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In the developed world, the demand for healthcare is rising faster than supply, so that governments are faced with the need to allocate limited resources for maximum benefit. Many governments are responding to these pressures by developing health technology assessment agencies, which evaluate the cost effectiveness of new pharmaceutical and medical products relative to existing interventions. In England and Wales, the agency concerned with health technology assessment is the National Institute for Clinical Excellence (NICE). NICE brings together evidence of clinical and cost effectiveness to judge the value of the treatment relative to alternative uses of National Health Service (NHS) resources and makes recommendations on use of the treatment by the NHS in England and Wales. NICE evaluates technologies where they may result in significant impact on NHS resources or key healthcare policy. The health technology assessment includes a review of the clinical effectiveness, cost effectiveness and service impact of the technology under consideration. This health technology assessment report, together with submissions from the technology manufacturer, and patient and healthcare professionals groups, is then considered by an appraisal committee that formulates guidance to the NHS and is ultimately published by NICE.A number of countries have formal guidelines on the use of outcome measures and economic evaluations in the submissions required for health technology assessment prior to market access. These guidelines vary in both the detail and level of mandatory requirement to be followed by technology manufacturers. NICE has recently updated its guidance to technology manufacturers on their submissions. These guidelines, developed in consultation with the healthcare industry, provide detailed specification of the requirements of NICE for health outcomes data and economic evaluation. These details are described in more detail in this paper. [ABSTRACT FROM AUTHOR]

Background: Chest low-dose computed tomography (LDCT) is a promising technology for population-based screening because it is non-invasive, relatively inexpensive, associated with low radiation and highly sensitive to lung cancer. To improve the cost-effectiveness of lung cancer screening, simultaneous screening for other diseases could be considered. This systematic review was conducted to analyse studies that published evidence on the cost-effectiveness of chest LDCT screening programs for different diseases. Methods: Scopus and PubMed were searched for English publications (1 January 2011–22 July 2022) using search terms related to screening, computed tomography and cost-effectiveness. An additional search specifically searched for the cost-effectiveness of screening for lung cancer, chronic obstructive pulmonary disease or cardiovascular disease. Included publications should present a full health economic evaluation of population screening with chest LDCT. The extracted data included the disease screened for, model type, country context of screening, inclusion of comorbidities or incidental findings, incremental costs, incremental effects and the resulting cost-effectiveness ratio amongst others. Reporting quality was assessed using the 2022 Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: The search yielded 1799 unique papers, of which 43 were included. Most papers focused on lung cancer screening (n = 40), and three were on coronary calcium scoring. Microsimulation was the most commonly applied modelling type (n = 16), followed by life table analysis (n = 10) and Markov cohort models (n = 10). Studies reflected the healthcare context of the US (n = 15), Canada (n = 4), the UK (n = 3) and 13 other countries. The reported incremental cost-effectiveness ratio ranged from US$10,000 to US$90,000/quality-adjusted life year (QALY) for lung cancer screening compared to no screening and was US$15,900/QALY–US$45,300/QALY for coronary calcium scoring compared to no screening. Discussion: Almost all health economic evaluations of LDCT screening focused on lung cancer. Literature regarding the health economic benefits of simultaneous LDCT screening for multiple diseases is absent. Most studies suggest LDCT screening is cost-effective for current and former smokers aged 55–74 with a minimum of 30 pack-years of smoking history. Consequently, more evidence on LDCT is needed to support further cost-effectiveness analyses. Preferably evidence on simultaneous screening for multiple diseases is needed, but alternatively, on single-disease screening. Registration of systematic review: Prospective Register of Ongoing Systematic Reviews registration CRD42021290228 can be accessed https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=290228. [ABSTRACT FROM AUTHOR]

Since 1999, the National Institute for Health and Clinical Excellence (NICE) Technology Appraisal Programme has been charged with producing guidance for the NHS in England and Wales on the appropriate use of new and existing healthcare programmes. Guidance is based on an assessment of a number of factors, including cost effectiveness. The identification, measurement and valuation of costs are important components of any cost-effectiveness analysis. However, working through these steps raises a number of important methodological questions. For example, how should ‘future’ resource use be estimated, and is there a need to consider all ‘future’ costs? Given that NICE produces national guidance, should national unit cost data be used to value resources or should local variations in negotiated prices be taken into account? This paper was initially prepared as a briefing paper as part of the process of updating NICE’s 2004 Guide to the Methods of Technology Appraisal for a workshop on ‘costs’. It outlines the issues that were raised in the original briefing paper and the subsequent questions that were discussed at the workshop. [ABSTRACT FROM AUTHOR]

Background: This paper describes the first evaluation of the construct validity and performance of the newly developed preference-based measure of health, the SF-6D version 2 (SF-6Dv2). Method: Utilising data from the Multi-Instrument Comparison (MIC) project (n = 7932), we explored the descriptive differences in utility values between the SF-6Dv2 and the SF-6D and evaluated the known group validity of both measures by testing the statistical significance of differences in utility values and calculating the effect sizes across known groups. The convergent validity of the SF-6Dv2 was explored by examining whether the SF-6Dv2 is related to alternative validated measures, including the EQ-5D-5L and AQoL-8D. Results: Differences between the utility values of the SF-6Dv2 and SF-6D were evident; utilities were generally lower for the SF-6Dv2, with larger standard deviations resulting in larger absolute differences between groups. The SF-6Dv2 performed well in terms of known-group validity and successfully distinguished disease severity and between the disease and healthy groups, outperforming the SF-6D in some but not all groups. Convergent validity analyses indicated strong associations between the SF-6Dv2 and the SF-6D, EQ-5D-5L and AQoL-8D utilities. Conclusions: The psychometric performance of the SF-6Dv2 is favourable with respect to known group validity and convergent validity, but does not seem to have improved, compared with the SF-6D. However, the new method of valuation has had a substantial impact on the size of absolute differences in utility values, which could impact quality-adjusted life-year results. The economic evaluation of health interventions may therefore be influenced by the choice of the SF-6Dv2 over the SF-6D. [ABSTRACT FROM AUTHOR]

