Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator.

BACKGROUND: Adoption of high-throughput, gene panel-based, next-generation sequencing (NGS) into routine cancer care is widely supported, but hampered by concerns about cost. To inform policies regarding genomic testing strategies, we propose a simple metric, cost per correctly identified patient (CCIP), that compares sequential single-gene testing (SGT) vs. multiplex NGS in different tumor types. MATERIALS AND METHODS: A genomic testing cost calculator was developed based on clinically actionable genomic alterations identified in the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets. Using sensitivity/specificity data for SGTs (immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization) and NGS and marker prevalence, the number needed to predict metric was monetarized to estimate CCIP. RESULTS: At base case, CCIP was lower with NGS than sequential SGT for advanced/metastatic non-squamous non-small cell lung cancer (NSCLC), breast, colorectal, gastric cancers, and cholangiocarcinoma. CCIP with NGS was also favorable for squamous NSCLC, pancreatic, and hepatic cancers, but with overlapping confidence intervals. CCIP favored SGT for prostate cancer. Alternate scenarios using different price estimates for each test showed similar trends, but with incremental changes in the magnitude of difference between NGS and SGT, depending on price estimates for each test. CONCLUSIONS: The cost to correctly identify clinically actionable genomic alterations was lower for NGS than sequential SGT in most cancer types evaluated. Decreasing price estimates for NGS and the rapid expansion of targeted therapies and accompanying biomarkers are anticipated to further support NGS as a preferred diagnostic standard for precision oncology.

The Hemophilia Gene Therapy Patient Journey: Questions and Answers for Shared Decision-Making.

Purpose: The anticipated emergence of hemophilia gene therapy will present people with hemophilia (PWH) and treating clinicians with increasingly complex treatment options. It will be critical that PWH and their families be empowered to participate fully in decision-making through transparent communication and the development of targeted educational resources. Methods: The Council of Hemophilia Community (CHC) convened across a series of roundtable meetings to define the patient journey for hemophilia gene therapy, and to develop a question-and-answer style resource to guide discussion between healthcare professionals (HCPs) and their patients. Patient groups were also consulted during the development of this tool. Results: The CHC defined 5 key stages in the hemophilia gene therapy patient journey: pre-gene therapy (information-seeking and decision-making), treatment initiation, short- and long-term post-gene therapy follow-up. PWH will have different questions and concerns at each stage of their journey, which should be discussed with their HCP to aid decision-making. The resulting patient journey infographic and Q&A resource (see Supplementary Materials) has been developed for HCPs and PWH to provide a novel and practical roadmap of key issues and considerations throughout all stages. Conclusion: These resources support a collaborative, patient-centric, shared decision-making approach to inform treatment decision discussions between HCPs and PWH. The value of such discussions will be influenced by the language adopted; health literacy is a particularly important consideration, and these discussions should be accessible and tailored to PWH. HCPs and PWH can benefit from awareness of the common questions and uncertainties as they progress together along the patient journey. While the contents of this article are specific to hemophilia gene therapy, the concepts developed here could be adapted to aid patients in other disease states.

Alternative payment models for durable and potentially curative therapies: The case of gene therapy for haemophilia A.

INTRODUCTION: The emergence of durable and potentially curative cell and gene therapies (also known as advanced therapy medicinal products) with high price tags is challenging conventional health care payment systems. Among these are gene therapies in various phases of development for haemophilia A and B. The emergence of these therapies comes with clinical and economic uncertainties for payers, providers, patients, and manufacturers. These include uncertainties about expression of the intended physiological response, patient outcomes, and duration of treatment effect, along with potentially high upfront costs, variable additional costs, and uncertainties about uptake of the therapy among indicated patient populations. These clinical and economic uncertainties raise interest among payers, providers, and manufacturers in risk-sharing arrangements, including alternative payment models (APMs). SUMMARY: APMs differ from traditional fee-for-service payment for health care. For example, some APMs are designed to reward clinicians and provider organizations for delivering high-quality and cost-effective care. The APMs described here, outcomes-based models (or value- or performance-based models) and finance-based models, are designed to mitigate or otherwise manage financial risks associated with health care payment, including instances in which patient outcomes for costly therapies are uncertain. We examine how such APMs may be applicable in the context of emerging gene therapies for haemophilia A, including considerations in determining whether any particular APM may be most suitable. KEY POINTS OF CONSIDERATION: Gene therapies for haemophilia are among the emerging durable and potentially curative cell and gene therapies with high price tags that are challenging conventional payment systems. These therapies present clinical and economic uncertainties for payers, providers, patients, and manufacturers, including regarding expression of the intended physiological response, duration of treatment effect, patient outcomes, potentially high upfront costs and variable additional costs, and uptake among potentially indicated, diverse patient subgroups. These uncertainties raise interest among payers, manufacturers, and providers in risk-sharing arrangements, including alternative payment models (APMs) such as various outcomes-based and finance-based models. This paper describes a taxonomy of APMs. Then, for the particular context of gene therapy for haemophilia A, we present a set of factors to be considered when determining whether an APM risk-sharing arrangement may be appropriate for a given gene therapy, and, if so, which APM may be most suitable. [Correction added on 21 February 2022, after first online publication: the 'Key Points of Consideration' have been added in this version.].

