Incorporating frailty to address the key challenges to geriatric economic evaluation.

BACKGROUND: The multidimensional and dynamically complex process of ageing presents key challenges to economic evaluation of geriatric interventions, including: (1) accounting for indirect, long-term effects of a geriatric shock such as a fall; (2) incorporating a wide range of societal, non-health outcomes such as informal caregiver burden; and (3) accounting for heterogeneity within the demographic group. Measures of frailty aim to capture the multidimensional and syndromic nature of geriatric health. Using a case study of community-based falls prevention, this article explores how incorporating a multivariate frailty index in a decision model can help address the above key challenges. METHODS: A conceptual structure of the relationship between geriatric shocks and frailty was developed. This included three key associations involving frailty: (A) the shock-frailty feedback loop; (B) the secondary effects of shock via frailty; and (C) association between frailty and intervention access. A case study of economic modelling of community-based falls prevention for older persons aged 60 + was used to show how parameterising these associations contributed to addressing the above three challenges. The English Longitudinal Study of Ageing (ELSA) was the main data source for parameterisation. A new 52-item multivariate frailty index was generated from ELSA. The main statistical methods were multivariate logistic and linear regressions. Estimated regression coefficients were inputted into a discrete individual simulation with annual cycles to calculate the continuous variable value or probability of binary event given individuals' characteristics. RESULTS: All three conceptual associations, in their parameterised forms, contributed to addressing challenge (1). Specifically, by worsening the frailty progression, falls incidence in the model increased the risk of falling in subsequent cycles and indirectly impacted the trajectories and levels of EQ-5D-3 L, mortality risk, and comorbidity care costs. Intervention access was positively associated with frailty such that the greater access to falls prevention by frailer individuals dampened the falls-frailty feedback loop. Association (B) concerning the secondary effects of falls via frailty was central to addressing challenge (2). Using this association, the model was able to estimate how falls prevention generated via its impact on frailty paid and unpaid productivity gains, out-of-pocket care expenditure reduction, and informal caregiving cost reduction. For challenge (3), frailty captured the variations within demographic groups of key model outcomes including EQ-5D-3 L, QALY, and all-cause care costs. Frailty itself was shown to have a social gradient such that it mediated socially inequitable distributions of frailty-associated outcomes. CONCLUSION: The frailty-based conceptual structure and parameterisation methods significantly improved upon the methods previously employed by falls prevention models to address the key challenges for geriatric economic evaluation. The conceptual structure is applicable to other geriatric and non-geriatric intervention areas and should inform the data selection and statistical methods to parameterise structurally valid economic models of geriatric interventions.

The association between health-related quality of life and problem gambling severity: a cross-sectional analysis of the Health Survey for England.

BACKGROUND: Problem gambling can lead to health-related harms, such as poor mental health and suicide. In the UK there is interest in introducing guidance around effective and cost-effective interventions to prevent harm from gambling. There are no estimates of the health state utilities associated with problem gambling severity from the general population in the UK. These are required to determine the cost-effectiveness of interventions. This study aims to use an indirect elicitation method to estimate health state utilities, using the EQ-5D, for various levels of problem gambling and gambling-related harm. METHODS: We used the Health Survey for England to estimate EQ-5D-derived health state utilities associated with the different categories of the Problem Gambling Severity Index (PGSI), PGSI score and a 7-item PGSI-derived harms variable. Propensity score matching was used to create a matched dataset with respect to risk factors for problem gambling and regression models were used to estimate the EQ-5D-derived utility score and the EQ-5D domain score whilst controlling for key comorbidities. Further exploratory analysis was performed to look at the relationship between problem gambling and the individual domains of the EQ-5D. RESULTS: We did not find any significant attributable decrements to health state utility for any of the PGSI variables (categories, score and 7-item PGSI derived harms variable) when key comorbidities were controlled for. However, we did find a significant association between the 7-item PGSI derived harms variable and having a higher score (worse health) in the anxiety/depression domain of the EQ-5D, when comorbidities were controlled for. CONCLUSIONS: This study found no significant association between problem gambling severity and HRQoL measured by the EQ-5D when controlling for comorbidities. There might be several reasons for this including that this might reflect the true relationship between problem gambling and HRQoL, the sample size in this study was insufficient to detect a significant association, the PGSI is insufficient for measuring gambling harm, or the EQ-5D is not sensitive enough to detect the changes in HRQoL caused by gambling. Further research into each of these possibilities is needed to understand more about the relationship between problem gambling severity and HRQoL.

