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

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

Capturing Value Attributes in the Economic Evaluation of Ceftazidime with Avibactam for Treating Severe Aerobic Gram-Negative Bacterial Infections in the United Kingdom.

INTRODUCTION: Antimicrobial resistance remains a serious and growing threat to public health, both globally and in the UK, leading to diminishing effectiveness of antimicrobials. Despite a clear need for new antimicrobials, the clinical pipeline is insufficient, driven by high research and development costs and limited expected returns on investment. To counteract this, National Institute for Health and Care Excellence (NICE) and National Health Service (NHS) England have launched a reimbursement mechanism, de-linked from volume of sales, that aims to reduce economic risk by recognising the broader population-level value of antimicrobials. The objective of this study was to quantify the value of ceftazidime-avibactam for treating gram-negative infections in the UK considering some of these broader value elements unique to antimicrobials. METHODS: A previously developed dynamic disease transmission and cost-effectiveness model was applied to assess the value of introducing ceftazidime-avibactam to UK treatment practice in the management of gram-negative hospital-acquired infections in line with the licenced indications for ceftazidime-avibactam. Model inputs were parameterised using sources aligned to the UK perspective. RESULTS: The introduction of ceftazidime-avibactam into a two-line treatment sequence saved over 2300 lives, leading to a gain of 27,600 life years and 22,000 quality-adjusted life years (QALY) at an additional cost of £17 million, over a ten-year transmission period. Ceftazidime-avibactam was associated with a net monetary benefit of £642 million at willingness to pay threshold of £30,000 per QALY; even at a lower threshold of £20,000 per QALY, the net monetary benefit is £422 million. DISCUSSION: Increasing the diversity of antimicrobial treatments through the introduction of an additional antimicrobial, in this instance ceftazidime-avibactam, was associated with substantial clinical and economic benefits, when considering broader population-level value. Despite revealing considerable benefits, the value of ceftazidime-avibactam is only partially reflected in this analysis. Further efforts are required to fully operationalise the spectrum, transmission, enablement, diversity and insurance (STEDI) value framework and accurately reflect the population-level value of antimicrobials.

Clinical and Economic Value of Reducing Antimicrobial Resistance in the Management of Hospital-Acquired Infections with Limited Treatment Options in Greece.

INTRODUCTION: Antimicrobial resistance (AMR) is a major public health threat worldwide. Greece has the highest burden of infections due to antibiotic-resistant bacteria among European Union/European Economic Area (EU/EEA) countries. One of the most serious AMR threats in Greece is hospital-acquired infections (HAIs) with limited treatment options (LTO) caused by resistant gram-negative pathogens. Thus, this study sought to estimate the current AMR burden in Greece and the value of reducing AMR to gram-negative pathogens for the Greek healthcare system. METHODS: The current model was adapted from a previously published and validated model of AMR to investigate the overall and AMR-specific burden of treating the most common HAIs with LTO in Greece and scenarios to demonstrate the benefits associated with reducing AMR levels from a third-party payer perspective. Clinical and economic outcomes were estimated over a 10-year time horizon; life years (LYs) and quality-adjusted life years (QALYs) were calculated over a lifetime (based on the annual number of infections over 10 years) at a willingness-to-pay of €30,000 per QALY gained and a 3.5% discount rate. RESULTS: In Greece, the current AMR levels in HAIs with LTO caused by four gram-negative pathogens account for > 316,000 hospital bed days, €73 million in hospitalisation costs, and > 580,000 LYs and 450,000 QALYs lost over 10 years. The monetary burden is estimated at €13.9 billion. A reduction in current AMR levels by 10-50% results in clinical and economic benefit; 29,264-151,699 bed days may be saved, leading to decreased hospitalisation costs (€6.8 million-€35.3 million) and a gain in LYs (85,328-366,162) and QALYs (67,421-289,331), associated with a monetary benefit of between €2.0 billion and €8.7 billion. CONCLUSION: This study shows the substantial clinical and economic burden AMR represents to the Greek healthcare system and the value that can be achieved by effectively reducing AMR levels.

Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.

INTRODUCTION: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making. METHODS: A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied. RESULTS: Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million. DISCUSSION: Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here. CONCLUSION: These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.

An Economic Evaluation Estimating the Clinical and Economic Burden of Increased Vancomycin-Resistant Enterococcus faecium Infection Incidence in Japan.

