Cost-effectiveness of Mechanical Thrombectomy More Than 6 Hours After Symptom Onset Among Patients With Acute Ischemic Stroke.

Importance: Two 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States. Objective: To compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset. Design, Setting, and Participants: This economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions. Data analysis was conducted from July 2018 to October 2019. Exposures: MT with SMC in the extended treatment window vs SMC alone. Main Outcomes and Measures: Expected costs and quality-adjusted life-years (QALYs) during lifetime were estimated. Deterministic results (incremental costs and effectiveness, incremental cost-effectiveness ratios, and net monetary benefit) were presented, and probabilistic analyses were performed for the total populations and 27 patient subgroups. Results: In the DAWN study, the MT group had a mean (SD) age of 69.4 (14.1) years and 42 of 107 (39.3%) were men, and the control group had a mean (SD) age of 70.7 (13.2) years and 51 of 99 (51.5%) were men. In the DEFUSE 3 study, the MT group had a median (interquartile range) age of 70 (59-79) years, and 46 of 92 (50.0%) were men, and the control group had a median (interquartile range) age of 71 (59-80) years, and 44 of 90 (48.9%) were men. For the total trial population, incremental cost-effectiveness ratios were $662/QALY and $13 877/QALY based on the DAWN and DEFUSE 3 trials, respectively. MT with SMC beyond 6 hours had a probability greater than 99.9% of being cost-effective vs SMC alone at a willingness-to-pay threshold of $100 000/QALY. Subgroup analyses showed a wide range of probabilities for MT with SMC to be cost-effective at a willingness-to-pay threshold of $50 000/QALY, with the greatest uncertainty observed for patients with a National Institute of Health Stroke Scale score of at least 16 and for those aged 80 years or older. Conclusions and Relevance: The results of this study suggest that late MT added to SMC is cost-effective in all subgroups evaluated in the DAWN and DEFUSE 3 trials, with most results being robust in probabilistic sensitivity analyses. Future MT evidence-gathering could focus on older patients and those with National Institute of Health Stroke Scale scores of 16 and greater.

Impact of hospitalisation on health-related quality of life in patients with chronic heart failure.

BACKGROUND: Empirical identification of the direct impact of hospitalisation in the change in utility could provide an interpretation for some of the unexplained variance in quality of life responses in clinical practice and clinical trials and provide assistance to researchers in assessing the impact of a hospitalisation in the context of economic evaluations. This study had the goal of determining the impact of nonfatal hospitalisations on the quality of life of a cohort of patients previously diagnosed with heart failure by using their quality of life measurements before and after hospitalisation. METHODS: The impact of hospitalisation on health-related quality of life was estimated by calculating the difference in utility measured using the EQ-5D-3L in patients that were hospitalised and had records of utility before and after hospitalisation. The variation in differences between the utilities pre and post hospitalisation was explained through two multiple linear regression models using (1) the individual patient characteristics and (2) the hospitalisation characteristics as explanatory variables. RESULTS: The mean difference between health-related quality of life measurement pre and post hospitalisation was found to be 0.020 [95% CI: - 0.020, 0.059] when measured with the EQ-5D index, while there was a mean decrease of - 0.012 [95% CI: - 0.043, 0.020] in the utility measured with the visual analogue scale. Differences in utility variation according to the primary cause for hospitalisation were found. Regression models showed a statistically significant impact of body mass index and serum creatinine in the index utility differences and of serum creatinine for utilities measured with the visual analogue scale. CONCLUSIONS: Knowing the impact of hospitalisation on health-related quality of life is particularly relevant for informing cost-effectiveness studies designed to assess health technologies aimed at reducing hospital admissions. Through using patient-level data it was possible to estimate the variation in utilities before and after the average hospitalisation and for hospitalisations due to the most common causes for hospital admission. These estimates for (dis) utility could be used in the calculations of effectiveness on economic evaluations, especially when discrete event simulations are the employed modelling technique.

A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa-coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon.

BACKGROUND: Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. METHODS: Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. RESULTS: The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively. CONCLUSIONS: TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

TECH-VER: A Verification Checklist to Reduce Errors in Models and Improve Their Credibility.