Clinical Utility of Genomic Testing in Cancer Care.

PURPOSE: In the era of personalized medicine, physicians rely on their understanding of clinical utility to assess the value of rapidly evolving genetic and genomic tests. Current definitions of the clinical utility of genetic testing sufficiently capture a range of benefits and risks that derive from positive and negative results of tests that assess one gene or a few genes. However, these definitions of clinical utility are inadequate to recognize the wider scope of benefits that accrue from more comprehensive genomic tests, which can develop data sets that inform clinical decision making as well as population health and scientific advancement in novel ways. METHODS: An expert roundtable discussion with leaders from multiple sectors of the health care ecosystem was convened to develop a contemporary, fuller definition of the clinical utility of genomic testing in cancer care. RESULTS: We present an updated definition and offer recommendations for successful implementation. CONCLUSION: Applying this expanded definition will encourage evidence-based use of genomic testing in cancer care by helping physicians and other health care decision makers account for the broader range of benefits and risks of testing for individual patients, health systems, population health, and scientific advancement.

Regulatory, Policy, and Operational Considerations for Outcomes-Based Risk-Sharing Agreements in the U.S. Market: Opportunities for Reform.

BACKGROUND: Although interest in outcomes-based risk-sharing agreements (OBRSAs) and other value-based contracts (VBCs) continues to grow, the number of VBCs in the United States is still limited. A better understanding of the evolving and fluid context of policies, regulations, and operational factors affecting their uptake in the United States is needed in order to lower or obviate barriers and advance OBRSAs. OBJECTIVES: To (a) identify and recognize priorities among policies, regulations, and other factors that are most likely to influence the feasibility, design, and execution of OBRSAs and (b) suggest opportunities for reform and other modifications that may advance OBRSAs in the United States. METHODS: Across 18 months during 2017-2018, we reviewed health policy literature, examined stakeholder group communications, and conducted semistructured interviews with representatives of 12 diverse stakeholder organizations. Across these, and incorporating real-time contextual changes, we identified priorities for enabling and improving OBRSAs. RESULTS: Regulatory and policy priorities most often cited by manufacturers were Medicaid best price rule, Medicare Part B average sales pricing, FDA restrictions on communications, and the Anti-Kickback Statute. While recognizing these, health plans were more concerned about operational barriers, particularly associated with data collection and analysis, selection of outcomes that are feasible to assess, bandwidth for managing OBRSAs, and implementation costs relative to return on investment. Most recognized limitations on access to personal health information, target population turnover, and insufficient information sharing of OBRSA experiences. Noteworthy were asymmetries of administrative burden and cost management: individual manufacturers may pursue OBRSAs for 1 or a few products per year, while health plans are approached by multiple manufacturers about OBRSAs for their respective products; manufacturers focus on drugs, while health plans must manage broader costs of care. CONCLUSIONS: While all stakeholders express interest in OBRSAs, health plans tend to consider them as a narrower priority than manufacturers. Solving operational barriers, in addition to addressing policy and regulatory barriers, is essential for aligning efforts to advance OBRSAs. Doing so depends on collaboration to improve decisions about when and how to pursue OBRSAs, with attention to data management, modeling and piloting OBRSAs, and information sharing. These findings pertain to companies operating in the United States and some likely extend to certain value-based arrangements in other countries. DISCLOSURES: This analysis was funded by Merck Sharp & Dohme (MSD), a subsidiary of Merck, as a component of the Learning Laboratory for Advancing Value-Based Healthcare, which is a multiyear collaboration of MSD and Optum, a health services, technology, and data company. The manuscript underwent an internal review by the sponsor. The Lewin Group (Lewin) is a subsidiary of OptumServe. OptumServe is wholly owned by UnitedHealth Group (UHG). Neither OptumServe nor UHG or its subsidiaries review the work products of Lewin. Lewin operates with editorial independence and provides its clients with health care and human services policy research and consulting services. Goodman and Villarivera are employees of Lewin; Gregor is an employee of Optum; and van Bavel is an employee of MSD. Goodman and Villarivera report fees from UHG, unrelated to this study. A poster presentation based on this manuscript was accepted and presented at the ISPOR Europe 2018 Conference in Barcelona, Spain, on November 13, 2018.