The UK's National Institute for Health and Care Excellence (NICE) recently launched a consultation on the methods it uses to evaluate new health technologies, and has highlighted the issue of how 'modifiers', including equity weights, should be incorporated into its processes. The practice of applying equity weights to specific population subgroups, as a means for increasing the effective cost-effectiveness threshold for some new health technologies, is well established in health technology assessment. It is also the subject of extensive discussion in the academic literature. In this paper, we demonstrate that NICE's current approach to equity weighting has the effect of reducing both population health and equity-weighted population health, a fundamental problem that appears to place NICE in contravention of its principles and obligations. We consider two potential methods for modifying NICE's current approach to address this problem. We also consider the merits of NICE abandoning its current approach to equity weighting and adopting a standard 'net benefit' approach in its place. We find that adopting a standard 'net benefit' approach is the most desirable option, as it provides for the most transparency while avoiding specific issues that arise when attempting to modify NICE's current approach. Regardless of the approach NICE uses for equity weighting, we find that protecting the health of National Health Service patients requires that some new technologies be evaluated using an effective cost-effectiveness threshold lower than the 'supply-side' cost-effectiveness threshold. This poses a particular challenge for NICE, given its obligations under the 2019 'Voluntary Scheme' between the UK pharmaceutical industry, the National Health Service, and the UK Government. We conclude by making some recommendations as to how NICE can move forward with the use of 'modifiers' in its decision making. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions. The clinical evidence was derived from two phase III, company-sponsored, randomised, open-label studies. Most evidence on obinutuzumab was based on the GALLIUM trial that compared obinutuzumab in combination with chemotherapy as induction followed by obinutuzumab maintenance monotherapy with rituximab in combination with chemotherapy as induction followed by rituximab maintenance monotherapy in previously untreated patients with FL (grades 1-3a). Long-term clinical evidence was based on the PRIMA trial, studying the benefit of two years of rituximab maintenance after first-line treatment in patients with FL. The cost-effectiveness evidence submitted by the company relied on a partitioned survival cost-utility model, implemented in Microsoft® Excel. The base-case incremental cost-effectiveness ratio (ICER) presented in the company submission was <£20,000 per quality-adjusted life-year (QALY) gained. Although the ERG concluded that the economic model met the NICE reference case to a reasonable extent, some errors were identified and several assumptions made by the company were challenged. A new base-case scenario produced by the ERG suggested an ICER that was higher than the company base case, but still below £30,000 per QALY gained. However, some ERG scenario analyses were close to or even above the threshold. This was the case in particular for assuming a treatment effect that did not extend beyond trial follow-up. These results led to an initial negative recommendation by the appraisal committee. Subsequently, the company submitted a revised base case focusing on patients at intermediate or high risk of premature mortality. Simultaneously, a further price discount for obinutuzumab was granted. In addition to the company's revised base case, the ERG suggested a restriction of the treatment effect to 5 years and implemented biosimilar uptake and cheaper prices for rituximab. All of these adjustments did not exceed £30,000 per QALY gained and therefore the use of obinutuzumab for patients with advanced FL and a Follicular Lymphoma International Predictive Index (FLIPI) score of two or more could be recommended. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited Servier, the company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf®), to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care (BSC) for metastatic colorectal cancer (third-line or later). 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's submission (CS), the ERG report 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 T/T based upon the CS. In the CS, pooled evidence of two trials (a phase II trial and RECOURSE) showed that T/T resulted in a significant increase in overall survival [OS; hazard ratio (HR) 0.67, 95% CI 0.58-0.78] and progression-free survival (PFS; HR 0.46, 95% CI 0.40-0.53). The AC considered the survival benefit of T/T clinically meaningful although relatively small. The ERG highlighted that none of the participants in the phase II trial and approximately half of the RECOURSE participants (394 of 800) were from Europe, which might limit the applicability of the study findings to the NHS. Moreover, the ERG's critical assessment of the company's economic evaluation highlighted a number of concerns that resulted in 11 adjustments to the company's base-case analysis. The ERG adjustments that had the largest impact were using the RECOURSE trial data only (instead of the pooled evidence), fixing errors and violations and using the utilities from the CORRECT trial (identified in the literature review) only. The ERG preferred to use the RECOURSE trial data only given the suboptimal methodology used by the company to pool the evidence. However, since there were no fundamental arguments to prevent the two trials from being pooled, the ERG also presented its base-case analysis based on the pooled effectiveness estimates. The company base-case resulted in an incremental cost effectiveness ratio (ICER) of £44,032 per QALY gained while the ERG base-case resulted in ICERs of £52,695 and £49,392 per QALY gained based on the RECOURSE trial only and pooled evidence, respectively. Since the AC concluded that the most plausible ICER was £49,392 per QALY gained, and that T/T meets end-of-life criteria, T/T was recommended as a cost effective use of NHS resources. [ABSTRACT FROM AUTHOR]

Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature. [ABSTRACT FROM AUTHOR]

The objective of this paper is to examine how well the QALY captures the health gains generated by cancer treatments, with particular focus on the methods for constructing QALYs preferred by the UK National Institute for Health and Clinical Excellence (NICE). Data were obtained using a keyword search of the MEDLINE database and a hand search of articles written by leading researchers in the subject area (with follow up of the references in these articles). Key arguments were discussed and developed at an oncology workshop in September 2009 at the Office of Health Economics. Three key issues emerged. First, the EQ-5D, NICE's preferred measure of health-related quality of life (QOL) in adults, has been found to be relatively insensitive to changes in health status of cancer patients. Second, the time trade-off, NICE's preferred technique for estimating the values of health states, involves making assumptions that are likely to be violated in endof- life scenarios. Third, the practice of using valuations of members of the general population, as recommended by NICE, is problematic because such individuals typically display a misunderstanding of what it is really like for patients to live with cancer. Because of the way in which it is constructed, the QALY shows important limitations in terms of its ability to accurately capture the value of the health gains deemed important by cancer patients. A research agenda for addressing these limitations is proposed. [ABSTRACT FROM AUTHOR]

The use of decision-analytic modelling for the purpose of health technology assessment (HTA) has increased dramatically in recent years. Several guidelines for best practice have emerged in the literature; however, there is no agreed standard for what constitutes a ‘good model’ or how models should be formally assessed. The objective of this paper is to identify, review and consolidate existing guidelines on the use of decision-analytic modelling for the purpose of HTA and to develop a consistent framework against which the quality of models may be assessed.The review and resultant framework are summarised under the three key themes of Structure, Data and Consistency. ‘Structural’ aspects relate to the scope and mathematical structure of the model including the strategies under evaluation. Issues covered under the general heading of ‘Data’ include data identification methods and how uncertainty should be addressed. ‘Consistency’ relates to the overall quality of the model.The review of existing guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, such as the need for transparency, they are contradictory in other areas. Particular areas of disagreement are how data should be incorporated into models and how uncertainty should be assessed.For the purpose of evaluation, the resultant framework is applied to a decision-analytic model developed as part of an appraisal for the National Institute for Health and Clinical Excellence (NICE) in the UK. As a further assessment, the review based on the framework is compared with an assessment provided by an independent experienced modeller not using the framework.It is hoped that the framework developed here may form part of the appraisals process for assessment bodies such as NICE and decision models submitted to peer review journals. However, given the speed with which decision-modelling methodology advances, there is a need for its continual update. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry's core business is the innovation, development and marketing of new drugs. Pharmacogenetic (PG) testing and technology has the potential to increase a drug's value in many ways. A critical issue for the industry is whether products in development should be teamed with genetic tests that could segment the total population into responders and non-responders. In this paper we use a cost-effectiveness framework to model the strategic decision-making considerations by pharmaceutical manufacturers as they relate to drug development and the new technology of PG (the science of using genetic markers to predict drug response). In a simple, static, one-period model we consider three drug development strategies: a drug is exclusively developed and marketed to patients with a particular genetic marker; no distinguishing among patients based on the expression of a genetic marker is made (traditional approach); and a strategy whereby a drug is marketed to patients both with and without the genetic marker but there is price discrimination between the two subpopulations. We developed three main principles: revenues under a strategy targeting only the responder subpopulation will never generate more revenue than that which could have been obtained under a traditional approach; total revenues under a targeted PG strategy will be less than that under a traditional approach but higher than a naive [corrected] view would believe them to be; and a traditional [corrected] approach will earn the same total revenues as a price discrimination strategy, assuming no intermarket arbitrage. While these principles relate to the singular (and quite narrow) consideration of drug revenues, they may nevertheless partially explain why PG is not being used as widely as was predicted several years ago when the technology first became available, especially in terms of pharmaceutical manufacturer-developed tests. [ABSTRACT FROM AUTHOR]

