Impact of including productivity costs in economic analyses of vaccines for C. difficile infections and infant respiratory syncytial virus, in a UK setting.

OBJECTIVES: It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated. METHODS: For two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results. RESULTS: In this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person. CONCLUSIONS: Considering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102.

PURPOSE: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

Estimating the Treatment and Prophylactic Economic Value of New Antimicrobials in Managing Antibiotic Resistance and Serious Infections for Common Pathogens in the USA: A Population Modelling Study.

BACKGROUND: Antimicrobial resistance is a growing public health concern. There is a global need to estimate the population-level value of developing new antimicrobials and to ensure the effective use of existing antimicrobials as strategies to counteract antimicrobial resistance. To this aim, population-level value criteria need to be considered alongside conventional value measures. OBJECTIVE: The objective of this study was to develop a novel modelling approach to estimate the value of new antimicrobials, considering the transmission, diversity and enablement elements of STEDI value. METHODS: We developed a population-based mathematical model for the assessment of antimicrobial value considering both prophylactic use of antimicrobials and the treatment of selected serious hospital-acquired infections in hospitals in the USA at a population level. Large-scale clinical and population healthcare data were used to inform a modelling-based analysis assessing the impact of introducing a new antimicrobial compared with continuing with no new antimicrobial, accounting for the transmission, diversity and enablement value of antimicrobial agents. RESULTS: Over a 10-year period, the addition of a new antimicrobial as part of an antimicrobial stewardship strategy in the USA was estimated to result in a proportional reduction of 9.03% in projected antimicrobial resistance levels. This yielded an estimated reduction of $64.3 million in hospitalization costs and a gain of over 153,000 quality-adjusted life-years at an economic value of over $15.4 billion over 10 years. Considering input uncertainty, the estimate of monetary benefit ranged from $11.1 to $21.4 billion. CONCLUSIONS: The use of a new antimicrobial for treatment and prophylactic indications yields considerable clinical and economic benefits including transmission diversity and enablement value. These findings may provide decision makers with important evidence to support investment in new antimicrobials and antimicrobial stewardship policy that address the patient, population and system burden associated with antimicrobial resistance.

Value assessment of antimicrobials using the STEDI framework - How steady is the outcome?

Antimicrobial resistance (AMR) is one of the major threats to global population health, and the antimicrobial market requires substantial reimbursement reform and/or significant financial incentives to function properly. To address these challenges, England piloted a new health technology evaluation process in conjunction with a new payment model in 2019. The value assessment was performed using a dedicated broader value framework for antibiotics for the first time. This so-called STEDI framework is an acronym based on the five value elements it covers (Spectrum, Transmission, Enablement, Diversity, and Insurance value). Learnings from the pilot show that there are important considerations when implementing this value framework: The STEDI value profile of an antibiotic strongly depends on the local context and is impacted by trade-offs between individual value elements. Decision makers should therefore act carefully when applying STEDI to avoid distorting the overall evaluation result. Considering the STEDI value profile of an antibiotic is an important part of its value assessment as it allows for distinguishing between higher- and lower-value products. However, given the complexities surrounding its value assessment, further research must be undertaken to improve the overall STEDI evaluation process.

Recognizing the Broader Value of Meningococcal Vaccination: A Matter of Evidence, Ability, or Willingness?

OBJECTIVES: It is widely argued that the value of meningococcal vaccination extends beyond the narrow value elements traditionally considered in health technology assessment. Nevertheless, measuring broader value presents challenges, whereas assessment methods and outcomes vary widely. This article investigates the extent to which the broader value of meningococcal vaccination is recognized, considering the available evidence and decision maker's methodological ability and willingness. METHODS: A targeted literature review informed the classification of broader value elements according to their relevance to meningococcal vaccination and the quality of existing evidence. Focusing on relevant value elements with good evidentiary standards, decision makers' perspectives and methodological ability to consider them were assessed through case studies of health technology assessment of meningococcal B vaccination in England and The Netherlands. RESULTS: Value elements of high relevance to meningococcal vaccination with good quality evidence include caregivers' health gains, patients' lifetime productivity gains, and disease severity. The willingness and methodological ability to incorporate them into value assessments have been mixed. This is attributable to the scope of the value assessment perspective and the use of evaluation methods that do not fully capture broader value. For other broader value elements, evidence gaps are another potential barrier to value demonstration and recognition. CONCLUSIONS: The current evidence base confirms that the value of meningococcal vaccination spans beyond healthcare sector effects to health-related externalities, allocative value, and societal economic benefits. To ensure that the most efficient resource allocation outcomes are achieved, countries should consider how to improve their perspective and methodological ability to assess broader value elements accurately.