What impact would reducing low-acuity attendance have on emergency department length of stay? A discrete event simulation modelling study.

BACKGROUND: Long waiting times in the ED have been shown to cause negative outcomes for patients. This study aims to assess the effect in reducing length of stay of (1) preventing low-acuity attenders from attending the ED and (2) diverting low-acuity attenders at triage to a colocated general practice (GP) service. METHODS: Discrete event simulation was used to model a large urban teaching hospital in the UK, as a case study, with a colocated GP service. The Centre for Urgent and Emergency Care research database patient-level database (May 2015-April 2016), secondary literature and expert elicitation were used to inform the model. The model predicted length of stay, the percentage of patients being seen within 4 hours and the incremental cost-effectiveness of the colocated GP service. RESULTS: The model predicted that diverting low-acuity patients to a colocated GP open 9:00 to 17:00 reduces the average time in the system for higher acuity attenders by 29 min at an estimated additional cost of £6.76 per patient on average. The percentage of higher acuity patients being seen within 4 hours increased from 61% to 67% due to the reduction in the length of stay of those who were in the ED for the longest time. However, the model is sensitive to changes in model inputs and there is uncertainty around ED activity durations, for which further primary data collection would be useful. CONCLUSION: Reducing the proportion of low-acuity attenders at the ED could have an impact on the time in the ED for higher acuity patients due to their use of shared resources, but is insufficient alone to meet current targets. The simulation model could be adapted for further analyses to understand which other changes would be needed to meet current government targets.

Reflecting Parameter Uncertainty in Addition to Variability in Constrained Healthcare Resource Discrete Event Simulations: Worth Going the Extra Mile or a Road to Nowhere?

OBJECTIVES: Probabilistic sensitivity analysis (PSA) has been shown to reduce bias in outcomes of health economic models. However, only 1 existing study has been identified that incorporates PSA within a resource-constrained discrete event simulation (DES) model. This article aims to assess whether it is feasible and appropriate to use PSA to characterize parameter uncertainty in DES models that are primarily constructed to explore the impact of constrained resources. METHODS: PSA is incorporated into a new case study of an Emergency Department DES. Structured expert elicitation is used to derive the variability and uncertainty input distributions associated with length of time taken to complete key activities within the Emergency Department. Potential challenges of implementation and analysis are explored. RESULTS: The results of a trial of the model, which used the best estimates of the elicited means and variability around the time taken to complete activities, provided a reasonable fit to the data for length of time within the Emergency Department. However, there was substantial and skewed uncertainty around the activity times estimated from the elicitation exercise. This led to patients taking almost 3 weeks to leave the Emergency Department in some PSA runs, which would not occur in practice. CONCLUSIONS: Structured expert elicitation can be used to derive plausible estimates of activity times and their variability, but experts' uncertainty can be substantial. For parameters that have an impact on interactions within a resource-constrained simulation model, PSA can lead to implausible model outputs; hence, other methods may be needed.

The long-term effectiveness and cost-effectiveness of public health interventions; how can we model behavior? A review.

The effectiveness and cost of a public health intervention is dependent on complex human behaviors, yet health economic models typically make simplified assumptions about behavior, based on little theory or evidence. This paper reviews existing methods across disciplines for incorporating behavior within simulation models, to explore what methods could be used within health economic models and to highlight areas for further research. This may lead to better-informed model predictions. The most promising methods identified which could be used to improve modeling of the causal pathways of behavior-change interventions include econometric analyses, structural equation models, data mining and agent-based modeling; the latter of which has the advantage of being able to incorporate the non-linear, dynamic influences on behavior, including social and spatial networks. Twenty-two studies were identified which quantify behavioral theories within simulation models. These studies highlight the importance of combining individual decision making and interactions with the environment and demonstrate the importance of social norms in determining behavior. However, there are many theoretical and practical limitations of quantifying behavioral theory. Further research is needed about the use of agent-based models for health economic modeling, and the potential use of behavior maintenance theories and data mining.