The National Institute for Clinical Excellence (NICE) responds to requests by the Department of Health for guidance on the use of selected new and established technologies in the National Health Service (NHS) in England and Wales. This paper asks whether the NICE methodological guidelines help NHS decision makers meet the objectives of maximum health improvements from NHS resources and an equitable availability of technologies. The analytical basis of the guidelines is a comparison of the costs and consequences of new and existing methods of dealing with particular conditions using the incremental cost-effectiveness ratio. We explain why information on the costs and consequences of a particular technology in isolation is insufficient to address issues of efficiency of resource use. We argue that to increase efficiency, decision makers need information on opportunity costs. We show that in the absence of such information decision makers cannot identify the efficient use of resources. Finally we argue that economics provides valid methods for identifying the maximisation of health improvements for a given allocation of resources and we describe an alternative practical approach to this problem. Drawing on the experience of Ontario, Canada where an approach similar to that proposed by NICE has been in use for almost a decade, and recent reports about the consequences of NICE decisions to date, we conclude that instead of increasing the efficiency or equity of the use of NHS resources, NICE methodological guidelines may lead to: uncontrolled increases in NHS expenditures without evidence of any increase in total health improvements; increased inequities in the availability of services; and concerns about the sustainability of public funding for new technologies. [ABSTRACT FROM AUTHOR]

One of the principal roles of the National Institute for Clinical Excellence (NICE) is to appraise selected existing and emerging healthcare technologies and, as a result, produce guidance for the National Health Service (NHS) in England and Wales. A central part of this appraisal is the potential for manufacturers and sponsors to make a data submission. This paper describes the process of development of the second edition of technical guidance to manufacturers and sponsors for submission to NICE. The revision process took place during the period May 2000 and January 2001 and involved a number of key steps -- establishment of a guidance steering committee, review of current international guidelines of clinical and cost effectiveness, drafting of the guidance, detailed consultation with stakeholders, revision of the guidance and, finally, publication. The lessons learnt from revision of the NICE guidance for manufacturers and sponsors and some main issues for its future development are discussed. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^9/L and 400 × 10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than d30 000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from d33 561 to d103 500 per QALY (splenectomized) and d39 657 to d150 245 per QALY (non-splenectomized). All costs are presented in d, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of d30 000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although longterm follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators. [ABSTRACT FROM AUTHOR]

This paper describes the key principles of why an assessment of uncertainty and its consequences are critical for the types of decisions that a body such as the UK National Institute for Health and Clinical Excellence (NICE) has to make. In doing so, it poses the question of whether formal methods may be useful to NICE and its advisory committees in making such assessments. Broadly, these include the following: (i) should probabilistic sensitivity analysis continue to be recommended as a means to characterize parameter uncertainty; (ii) which methods should be used to represent other sources of uncertainty; (iii) when can computationally expensive models be justified and is computation expense a sufficient justification for failing to express uncertainty; (iv) which summary measures of uncertainty should be used to present the results to decision makers; and (v) should formal methods be recommended to inform the assessment of the need for evidence and the consequences of an uncertain decision for the UK NHS? [ABSTRACT FROM AUTHOR]

The article discusses the significance of the "Guide to the Methods of Technology Appraisal" from the National Institute for Health and Clinical Excellence (NICE) Technology Appraisals Programme in Great Britain in 2008. The updated guide focuses on specific reference to clinical and cost effectiveness and designed based on the principles of robustness, transparency and inclusiveness. Moreover, it discusses various issues in science, health technology assessment and techniques.

Assessing the cost effectiveness of a new health intervention often requires modelling to estimate the impact of the intervention on cost, survival and quality of life over the lifetime of a cohort of patients. Markov modelling is a methodology that is commonly employed to estimate these long-term costs and benefits. As commonly used, these models assume that the patients continue to get the treatments assigned regardless of the change in health states. In this paper, we describe an extension to the Markov modelling approach, called Markov decision modelling. Such a model starts with a set of health states and treatments and optimally assigns treatments to each of the health states.A Markov decision model can be used to identify the optimal treatment strategy not just for the initial disease state, but also as the disease state changes over time. We present a dynamic programming approach to identifying the optimal assignment of treatments, and illustrate this methodology using an example.The Markov decision modelling approach provides an efficient way of identifying optimal assignment of treatments to health states, but, like the standard Markov model, may be of limited use when probabilities of future events depend on past history in a complex fashion. Even with its limitations, Markov decision models offer an opportunity for health economists to inform healthcare decision-makers on how to modify current treatment pathways to incorporate new treatments as they become available. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a modern-day epidemic in most developed countries. As such, it is both common and costly. Contrary to the impression given by clinical trial data, CHF mainly affects older individuals with approximately equal numbers of men and women and concurrent disease profiles likely to complicate or even prohibit the application of proven treatments. It is within this context that there has been an increasing interest in specific CHF-management programmes designed to limit costly hospital use in typically older individuals at high risk for poor quality of life, recurrent readmissions and premature death. This paper examines the evidence to suggest that CHF programmes involving individualised multidisciplinary post-discharge healthcare, with a major focus on specialist nurse management to ensure that the patient receives optimal treatment, are clinically and economically effective in reducing the typical burden imposed by CHF. These programmes appear to be most effective in ‘high-risk’ patients who typically have recurrent readmissions in high-cost units. Overall, the literature suggests that these programmes are able to reduce recurrent hospital stay by 30-50% relative to usual care (even in the presence of gold-standard treatment) in the short to medium term with comparable cost benefits. Recent data from a management programme involving a cohort of typically older and fragile patients with CHF in Australia showed that at 3 years post index admission, hospital utilisation costs were reduced by one-third relative to usual care. The potential for enormous cost benefits (both in terms of absolute cost savings and in terms of facilitating a more efficient healthcare system) if a specialist nurse programme of care was applied in the form of a UK-wide heart failure service was also recently examined. Based on year 2000 activity levels, it was found that for each specialist heart failure nurse appointed in the UK (with a caseload of 200-250 patients per annum), nominal savings of £49 000 per annum could be generated in order to make the healthcare system more efficient. [ABSTRACT FROM AUTHOR]

This paper analyses the 32 technology appraisals completed by the National Institute for Clinical Excellence (NICE) in the UK from its establishment to the end of January 2002. It looks at why technologies have been rejected, what has happened to products reviewed at launch, evidence of rationing on cost-effectiveness grounds, and the issues raised for manufacturers and for NICE in the collection and analysis of economic data. It finds that around two-thirds of NICE appraisals have been of pharmaceuticals. Only two ‘first in class’ products have been reviewed at launch, with quite different results. There is clear evidence of the use of cost-effectiveness criteria to restrict or reject technologies, although these are not the only criteria used in decision making. While a number of concerns with the appraisal process raised by manufacturers have been addressed by NICE, and while the Department of Health is currently consulting on changes to the referral system whereby products are selected for review by NICE, manufacturers remain concerned about the timing of referrals in the product life cycle and about the quality and consistency of the reviews of evidence undertaken by academic groups for NICE. Concerns in the National Health Service centre on whether the right technologies are being referred to NICE and also on the opportunity cost of positive NICE recommendations. Given global budget constraints and the difficulty of withdrawing services, the NICE recommendations tend to pre-empt growth money that could be used for more cost-effective purposes. NICE should be asked to look at established technologies that may not be cost effective and whose discontinuance could therefore release resources for other more cost-effective treatments. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop prediction models for the individual-level impacts of cardiovascular events on UK healthcare costs. Methods: In the UK Biobank, people 40–70 years old, recruited in 2006–2010, were followed in linked primary (N = 192,983 individuals) and hospital care (N = 501,807 individuals) datasets. Regression models of annual primary and annual hospital care costs (2020 UK£) associated with individual characteristics and experiences of myocardial infarction (MI), stroke, coronary revascularization, incident diabetes mellitus and cancer, and vascular and nonvascular death are reported. Results: For both people without and with previous cardiovascular disease (CVD), primary care costs were modelled using one-part generalised linear models (GLMs) with identity link and Poisson distribution, and hospital costs with two-part models (part 1: logistic regression models the probability of incurring costs; part 2: GLM with identity link and Poisson distribution models the costs conditional on incurring any). In people without previous CVD, mean annual primary and hospital care costs were £360 and £514, respectively. The excess primary care costs were £190 and £360 following MI and stroke, respectively, whereas excess hospital costs decreased from £4340 and £5590, respectively, in the year of these events, to £190 and £410 two years later. People with previous CVD had more than twice higher annual costs, and incurred higher excess costs for cardiovascular events. Other characteristics associated with higher costs included older age, female sex, south Asian ethnicity, higher socioeconomic deprivation, smoking, lower level of physical activities, unhealthy body mass index, and comorbidities. Conclusions: These individual-level healthcare cost prediction models could inform assessments of the value of health technologies and policies to reduce cardiovascular and other disease risks and healthcare costs. An accompanying Excel calculator is available to facilitate the use of the models. [ABSTRACT FROM AUTHOR]