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

AIM: Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. METHODS: We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. RESULTS: Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. CONCLUSION: Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates.

NCCN Roundtable:Value-Based Decision-Making at the Bedside.

As part of the NCCN 20th Annual Conference: Advancing the Standard of Cancer Care, a distinguished and diverse group of experts on value-based decision-making in oncology discussed guidelines and pathways and how their use has impacted bedside evidence-based decision-making for both physicians and patients. Moderated by Clifford Goodman, PhD, the roundtable also reflected on the criteria used to assess shared decision-making and the relationship between outcomes and cost when determining value.

PACE Continuous Innovation Indicators-a novel tool to measure progress in cancer treatments.

Concerns about rising health care costs and the often incremental nature of improvements in health outcomes continue to fuel intense debates about 'progress' and 'value' in cancer research. In times of tightening fiscal constraints, it is increasingly important for patients and their representatives to define what constitutes 'value' to them. It is clear that diverse stakeholders have different priorities. Harmonisation of values may be neither possible nor desirable. Stakeholders lack tools to visualise or otherwise express these differences and to track progress in cancer treatments based on variable sets of values. The Patient Access to Cancer care Excellence (PACE) Continuous Innovation Indicators are novel, scientifically rigorous progress trackers that employ a three-step process to quantify progress in cancer treatments: 1) mine the literature to determine the strength of the evidence supporting each treatment; 2) allow users to weight the analysis according to their priorities and values; and 3) calculate Evidence Scores (E-Scores), a novel measure to track progress, based on the strength of the evidence weighted by the assigned value. We herein introduce a novel, flexible value model, show how the values from the model can be used to weight the evidence from the scientific literature to obtain E-Scores, and illustrate how assigning different values to new treatments influences the E-Scores. The Indicators allow users to learn how differing values lead to differing assessments of progress in cancer research and to check whether current incentives for innovation are aligned with their value model. By comparing E-Scores generated by this tool, users are able to visualise the relative pace of innovation across areas of cancer research and how stepwise innovation can contribute to substantial progress against cancer over time. Learning from experience and mapping current unmet needs will help to support a broad audience of stakeholders in their efforts to accelerate and maximise progress against cancer.

The Affordable Care Act: where are we now? An NCCN roundtable.

The Affordable Care Act (ACA) is a transformational event for health care in the United States, with multiple impacts on health care, the economy, and society. Oncologists and other health care providers are already experiencing many changes-direct and indirect, anticipated and unanticipated. A distinguished and diverse panel assembled at the NCCN 19th Annual Conference to discuss the early phase of implementation of the ACA. The roundtable touched on early successes and stumbling blocks; the impact of the ACA on contemporary oncology practice and the new risk pool facing providers, payers, and patients; and some of the current and future challenges that lie ahead for all.

Roundtable--the changing oncology landscape: evolution or revolution?

Complex challenges face all players in the oncology landscape, from health care policy leaders and third-party payers, to practicing physicians and nurses, to patients and their families. In these unsteady economic times, possible answers proposed by some may represent part of the problem to others. A distinguished panel assembled at the NCCN 18th Annual Conference: Advancing the Standard of Cancer Care to explore the changing oncology landscape. This article is the synopsis of that discussion, with panelists shedding light on such issues as the astronomic cost of medical care, the need for clinicians to think outside the formulary, and the therapeutic decision-making process in the new world of "big data."

Analysis & commentary: The US Preventive Services Task Force should consider a broader evidence base in updating its diabetes screening guidelines.

Diabetes, especially type 2 diabetes, is on the rise throughout the United States. Several national health organizations and professional medical societies advocate screening people in high-risk groups for diabetes. However, the US Preventive Services Task Force recommends screening only adults with hypertension. We examined evidence supporting screening high-risk adults, including studies using intermediate outcomes and modeling studies. We found a broad range of evidence of practical relevance to diabetes screening that merits consideration in developing new screening guidelines. This evidence could inform recommendations to expand coverage to screening of other high-risk groups and could facilitate the prevention and early treatment of diabetes. We recommend that the US Preventive Services Task Force consider these expanded sources of evidence and revise its recommendations accordingly.

Special challenges in comparative effectiveness research on children's and adolescents' health.

The United States is undertaking a major expansion of comparative effectiveness research, with the potential to achieve systemwide improvements in health care quality, outcomes, and resource allocation. However, to achieve these improvements in children's health and health care, comparative effectiveness research needs to be targeted, designed, conducted, and reported in ways that are responsive to the unique circumstances of children and adolescents. These include clinically important differences in the type and course of disease in children; demographic differences between the overall child and adult population in the United States, such as racial and ethnic makeup; and methodological issues involving study design. Our overarching point is that the base of evidence in pediatrics must not fall even further behind that for the adult population in an era of rapid advancement and funding of comparative effectiveness research.

Assessment of the quality of cost analysis literature in physical therapy.

BACKGROUND: Policy makers, payers, and other stakeholders increasingly call for greater evidence of the cost-effectiveness of health care interventions. OBJECTIVE: The purposes of this study were to identify and rate the quality of cost analysis literature in physical therapy and to report summary information on the findings from the reviewed studies. DESIGN: This study was a targeted literature review and rating of relevant studies published in the last decade using a quality evaluation tool for economic studies. MEASUREMENTS: The Quality of Health Economic Studies (QHES) instrument was used to obtain quality scores. RESULTS: Ninety-five in-scope studies were identified and rated using the QHES instrument. The average quality score was 82.2 (SD=15.8), and 81 of the studies received a score of 70 or higher, placing them in the "good" to "excellent" quality range. Investigators in nearly two thirds of the studies found the physical therapy intervention under investigation to be cost-effective. LIMITATIONS: The small number of studies meeting the inclusion criteria was a limitation of the study. CONCLUSIONS: The quality of the literature regarding the cost-effectiveness of physical therapy is very good, although the magnitude of this body of literature is small. Greater awareness of the strengths and limitations of cost analyses in physical therapy should provide guidance for conducting high-quality cost-effectiveness studies as demand increases for demonstrations of the value of physical therapy.

The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology.

Skin disease is one of the top 15 groups of medical conditions for which prevalence and health care spending increased the most between 1987 and 2000, with approximately 1 of 3 people in the United States with a skin disease at any given time. Even so, a national data profile on skin disease has not been conducted since the late 1970s. This study closes the gap by estimating the prevalence, economic burden, and impact on quality of life for 22 leading categories of skin disease. The estimated annual cost of skin disease in 2004 was 39.3 billion dollars, including 29.1 billion dollars in direct medical costs (costs of health services and products) and 10.2 billion dollars in lost productivity costs (defined as costs related to consumption of medical care, costs associated with impaired ability to work, and lost future earning potential because of premature death). Based on a methodology of willingness to pay for symptom relief, the additional economic burden of skin disease on quality of life amounted to an estimated 56.2 billion dollars. Including the economic burden on quality of life, the total economic burden of skin disease to the US public in 2004 was approximately 96 billion dollars.

Что известно об эффективности экономических мер, направленных на снижение уровня потребления пищевых продуктов с высоким содержанием насыщенных жиров и других высококалорийных продуктов, для профилактики и лечения ожирения?

Вашему вниманию предлагается синтезированный доклад Сети фактических данных по вопросам здоровья (СФДЗ), в котором обобщаются имеющиеся фактические данные о том, насколько эффективны экономические меры (в том числе налоги, ценовая политика и материальные стимулы) в сдерживании или снижении потребления пищевых продуктов, прежде всего продуктов с высоким содержанием насыщенных жиров и других высококалорийных продуктов. Имеющиеся фактические данные позволяют предположить (но не демонстрируют), что введение экономических инструментов реализации политики, прежде всего в виде налогов и ценовой политики, могло бы снизить уровень потребления пищевых продуктов, в том числе продуктов с высоким содержанием насыщенного жира и других высококалорийных продуктов, и привести к росту объемов покупки здоровых пищевых продуктов. Сеть фактических данных по вопросам здоровья (СФДЗ), работа которой была инициирована и координируется Eвропейским региональным бюро ВОЗ, представляет собой информационную службу для лиц, принимающих решения в области общественного здравоохранения и медицинской помощи, в Европейском регионе ВОЗ. СФДЗ может также быть полезна и другим заинтересованным сторонам.

What is known about the effectiveness of economic instruments to reduce consumption of foods high in saturated fats and other energy-dense foods for preventing and treating obesity?

This is a Health Evidence Network (HEN) synthesis report summarizing the available evidence concerning the effectiveness of economic instruments (including taxes, price policies and incentives) in containing or reducing food consumption, particularly of foods high in saturated fats and other energy-dense foods. Available evidence suggests – but does not demonstrate – that introduction of policy-related economic instruments, particularly in the form of taxes and price policies, could reduce food consumption, including of high saturated fat and other energy-dense foods, and increase the purchasing of healthful foods. HEN, initiated and coordinated by the WHO Regional Office for Europe, is an information service for public health and health care decision-makers in the WHO European Region. Other interested parties might also benefit from HEN.

Насколько эффективными в уменьшении воздействия следующей пандемии гриппа будут стратегии противовирусной вакцинации и профилактики и лечения антивирусными препаратами?

Данный сводный доклад Сети фактических данных по вопросам здоровья (СФДЗ) посвящен вопросу о потенциальной эффективности антивирусной вакцинации и лечебно-профилактического применения антивирусных препаратов для снижения тяжести пандемии гриппа. Пандемия гриппа представляется неизбежной, однако неизвестно будет ли она вызвана вирусом H5N1 или другим вирусом и насколько она будет тяжелой. До момента реального появления вирусного штамма, который вызовет пандемию гриппа, нет возможности получить прямые доказательства эффективности вакцины и стратегий лечебно-профилактического применения антивирусных препаратов для снижения смертности и заболеваемости или для сдерживания или замедления распространения пандемии гриппа. В настоящем сводном докладе СФДЗ обобщены существующие сведения (включая, но не ограниченные документами ВОЗ) и фактические данные, относящиеся к пандемиям гриппа, которые могут быть полезны для руководителей и организаторов здравоохранения. В списке источников приведены ссылки на ряд стратегических документов, содержащих более детальную информацию. Сеть фактических данных по вопросам здоровья (СФДЗ) – это инициированная и координируемая Европейским региональным бюро ВОЗ информационная служба для лиц, ответственных за принятие решений в системах общественного здравоохранения стран Европейского региона ВОЗ. Информация, предоставляемая СФДЗ, может быть полезна и для других заинтересованных сторон.

How effective would antiviral vaccination and antiviral drug prevention and treatment strategies be for reducing the impact of the next influenza pandemic?

This is a Health Evidence Network (HEN) synthesis report on the potential effectiveness of antiviral vaccination and antiviral drug prevention and treatment for reducing the impact of an influenza pandemic. An influenza pandemic seems inevitable, but it is not known whether this will be caused by H5N1 or another virus or how severe it will be. Until the actual emergence of the influenza virus strain responsible for an influenza pandemic, there is no direct evidence of the effectiveness of vaccine and antiviral drug prevention and treatment strategies for lowering mortality and morbidity, or for containing or delaying the spread, of an influenza pandemic. This HEN synthesis report is a summary of existing information (including but not limited to WHO policy documents) and evidence related to influenza pandemics that might be useful to policy-makers. The list of references includes links to several policy documents for further details. HEN, initiated and coordinated by the WHO Regional Office for Europe, is an information service for public health and health care decision-makers in the WHO European Region. Other interested parties might also benefit from HEN.