Guidance on the use of complex systems models for economic evaluations of public health interventions.

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making.

Economic model of community-based falls prevention: seeking methodological solutions in evaluating the efficiency and equity of UK guideline recommendations.

BACKGROUND: Falls significantly harm geriatric health and impose substantial costs on care systems and wider society. Decision modelling can inform the commissioning of falls prevention but face methodological challenges, including: (1) capturing non-health outcomes and societal intervention costs; (2) considering heterogeneity and dynamic complexity; (3) considering theories of human behaviour and implementation; and (4) considering issues of equity. This study seeks methodological solutions in developing a credible economic model of community-based falls prevention for older persons (aged 60 +) to inform local falls prevention commissioning as recommended by UK guidelines. METHODS: A framework for conceptualising public health economic models was followed. Conceptualisation was conducted in Sheffield as a representative local health economy. Model parameterisation used publicly available data including English Longitudinal Study of Ageing and UK-based falls prevention trials. Key methodological developments in operationalising a discrete individual simulation model included: (1) incorporating societal outcomes including productivity, informal caregiving cost, and private care expenditure; (2) parameterising dynamic falls-frailty feedback loop whereby falls influence long-term outcomes via frailty progression; (3) incorporating three parallel prevention pathways with unique eligibility and implementation conditions; and (4) assessing equity impacts through distributional cost-effectiveness analysis (DCEA) and individual-level lifetime outcomes (e.g., number reaching 'fair innings'). Guideline-recommended strategy (RC) was compared against usual care (UC). Probabilistic sensitivity, subgroup, and scenario analyses were conducted. RESULTS: RC had 93.4% probability of being cost-effective versus UC at cost-effectiveness threshold of £20,000 per QALY gained under 40-year societal cost-utility analysis. It increased productivity and reduced private expenditure and informal caregiving cost, but productivity gain and private expenditure reduction were outstripped by increases in intervention time opportunity costs and co-payments, respectively. RC reduced inequality delineated by socioeconomic status quartile. Gains in individual-level lifetime outcomes were small. Younger geriatric age groups can cross-subsidise their older peers for whom RC is cost-ineffective. Removing the falls-frailty feedback made RC no longer efficient or equitable versus UC. CONCLUSION: Methodological advances addressed several key challenges associated with falls prevention modelling. RC appears cost-effective and equitable versus UC. However, further analyses should confirm whether RC is optimal versus other potential strategies and investigate feasibility issues including capacity implications.

Systematic review and critical methodological appraisal of community-based falls prevention economic models.

BACKGROUND: Falls impose significant health and economic burdens on community-dwelling older persons. Decision modelling can inform commissioning of alternative falls prevention strategies. Several methodological challenges arise when modelling public health interventions including community-based falls prevention. This study aims to conduct a systematic review (SR) to: systematically identify community-based falls prevention economic models; synthesise and critically appraise how the models handled key methodological challenges associated with public health modelling; and suggest areas for further methodological research. METHODS: The SR followed the 2021 PRISMA reporting guideline and covered the period 2003-2020 and 12 academic databases and grey literature. The extracted methodological features of included models were synthesised by their relevance to the following challenges: (1) capturing non-health outcomes and societal intervention costs; (2) considering heterogeneity and dynamic complexity; (3) considering theories of human behaviour and implementation; and (4) considering equity issues. The critical appraisal assessed the prevalence of each feature across models, then appraised the methods used to incorporate the feature. The methodological strengths and limitations stated by the modellers were used as indicators of desirable modelling practice and scope for improvement, respectively. The methods were also compared against those suggested in the broader empirical and methodological literature. Areas of further methodological research were suggested based on appraisal results. RESULTS: 46 models were identified. Comprehensive incorporation of non-health outcomes and societal intervention costs was infrequent. The assessments of heterogeneity and dynamic complexity were limited; subgroup delineation was confined primarily to demographics and binary disease/physical status. Few models incorporated heterogeneity in intervention implementation level, efficacy and cost. Few dynamic variables other than age and falls history were incorporated to characterise the trajectories of falls risk and general health/frailty. Intervention sustainability was frequently based on assumptions; few models estimated the economic/health returns from improved implementation. Seven models incorporated ethnicity- and severity-based subgroups but did not estimate the equity-efficiency trade-offs. Sixteen methodological research suggestions were made. CONCLUSION: Existing community-based falls prevention models contain methodological limitations spanning four challenge areas relevant for public health modelling. There is scope for further methodological research to inform the development of falls prevention and other public health models.