BACKGROUND: In health economic literature, checklists or best practice recommendations on model validation/credibility always declare verification of the programmed model as a fundamental step, such as 'is the model implemented correctly and does the implementation accurately represent the conceptual model?' However, to date, little operational guidance for the model verification process has been given. In this study, we aimed to create an operational checklist for model users or reviewers to verify the technical implementation of health economic decision analytical models and document their verification efforts. METHODS: Literature on model validation, verification, programming errors and credibility was reviewed systematically from scientific databases. An initial beta version of the checklist was developed based on the checklists/tests identified from the literature and from authors' previous modeling/appraisal experience. Next, the first draft checklist was presented to a number of health economists on several occasions and was tested on different models (built in different software, developed by different stakeholders, including drug manufacturers, consultancies or academia), each time leading to an update of the checklist and culminating in the final version of the TECHnical VERification (TECH-VER) checklist, introduced in this paper. RESULTS: The TECH-VER necessitates a model reviewer (preferably independent), an executable and transparent model, its input sources, and detailed documentation (e.g. technical report/scientific paper) in which the conceptual model, its implementation, programmed model inputs, and results are reported. The TECH-VER checklist consists of five domains: (1) input calculations; (2) event-state (patient flow) calculations; (3) result calculations; (4) uncertainty analysis calculations; and (5) other overall checks (e.g. validity or interface). The first four domains reflect the verification of the components of a typical health economic model. For these domains, as a prerequisite of verification tests, the reviewer should identify the relevant calculations in the electronic model and assess the provided justifications for the methods used in the identified calculations. For this purpose, we recommend completeness/consistency checks. Afterwards, the verification tests can be conducted for the calculations in each of these stages by checking the correctness of the implementation of these calculations. For this purpose, the following type of tests are recommended in consecutive order: (i) black-box tests, i.e. checking if model calculations are in line with a priori expectations; (ii) white-box testing, i.e. going through the program code details line by line, or cell by cell (recommended for some crucial calculations and if there are some unexpected results from the black-box tests); and (iii) model replication/parallel programming (recommended only in certain situations, and if the issues related to the identified unexpected results from black-box tests could not be resolved through white-box testing). To reduce the time burden of model verification, we suggest a hierarchical order in tests i-iii, where going to the next step is necessary when the previous step fails. CONCLUSIONS: The TECH-VER checklist is a comprehensive checklist for the technical verification of decision analytical models, aiming to help identify model implementation errors and their root causes while improving the transparency and efficiency of the verification efforts. In addition to external reviews, we consider that the TECH-VER can be used as an internal training and quality control tool for new health economists, while developing their initial models. It is the authors' aim that the TECH-VER checklist transforms itself to an open-source living document, with possible future versions, or 'bolt-on' extensions for specific applications with additional 'fit-for-purpose' tests, as well as 'tips and tricks' and some demonstrative error examples. For this reason, the TECH-VER checklist and the list of black-box tests created in this paper and a few model verification examples is uploaded to an open access, online platform (github and the website of the institute), where other users will also be able to upload their original verification efforts and tests.

Systematic reviews as a "lens of evidence": Determinants of cost-effectiveness of breast cancer screening.

Systematic reviews with economic components are important decision tools for stakeholders seeking to evaluate technologies, such as breast cancer screening (BCS) programs. This overview of systematic reviews explores the determinants of the cost-effectiveness of BCS and assesses the quality of secondary evidence. The search identified 30 systematic reviews that reported on the determinants of the cost-effectiveness of BCS, including the costs of breast cancer and BCS. While the quality of the reviews varied widely, only four out of 30 papers were considered to be of a high quality. We did not identify publication bias in the original evidence on the cost-effectiveness of mammography screening; however, we highlight a need for improved clarity in both reporting and data verification. The reviews consisted mainly of studies from high-income countries. Breast cancer costs varied widely among the studies. Factors leading to higher costs included: time (diagnosis and last months before death), later stage or metastases, recurrence of the disease, age below 64 years and type of follow-up (more intensive or more specialized). Overall, screening with mammography was considered cost-effective in the age range 50-69 years in Western European and Northern American countries but not for older or younger women. Its cost-effectiveness was questionable for low-income settings and Asia. Mammography screening was more cost-effective with biennial screening compared to annual screening and single reading using computer-aided detection vs double reading. No information on the cost-effectiveness of ultrasonography was found, and there is much uncertainty on the cost-effectiveness of CBE because of methodological limitations.