Progress toward Health System Readiness for Genome-Based Testing in Canada.

(1) Background: Genomic medicine harbors the real potential to improve the health and healthcare journey of patients, care provider experiences, and improve the health system efficiency-even reducing healthcare costs. There is expected to be an exponential growth in medically necessary new genome-based tests and test approaches in the coming years. Testing can also create scientific research and commercial opportunities beyond healthcare decision making. The purpose of this research is to generate a better understanding of Canada's state of readiness for genomic medicine, and to provide some insights for other healthcare systems. (2) Methods: A mixed-methods approach of a review of the literature and key informant interviews with a purposive sample of experts was used. The health system readiness was assessed using a previously published set of conditions. (3) Results: Canada has created some of the established conditions, but further action needs to be taken to improve the state of readiness for genome-based medicine. The important gaps to be filled are the need for linked information systems and data integration; evaluative processes that are timely and transparent; navigational tools for care providers; dedicated funding to facilitate rapid onboarding and support test development and proficiency testing; and broader engagement with innovation stakeholders beyond care providers and patients. These findings highlight the role of the organizational context, social influence, and other factors that are known to affect the diffusion of innovation within health systems.

Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101.

BMT CTN 1101 was a Phase III randomized controlled trial comparing reduced-intensity conditioning followed by double unrelated umbilical cord blood transplantation (UCBT) versus HLA-haploidentical related donor bone marrow transplantation (haplo-BMT) for patients with high-risk hematologic malignancies. Here we report the results of a parallel cost-effectiveness analysis of these 2 hematopoietic stem cell transplantation (HCT) techniques. In this study, 368 patients were randomized to unrelated UCBT (n = 186) or haplo-BMT (n = 182). We estimated healthcare utilization and costs using propensity score-matched haplo-BMT recipients from the OptumLabs Data Warehouse for trial participants age <65 years and Medicare claims for participants age ≥65 years. Weibull models were used to estimate 20-year survival. EQ-5D surveys by trial participants were used to estimate quality-adjusted life-years (QALYs). At a 5-year follow-up, survival was 42% for haplo-BMT recipients versus 36% for UCBT recipients (P = .06). Over a 20-year time horizon, haplo-BMT is expected to be more effective (+.63 QALY) and more costly (+$118,953) for persons age <65 years. For those age ≥65 years, haplo-BMT is expected to be more effective and less costly. In one-way uncertainty analyses, for persons age <65, the cost per QALY result was most sensitive to life-years and health state utilities, whereas for those age ≥65, life- years were more influential than costs and health state utilities. Compared to UCBT, haplo-BMT was moderately more cost-effective for patients age <65 years and less costly and more effective for persons age ≥65 years. Haplo-BMT is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BMT is a preferred choice when considering costs and outcomes.

The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as a Case Study.

Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted, combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements ongoing efforts aimed towards a broader recognition of the full societal value of vaccines.

The Value of Vaccines in Maintaining Health System Capacity in England.

OBJECTIVES: In situations of excess demand for healthcare, treating one patient means losing the opportunity to treat another. Therefore, each decision bears an opportunity cost. Nevertheless, when assessing the value of health technologies, these opportunity costs are not always fully considered. We present a pragmatic approach for conceptualizing vaccines' health system capacity value when considering opportunity costs. METHODS: Our approach proxies opportunity costs through the net monetary benefit forgone as scarce healthcare resources are used to treat a vaccine-preventable disease instead of a patient from the waiting list. We apply this approach to cost the resource "hospital beds" for 3 different scenarios of excess demand. Empirically, we estimate the opportunity costs saved for 4 selected vaccination programs from the national schedule in England during a hypothetical scenario of long-lasting excess demand induced by the pandemic. RESULTS: The opportunity cost avoided through vaccination rises with excess demand for treatment. When treating an acute vaccine-preventable outcome is a suboptimal choice compared with treating elective patients, preventing a vaccine-preventable disease from blocking a hospital bed generates opportunity cost savings of approximately twice the direct costs saved by avoiding vaccine-preventable hospitalizations. CONCLUSIONS: Policy makers should be aware that, in addition to preventing the outcome of interest, vaccines and other preventative health technologies deliver value in maintaining regular healthcare services and clearing the pent-up demand from the pandemic. Therefore, health system capacity value should be a key-value element in health technology assessment. Existing and potential future vaccination programs deliver more value than hitherto quantified.

Effective and Efficient Delivery of Genome-Based Testing-What Conditions Are Necessary for Health System Readiness?