Economic evaluation of community-based falls prevention interventions for older populations: a systematic methodological overview of systematic reviews.

BACKGROUND: Falls impose significant health and economic burdens on older people. The volume of falls prevention economic evaluations has increased, the findings from which have been synthesised by systematic reviews (SRs). Such SRs can inform commissioning and design of future evaluations; however, their findings can be misleading and incomplete, dependent on their pre-specified criteria. This study aims to conduct a systematic overview (SO) to: (1) systematically identify SRs of community-based falls prevention economic evaluations; (2) describe the methodology and findings of SRs; (3) critically appraise the methodology of SRs; and (4) suggest commissioning recommendations based on SO findings. METHODS: The SO followed the PRISMA guideline and the Cochrane guideline on SO, covering 12 databases and grey literature for the period 2003-2020. Eligible studies were SRs with 50% or more included studies that were economic evaluations of community-based falls prevention (against any comparator) for older persons (aged 60 +) or high-risk individuals aged 50-59. Identified SRs' aims, search strategies and results, extracted data fields, quality assessment methods/results, and commissioning and research recommendations were synthesised. The comprehensiveness of previous SRs' data synthesis was judged against criteria drawn from literature on falls prevention/public health economic evaluation. Outcomes of general population, lifetime decision models were re-analysed to inform commissioning recommendations. The SO protocol is registered in the Prospective Register of Systematic Reviews (CRD42021234379). RESULTS: Seven SRs were identified, which extracted 8 to 33 data fields from 44 economic evaluations. Four economic evaluation methodological/reporting quality checklists were used; three SRs narratively synthesised methodological features to varying extent and focus. SRs generally did not appraise decision modelling features, including methods for characterising dynamic complexity of falls risk and intervention need. Their commissioning recommendations were based mainly on cost-per-unit ratios (e.g., incremental cost-effectiveness ratios) and neglected aggregate impact. There is model-based evidence of multifactorial and environmental interventions, home assessment and modification and Tai Chi being cost-effective but also the risk that they exacerbate social inequities of health. CONCLUSIONS: Current SRs of falls prevention economic evaluations do not holistically inform commissioning and evaluation. Accounting for broader decisional factors and methodological nuances of economic evaluations, particularly decision models, is needed.

Economic models of community-based falls prevention: a systematic review with subsequent commissioning and methodological recommendations.

BACKGROUND: Falls impose significant health and economic burdens among older populations, making their prevention a priority. Health economic models can inform whether the falls prevention intervention represents a cost-effective use of resources and/or meet additional objectives such as reducing social inequities of health. This study aims to conduct a systematic review (SR) of community-based falls prevention economic models to: (i) systematically identify such models; (ii) synthesise and critically appraise modelling methods/results; and (iii) formulate methodological and commissioning recommendations. METHODS: The SR followed PRISMA 2021 guideline, covering the period 2003-2020, 12 academic databases and grey literature. A study was included if it: targeted community-dwelling persons aged 60 and over and/or aged 50-59 at high falls risk; evaluated intervention(s) designed to reduce falls or fall-related injuries; against any comparator(s); reported outcomes of economic evaluation; used decision modelling; and had English full text. Extracted data fields were grouped by: (A) model and evaluation overview; (B) falls epidemiology features; (C) falls prevention intervention features; and (D) evaluation methods and outcomes. A checklist for falls prevention economic evaluations was used to assess reporting/methodological quality. Extracted fields were narratively synthesised and critically appraised to inform methodological and commissioning recommendations. The SR protocol is registered in the Prospective Register of Systematic Reviews (CRD42021232147). RESULTS: Forty-six models were identified. The most prevalent issue according to the checklist was non-incorporation of all-cause care costs. Based on general population, lifetime models conducting cost-utility analyses, seven interventions produced favourable ICERs relative to no intervention under the cost-effectiveness threshold of US$41,900 (£30,000) per QALY gained; of these, results for (1) combined multifactorial and environmental intervention, (2) physical activity promotion for women, and (3) targeted vitamin D supplementation were from validated models. Decision-makers should explore the transferability and reaches of interventions in their local settings. There was some evidence that exercise and home modification exacerbate existing social inequities of health. Sixteen methodological recommendations were formulated. CONCLUSION: There is significant methodological heterogeneity across falls prevention models. This SR's appraisals of modelling methods should facilitate the conceptualisation of future falls prevention models. Its synthesis of evaluation outcomes, though limited to published evidence, could inform commissioning.