INTRODUCTION: While incidence rates of vancomycin-resistant Enterococcus faecium have remained comparatively low in Japan, there have been increasing reports of more vancomycin-resistant Enterococcus (VRE) outbreaks, requiring costly measures to contain. Increased incidence of VRE in Japan may lead to more frequent and harder to contain outbreaks with current control measures, causing a significant burden to the healthcare system in Japan. This study aimed to demonstrate the clinical and economic burden of vancomycin-resistant E. faecium infections to the Japanese healthcare system and the impact of increasing rates of vancomycin resistance. METHODS: A de novo deterministic analytic model was developed to assess the health economic outcomes of treating hospital-acquired VRE infections; patients are treated according to a two-line treatment strategy, dependent on their resistance status. The model considers hospitalisation costs and the additional cost of infection control. Scenarios investigated the current burden of VRE infections and the additional burden of increased incidence of VRE. Outcomes were assessed over a 1-year and 10-year time horizon from a healthcare payer's perspective in a Japanese setting. Quality-adjusted life years (QALYs) were valued with a willingness-to-pay threshold of ¥5,000,000 ($38,023), and costs and benefits were discounted at a rate of 2%. RESULTS: Current VRE incidence levels in enterococcal infections in Japan equates to ¥130,209,933,636 ($996,204,669) in associated costs and a loss of 185,361 life years (LYs) and 165,934 QALYs over 10 years. A three-fold increase (1.83%) is associated with an additional ¥4,745,059,504 ($36,084,651) in total costs on top of the current cost burden as well as an additional loss of 683 LYs over a lifetime, corresponding to 616 QALYs lost. CONCLUSION: Despite low incidence rates, VRE infections already represent a substantial economic burden to the Japanese healthcare system. The substantial increase in costs associated with a higher incidence of VRE infections could result in a significant economic challenge for Japan.

Estimating the Clinical and Economic Impact of Introducing a New Antibacterial into Greek Clinical Practice for the Management of Hospital-Acquired Infections with Limited Treatment Options.

INTRODUCTION: Hospital-acquired infections (HAIs) and growing antimicrobial resistance (AMR) represent a significant healthcare burden globally. Especially in Greece, HAIs with limited treatment options (LTO) pose a serious threat due to increased morbidity and mortality. This study aimed to estimate the clinical and economic value of introducing a new antibacterial for HAIs with LTO in Greece. METHODS: A previously published and validated dynamic model of AMR was adapted to the Greek setting. The model estimated the clinical and economic outcomes of introducing a new antibacterial for the treatment of HAIs with LTO in Greece. The current treatment pathway was compared with introducing a new antibacterial to the treatment sequence. Outcomes were assessed from a third-party payer perspective, over a 10-year transmission period, with quality-adjusted life years (QALYs) and life years (LYs) gained considered over a lifetime horizon. RESULTS: Over the next 10 years, HAIs with LTO in Greece account for approximately 1.4 million hospital bed days, hospitalisation costs of more than €320 million and a loss of approximately 403,000 LYs (319,000 QALYs). Introduction of the new antibacterial as first-line treatment provided the largest clinical and economic benefit, with savings of up to 93,000 bed days, approximately €21 million in hospitalisation costs and an additional 286,000 LYs (226,000 QALYs) in comparison to the current treatment strategy. The introduction of a new antibacterial was linked to a monetary benefit of €6.8 billion at a willingness to pay threshold of €30,000 over 10 years. CONCLUSION: This study highlights the considerable clinical and economic benefit of introducing a new antibacterial for HAIs with LTO in Greece. This analysis shows the additional benefit when a new antibacterial is introduced to treatment sequences. These findings can be used to inform decision makers to implement policies to ensure timely access to new antibacterial treatments in Greece.

Antimicrobial resistance is a major issue for the Greek healthcare system. The overuse of antibacterial agents contributes to the growing resistance levels, making currently available treatment options less effective. As a result, there is an imperative need to address antimicrobial resistance in Greece. This study developed a mathematical model to investigate the clinical and economic benefits of introducing a new antibacterial to current treatment practice. The model uses regression equations to describe the relationships between inputs and outputs from a published and validated model, which describes the transmission and treatment of infections. The model is used to estimate the impact of a new treatment in Greece, considering differing treatment sequence scenarios. The largest health and financial benefits were seen when a new antibacterial was introduced at first line prior to currently used treatments. Over 10 years, savings of up to 93,000 hospital bed days and €21 million in hospitalisation costs could be achieved, as well as a gain of 286,000 patient life years and 226,000 patient quality-adjusted life years (QALYs), a measure of a patient's quality and length of life, over their remaining lifetime. The introduction of a new antibacterial into the current treatment pathway resulted in an overall monetary benefit of €6.8 billion over 10 years, when additional QALYs are valued at €30,000. This study demonstrates considerable health economic benefits of introducing a new antibacterial in Greece and can help inform decision makers when developing a national action plan to combat resistance and improve access to treatments.