Health systems internationally must prepare for a future of genetic/genomic testing to inform healthcare decision-making while creating research opportunities. High functioning testing services will require additional considerations and health system conditions beyond traditional diagnostic testing. Based on a literature review of good practices, key informant interviews, and expert discussion, this article attempts to synthesize what conditions are necessary, and what good practice may look like. It is intended to aid policymakers and others designing future systems of genome-based care and care prevention. These conditions include creating communities of practice and healthcare system networks; resource planning; across-region informatics; having a clear entry/exit point for innovation; evaluative function(s); concentrated or coordinated service models; mechanisms for awareness and care navigation; integrating innovation and healthcare delivery functions; and revisiting approaches to financing, education and training, regulation, and data privacy and security. The list of conditions we propose was developed with an emphasis on describing conditions that would be applicable to any healthcare system, regardless of capacity, organizational structure, financing, population characteristics, standardization of care processes, or underlying culture.

Towards a Broader Assessment of Value in Vaccines: The BRAVE Way Forward.

BACKGROUND: The COVID-19 pandemic shows that the impact of effective vaccines can extend well beyond vaccinated individuals and healthcare systems. Yet, these broader value elements are not typically considered in Health Technology Assessment (HTA) which may underestimate vaccines' broader value. OBJECTIVES: This study aimed to (1) describe the gap between broader value elements identified in value frameworks for vaccines and those recognised in HTA of vaccines in nine developed markets, and (2) develop expert-informed, consensus-based recommendations on how hurdles for broader value recognition could be overcome. METHODS: We used a four-step modified Delphi method consisting of literature research (phase I, pearl-growing approach using PubMed Web of Science and Google covering the years 2000-2019), two consecutive phases of expert elicitation (phase II and III, including two email surveys and one virtual round table with 10 experts from 9 countries) and synthesis of recommendations (phase IV). RESULTS: Results show that about half of the broader value elements relevant to vaccines are not (consistently) considered in HTA processes of multiple higher-income countries. Experts identified five priority areas for broader value recognition, including considering (1) more comprehensive cost offsets within the health care system, (2) carer quality of life, (3) transmission value, (4) prevention of antimicrobial resistance and (5) macroeconomic effects. CONCLUSION: To achieve a broader recognition of the value of vaccines, a three-pronged approach was recommended, focusing on (1) Evidence: proactively steering generation of high-quality evidence to quantify the broader value of vaccines to society; (2) Ability: leveraging and further developing existing methodological and analytic expertise to appropriately recognise the broad value of vaccines within HTA processes; (3) Willingness: Stimulating stakeholder engagement to change the status quo and move towards more transparent and comprehensive value assessment processes for vaccines globally.

Realising the broader value of vaccines in the UK.

Many health technology assessment (HTA) agencies limit their assessments of vaccines to the health benefits for the vaccinated individual, the costs associated with vaccine administration and the disease avoided. However, because the value of vaccines tends to accrue to a large extent beyond the vaccinated individual, they are systematically undervalued in many current HTA processes. This is also the case in the UK, where the Joint Committee on Vaccination and Immunisation (JCVI) is in charge of assessing preventative vaccines, while therapeutic vaccines fall in the realm of the National Institute for Clinical Excellence (NICE). To contribute to a forward-looking perspective, we designed a framework to capture the broader value of vaccination. We reviewed the current state of the global vaccines pipeline and selected seven preventative and three therapeutic vaccines that are likely to enter the UK market within five years. We assessed on which value elements the selected vaccines would potentially generate value, and compared those against the novel broader value framework. A review of the current value elements considered by the JCVI and NICE allowed identifying the critical gaps between potential value generation and value recognition. To our knowledge, this is the first time that the broader value of vaccination has been pro-actively assessed for pipeline vaccinations. Our findings show that the existing narrow evaluation frameworks are likely to systematically undervalue the value of potential future vaccines coming to the UK market. This is particularly relevant, where their impact on AMR and other health interventions, and on the productivity of the workforce is of concern. Recommendations to overcome this include an explicit and more consistent inclusion of, and data collection on, the impact of vaccines on AMR and other health interventions by JCVI and NICE; the consideration of a societal perspective and the fiscal impact of vaccines to societies.

Value of Information Analytical Methods: Report 2 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

The allocation of healthcare resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities and of the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using value of information (VOI) analysis. This report from the ISPOR VOI Task Force describes methods for computing 4 VOI measures: the expected value of perfect information, expected value of partial perfect information (EVPPI), expected value of sample information (EVSI), and expected net benefit of sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted.