Qualitative research to inform economic modelling: a case study in older people's views on implementing the NICE falls prevention guideline.

BACKGROUND: High prevalence of falls among older persons makes falls prevention a public health priority. Yet community-based falls prevention face complexity in implementation and any commissioning strategy should be subject to economic evaluation to ensure cost-effective use of healthcare resources. The study aims to capture the views of older people on implementing the National Institute for Health and Care Excellence (NICE) guideline on community-based falls prevention and explore how the qualitative data can be used to inform commissioning strategies and conceptual modelling of falls prevention economic evaluation in the local area of Sheffield. METHODS: Focus group and interview participants (n = 27) were recruited from Sheffield, England, and comprised falls prevention service users and eligible non-users of varying falls risks. Topics concerned key components of the NICE-recommended falls prevention pathway, including falls risk screening, multifactorial risk assessment and treatment uptake and adherence. Views on other topics concerning falls prevention were also invited. Framework analysis was applied for data analysis, involving data familiarisation, identifying themes, indexing, charting and mapping and interpretation. The qualitative data were mapped to three frameworks: (1) facilitators and barriers to implementing the NICE-recommended pathway and contextual factors; (2) intervention-related causal mechanisms for formulating commissioning strategies spanning context, priority setting, need, supply and demand; and (3) methodological and evaluative challenges for public health economic modelling. RESULTS: Two cross-component factors were identified: health motives of older persons; and professional competence. Participants highlighted the need for intersectoral approaches and prioritising the vulnerable groups. The local commissioning strategy should consider the socioeconomic, linguistic, geographical, legal and cultural contexts, priority setting challenges, supply-side mechanisms spanning provider, organisation, funding and policy (including intersectoral) and health and non-health demand motives. Methodological and evaluative challenges identified included: incorporating non-health outcomes and societal intervention costs; considering dynamic complexity; considering social determinants of health; and conducting equity analyses. CONCLUSIONS: Holistic qualitative research can inform how commissioned falls prevention pathways can be feasible and effective. Qualitative data can inform commissioning strategies and conceptual modelling for economic evaluations of falls prevention and other geriatric interventions. This would improve the structural validity of quantitative models used to inform geriatric public health policies.

Conceptualising changes to tobacco and alcohol policy as affecting a single interlinked system.

BACKGROUND: To support a move towards a coordinated non-communicable disease approach in public health policy, it is important to conceptualise changes to policy on tobacco and alcohol as affecting a single interlinked system. For health economic models to effectively inform policy, the first step in their development should be to develop a conceptual understanding of the system complexity that is likely to affect the outcomes of policy change. Our aim in this study was to support the development and interpretation of health economic models of the effects of changes to tobacco and alcohol policies by developing a conceptual understanding of the main components and mechanisms in the system that links policy change to outcomes. METHODS: Our study was based on a workshop from which we captured data on participant discussions on the joint tobacco-alcohol policy system. To inform these discussions, we prepared with a literature review and a survey of participants. Participants were academics and policy professionals who work in the United Kingdom. Data were analysed thematically to produce a description of the main components and mechanisms within the system. RESULTS: Of the people invited, 24 completed the survey (18 academic, 6 policy); 21 attended the workshop (16 academic, 5 policy). Our analysis identified eleven mechanisms through which individuals might modify the effects of a policy change, which include mechanisms that might lead to linked effects of policy change on tobacco and alcohol consumption. We identified ten mechanisms by which the tobacco and alcohol industries might modify the effects of policy changes, grouped into two categories: Reducing policy effectiveness; Enacting counter-measures. Finally, we identified eighteen research questions that indicate potential avenues for further work to understand the potential outcomes of policy change. CONCLUSIONS: Model development should carefully consider the ways in which individuals and the tobacco and alcohol industries might modify the effects of policy change, and the extent to which this results in an unequal societal distribution of outcomes. Modelled evidence should then be interpreted in the light of the conceptual understanding of the system that the modelling necessarily simplifies in order to predict the outcomes of policy change.

