 0.6%; P < .001). However, registry patients receiving temsirolimus were less likely to have poor-risk disease (poor, 10.2% v 69.4%; P < .001; favorable, 16.9% v 0%; P < .001). Thus, 39.0% of registry patients would have been excluded from the phase III clinical trial testing the drug they received. CONCLUSION Patients with mRCC treated with tyrosine kinase inhibitors in real-world clinical practice are sicker than those enrolled onto pivotal clinical trials, and more than one third are trial ineligible. Application of clinical trial findings to dissimilar populations may result in patient harm. Clinical research with more inclusive eligibility criteria is needed to appropriately guide real-world practice.

Breast Cancer Screening with Mammography

INTRODUCTION As new therapeutics for metastatic renal cell carcinoma (mRCC) are quickly introduced to market, comparative randomized trial evidence guiding treatment decisions is lacking, especially in the second treatment exposure and beyond. As a demonstration case, we studied mRCC in real-world clinical settings by creating a joint community-academic retrospective mRCC registry to assess outcomes. MATERIALS AND METHODS For this overall survival (OS) analysis, the analytic cohort included all patients in the registry diagnosed between January 1, 2007, to May 31, 2011 (N = 384). Patients were grouped by up to three treatment exposures according to each drugs mechanism of action: vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI), mammalian target of rapamycin inhibitor (mTOR), or no systemic treatment (NSTx, which could include radiation or surgery). OS by exposure sequence was evaluated using Kaplan-Meier, pairwise comparison, and Cox regression analyses. RESULTS Median OS was 17.2 months. OS (months) for one exposure was: mTOR 5.4, TKI 18.2, NSTx 18.4; for two exposures: mTOR/TKI 9.3, TKI/mTOR 13.9, TKI/TKI 35.2; and for three exposures: TKI/mTOR/TKI 20.9, TKI/TKI/mTOR 33.1. By pairwise comparison, OS for TKI, mTOR/TKI, TKI/mTOR, TKI/TKI, TKI/mTOR/TKI and TKI/TKI/mTOR sequences was greater than mTOR (all P < .04); demographics confirmed that individuals treated with early mTOR inhibition more commonly had adverse prognostic features. In Cox regression analysis, compared with the referent (TKI), TKI/TKI (hazard ratio = 0.53; P = .03) had a lower risk of death, and mTOR (hazard ratio = 2.16; P = .002) had a higher risk of death. CONCLUSIONS mRCC survival outcomes are different by pattern, with general findings consistent with trial-based expectations in similar patient populations. Real-world data can provide context around patterns of care and impact when experimental trial data are lacking.

Informatics in action: lessons learned in comparative effectiveness research.

BackgroundThe 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 bio-similar agents in the US, similar to their recent approval in Europe.ObjectivesThe objective of this paper is to review the available pharmaco-economic 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.MethodsA MEDLINE search was performed to find studies that became available since the prior review of this topic was published in Pharmacoeconomics in 2003.ResultsAcceptable 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.ConclusionThis evidence will prove valuable in assessing the overall cost effectiveness and cost utility of the MGFs in patients receiving cancer chemotherapy.