Value of Information Analysis for Research Decisions-An Introduction: Report 1 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

Healthcare resource allocation decisions made under conditions of uncertainty may turn out to be suboptimal. In a resource constrained system in which there is a fixed budget, these suboptimal decisions will result in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to make better resource allocation decisions. This value can be quantified using a value of information (VOI) analysis. This report, from the ISPOR VOI Task Force, introduces VOI analysis, defines key concepts and terminology, and outlines the role of VOI for supporting decision making, including the steps involved in undertaking and interpreting VOI analyses. The report is specifically aimed at those tasked with making decisions about the adoption of healthcare or the funding of healthcare research. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing the results of VOI analyses.

Cost-Effectiveness Analysis of a Procalcitonin-Guided Decision Algorithm for Antibiotic Stewardship Using Real-World U.S. Hospital Data.

Medical decision-making is revolutionizing with the introduction of artificial intelligence and machine learning. Yet, traditional algorithms using biomarkers to optimize drug treatment continue to be important and necessary. In this context, early diagnosis and rational antimicrobial therapy of sepsis and lower respiratory tract infections (LRTI) are vital to prevent morbidity and mortality. In this study we report an original cost-effectiveness analysis (CEA) of using a procalcitonin (PCT)-based decision algorithm to guide antibiotic prescription for hospitalized sepsis and LRTI patients versus standard care. We conducted a CEA using a decision-tree model before and after the implementation of PCT-guided antibiotic stewardship (ABS) using real-world U.S. hospital-specific data. The CEA included societal and hospital perspectives with the time horizon covering the length of hospital stay. The main outcomes were average total costs per patient, and numbers of patients with Clostridium difficile and antibiotic resistance (ABR) infections. We found that health care with the PCT decision algorithm for hospitalized sepsis and LRTI patients resulted in shorter length of stay, reduced antibiotic use, fewer mechanical ventilation days, and lower numbers of patients with C. difficile and ABR infections. The PCT-guided health care resulted in cost savings of $25,611 (49% reduction from standard care) for sepsis and $3630 (23% reduction) for LRTI, on average per patient. In conclusion, the PCT decision algorithm for ABS in sepsis and LRTI might offer cost savings in comparison with standard care in a U.S. hospital context. To the best of our knowledge, this is the first health economic analysis on PCT implementation using U.S. real-world data. We suggest that future CEA studies in other U.S. and worldwide settings are warranted in the current age when PCT and other decision algorithms are increasingly deployed in precision therapeutics and evidence-based medicine.

Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer.

BACKGROUND: Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib. OBJECTIVE: To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial. METHODS: A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty. RESULTS: Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311. CONCLUSIONS: Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature. DISCLOSURES: No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.

Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States.

INTRODUCTION: While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective. METHODS: We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs. CONCLUSION: Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

Cost Effectiveness of Multigene Panel Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: Compared with single-marker genetic testing (SMGT), multigene panel sequencing (MGPS) has the potential to identify more patients with cancer who could benefit from targeted therapies, but the effects on outcome and total cost of care are uncertain. Our goal was to estimate the clinical and cost effectiveness of MGPS versus SMGT among patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: Patients with aNSCLC-stage IIIB or metastatic-who were diagnosed between 2011 and 2016 were identified from the Flatiron Health database. After stratifying patients into MGPS or SMGT cohorts, we analyzed the percentage of patients who received targeted treatment, survival, and total costs of care. SMGT included epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase testing. MGPS also allowed for the detection of BRAF, RET, ROS1, HER2, and MET mutations. Cost data sources were the Centers for Medicare & Medicaid Services Fee Schedule and 2017 average sales price drug cost. We estimated the incremental cost-effectiveness ratio from a US payer perspective over a lifetime horizon using a decision model. RESULTS: We identified 5,688 patients with aNSCLC who received MGPS (n = 875) or SMGT (n = 4,813), of which 22% tested positive for epidermal growth factor receptor (18.5% MGPS; 17.3% SMGT) or anaplastic lymphoma kinase (3.59% MGPS; 3.78% SMGT). Among MGPS-tested patients, an additional 8% were found to have BRAF, RET, ROS1, HER2, or MET mutations. Of MGPS-tested patients, 21% received treatments that were targeted to the specific mutations versus 19% with SMGT. Expected survival was 1.14 life years (LYs) in SMGT versus 1.20 LYs in MGPS. Lifetime total costs were $8,814 higher per patient for MGPS. The incremental cost-effectiveness ratio of MGPS versus SMGT was $148,478 per LY gained. CONCLUSION: On the basis of data from a nationwide oncology patient database, MGPS is shown to have moderate cost effectiveness compared with SMGT in patients with aNSCLC.