What are the cost-savings and health benefits of improving detection and management for six high cardiovascular risk conditions in England? An economic evaluation.

OBJECTIVES: To estimate the cost savings and health benefits of improving detection of individuals at high risk of cardiovascular disease (CVD) in England, to determine to which patient subgroups these benefits arise, and to compare different strategies for subsequent management. DESIGN: An economic analysis using the School for Public Health Research CVD Prevention Model. SETTING: England 2018. PARTICIPANTS: Adults aged 16 and older with one or more high cardiovascular risk conditions, including hypertension, diabetes, non-diabetic hyperglycaemia, atrial fibrillation, chronic kidney disease and high cholesterol. INTERVENTIONS: Detection of 100% of individuals with CVD high risk conditions compared with current levels of detection in England. Detected individuals are assumed to be managed either according to current levels of care or National Institute of Health and Care Excellence (NICE) guidelines. MAIN OUTCOME MEASURES: Incremental and cumulative costs, savings, quality adjusted life years (QALYs), CVD cases, and net monetary benefit, from a UK NHS and Personal Social Services perspective. RESULTS: £68 billion could be saved, 4.9 million QALYs gained and 3.4 million cases of CVD prevented over 25 years if all individuals in England with the six CVD high risk conditions were diagnosed and subsequently managed at current levels. Additionally, if all detected individuals were managed according to NICE guidelines, total savings would be £61 billion, 8.1 million QALYs would be gained and 5.2 million CVD cases prevented. Most benefits come from detection of high cholesterol in the short term and diabetes in the long term. CONCLUSIONS: Substantial cost savings and health benefits would accrue if all individuals with conditions that increase CVD risk could be diagnosed, with detection of undiagnosed diabetes producing greatest benefits. Ensuring all conditions are managed according to NICE guidelines would further increase health benefits. Projected cost-savings could be invested in developing acceptable and cost-effective solutions for improving detection and management.

Adalimumab for non-infectious uveitis: is it cost-effective?

BACKGROUND/AIMS: Uveitis is inflammation inside the eye. Our objective was to assess the cost-effectiveness of adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or panuveitis and to identify areas for future research. METHODS: A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the available relevant clinical and cost-effectiveness evidence. Data collected in two key randomised controlled trials (VISUAL I and VISUAL II) were used to estimate the interventions' effectiveness compared with the trials' comparator arms (placebo plus limited current practice (LCP)). The analysis was performed from the National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The estimated incremental cost-effectiveness ratios (ICERs) of adalimumab versus LCP for the base case are £92 600 and £318 075 per quality-adjusted life year (QALY) gained for active and inactive uveitis, respectively. In sensitivity analyses, the ICER varied from £15 579 to £120 653 and £35 642 to £800 775 per QALY for active and inactive uveitis. CONCLUSION: The estimated ICERs of adalimumab versus LCP are above generally accepted thresholds for cost-effectiveness in the UK. Adalimumab may be more cost-effective in patients with active uveitis at greater risk of blindness. However, there is an unmet need for additional primary data to provide more reliable estimates in several important areas, including effectiveness of adalimumab versus current practice (instead of LCP), incidence of long-term blindness, adalimumab effectiveness in avoiding blindness, and rates and time to remission while on adalimumab.

Dexamethasone implant for non-infectious uveitis: is it cost-effective?