The authors comment on the EQ-5D-3L instruments and its value set recommended by the National Institute for Health and Care Excellence (NICE) of Great Britain. They discuss the differences between the 3L and the 5L in regard to description of patient health via the health state classifier and the way they value health, as well as its impact on estimates of quality-adjusted life-years and cost effectiveness rations. They point out the impact of these differences on health technology assessment.

Objectives: The aim of this study was to estimate the relationship between EQ-5D-3L and EQ-5D-5L, in both directions, using a single model. Methods: An online survey containing both variants of EQ-5D, with randomised ordering, was administered to a large UK sample in 2020. A joint statistical model of the ten EQ-5D responses (five at 5L, five at 3L), using a multi-equation ordinal regression framework was estimated. The joint model ensures mappings in either direction are fully consistent with the information in the sample and satisfy Bayes' rule. Three extensions enhance model flexibility: a copula specification allows differing degrees of correlation between the 3L and 5L responses at the upper and lower extremes of health; a normal mixture residual distribution gives flexibility in the distributional form of responses; and a common factor captures correlations in responses across the five dimensions. Results: Almost 50,000 responses were received. Thirty-five percent of respondents reported an existing medical condition. Ninety percent of possible 3L and 43% of possible 5L health states were observed. The preferred model specification includes age, sex and the responses to the EQ-5D instrument. Close alignment to the observed data was observed both in within-sample and out-of-sample comparisons. Conclusion: The results from this study provide a means of translating evidence to or from EQ-5D-3L to or from 5L based on a large-scale UK population survey with randomised ordering. Mapping can be performed either using descriptive system responses, individual utility scores or summary statistics. [ABSTRACT FROM AUTHOR]

Background and Objective: Most guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK. Methods: We used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective. Results: All screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies. Conclusions: Of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies. [ABSTRACT FROM AUTHOR]

Background: The UK Medical Research Council approach to evaluating complex interventions moves through development, feasibility, piloting, evaluation and implementation in an iterative manner. This approach might be useful as a conceptual process underlying complex valuation tasks.Objective: The objective of the study was to explore the applicability of such a framework using a single case study (valuing the ICECAP-Supportive Care Measure) and considering three key uncertainties: the number of response categories for the measure; experimental design; and the potential for using slightly different variants of the measure with the same value set.Methods: Three on-line pilot studies (n = 204, n = 100, n = 102) were undertaken during 2012 and 2013 with adults from the UK general population. Each used variants of discrete choice and best-worst scaling tasks; respondents were randomly allocated to different groups to allow exploration of the number of levels for the instrument (four or five), optimal experimental design and the values for alternative wording around prognosis. Conditional logit regression models were used in the analysis and variance scale factors were explored.Results: The five-level version of the measure seemed to result in simplifying heuristics. Plotting the variance scale factors suggested that best-worst scaling answers were approximately four times more consistent than the discrete choice answers. The likelihood ratio test indicated there was virtually no difference in values between the differently worded versions.Conclusion: Rigorous piloting can improve the design of valuation studies. Thinking in terms of a 'complex valuation framework' may emphasise the importance of conducting and funding such rigorous pilots. [ABSTRACT FROM AUTHOR]

Background: Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as "BRACETD") often switch to natalizumab or fingolimod. Objective: The aim was to estimate the comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD using real-world data and to evaluate the cost-effectiveness of switching to natalizumab versus fingolimod using a United Kingdom (UK) third-party payer perspective. Methods: Real-world data were obtained from MSBase for patients relapsing on BRACETD in the year before switching to natalizumab or fingolimod or within BRACETD. Three-way-multinomial-propensity-score–matched cohorts were identified, and comparisons between treatment groups were conducted for annualised relapse rate (ARR) and 6-month–confirmed disability worsening (CDW6M) and improvement (CDI6M). Results were applied in a cost-effectiveness model over a lifetime horizon using a published Markov structure with health states based on the Expanded Disability Status Scale. Other model parameters were obtained from the UK MS Survey 2015, published literature, and publicly available UK sources. Results: The MSBase analysis found a significant reduction in ARR (rate ratio [RR] = 0.64; 95% confidence interval [CI] 0.57–0.72; p < 0.001) and an increase in CDI6M (hazard ratio [HR] = 1.67; 95% CI 1.30–2.15; p < 0.001) for switching to natalizumab compared with BRACETD. For switching to fingolimod, the reduction in ARR (RR = 0.91; 95% CI 0.81–1.03; p = 0.133) and increase in CDI6M (HR = 1.30; 95% CI 0.99–1.72; p = 0.058) compared with BRACETD were not significant. Switching to natalizumab was associated with a significant reduction in ARR (RR = 0.70; 95% CI 0.62–0.79; p < 0.001) and an increase in CDI6M (HR = 1.28; 95% CI 1.01–1.62; p = 0.040) compared to switching to fingolimod. No evidence of difference in CDW6M was found between treatment groups. Natalizumab dominated (higher quality-adjusted life-years [QALYs] and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient). Results were consistent across sensitivity analyses. Conclusions: This novel real-world analysis suggests a clinical benefit for therapy escalation to natalizumab versus fingolimod based on comparative effectiveness results, translating to higher QALYs and lower costs for UK patients inadequately responding to BRACETD. [ABSTRACT FROM AUTHOR]

Background: Antibiotics have led to considerable increases in life expectancy. However, over time, antimicrobial resistance has accelerated and is now a significant global public health concern. Understanding societal preferences for the use of antibiotics as well as eliciting the willingness to pay for future research is crucial. Objective: To investigate preferences for different strategies to optimize antibiotic use and to understand the willingness to pay for future research in antimicrobial resistance and antimicrobial drug development. Methods: A discrete-choice experiment was administered to a sample of the UK general population. Respondents were asked to make nine choices, each offering three options—two hypothetical "doctor and antibiotics" and one "no doctor—no antibiotics"—defined by five attributes: treatment, days needed to recover, risk of bacterial infection that needs antibiotics, risk of common side effects, and risk of antimicrobial resistance by 2050. Data were analyzed using random parameters logit models. A double-bounded contingent valuation was also included in the survey to explore the willingness to pay for policies to contain antimicrobial resistance. Results: Among the 2579 respondents who completed the survey, 1151 always selected "no doctor—no antibiotics" and 57 never varied their choices; therefore, 1371 responses were used in the analysis. Risk of antimicrobial resistance by 2050 was the most important attribute and the "treatment" was the least important attribute, although this was sensitive to a higher risk of bacterial infection. The aggregate annual willingness to pay for containing antimicrobial resistance was approximately £8.35 billion (~£5–£10 billion). Conclusions: The antimicrobial resistance risk is relevant and important to the general public. The high willingness to pay suggests that large investments in policies or interventions to combat antimicrobial resistance are justified. [ABSTRACT FROM AUTHOR]