Exploring the Cost-Effectiveness of Mechanical Thrombectomy Beyond 6 Hours Following Advanced Imaging in the United Kingdom.

Background and Purpose- In the United Kingdom, mechanical thrombectomy (MT) for acute ischemic stroke patients assessed beyond 6 hours from symptom onset will be commissioned up to 12 hours provided that advanced imaging (AdvImg) demonstrates salvageable brain tissue. While the accuracy of AdvImg differs across technologies, evidence is limited regarding the proportion of patients who would benefit from late MT. We compared the cost-effectiveness of 2 care pathways: (1) MT within and beyond 6 hours based on AdvImg selection versus (2) MT only within 6 hours based on conventional imaging selection. The impact of varying AdvImg accuracy and prior probability for acute ischemic stroke patients to benefit from late MT was assessed. Methods- A decision tree and a Markov trace were developed. A hypothetical United Kingdom cohort of suspected stroke patients aged 71 years with first event was modeled. Costs, health outcomes, and probabilities were obtained from the literature. Outcomes included costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Probabilistic sensitivity analyses were performed. Various scenarios with prior probabilities of 10%, 20%, and 30%, respectively, for acute ischemic stroke patients to benefit from late MT, and with perfect accuracy, 80% sensitivity, and 70% specificity of AdvImg were studied. Results- Incremental cost-effectiveness ratios resulting from our deterministic analyses varied from $8199 (£6164) to $49 515 (£37 229) per QALY gained. AdvImg accuracy impacted the incremental cost-effectiveness ratio only when its specificity decreased. Over lifetime horizons, all scenarios including late MT improved QALYs and LYs. Depending on the scenario, the probabilistic sensitivity analyses showed probabilities varying between 46% and 93% for the late MT pathway to be cost-effective at a willingness to pay threshold of $39 900 (£30 000) per QALY. Conclusions- Late MT based on AdvImg selection may be good value for money. However, additional data regarding the implementation of AdvImg and prior probability to benefit from late MT are needed before its cost-effectiveness can be fully assessed.

Value of information analysis in telehealth for chronic heart failure management.

OBJECTIVES: Value of information (VOI) analysis provides information on opportunity cost of a decision in healthcare by estimating the cost of reducing parametric uncertainty and quantifying the value of generating additional evidence. This study is an application of the VOI methodology to the problem of choosing between home telemonitoring and nurse telephone support over usual care in chronic heart failure management in the Netherlands. METHODS: The expected value of perfect information (EVPI) and the expected value of partially perfect information (EVPPI) analyses were based on an informal threshold of €20K per quality-adjusted life-year. These VOI-analyses were applied to a probabilistic Markov model comparing the 20-year costs and effects in three interventions. The EVPPI explored the value of decision uncertainty caused by the following group of parameters: treatment-specific transition probabilities between New York Heart Association (NYHA) defined disease states, utilities associated with the disease states, number of hospitalizations and ER visits, health state specific costs, and the distribution of patients per NYHA group. We performed the analysis for two population sizes in the Netherlands-patients in all NYHA classes of severity, and patients in NYHA IV class only. RESULTS: The population EVPI for an effective population of 2,841,567 CHF patients in All NYHA classes of severity over the next 20 years is more than €4.5B, implying that further research is highly cost-effective. In the NYHA IV only analysis, for the effective population of 208,003 patients over next 20 years, the population EVPI at the same informal threshold is approx. €590M. The EVPPI analysis showed that the only relevant group of parameters that contribute to the overall decision uncertainty are transition probabilities, in both All NYHA and NYHA IV analyses. CONCLUSIONS: Results of our VOI exercise show that the cost of uncertainty regarding the decision on reimbursement of telehealth interventions for chronic heart failure patients is high in the Netherlands, and that future research is needed, mainly on the transition probabilities.

Integrating clinical and economic evidence in clinical guidelines: More needed than ever!