BACKGROUND: Uveitis is inflammation inside the eye. The objective of this study is to assess the cost-effectiveness of a dexamethasone implant plus current practice (immunosuppressants and systemic corticosteroids) compared with current practice alone, in patients with non-infectious intermediate, posterior or pan-uveitis and to identify areas for future research. METHODS: A Markov model was built to estimate the costs and benefits of dexamethasone. Systematic reviews were performed to identify available relevant evidence. Quality of life data from the key randomised-controlled trial (HURON) was used to estimate the interventions' effectiveness compared with the trial's comparator arm (placebo plus limited current practice (LCP)). The analysis took a National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant compared with LCP is estimated as £19 509 per quality-adjusted life year (QALY) gained. The factors with the largest impact on the results were rate of blindness and relative proportion of blindness cases avoided by dexamethasone. Using plausible alternative assumptions, dexamethasone could be cost saving or it may be associated with an ICER of £56 329 per QALY gained compared with LCP. CONCLUSIONS: Dexamethasone is estimated to be cost-effective using generally accepted UK thresholds. However, there is substantial uncertainty around these results due to scarcity of evidence. Future research on the following would help provide more reliable estimates: effectiveness of dexamethasone versus current practice (instead of LCP), with subgroup analyses for unilateral and bilateral uveitis, incidence of long-term blindness and effectiveness of dexamethasone in avoiding blindness.

Pembrolizumab for Locally Advanced or Metastatic Urothelial Cancer Where Cisplatin is Unsuitable: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme) of pembrolizumab (Keytruda®) to submit evidence of its clinical and cost effectiveness for the treatment of locally advanced or metastatic urothelial cancer where cisplatin is unsuitable. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission (CS) to NICE. The clinical effectiveness evidence in the CS for pembrolizumab was based on one phase II, single-arm, open-label, non-randomised study (KEYNOTE-052), while the evidence for the comparator (carboplatin plus gemcitabine) was based on four studies, including one randomised controlled trial and three cohort studies. In the absence of head-to-head trials, the company conducted an indirect treatment comparison for both progression-free survival (PFS) and overall survival (OS), by firstly adjusting cross-study differences using a simulated treatment comparison approach and then synthesizing the evidence based on an assumption of constant hazard ratios using a standard meta-analysis model and time-varying hazard ratios using fractional polynomial models. The treatment effect of pembrolizumab was more favourable in the adjusted population compared with the observed effect in the KEYNOTE-052 study. The company submitted a de novo partitioned survival cohort simulation model, which partitions the OS time into PFS and post-progression survival. The probabilistic incremental cost-effectiveness ratio (ICER) for pembrolizumab compared with carboplatin plus gemcitabine was estimated to be £37,081 per quality-adjusted life-year (QALY) gained, based on the results within the company's health economic model. Following a critique of the model, for their preferred base case the ERG corrected some minor model errors, chose a progression approach for estimating utilities, and revised the extrapolation of PFS and OS. The ERG's probabilistic base case ICER was estimated to be £67,068 per QALY gained. The ERG also undertook a range of exploratory sensitivity analyses which suggested that the ICER was highly uncertain. In particular, the choices of extrapolation for the OS of pembrolizumab and the stopping rule for pembrolizumab had the largest impacts on the ICER. The NICE Appraisal Committee recommended pembrolizumab for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy, provided that pembrolizumab was stopped at 2 years of uninterrupted treatment, or earlier if the disease progresses, and the conditions of the managed access agreement for pembrolizumab are followed.