Background: Over 200 million people have chronic obstructive pulmonary disease (COPD) worldwide. The number of disease-year equivalents and deaths attributable to COPD are high.Guidelines for the pharmacological treatment of the disease recommend an individualized step-up approach in which treatment is intensified when results are unsatisfactory. Objective: Our objective was to present a systematic review of the cost effectiveness of pharmacological maintenance treatment for COPD and to discuss the methodological strengths and weaknesses of the studies. Methods: A systematic literature search for economic evaluations of drug therapy in COPDwas performed inMEDLINE, EMBASE, the Economic Evaluation Database of the UK NHS (NHS-EED) and the European Network of Health Economic Evaluation Databases (EURONHEED). Full economic evaluations presenting both costs and health outcomes were included. Results: A total of 40 studies were included in the review.Of these, 16 were linked to a clinical trial, 14 usedMarkovmodels, eight were based on observational data and two used a different approach. The few studies on combining short-acting bronchodilators were consistent in finding net cost savings compared with monotherapy. Studies comparing inhaled corticosteroids (ICS) with placebo or no maintenance treatment reported inconsistent results. Studies comparing fluticasone with salmeterol consistently found salmeterol to be more cost effective. The cost-effectiveness studies of tiotropium versus placebo, ipratropium or salmeterol pointed towards a reduction in total COPD-related healthcare costs for tiotropium in many but not all studies. All of these studies reported additional health benefits of tiotropium. The cost-effectiveness studies of the combination of inhaled long-acting b2-agonists and ICS all report additional health benefits at an increase in total COPD-related costs in most studies. The cost-per-QALY estimates of this combination treatment vary widely and are very sensitive to the assumptions on mortality benefit and time horizon. Conclusions: The currently available economic evaluations indicate differences in cost effectiveness between COPD maintenance therapies, but for a more meaningful comparison of results it is important to improve the consistency with respect to study methodology and choice of comparator. [ABSTRACT FROM AUTHOR]

Economic evaluation of health technologies in the form of cost-utility analysis is increasingly advocated. The most common outcome measure in this type of analysis is the QALY. In order to estimate QALYs, appropriate utility values are required. The objective of this review was to identify and critique utility values for schizophrenia-related health states. A critical appraisal was performed on utility values for schizophrenia identified in the systematic literature review that informed the economic analysis of the updated edition of the National Institute for Health and Clinical Excellence (NICE) clinical guideline on schizophrenia for England and Wales. Seven studies reporting utility values for schizophrenia were identified. The studies employed a variety of methods for generating utility values. None of the reported sets of utility values for schizophrenia were generated using the EQ-5D, which is a measure widely used in cost-utility analysis and preferred by NICE. Nevertheless, the EQ-5D may be less sensitive in capturing aspects of health-related quality of life in patients with schizophrenia. A condition-specific preference-based instrument may be more appropriate than a generic measure to inform cost-utility analyses of interventions for schizophrenia. [ABSTRACT FROM AUTHOR]

The author discusses the changes made to the National Health Service (NHS) in Great Britain. She mentions that a key alteration is to shift duty for commissioning services to general practitioners (GPs) responsible for determining how to spend approximately 80% of the budget of the NHS. She states that organizations owned by NHS that operate hospitals will be converted to the status of independent Foundation Trust.

The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies. [ABSTRACT FROM AUTHOR]

Background: Cannabidiol (CBD) is a novel therapy for the treatment of Lennox-Gastaut Syndrome (LGS), a rare, treatment-refractory epileptic encephalopathy. Two pivotal trials found CBD 20 mg/kg/day conferred a reduction from baseline in median drop seizure frequency of 44% and 42%, respectively, compared with 22% and 17%, respectively, in the usual care arms. No economic evaluations have been published to date. This analysis assessed the cost effectiveness of CBD adjunct therapy compared with usual care alone in LGS from the US payer perspective. Methods: We developed a lifetime horizon Markov decision analytic model. Efficacy, healthcare costs (2020 US$), and health state utilities were ascertained from published clinical trials, retrospective analyses, and time trade-off interviews conducted in the UK, respectively. Fifteen-year-old patients entering the model transitioned to states representing a percentage reduction in drop seizure frequency from baseline, where they remained until reverting back to baseline drop seizure frequency, or death. One-way and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty, and scenario analyses investigated the impact of various assumptions. Costs and outcomes were discounted at 3%. Results: Compared with usual care alone, CBD yielded 0.7 additional quality-adjusted life-years (QALYs) and $314,900 additional healthcare expenditure, resulting in $451,800 per QALY. Uncertainty in health state utilities were the largest contributor to uncertainty in the results. Results from the 5000-simulation probabilistic sensitivity analysis indicated a 0% chance of CBD being cost effective at a $150,000 per QALY willingness-to-pay threshold, with a 95% credible range for the incremental cost-effectiveness ratio of $325,300–$690,000 per QALY. Conclusion: CBD does not appear to be a cost-effective therapeutic option in LGS patients at a willingness-to-pay threshold of $150,000/QALY. [ABSTRACT FROM AUTHOR]

Objectives: Antimicrobial resistance (AMR) represents a significant threat to patient and population health. The study aim was to develop and validate a model of AMR that defines and quantifies the value of new antibiotics. Methods: A dynamic disease transmission and cost-effectiveness model of AMR consisting of three components (disease transmission, treatment pathway and optimisation) was developed to evaluate the health economic value of new antibiotics. The model is based on the relationship between AMR, antimicrobial availability and consumption. Model analysis explored the impact of different antibiotic treatment strategies on the development of AMR, patient and population estimates of health benefit, across three common treatment indications and pathogens in the UK. Results: Population-level resistance to existing antimicrobials was estimated to increase from 10.3 to 16.1% over 10 years based on current antibiotic availability and consumption. In comparison, the diversified use of a new antibiotic was associated with significant reduction in AMR (12.8% vs. 16.1%) and quality-adjusted life year (QALY) gains at a patient (7.7–10.3, dependent on antimicrobial efficacy) and population level (3657–8197, dependent on antimicrobial efficacy and the prevalence of AMR). Validation across several real-world data sources showed that the model output does not tend to systematically under- or over-estimate observed data. Conclusions: The development of new antibiotics and the appropriate use of existing antibiotics are key to addressing the threat of AMR. This study presents a validated model that quantifies the value of new antibiotics through clinical and economic outcomes of relevance, and accounts for disease transmission of infection and development of AMR. In this context, the model may be a useful tool that could contribute to the decision-making process alongside other potential models and expert advice. [ABSTRACT FROM AUTHOR]

This article provides an educational review covering the consideration of conducting 'value for money' analyses as part of non-randomised study designs including service evaluations. These evaluations represent a vehicle for producing evidence such as value for money of a care intervention or service delivery model. Decision makers including charities and local and national governing bodies often rely on evidence from non-randomised data and service evaluations to inform their resource allocation decision-making. However, as randomised data obtained from randomised controlled trials are considered the 'gold standard' for assessing causation, the use of this alternative vehicle for producing an evidence base requires careful consideration. We refer to value for money analyses, but reflect on methods associated with economic evaluations as a form of analysis used to inform resource allocation decision-making alongside a finite budget. Not all forms of value for money analysis are considered a full economic evaluation with implications for the information provided to decision makers. The type of value for money analysis to be conducted requires considerations such as the outcome(s) of interest, study design, statistical methods to control for confounding and bias, and how to quantify and describe uncertainty and opportunity costs to decision makers in any resulting value for money estimates. Service evaluations as vehicles for producing evidence present different challenges to analysts than what is commonly associated with research, randomised controlled trials and health technology appraisals, requiring specific study design and analytic considerations. This educational review describes and discusses these considerations, as overlooking them could affect the information provided to decision makers who may make an 'ill-informed' decision based on 'poor' or 'inaccurate' information with long-term implications. We make direct comparisons between randomised controlled trials relative to non-randomised data as vehicles for assessing causation; given 'gold standard' randomised controlled trials have limitations. Although we use UK-based decision makers as examples, we reflect on the needs of decision makers internationally for evidence-based decision-making specific to resource allocation. We make recommendations based on the experiences of the authors in the UK, reflecting on the wide variety of methods available, used as documented in the empirical literature. These methods may not have been fully considered relevant to non-randomised study designs and/or service evaluations, but could improve and aid the analysis conducted to inform the relevant value for money decision problem. [ABSTRACT FROM AUTHOR]

Background: An increasing number of technologies are obtaining marketing authorisation based on sparse evidence, which causes growing uncertainty and risk within health technology reimbursement decision making. To ensure that uncertainty is considered and addressed within health technology assessment (HTA) recommendations, uncertainties need to be identified, included in health economic models, and reported.Objective: Our objective was to develop the TRansparent Uncertainty ASsessmenT (TRUST) tool for systematically identifying, assessing, and reporting uncertainties in decision models, with the aim of making uncertainties and their impact on cost effectiveness more explicit and transparent.Methods: TRUST was developed by drawing on the uncertainty and risk assessment literature. To develop and validate this tool, we conducted HTA stakeholder discussion meetings and interviews and applied it in six real-world HTA case studies in the Netherlands and the UK.Results: The TRUST tool enables the identification and categorisation of uncertainty according to its source (transparency issues, methodology issues, and issues with evidence: imprecision, bias and indirectness, and unavailability) in each model aspect. The source of uncertainty determines the appropriate analysis. The impact of uncertainties on cost effectiveness is also assessed. Stakeholders found using the tool to be feasible and of value for transparent uncertainty assessment. TRUST can be used during model development and/or model review.Conclusion: The TRUST tool enables systematic identification, assessment, and reporting of uncertainties in health economic models and may contribute to more informed and transparent decision making in the face of uncertainty. [ABSTRACT FROM AUTHOR]

Background: Peripheral arterial disease (PAD) is a common condition that causes significant morbidity and reduced life expectancy, and can have a serious economic impact. It is often underdiagnosed in primary care, partially due to the fact that the current National Institute for Health Care and Excellence-recommended ankle-brachial pressure index (ABPI) test for PAD in primary care is time-consuming and is technically challenging to perform. The availability of a simple, reliable diagnostic test has the potential to facilitate early PAD identification and treatment. Objective: The aim of this study was to evaluate the preferences of primary care practitioners relating to the key characteristics for a new medical device for PAD detection. Participants: A sample of 116 UK primary care setting clinicians involved in the diagnosis and/or management of PAD, comprising of doctors (n = 95), nurses (n = 17), health care assistants (n = 1) and other unspecified clinicians (n = 3). Outcomes: Relative weights derived from a discrete choice experiment (DCE), by primary care practitioners regarding six key characteristics of the new device: device display, data integration, training, power supply, portability of the device, and cost. Results: Five characteristics were important for preferences. Practitioners favoured manual, as opposed to automated, integration of test results into patient records. Practitioners strongly preferred disposable batteries as the power supply for the device compared with other alternatives. Conclusions: This novel study has successfully utilised a DCE to elicit primary care practitioner's preferences for the development of the new device. The preferences can help inform device design and therefore facilitate/help to maximise its uptake and buy-in from the outset. [ABSTRACT FROM AUTHOR]

Introduction: The selective estrogen receptor degrader fulvestrant is approved for the first-line treatment of postmenopausal patients with hormone receptor-positive (HR+), locally advanced or metastatic breast cancer who have not received prior endocrine therapy. We evaluated the cost-effectiveness of fulvestrant versus comparator treatments in endocrine therapy-naïve patients with locally advanced or metastatic breast cancer. Methods: A three-health-state (progression free, progressed disease, and death) partitioned survival model from the UK National Health Service and Personal Social Services perspective was developed to extrapolate study data for the cumulative probability of progression-free survival and overall survival to a lifetime (30-year) horizon. Relative comparator data were derived from a systematic literature review-informed network meta-analysis. Sensitivity analyses were applied to assess the impact of uncertainty in the parameter input values on the results. Results: Over a lifetime horizon (30 years), the incremental cost (British pounds sterling) per patient associated with fulvestrant treatment was £18,867 versus anastrozole, £23,097 versus letrozole, and £17,131 versus tamoxifen, with incremental quality-adjusted life-years of 0.55, 0.77, and 0.76, respectively, and incremental cost-effectiveness ratios of £34,109, £29,827, and £22,532, respectively. The largest difference in costs between fulvestrant and the comparators was related to treatment costs. Conclusions: Results suggest that fulvestrant could potentially be a cost-effective option compared with other endocrine monotherapies (anastrozole, letrozole, and tamoxifen) for treating endocrine therapy-naïve, postmenopausal women with HR+, locally advanced or metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Background: Mapping algorithms have been indicated as a second-best solution for estimating health state utilities for the calculation of quality-adjusted life-years within cost-utility analysis when no generic preference-based measure is incorporated into the study. However, the predictive performance of these algorithms may be variable and hence it is important to assess their external validity before application in different settings.Objective: The aim of this study was to assess the external validity and generalisability of existing mapping algorithms for predicting preference-based Child Health Utility 9D (CHU9D) utilities from non-preference-based Pediatric Quality of Life Inventory (PedsQL) scores among children and adolescents living with or without disabilities or health conditions.Methods: Five existing mapping algorithms, three developed using data from an Australian community population and two using data from a UK population with one or more self-reported health conditions, were externally validated on data from the Longitudinal Study of Australian Children (n = 6623). The predictive accuracy of each mapping algorithm was assessed using the mean absolute error (MAE) and the mean squared error (MSE).Results: Values for the MAE (0.0741-0.2302) for all validations were within the range of published estimates. In general, across all ages, the algorithms amongst children and adolescents with disabilities/health conditions (Australia MAE: 0.2085-0.2302; UK MAE: 0.0854-0.1162) performed worse relative to those amongst children and adolescents without disabilities/health conditions (Australia MAE: 0.1424-0.1645; UK MAE: 0.0741-0.0931).Conclusions: The published mapping algorithms have acceptable predictive accuracy as measured by MAE and MSE. The findings of this study indicate that the choice of the most appropriate mapping algorithm to apply may vary according to the population under consideration. [ABSTRACT FROM AUTHOR]