RATIONALE, AIMS, AND OBJECTIVES: In recent years, several expensive new health technologies have been introduced. The availability of those technologies intensifies the discussion regarding the affordability of these technologies at different decision-making levels. On the meso level, both hospitals and clinicians are facing budget constraints resulting in a tension to balance between different patients' interests. As such, it is crucial to make optimal use of the available resources. Different strategies are in place to deal with this problem, but decisions on a macro level on what to fund or not can limit the role and freedom of clinicians in their decisions on a micro level. At the same time, without central guidance regarding such decisions, micro level decisions may lead to inequities and undesirable treatment variation between clinicians and hospitals. The challenge is to find instruments that can balance both levels of decision making. DISCUSSION: Clinicians are becoming increasingly aware that their decisions to spend more resources (like time and budget) on 1 particular patient group reduce the resources available to other patients. Involving clinicians in thinking about the optimal use of limited resources, also in an attempt to bridge the world of economic reasoning and clinical practice, is crucial therefore. We argue that clinical guidelines may prove a clear vehicle for this by including both clinical and economic evidence to support the recommendations made. The development of such guidelines requires cooperation of clinicians, and health economists are cooperating with each other. CONCLUSION: The development of clinical guidelines which combine economic and clinical evidence should be stimulated, to balance central guidance and uniformity while maintaining necessary decentralized freedom. This is an opportunity to combine the reality of budgets and opportunity costs with clinical practice. Missing this opportunity risks either variation and inequity or central and necessarily crude measures.

Economic Analysis of Vaccination Programs: An ISPOR Good Practices for Outcomes Research Task Force Report.

This report provides recommendations for budget holders and decision makers in high-, middle, and low-income countries requiring economic analyses of new vaccination programs to allocate scarce resources given budget constraints. ISPOR's Economic Evaluation of Vaccines Designed to Prevent Infectious Disease: Good Practices Task Force wrote guidelines for three analytic methods and solicited comments on them from external reviewers. Cost-effectiveness analyses use decision-analytic models to estimate cumulative changes in resource use, costs, and changes in quality- or disability-adjusted life-years attributable to changes in disease outcomes. Constrained optimization modeling uses a mathematical objective function to be optimized (e.g. disease cases avoided) for a target population for a set of interventions including vaccination programs within established constraints. Fiscal health modeling estimates changes in net present value of government revenues and expenditures attributable to changes in disease outcomes. The task force recommends that those designing economic analyses for new vaccination programs take into account the decision maker's policy objectives and country-specific decision context when estimating: uptake rate in the target population; vaccination program's impact on disease cases in the population over time using a dynamic transmission epidemiologic model; vaccination program implementation and operating costs; and the changes in costs and health outcomes of the target disease(s). The three approaches to economic analysis are complementary and can be used alone or together to estimate a vaccination program's economic value for national, regional, or subregional decision makers in high-, middle-, and low-income countries.

Cost-Effectiveness Analysis in Telehealth: A Comparison between Home Telemonitoring, Nurse Telephone Support, and Usual Care in Chronic Heart Failure Management.

OBJECTIVES: To assess the cost effectiveness of home telemonitoring (HTM) and nurse telephone support (NTS) compared with usual care (UC) in the management of patients with chronic heart failure, from a third-party payer's perspective. METHODS: We developed a Markov model with a 20-year time horizon to analyze the cost effectiveness using the original study (Trans-European Network-Home-Care Management System) and various data sources. A probabilistic sensitivity analysis was performed to assess the decision uncertainty in our model. RESULTS: In the original scenario (which concerned the cost inputs at the time of the original study), HTM and NTS interventions yielded a difference in quality-adjusted life-years (QALYs) gained compared with UC: 2.93 and 3.07, respectively, versus 1.91. An incremental net monetary benefit analysis showed €7,697 and €13,589 in HTM and NTS versus UC at a willingness-to-pay (WTP) threshold of €20,000, and €69,100 and €83,100 at a WTP threshold of €80,000, respectively. The incremental cost-effectiveness ratios were €12,479 for HTM versus UC and €8,270 for NTS versus UC. The current scenario (including telenurse cost inputs in NTS) yielded results that were slightly different from those for the original scenario, when comparing all New York Heart Association (NYHA) classes of severity. NTS dominated HTM, compared with UC, in all NYHA classes except NYHA IV. CONCLUSIONS: This modeling study demonstrated that HTM and NTS are viable solutions to support patients with chronic heart failure. NTS is cost-effective in comparison with UC at a WTP of €9000/QALY or higher. Like NTS, HTM improves the survival of patients in all NYHA classes and is cost-effective in comparison with UC at a WTP of €14,000/QALY or higher.