Pertuzumab for the Neoadjuvant Treatment of Early-Stage HER2-Positive Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer of pertuzumab (Perjeta®; Roche Products Limited) to submit evidence of its clinical and cost- effectiveness for the neoadjuvant treatment of women with high-risk, early-stage, HER2-positive breast cancer when used in combination with trastuzumab and chemotherapy. High-risk women included those with locally advanced (including inflammatory) breast cancer and women with high-risk early-stage breast cancer (classified as T2/3 or N1). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group. This article presents the critical review of the company's submission by the Evidence Review Group and the outcome of the National Institute for Health and Care Excellence guidance. The clinical data were mainly taken from a phase II, randomised, open-label, active controlled study (NeoSphere), which reported a significant advantage in terms of pathological complete response rates of pertuzumab in combination with trastuzumab and chemotherapy, compared with trastuzumab alone with chemotherapy (45.8 vs. 29.0%, p = 0.0141). The company did not make any indirect comparisons. A meta-analysis of 12 neoadjuvant studies investigating the relationship between pathological complete response and event-free survival was used to extrapolate the outcomes reported in the NeoSphere study. A cardiac safety study (TRYPHAENA) demonstrated the safety of pertuzumab. The company undertook a model-based economic evaluation of neoadjuvant pertuzumab plus trastuzumab and docetaxel compared with neoadjuvant trastuzumab and docetaxel over a lifetime horizon from the National Health Service and Personal Social Services perspective. The probabilistic incremental cost-effectiveness ratio was estimated to be £20,104 per quality-adjusted life-year gained for pertuzumab alongside trastuzumab and docetaxel compared with trastuzumab and docetaxel, which was revised to £21,869 per quality-adjusted life-year gained following the clarification process. The Evidence Review Group corrected an error in the digitisation of the survivor functions and modified the clinically inappropriate assumption that recurrence is zero after 7 years. The Evidence Review Group's probabilistic base case was £23,962 per quality-adjusted life-year gained. During the appraisal, to mitigate the uncertainties associated with the evidence, the company offered a patient access scheme, which led to the National Institute for Health and Care Excellence Appraisal Committee recommending pertuzumab in this patient group, subject to the company providing the agreed discount in the patient access scheme.

A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults.

BACKGROUND: Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex®; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis. DATA SOURCES: Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016. REVIEW METHODS: Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken. RESULTS: Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; p < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; p = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; p = 0.010) but not the VISUAL II trial (mean difference 2.12; p = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero (p < 0.014), the mean best corrected visual acuity improvement (p ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score (p < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness. LIMITATIONS: The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base. CONCLUSIONS: Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016041799. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Assessing the potential return on investment of the proposed UK NHS diabetes prevention programme in different population subgroups: an economic evaluation.

OBJECTIVES: To evaluate potential return on investment of the National Health Service Diabetes Prevention Programme (NHS DPP) in England and estimate which population subgroups are likely to benefit most in terms of cost-effectiveness, cost-savings and health benefits. DESIGN: Economic analysis using the School for Public Health Research Diabetes Prevention Model. SETTING: England 2015-2016. POPULATION: Adults aged ≥16 with high risk of type 2 diabetes (HbA1c 6%-6.4%). Population subgroups defined by age, sex, ethnicity, socioeconomic deprivation, baseline body mass index, baseline HbA1c and working status. INTERVENTIONS: The proposed NHS DPP: an intensive lifestyle intervention focusing on dietary advice, physical activity and weight loss. Comparator: no diabetes prevention intervention. MAIN OUTCOME MEASURES: Incremental costs, savings and return on investment, quality-adjusted life-years (QALYs), diabetes cases, cardiovascular cases and net monetary benefit from an NHS perspective. RESULTS: Intervention costs will be recouped through NHS savings within 12 years, with net NHS saving of £1.28 over 20 years for each £1 invested. Per 100 000 DPP interventions given, 3552 QALYs are gained. The DPP is most cost-effective and cost-saving in obese individuals, those with baseline HbA1c 6.2%-6.4% and those aged 40-74. QALY gains are lower in minority ethnic and low socioeconomic status subgroups. Probabilistic sensitivity analysis suggests that there is 97% probability that the DPP will be cost-effective within 20 years. NHS savings are highly sensitive to intervention cost, effectiveness and duration of effect. CONCLUSIONS: The DPP is likely to be cost-effective and cost-saving under current assumptions. Prioritising obese individuals could create the most value for money and obtain the greatest health benefits per individual targeted. Low socioeconomic status or ethnic minority groups may gain fewer QALYs per intervention, so targeting strategies should ensure the DPP does not contribute to widening health inequalities. Further evidence is needed around the differential responsiveness of population subgroups to the DPP.

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England.

BACKGROUND: Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. METHODS: An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13-24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. RESULTS: The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost-effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. CONCLUSION: CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden.