Cost Effectiveness in Health and Medicine.

Background: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1 G93A mice during defined disease stages. Methods: hSOD1 G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1 G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results: We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1 G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions: These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1 G93A mouse. Hence, reducing complement-induced

of amyotrophic lateral sclerosis

Organization for Economic Cooperation and Development (OECD)

Health care costs in the United States present a major challenge to the national economic well being. The Centers for Medicare and Medicaid Services (CMS) has projected that US health care spending will reach $4.3 trillion and account for 19.3% of the national gross domestic product by 2019.1 This growth in spending—both in absolute terms and as a proportion of our gross domestic product—has not been accompanied by commensurate improvements in health outcomes, despite expenditures far exceeding those of other countries.2–4 One of the fastest growing components of US health care costs is cancer care, the cost of which is now estimated to increase from $125 billion in 2010 to $158 billion in 2020.1 Although cancer care represents a small fraction of overall health care costs, its contribution to health care cost escalation is increasing faster than those of most other areas because of several factors: the increasing prevalence of cancer due to the overall aging of the population and better control of some causes of competing mortality; the introduction of costly new drugs and techniques in radiation therapy and surgery; and the adoption of more expensive diagnostic tests. In some cases, the adoption of newer, more expensive diagnostic and therapeutic interventions may not be well supported by medical evidence, thereby raising costs without improving outcomes.5 Coupled with, or even driving, some of these rising costs are sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.6

Historically, most individuals in the United States were shielded from the acute economic impact of expensive care because they had health insurance. However, current trends suggest that patients will find themselves increasingly responsible for a greater proportion of the cost of their health care. Cost shifting or sharing can occur through the increased use of high-deductible policies and larger copayments. These increased costs are already commonplace and may not be affordable for many families. Indeed, health care expenditures are cited as a major cause of personal bankruptcy,7 and the term financial toxicity has entered the vernacular as a means of describing the financial distress that now often accompanies cancer treatment.8 Like other toxicities of cancer treatment, financial toxicity resulting from out-of-pocket treatment expenses can reduce quality of life and impede delivery of high-quality care.9,10 Patients experiencing high out-of-pocket costs have reported reducing their spending on food and clothing, reducing the frequency with which they take prescribed medications, avoiding recommended procedures, and skipping physician appointments to save money.10,11 These unintended consequences risk an increase in health disparities, which runs counter to some of the key goals of health care reform.

In many communities, the high costs associated with cancer care have created a difficult situation for patients and the oncologists who care for them. Addressing this situation will require greater understanding of all the risks and benefits of various treatment options as well as the consequences of specific choices. In this regard, studies have shown that patients specifically want financial information about treatment alternatives along with information about medical effectiveness and treatment toxicity. However, they often do not receive it. Closing this knowledge gap will require educated providers who are able to sensitively initiate a dialogue about the cost of care with their patients when appropriate.12,13 Patients with cancer are often surprised by and unprepared for the high out-of-pocket costs of treatments. They also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all. Oncologists are generally aware of this conundrum but uncertain about whether and how the cost of care should affect their recommendations.14 Although raising awareness of costs and providing tools to assess value may help to manage costs while maintaining high-quality care, some oncologists see this as being in conflict with their duty to individual patients.15

Recent American Society of Clinical Oncology Efforts
Motivated by our responsibility to help oncologists deliver the highest-quality care to patients everywhere, the American Society of Clinical Oncology (ASCO) formed the Task Force on the Cost of Cancer Care in 2007. Its mission includes educating oncologists about the importance of discussing costs associated with recommended treatments, empowering patients to ask questions pertaining to the anticipated costs of their treatment options, identifying the drivers of the rising costs of cancer care, and ultimately developing policy positions that will help Americans move toward more equal access to the highest-quality care at the lowest cost.16

In 2012, through the work of the Task Force, ASCO responded to the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation and identified specific instances of overuse in the delivery of cancer care. ASCO used a deliberative consensus process to identify five common clinical practices that are not supported by high-level evidence. A second list of five was developed using the same process and submitted to the Choosing Wisely Campaign in 2013. ASCO amplified the evidence basis for both top-five lists in two publications17,18 and is now developing measures to evaluate the use of these practices as part of its Quality Oncology Practice Initiative. These exercises have provided opportunities to develop a rigorous but flexible approach to assessing efficacy across diagnostic and treatment domains.

/pdf/american-society-of-clinical-oncology-statement-a-conceptual-37togw8087.pdf

American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options

Objective To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes. Design Metaepidemiological study. Eligibility criteria Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care). Data sources Medline and Cochrane Database of Systematic Reviews, May 2013. Main outcome measure Mortality. Data synthesis We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis. Results We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339 274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14 716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant. Conclusions Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.

https://www.bmj.com/content/bmj/347/bmj.f5577.full.pdf

Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study

This book provides a detailed review of the role of health technology assessment (HTA) in the European Union. It examines both method and process in the prioritization and financing of modern health care, and presents extensive case studies from Sweden, the Netherlands, Finland, France, Germany and the United Kingdom.

/pdf/ensuring-value-for-money-in-health-care-the-role-of-health-34jan8ztec.pdf

Ensuring value for money in health care: the role of health technology assessment in the European Union

Health care spending has risen steadily in most countries, becoming a concern for decision-makers worldwide. Commentators often point to new medical technology as the key driver for burgeoning expenditures. This paper critically appraises this conjecture, based on an analysis of the existing literature, with the aim of offering a more detailed and considered analysis of this relationship. Several databases were searched to identify relevant literature. Various categories of studies (eg, multivariate and cost-effectiveness analyses) were included to cover different perspectives, methodological approaches, and issues regarding the link between medical technology and costs. Selected articles were reviewed and relevant information was extracted into a standardized template and analyzed for key cross-cutting themes, ie, impact of technology on costs, factors influencing this relationship, and methodological challenges in measuring such linkages. A total of 86 studies were reviewed. The analysis suggests that the relationship between medical technology and spending is complex and often conflicting. Findings were frequently contingent on varying factors, such as the availability of other interventions, patient population, and the methodological approach employed. Moreover, the impact of technology on costs differed across technologies, in that some (eg, cancer drugs, invasive medical devices) had significant financial implications, while others were cost-neutral or cost-saving. In light of these issues, we argue that decision-makers and other commentators should extend their focus beyond costs solely to include consideration of whether medical technology results in better value in health care and broader socioeconomic benefits.

/pdf/medical-technology-as-a-key-driver-of-rising-health-1kahzs996w.pdf

Medical technology as a key driver of rising health expenditure: disentangling the relationship.

Context: Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States andEuropetoensuretheirperformance,safety,andquality.Thisarticleprovides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients. Methods: We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peerreviewed literature and legislative documents. Findings: The two regulatory systems differ in their mandate and orientation, organization, pre- and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring realworlduse,andexchangingpertinentinformationondeviceswithkeyuserssuch as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered. Conclusions: Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring

/pdf/improving-medical-device-regulation-the-united-states-and-hw7jwis5tw.pdf

Improving Medical Device Regulation: The United States and Europe in Perspective

Medical technology procurement in Europe: a cross-country comparison of current practice and policy

Medical devices pose unique challenges for economic evaluation and associated decision-making processes that differ from pharmaceuticals. We highlight and discuss these challenges in the context of cardiac device therapy, based on a systematic review of relevant economic evaluations. Key challenges include practical difficulties in conducting randomized clinical trials, allowing for a 'learning curve' and user characteristics, accounting for the wider organizational impacts of introducing new devices, and allowing for variations in product characteristics and prices over time.

/pdf/applying-health-economics-for-policy-decision-making-do-i88m24po97.pdf

Corinna Sorenson

Papers

Ensuring value for money in health care: the role of health technology assessment in the European Union

Medical technology as a key driver of rising health expenditure: disentangling the relationship.

Improving Medical Device Regulation: The United States and Europe in Perspective

Medical technology procurement in Europe: a cross-country comparison of current practice and policy

Applying health economics for policy decision making: do devices differ from drugs?