Socioeconomic benefit to individuals of achieving 2020 targets for four neglected tropical diseases controlled/eliminated by innovative and intensified disease management: Human African trypanosomiasis, leprosy, visceral leishmaniasis, Chagas disease.

BACKGROUND: The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). METHODS: A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011-2020 and 2021-2030. The ideal scenario in which the WHO's 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. RESULTS: The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 -I$ 34.0) billion in 2011-2020 and I$ 35.9 (I$ 25.0 -I$ 51.9) billion in 2021-2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 -US$ 15.7) and US$ 16.6 billion (US$ 11.6 -US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. CONCLUSIONS: We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world's prosperity more equitably and reduce inequity.

Health care input constraints and cost effectiveness analysis decision rules.

Results of cost effectiveness analyses (CEA) studies are most useful for decision makers if they face only one constraint: the health care budget. However, in practice, decision makers wishing to use the results of CEA studies may face multiple resource constraints relating to, for instance, constraints in health care inputs such as a shortage of skilled labour. The presence of multiple resource constraints influences the decision rules of CEA and limits the usefulness of traditional CEA studies for decision makers. The goal of this paper is to illustrate how results of CEA can be interpreted and used in case a decision maker faces a health care input constraint. We set up a theoretical model describing the optimal allocation of the health care budget in the presence of a health care input constraint. Insights derived from that model were used to analyse a stylized example based on a decision about a surgical robot as well as a published cost effectiveness study on eye care services in Zambia. Our theoretical model shows that applying default decision rules in the presence of a health care input constraint leads to suboptimal decisions but that there are ways of preserving the traditional decision rules of CEA by reweighing different cost categories. The examples illustrate how such adjustments can be made, and makes clear that optimal decisions depend crucially on such adjustments. We conclude that it is possible to use the results of cost effectiveness studies in the presence of health care input constraints if results are properly adjusted.

What are the images used to diagnose and assess suspected strokes?: A systematic literature review of care in four European countries.

INTRODUCTION: The cost-effectiveness of clinical interventions is often assessed using current care as comparator. However, evidence suggests practice variation in stroke imaging across countries. For the purpose of feeding into cost-effectiveness analysis, this research aims to describe the patterns of stroke imaging, examine practice variations across countries and, as such, obtain results reflecting current care. AREAS COVERED: A systematic literature review was conducted to identify original studies reporting the imaging workup used in acute stroke care in clinical practice in Hungary, Germany, Sweden and the UK. Information regarding the type and frequency of stroke imaging was analysed. Computed Tomography (CT) was reported as the main diagnostic imaging modality used in stroke care (78-98% across patient profiles and time periods). This review revealed patterns that were not observed in individual studies. Comparisons of UK studies revealed considerable variations in the proportion of scanned patients and timing of imaging. EXPERT COMMENTARY: While the evidence about thrombectomy is difficult to translate in clinical practice, the evidence regarding the optimal imaging approach to diagnose stroke patients is lacking. The heterogeneity in stroke imaging reinforces the need to compare the quality of stroke care within and between countries.

Early warning systems for the management of chronic heart failure: a systematic literature review of cost-effectiveness models.

INTRODUCTION: Describing the general and methodological characteristics of decision-analytical models used in the economic evaluation of early warning systems for the management of chronic heart failure patients and performing a quality assessment of their methodological characteristics is expected to provide concise and useful insight to inform the future development of decision-analytical models in the field of heart failure management. AREAS COVERED: The literature on decision-analytical models for the economic evaluation of early warning systems for the management of chronic heart failure patients was systematically reviewed. Nine electronic databases were searched through the combination of synonyms for heart failure and sensitive filters for cost-effectiveness and early warning systems. EXPERT COMMENTARY: The retrieved models show some variability with regards to their general study characteristics. Overall, they display satisfactory methodological quality, even though some points could be improved, namely on the consideration and discussion of any competing theories regarding model structure and disease progression, identification of key parameters and the use of expert opinion, and uncertainty analyses. A comprehensive definition of early warning systems and further research under this label should be pursued. To improve the transparency of economic evaluation publications, authors should make available detailed technical information regarding the published models.