As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (EUSA Pharma) of dinutuximab beta (Qarziba®) to submit evidence of its clinical and cost effectiveness for treating neuroblastoma. The BMJ Technology Assessment Group (BMJ-TAG) was commissioned to act as the Evidence Review Group (ERG), reviewing the submission from the company. The Decision Support Unit (DSU) was commissioned to review additional evidence submitted by the company and to undertake further analyses. This article presents the critical review of the company's submissions by the ERG and DSU, further analyses undertaken by the DSU, and the outcome of the NICE guidance. The clinical effectiveness for dinutuximab beta was derived from a phase III randomised controlled trial (RCT) that assessed the safety and efficacy of the addition of interleukin (IL)-2 to dinutuximab beta plus isotretinoin. This trial did not inform the relative effectiveness of dinutuximab beta versus isotretinoin alone, which was established practice in the UK for maintenance treatment. In the absence of direct evidence, the company initially conducted a naïve indirect treatment comparison against a historical control, and later performed a matching-adjusted indirect comparison (MAIC) against the isotretinoin arm of an RCT comparing dinutuximab alpha and isotretinoin. The company submitted a partitioned survival analysis model that calculated the incremental cost effectiveness of dinutuximab beta versus isotretinoin. The company's original incremental cost-effectiveness ratio (ICER) was £22,338 per quality-adjusted life-year (QALY) gained. However, the ERG were concerned that the company's ICER was not suitable for decision making, and thus carried out initial exploratory analysis as a first step to overcome the naïve estimation of treatment effectiveness in the model. The ERG's analysis estimated an ICER of £111,858 per QALY gained. In their revised analysis incorporating the MAIC and other changes as requested by the appraisal committee, the company's ICER was £24,661 per QALY gained. When the DSU incorporated longer-term isotretinoin data and made corrections to the model, the ICER increased to between £62,886 and £87,164 per QALY gained depending on the choice of survival model. A confidential Patient Access Scheme (PAS) decreased the ICERs. The ICERs with the PAS were over £40,000 per QALY gained, but the NICE committee additionally considered the patient population and its size, the disease severity, the potential for significant survival benefit and uncaptured health benefits, and recommended dinutuximab beta as a treatment option, subject to the company providing the agreed discount in the PAS. [ABSTRACT FROM AUTHOR]

Background: The Cancer Drugs Fund (CDF) was established in 2010 to improve access to treatments not routinely available. Having widely overspent, stricter budgeting rules were introduced in 2016. The CDF can now only include treatments with potential to be cost effective once sufficient data are collected.Objectives: Our objective was to explore the process and criteria used for consideration of treatments under the new CDF framework and to describe the extent of evidence collection.Methods: We identified CDF list, UK National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium documents (10 May 2018). Data were collected on drugs and indications, reasons for inclusion in the CDF, data collection, incremental cost-effectiveness ratios (ICERs), and corresponding recommendations for Scotland.Results: In total, 12 drugs were listed on the CDF in 17 indications, 12 of which were considered end-of-life care. The most common cancers were non-small-cell lung (n = 4), urothelial (n = 3), lymphocytic leukaemia (n = 2) and multiple myeloma (n = 2). The companies' ICERs were generally lower than those from the committee and the evidence review group. Drugs were included in the CDF for 6-42 months, with the majority included for ≥18 months. Data were frequently collected on overall survival (n = 16) and progression-free survival (n = 5) using NHS systems and, frequently, ongoing trials.Conclusions: Data collection frequently included overall survival and exceeded the 2 years recommended in the CDF strategy. It appears the CDF is allowing patients access to drugs long before they may become available for routine use. Our results are limited by the availability of published information and the small dataset. [ABSTRACT FROM AUTHOR]

As part of its Single Technology Appraisal process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of ibrutinib (Janssen) to submit evidence on the clinical effectiveness and cost effectiveness of ibrutinib for the treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL). The School of Health and Related Research Technology Assessment Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness evidence for ibrutinib included one randomised controlled trial comparing ibrutinib and temsirolimus and two single-arm studies. The company's indirect comparison of ibrutinib versus rituximab plus chemotherapy (R-chemo) produced a hazard ratio (HR) for progression-free survival (PFS) of 0.28. The ERG's random effects network meta-analysis (NMA) indicated that the treatment effect on PFS was highly uncertain (HR 0.27; 95% credible interval (CrI) 0.06-1.26). The company's Markov model assessed the cost effectiveness of ibrutinib versus R-chemo for the treatment of R/R MCL from the perspective of the National Health Service (NHS) and Personal Social Services over a lifetime horizon. Based on a re-run of the company's model by the ERG, the incremental cost-effectiveness ratio (ICER) for ibrutinib versus R-chemo [including the company's original patient access scheme (PAS)] was expected to be £76,014 per quality-adjusted life-year (QALY) gained. The ERG had several concerns regarding the company's model structure and the evidence used to inform its parameters. The ERG's preferred analysis, which used the ERG's NMA and the observed Kaplan-Meier curve for time to ibrutinib discontinuation and excluded long-term disutilities for R-chemo, produced ICERs of £63,340 per QALY gained for the overall R/R MCL population and of £44,711 per QALY gained for patients with one prior treatment. Following an updated PAS and consideration of evidence from a later data-cut of the RAY trial, the appraisal committee concluded that the most plausible ICER for the one prior treatment subgroup was likely to be lower than the company's estimate of £49,848 per QALY gained. The company's ICER for the overall R/R MCL population was higher, at £62,650 per QALY gained. The committee recommended ibrutinib as an option for treating R/R MCL in adults only if they have received only one previous line of therapy and the company provides ibrutinib with the discount agreed in the commercial access agreement with NHS England. [ABSTRACT FROM AUTHOR]

Background: Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective.Objective: The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases.Methods: We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines.Results: Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment.Conclusions: The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive. [ABSTRACT FROM AUTHOR]

Background: Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs), which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in health technology assessment (HTA) of melanoma drugs by European HTA agencies, as well as differences in RWD use between agencies and across time.Methods: HTA reports published between 1 January 2011 and 31 December 2016 were retrieved from websites of agencies representing five jurisdictions: England [National Institute for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium (SMC)], France [Haute Autorité de santé (HAS)], Germany [Institute for Quality and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland (ZIN)]. A standardized data extraction form was used to extract information on RWD inclusion for both REAs and CEAs.Results: Overall, 52 reports were retrieved, all of which contained REAs; CEAs were present in 25 of the reports. RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term effectiveness and/or identify drug-related costs. Differences emerged between agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed.Conclusion: In general, RWD inclusion was higher in CEAs than REAs, and was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD; however, no visible trends for RWD use over time were observed. [ABSTRACT FROM AUTHOR]

Objectives: When preparing administrative medical and pharmacy claims data for analysis, decisions about data clean up and analytical approach need to be made. However, information about the effects of various modelling decisions on adherence measures such as the medication possession ratio (MPR) is limited. We address this gap with this study.Methods: We utilized cross-sectional administrative claims data for commercially insured members filling at least two prescriptions for drugs within five classes of hypertension medication between 2008 and 2010. We divided nine modelling decisions into three categories: data scrubbing, study design, and MPR definition/calculations. We defined the base-case settings with commonly used values, varied each modelling decision singly and in combination, and measured the effects on the MPR.Results: Claims data for 358,418 individuals were available for analysis. Two modelling decisions were found to be highly influential, each yielding a difference of over 25 percentage points from the base case: the decision of whether to use interval- or prescription-based study periods, and the decision of how to handle overlapping prescription claims. The effect of other decisions was smaller, with a difference of 1-9 percentage points from the base case.Conclusions: Some of the decisions considered had a large impact on the MPR. Therefore, it is important for researchers to standardize approaches for study period length and overlapping prescription claims. We also conclude that transparent reporting of modelling decisions will facilitate the interpretation of results and comparisons across studies. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Shire Pharmaceuticals) of pegylated liposomal irinotecan hydrochloride trihydrate (liposomal irinotecan) to submit clinical and cost-effectiveness evidence for its use in combination with 5-fluorouracil (5-FU) and folic acid/leucovorin (LV) for treating patients with pancreatic cancer following prior treatment with gemcitabine as part of the institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's evidence, the ERG review and the resulting NICE guidance (TA440), issued on 26 April 2017. Clinical evidence for liposomal irinotecan + 5-FU/LV versus 5-FU/LV was derived from 236 patients with metastatic pancreatic cancer in the multinational, open-label, randomised controlled NAPOLI-1 trial. Results from analyses of progression-free survival and overall survival showed statistically significant improvements for patients treated with liposomal irinotecan + 5-FU/LV compared with those treated with 5-FU/LV. However, 5-FU/LV alone is rarely used in National Health Service clinical practice for patients with metastatic pancreatic cancer previously treated with gemcitabine. The company, ERG and Appraisal Committee (AC) all agreed that oxaliplatin + 5-FU/LV is the most commonly used treatment. Oxaliplatin + 5-FU/LV was compared with 5-FU/LV in two trials identified by the company. However, the company and the ERG both considered attempts to compare the efficacy of liposomal irinotecan + 5-FU/LV with oxaliplatin + 5-FU/LV to be methodologically flawed; not only was there heterogeneity between trials and their populations but also the proportional hazards assumption required to conduct a robust indirect treatment comparison (ITC) was violated. Nonetheless, data derived from an ITC were used to inform the company's economic model. Using the discounted patient access scheme price for liposomal irinotecan + 5-FU/LV, the company reported an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £54,412 for the comparison with oxaliplatin + 5-FU/LV. The ERG considered that the company's base-case cost-effectiveness results for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV were underestimates and should be interpreted with extreme caution. Following implementation of a number of model amendments, the ERG's modified exploratory ICER for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV was £106,898 per QALY gained. The AC accepted the majority of the ERG's amendments to the model, and also highlighted that the total QALYs for oxaliplatin + 5-FU/LV were lower than for 5-FU/LV in the company's model, which the AC considered to be clinically implausible. The AC therefore considered results from exploratory analyses, undertaken by the ERG, which included altering the QALY difference between liposomal irinotecan + 5-FU/LV and oxaliplatin + 5-FU/LV by ± 10%. These analyses resulted in ICERs for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV of between £201,019 per QALY gained to liposomal irinotecan + 5-FU/LV being dominated by oxaliplatin + 5-FU/LV. Therefore, despite uncertainty around the clinical-effectiveness evidence and cost-effectiveness results, the AC was confident that the ICER was in excess of £50,000 per QALY gained. The final guidance issued by NICE is that liposomal irinotecan + 5-FU/LV is not recommended within its marketing authorisation for treating metastatic adenocarcinoma of the pancreas in adults whose disease has progressed after gemcitabine-based therapy. [ABSTRACT FROM AUTHOR]

The article discusses the economic evaluation which has increasingly become an integral component of randomised controlled trial (RCT) designs. It states that organizations in Great Britain such as the National Institute for Health Research's Health Technology Assessment Programme and the Medical Research Council are funding RCTs that are trying to address both clinical effectiveness issues as well as cost-effectiveness considerations.

Objectives: This study responds to a request in the National Institute for Health and Care Excellence (NICE) guidance to assess the impact of using alternative sources of utility values, applied to multiple sclerosis (MS).Methods: Incremental cost-effectiveness ratios (ICERs) were calculated using utility values based on UK and Dutch values of EQ-5D, two UK mappings and one Dutch mapping of EQ-5D and two condition-specific instruments: the UK eight-dimensional Multiple Sclerosis Impact Scale (MSIS-8D) and the Dutch Multiple Sclerosis Impact Scale Preference-Based Measure (MSIS-PBM). Deterministic and Monte-Carlo simulation-based ICERs were estimated for glatiramer acetate versus symptom management using a lifetime Markov model.Results: For both UK and Dutch perspectives, mapped and condition-specific utility values expressed significantly higher quality of life for the worst health state of the model than did EQ-5D. The ICER of glatiramer acetate with EQ-5D was US$182,291 for The Netherlands and US$153,476 for the UK. Ratios for mapped and condition-specific utilities were between 20 and 60 % higher.Conclusion: The overestimation of quality of life of patients with MS by mapped EQ-5D or condition-specific utility values, relative to observed EQ-5D, increases the ICER substantially in a lifetime Markov model. [ABSTRACT FROM AUTHOR]

Health policy instruments such as the public financing of health technologies (e.g., new drugs, vaccines) entail consequences in multiple domains. Fundamentally, public health policies aim at increasing the uptake of effective and efficient interventions and at subsequently leading to better health benefits (e.g., premature mortality and morbidity averted). In addition, public health policies can provide non-health benefits in addition to the sole well-being of populations and beyond the health sector. For instance, public policies such as social and health insurance programs can prevent illness-related impoverishment and procure financial risk protection. Furthermore, public policies can improve the distribution of health in the population and promote the equalization of health among individuals. Extended cost-effectiveness analysis was developed to address health policy assessment, specifically to evaluate the health and financial consequences of public policies in four domains: (1) the health gains; (2) the financial risk protection benefits; (3) the total costs to the policy makers; and (4) the distributional benefits. Here, we present a tutorial that describes both the intent of extended cost-effectiveness analysis and its keys to allow easy implementation for health policy assessment. [ABSTRACT FROM AUTHOR]

The authors discuss the implications of the 2015 proposed revision of the Cancer Drugs Fund (CDF), established to provide a means by which National Health Service (NHS) patients could get cancer drugs that are not available on the NHS in Great Britain. They argues against the threats of the revised scheme on public health. They describe how the revised CDF could maximize the value of the benefit to cancer patients while minimizing its negative impact on the equity and efficiency of the NHS.

'Big data' is the collective name for the increasing capacity of information systems to collect and store large volumes of data, which are often unstructured and time stamped, and to analyse these data by using regression and other statistical techniques. This is a review of the potential applications of big data and health economics, using a SWOT (strengths, weaknesses, opportunities, threats) approach. In health economics, large pseudonymized databases, such as the planned care.data programme in the UK, have the potential to increase understanding of how drugs work in the real world, taking into account adherence, co-morbidities, interactions and side effects. This 'real-world evidence' has applications in individualized medicine. More routine and larger-scale cost and outcomes data collection will make health economic analyses more disease specific and population specific but may require new skill sets. There is potential for biomonitoring and lifestyle data to inform health economic analyses and public health policy. [ABSTRACT FROM AUTHOR]

Background: Expenditure on medicines is a readily identifiable element of health service costs. It is the focus of much attention by payers, not least in the UK even though the cost of medicines represents less than 10 % of total UK National Health Service (NHS) expenditure. Projecting future medicines spending enables the likely cost pressure to be allowed for in planning the scale and allocation of NHS resources. Simple extrapolations of past trends in expenditure fail to account for changes in the rate and mix of new medicines becoming available and in the scope for windfall savings when some medicines lose their patent protection. The objective of this study is to develop and test an improved method to project NHS pharmaceutical expenditure in the UK for the period 2012-2015. Methods: We have adopted a product-by-product, bottom-up approach, which means that our projections are built up from individual products to the total market. Our projections of the impact of generic and biosimilars entry on prices and quantities of medicines sold, and of the rate of uptake of newly launched medicines, have been obtained from regression analysis of UK data. To address uncertainty, we have created a baseline and two other illustrative scenarios. We have compared our projections with actual expenditure for 2012. Results: Our projections estimate that, between 2011 and 2015, with no change in policy or price regulation, the UK total medicines bill would increase at an average compound annual growth rate (CAGR) of between 3.1 and 4.1 %. Total NHS spending on branded medicines and total NHS spending on generics are projected to increase at average CAGRs of 0.5-1.8 and 10.0-11.0 %, respectively, over the same time period. For the total market, the actual growth rate for 2012 lay within our projected range. Conclusions: Our methodology provides a useful framework for projecting UK NHS medicines expenditure over the medium term and captures the impacts of existing medicines losing exclusivity and of new medicines being launched onto the market. [ABSTRACT FROM AUTHOR]