Assessment of a Business-to-Consumer (B2C) model for Telemonitoring patients with Chronic Heart Failure (CHF).

BACKGROUND: The purpose of this study is to assess the Business-to-Consumer (B2C) model for telemonitoring patients with Chronic Heart Failure (CHF) by analysing the value it creates, both for organizations or ventures that provide telemonitoring services based on it, and for society. METHODS: The business model assessment was based on the following categories: caveats, venture type, six-factor alignment, strategic market assessment, financial viability, valuation analysis, sustainability, societal impact, and technology assessment. The venture valuation was performed for three jurisdictions (countries) - Singapore, the Netherlands and the United States - in order to show the opportunities in a small, medium-sized, and large country (i.e. population). RESULTS: The business model assessment revealed that B2C telemonitoring is viable and profitable in the Innovating in Healthcare Framework. Analysis of the ecosystem revealed an average-to-excellent fit with the six factors. The structure and financing fit was average, public policy and technology alignment was good, while consumer alignment and accountability fit was deemed excellent. The financial prognosis revealed that the venture is viable and profitable in Singapore and the Netherlands but not in the United States due to relatively high salary inputs. CONCLUSIONS: The B2C model in telemonitoring CHF potentially creates value for patients, shareholders of the service provider, and society. However, the validity of the results could be improved, for instance by using a peer-reviewed framework, a systematic literature search, case-based cost/efficiency inputs, and varied scenario inputs.

Epidemiology and Management of Atrial Fibrillation and Stroke: Review of Data from Four European Countries.

In Europe, 1-3% of the population suffers from atrial fibrillation (AF) and has increased stroke risk. By 2060 a doubling in number of cases and great burden in managing this medical condition are expected. This paper offers an overview of data on epidemiology and management of AF and stroke in four European countries as well as the interconnection between these dimensions. A search index was developed to access multiple scientific and "grey" literatures. Information was prioritised based on strength of evidence and date. Information on country reports was double-checked with national experts. The overall prevalence of AF is consistent across countries. France has the lowest stroke incidence and mortality, followed by Netherland and UK, while Romania has higher rates. GPs or medical specialists are responsible for AF treatment; exception are the special thrombosis services in the Netherlands. Prevention measurements are only present in UK through screening programs. Although international and national guidelines are available, undertreatment is present in all countries. Despite differences in healthcare systems and management of AF, epidemiology is comparable between three of the countries. Romania is an outlier, by being limited in data accessibility. This knowledge can contribute to improved AF care in Europe.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

BACKGROUND: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. METHODS: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. RESULTS: The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. CONCLUSION: Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world's prosperity and reduce inequity.

Patients' preferences and economic considerations play an important role in treatment decisions: a discrete choice experiment among rheumatologists.

OBJECTIVE: To evaluate to what extent rheumatologists consider economic aspects and patients' preferences when choosing drug treatments in patients with active RA. METHODS: In a discrete choice experiment, rheumatologists were asked to choose between two unlabelled drug treatment options for a hypothetical RA patient with moderate disease activity who failed two synthetic DMARDs. Attributes and levels of drug treatments were selected based on existing literature, rheumatologists' opinion and expert consensus. This resulted in five attributes each described by three levels: efficacy (level of improvement and achieved state on DAS28), safety (probability of a serious adverse event), patients' preference (level of agreement), annual medication costs and cost-effectiveness (incremental cost-effectiveness ratio). An efficient experimental design generated 14 treatment choices and a random parameter logit model estimated the relative importance of attributes. RESULTS: Sixty-three rheumatologists from the Netherlands contributed to the analysis; 44% were female and mean (sd) age was 49 (8) years. Drug efficacy had the strongest relative contribution to the drug choice (44%) followed by medication costs (24%), patients' preference (17%) and cost-effectiveness (14%). Patients' preferences were most relevant when patients disliked a proposed treatment. The risk of serious but uncommon or rare side effects only played a minor role in the treatment choice (1%). CONCLUSION: In addition to drug efficacy, rheumatologists account for economic aspects and for patients' preferences when deciding on drugs. Decisions are more influenced by absolute costs than relative cost-effectiveness and by patients' disliking as opposed to favouring the treatment.

Abiraterone Acetate for the Treatment of Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspective of an NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited Janssen, the company manufacturing abiraterone acetate (AA; tradename Zytiga®), to submit evidence for the clinical and cost effectiveness of AA in combination with prednisone/prednisolone (AAP) compared with watchful waiting (i.e. best supportive care [BSC]) for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG report, subsequent addenda, and the development of the NICE guidance for the use of this drug in England and Wales by the Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost effectiveness of AAP based on the CS. An important question in this appraisal was, according to the ERG, whether AAP followed by docetaxel is more effective than BSC followed by docetaxel. In the COU-AA-302 trial, 239 of 546 (43.8 %) AAP patients and 304 of 542 (56.1 %) BSC patients received docetaxel as subsequent therapy, following AA or placebo. The results for this specific group of patients were not presented in the CS; therefore, the ERG asked the company to provide these data in the clarification letter; however, these data were presented as commercial-in-confidence and cannot therefore be reported here. The ERG's critical assessment of the company's economic evaluation highlighted a number of concerns, including (a) not using the intention-to-treat (ITT) population; (b) inconsistencies in estimating prediction equations; (c) not fully incorporating the impact of adverse events; (d) incorrectly incorporating the new patient access scheme (PAS); and (e) the assumption that AA non-compliance leads to recoverable drug costs. Although some of these issues were adjusted in the ERG base case, the ERG could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. With the exception of the ERG's preference for using the ITT population, the AC agreed with the approach taken in the ERG base case. The original company and ERG base-case incremental cost-effectiveness ratios (ICERs) were £46,722 and £57,688 per QALY gained, respectively; these changed to £28,563 and £38,061 per QALY gained, respectively, in the revised base cases applying a new PAS. Regarding the end-of-life criteria, after 24 months approximately 63 % of patients in the control group of the COU-AA-302 trial were still alive, and the median survival was 30.1 months (95 % CI 27.3-34.1). Therefore, it is unlikely that life expectancy would be less than 24 months. The AC stated that the most plausible ICER is likely between £28,600 and £32,800 per QALY gained, and concluded that AAP at this stage in the treatment pathway did not meet the end-of-life criterion for short life expectancy. Moreover, in March 2016, the AC produced the final guidance, stating that AAP is recommended, within its marketing authorisation, as an option for treating mCRPC.

Using meta-regression analyses in addition to conventional systematic review methods to examine the variation in cost-effectiveness results - a case study.

BACKGROUND: Systematic reviews of cost-effectiveness analyses summarize results and describe study characteristics. Variability in the study results is often explained qualitatively or based on sensitivity analyses of individual studies. However, variability due to input parameters and study characteristics (e.g., funding or study quality) is often not statistically explained. As a case study, a systematic review on the cost-effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) using meta-regression analyses is performed to explore the usefulness of such methods compared with conventional review methods. METHODS: We attempted to identify and review all modelling studies published until January 2012 that compared costs and consequences of DES versus BMS. We extracted general study information (e.g., funding), modelling methods, values of input parameters, and quality of the model using the Philips et al. checklist. Associations between study characteristics and the incremental costs and effectiveness of individual analyses were explored using regression analyses corrected for study ID. RESULTS: Sixteen eligible studies were identified, with a combined total of 508 analyses. The overall quality of the models was moderate (59% ± 15%). This study showed associations (e.g., type of lesion) that were expected (based on individual studies), however the meta-regression analyses revealed also unpredicted associations: e.g., model quality was negatively associated with repeat revascularizations avoided. CONCLUSIONS: Meta-regressions can be of added value, identifying significant associations that could not be identified using conventional review methods or by sensitivity analyses of individual studies. Furthermore, this study underlines the need to examine input parameters and perform a quality check of studies when interpreting the results.