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

BACKGROUND: Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. Globally, research and development of new antimicrobials has stalled due to unfavorable market conditions, which undervalue antimicrobials. Furthermore, Japan faces the additional challenge of delayed commercialization for a number of recently approved treatments. OBJECTIVE: This study aims to examine the impact on AMR of introducing a new anti-infective treatment, ceftazidime/avibactam, into current treatment strategies. It reports the resulting clinical and economic outcomes from the perspective of healthcare payers in Japan. METHODS: A previously published and validated dynamic disease transmission model was adapted to the Japanese setting. The model estimated health economic outcomes for treating three Gram-negative hospital-acquired infections, under different treatment strategies, from a healthcare payers' perspective. Outcomes were assessed over a 10-year time horizon with a willingness-to-pay threshold of ¥5,000,000 (US$45,556) per quality-adjusted life-year (QALY) gained and an annual discount rate of 2% applied to costs and benefits. RESULTS: Introducing ceftazidime/avibactam in the framework of a diversification strategy with piperacillin/tazobactam is associated with reducing 798,640 bed days, equating to ¥21.0 billion (US$190.9 million) savings in hospitalization costs, and a gain of 363,034 life-years, or 308,641 QALYs. This translates into a monetary benefit of ¥1.56 trillion (US$14.3 billion) to Japanese healthcare payers. DISCUSSION: Introducing a new antimicrobial agent into clinical practice is associated with considerable clinical and economic benefits. This analysis demonstrates that the approach taken to incorporate a new antimicrobial agent into clinical practice impacts on the scale of these clinical and economic benefits; greater benefits are associated with earlier use of antimicrobials as part of an antimicrobial stewardship program. CONCLUSION: This analysis shows that changing the way in which a new antimicrobial is used within a treatment strategy has the potential for additional significant clinical and economic value.

Identification of undiagnosed atrial fibrillation using a machine learning risk prediction algorithm and diagnostic testing (PULsE-AI) in primary care: cost-effectiveness of a screening strategy evaluated in a randomized controlled trial in England.

OBJECTIVE: The PULsE-AI trial sought to determine the effectiveness of a screening strategy that included a machine learning risk prediction algorithm in conjunction with diagnostic testing for identification of undiagnosed atrial fibrillation (AF) in primary care. This study aimed to evaluate the cost-effectiveness of implementing the screening strategy in a real-world setting. METHODS: Data from the PULsE-AI trial - a prospective, randomized, controlled trial conducted across six general practices in England from June 2019 to February 2021 - were used to inform a cost-effectiveness analysis that included a hybrid screening decision tree and Markov AF disease progression model. Model outcomes were reported at both individual- and population-level (estimated UK population ≥30 years of age at high-risk of undiagnosed AF) and included number of patients screened, number of AF cases identified, mean total and incremental costs (screening, events, treatment), quality-adjusted-life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: The screening strategy was estimated to result in 45,493 new diagnoses of AF across the high-risk population in the UK (3.3 million), and an estimated additional 14,004 lifetime diagnoses compared with routine care only. Per-patient costs for high-risk individuals who underwent the screening strategy were estimated at £1,985 (vs £1,888 for individuals receiving routine care only). At a population-level, the screening strategy was associated with a cost increase of approximately £322 million and an increase of 81,000 QALYs. The screening strategy demonstrated cost-effectiveness versus routine care only at an accepted ICER threshold of £20,000 per QALY-gained, with an ICER of £3,994/QALY. CONCLUSIONS: Compared with routine care only, it is cost-effective to target individuals at high risk of undiagnosed AF, through an AF risk prediction algorithm, who should then undergo diagnostic testing. This AF risk prediction algorithm can reduce the number of patients needed to be screened to identify undiagnosed AF, thus alleviating primary care burden.

Estimating the Economic and Clinical Value of Reducing Antimicrobial Resistance to Three Gram-negative Pathogens in Japan.

Background: Antimicrobial resistance (AMR) represents a significant global public health crisis. Despite ample availability of Gram-positive antibiotics, there is a distinct lack of agents against Gram-negative pathogens, including carbapenem-resistant Enterobacterales, which remains a real threat in Japan. The AMR Action Plans aim to mitigate the growing public health concern posed by AMR. Objective: This study aims to estimate the clinical and economic outcomes of drug-resistant Gram-negative pathogens forecasts for Japan to guide resource allocation defined within the upcoming National AMR Action Plan. Methods: A previously published and validated dynamic health economic model was adapted to the Japanese setting. The model used a 10-year time horizon with a willingness-to-pay threshold of ¥5 000 000 (US $46 827) and discounting was applied at a rate of 2% to costs and benefits. Clinical and economic outcomes were assessed as a function of varying AMR levels of three Gram-negative pathogens in Japan by up to 100% of the current level. Results: Reducing drug-resistant Gram-negative pathogens in Japan has the potential to save 4 249 096 life years, corresponding to 3 602 311 quality-adjusted life years. The associated maximum clinical and economic gains were estimated at up to 4 422 284 bed days saved, up to 3 645 480 defined daily doses of antibiotics avoided, up to ¥117.6 billion (US $1.1 billion) saved in hospitalization costs, and a net monetary benefit of up to ¥18.1 trillion (US $169.8 billion). Discussion: Learnings from this study can be used by the Japanese government to help inform decision-making on the strategies that may be included in the upcoming National AMR Action Plan and facilitate allocation of the required budget. Conclusions: This analysis demonstrated the considerable economic and clinical value of reducing AMR levels of three Gram-negative pathogens in Japan and could be utilized to support the valuation of antimicrobial treatment and resistance in Japan and more broadly.

Clinical cost evaluation and health benefits of post-bariatric intervention for patients with type 2 diabetes living in the UK.

To assess associated healthcare costs and risk of developing obesity-related comorbidities among patients with type 2 diabetes with severe obesity and receiving insulin treatment, following bariatric surgery (BS). A retrospective cohort study was conducted from a UK electronic primary care database. Propensity score matching (1:1) was performed for BS with non-BS cohort. Follow-up was over 5 years (694 person-years), comparing drug utilization with clinical cost differences, such as visits to General practitioners (GPs), hospitalization, and laboratory use. Cox proportional regression was used to compute differences in the risk of obesity-related comorbidities and chi-square analysis to explore differences in insulin independency and diabetes remission proportions during follow-up. Eighty patients who received BS were matched to 80 non-BS (N = 160). The baseline mean age was 48.3 years (SD: 12.9) (61% female), and body mass index was 39.3 kg/m2 (SD: 9.3). During follow-up, antidiabetic drug cost was significantly lower in the BS group than in the non-BS (median cost/person [£]: 527.77 [interquartile range (IQR): 1196.11] vs. 1564.13 [IQR: 1576.01]; p < 0.001). Overall, aggregate cost analysis showed a significant total healthcare cost reduction in the BS group (median cost/person [£]: 1597.96 [IQR: 2631.84] vs. 2440.12 [IQR: 2242.95]; p = 0.050). BS significantly protected against obesity-related comorbidities compared with the non-BS (adjusted hazard ratio: 0.56; 95% confidence interval: 0.32-0.96; p = 0.036) and increased insulin independency throughout all follow-up points: at year 5: 48.1% versus 28.9%; p = 0.044, respectively. While BS shows evidence of cost efficiency, cost saving was not identified. The efficiency is evident by the protective effect against crude obesity-related comorbidities associated with increased insulin independency.

Non-Price-Related Determinants of Value and Access for Novel Non-small Cell Lung Cancer Treatments: A Cross-Country Review of HTA Decision Making.

INTRODUCTION: Access and funding for newly approved treatments for non-small cell lung cancer (NSCLC) are often dependent on Health Technology Assessment (HTA) involving cost-effectiveness analysis. Whilst methods used by HTA agencies share many similarities, final decisions may differ. This may be the result, not just of price considerations, but also of variation in value judgements by different agencies. The aim of this study was to review international HTA evaluations to identify determinants of value and access for NSCLC treatments. METHODS: A targeted review and analysis was undertaken of published HTAs for NSCLC across HTA agencies in six countries (Australia, Canada, England, France, Ireland and Scotland). Analysis of extracted data consisted of three stages: descriptive analysis, bivariate analysis and multivariable analysis. RESULTS: The analysis included 163 HTAs that assessed oncological treatments for NSCLC from 2003 to 2019. The majority of HTA decisions (67.5%) were positive. However, some evidence of heterogeneity in HTA decisions and the factors informing them were identified. The most influential factors included in the multivariate model related to the HTA agency conducting the appraisal, the year of market authorisation, treatment type and the line of treatment. CONCLUSION: Heterogenous decision-making frameworks can present a challenge to developing HTA submissions. This research contributes to understanding decision-making factors and why countries make different decisions.

Estimating the Value of New Antimicrobials in the Context of Antimicrobial Resistance: Development and Application of a Dynamic Disease Transmission Model.

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.

Cost-effectiveness of targeted screening for the identification of patients with atrial fibrillation: evaluation of a machine learning risk prediction algorithm.

Aims: As many cases of atrial fibrillation (AF) are asymptomatic, patients often remain undiagnosed until complications (e.g. stroke) manifest. Risk-prediction algorithms may help to efficiently identify people with undiagnosed AF. However, the cost-effectiveness of targeted screening remains uncertain. This study aimed to assess the cost-effectiveness of targeted screening, informed by a machine learning (ML) risk prediction algorithm, to identify patients with AF.Methods: Cost-effectiveness analyses were undertaken utilizing a hybrid screening decision tree and Markov disease progression model. Costs and outcomes associated with the detection of AF compared traditional systematic and opportunistic AF screening strategies to targeted screening informed by a ML risk prediction algorithm. Model analyses were based on adults ≥50 years and adopted the UK NHS perspective.Results: Targeted screening using the ML risk prediction algorithm required fewer patients to be screened (61 per 1,000 patients, compared to 534 and 687 patients in the systematic and opportunistic strategies) and detected more AF cases (11 per 1,000 patients, compared to 6 and 8 AF cases in the systematic and opportunistic screening strategies). The targeted approach demonstrated cost-effectiveness under base case settings (cost per QALY gained of £4,847 and £5,544 against systematic and opportunistic screening respectively). The targeted screening strategy was predicted to provide an additional 3.40 and 2.05 QALYs per 1,000 patients screened versus systematic and opportunistic strategies. The targeted screening strategy remained cost-effective in all scenarios evaluated.Limitations: The analysis relied on assumptions that include the extended period of patient life span and the lack of consideration for treatment discontinuations/switching, as well as the assumption that the ML risk-prediction algorithm will identify asymptomatic AF.Conclusions: Targeted screening using a ML risk prediction algorithm has the potential to enhance the clinical and cost-effectiveness of AF screening, improving health outcomes through efficient use of limited healthcare resources.

Daclatasvir combined with asunaprevir is a cost-effective and cost-saving treatment for hepatitis C infection in China.

Aim: To evaluate the cost-effectiveness of the novel all-oral direct-acting antiviral regimen daclatasvir + asunaprevir (DUAL), versus interferon-based regimens for the treatment of chronic hepatitis C virus genotype 1b infection. Methods: Inputs for a lifetime Markov model were sourced from clinical trials and published literature. Outputs include disease management costs, life expectancy, quality-adjusted life-years and cost-effectiveness. Sensitivity analyses assessed the drivers of cost-effectiveness and sustained virologic response thresholds at which DUAL is cost-saving. Results: DUAL was associated with discounted incremental quality-adjusted life-years of 1.29-3.85 and incremental life-years of 0.85-2.59 per patient, with discounted lifetime cost savings of USD$1415-8525. Associated sustained virologic response rates could fall to 45.1-84.8%, while remaining dominant. Conclusion: Treatment with DUAL provides significant clinical benefit, while accruing lower lifetime costs.

A clinician's guide to the cost and health benefits of hepatitis C cure assessed from the individual patient perspective.

BACKGROUND AND AIMS: The hepatitis C virus (HCV) remains a considerable public health challenge. Novel direct-acting antiviral (DAA) regimens offer high cure rates and the promise of reduced HCV incidence and prevalence following the up-scaling of treatment. This has focused attention towards affordability. This study aimed to estimate the economic value of cure to evaluate the treatment costs justifiable from the patient perspective. PATIENTS AND METHODS: A published, validated HCV model was utilized to contrast clinical and cost outcomes for patients aged 30-70 years, stratified by METAVIR F0-F4, for (i) no treatment and (ii) successful treatment [i.e. sustained virologic response (SVR)] ignoring the cost of treatment. Regression equations were fitted and used to determine the financial expenditure justifiable to achieve a cost-neutral or a cost-effective [£20 000 per quality-adjusted life-year (QALY)] cure. Model inputs were derived from UK literature; costs and utilities were discounted at 3.5% over a lifetime horizon. RESULTS: To achieve cost-neutrality, the maximum discounted expenditure justifiable for SVR was £3774-43 607 across ages and fibrosis stages. Spending between £19 745 (70 years, F0) and £188 420 (30 years, F4) on SVR is expected to be cost-effective at £20 000/QALY willingness-to-pay threshold. CONCLUSION: Heterogeneity across HCV patients is considerable, which can obscure the relevance of conventional cohort-based economic models evaluated at the mean, particularly when considering the value of treatment at the individual patient level. By quantifying the full exposition of HCV cost-savings and health benefits realizable following HCV cure, this study provides insight into the economic value of successful treatment from the patient perspective.

Value of Sustained Virologic Response in Patients with Hepatitis C as a Function of Time to Progression of End-Stage Liver Disease.

BACKGROUND: Targeted intervention in patients with hepatitis C virus (HCV) closest to end-stage liver disease (ESLD) progression may offer an approach to treatment prioritisation whilst delivering benefits for patients and the healthcare system. In contrast to previous HCV economic analyses, this study aimed to estimate the health economic value of sustained virologic response (SVR) stratified by the patient's propensity to progress to ESLD. METHODS: An HCV natural history model was adapted to estimate the value of avoiding ESLD complications following SVR, assessed as cost offsets and quality-adjusted life year (QALY) gains, as a function of time to ESLD at treatment initiation. These outcomes were used to estimate the financial value of achieving SVR, defined as the maximum investment that could be allocated without exceeding a willingness-to-pay threshold of £20,000/QALY. RESULTS: Regardless of time to ESLD onset, achieving SVR was beneficial, resulting in cost offsets and QALY gains, due to avoidance of ESLD complications. The value of achieving SVR was greatest in patients closest to ESLD onset, resulting in increased cost offsets and QALY gains (up to £50,901 and 9.56 QALYs). In patients closest to ESLD onset, the financial value of achieving SVR was £242,051, compared with £127,116 in patients furthest from onset. CONCLUSIONS: Standard cost-effectiveness evaluations may underestimate the value of treatment in HCV patients closest to ESLD development. Targeted intervention would promote efficient allocation of limited healthcare resources and reconcile concerns surrounding the affordability of new direct-acting antivirals, by minimising the number-needed-to-treat to maximise health benefit, whilst minimising healthcare expenditure.

Hepatitis C disease transmission and treatment uptake: impact on the cost-effectiveness of new direct-acting antiviral therapies.

BACKGROUND: Hepatitis C virus (HCV) treatment can reduce the incidence of future infections through removing opportunities for onward transmission. This benefit is not captured in conventional cost-effectiveness evaluations of treatment and is particularly relevant in patient groups with a high risk of transmission, such as those people who inject drugs (PWID), where the treatment rates have been historically low. This study aimed to quantify how reduced HCV transmission changes the cost-effectiveness of new direct-acting antiviral (DAA) regimens as a function of treatment uptake rates. METHODS: An established model of HCV disease transmission and progression was used to quantify the impact of treatment uptake (10-100%), within the PWID population, on the cost-effectiveness of a DAA regimen versus pre-DAA standard of care, conducted using daclatasvir plus sofosbuvir in the UK setting as an illustrative example. RESULTS: The consequences of reduced disease transmission due to treatment were associated with additional net monetary benefit of £24,304-£90,559 per patient treated at £20,000/QALY, when 10-100% of eligible patients receive treatment with 100% efficacy. Dependent on patient genotype, the cost-effectiveness of HCV treatment using daclatasvir plus sofosbuvir improved by 36-79% versus conventional analysis, at 10-100% treatment uptake in the PWID population. CONCLUSIONS: The estimated cost-effectiveness of HCV treatment was shown to improve as more patients are treated, suggesting that the value of DAA regimens to the NHS could be enhanced by improved treatment uptake rates among PWID. However, the challenge for the future will lie in achieving increased rates of treatment uptake, particularly in the PWID population.

An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus.

AIMS: Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. MATERIALS AND METHODS: A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. RESULTS: A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. CONCLUSIONS: The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories.

Managing glycaemia in older people with type 2 diabetes: A retrospective, primary care-based cohort study, with economic assessment of patient outcomes.

AIMS: To describe the relative health and economic outcomes associated with different second-line therapeutic approaches to manage glycaemia in older type 2 diabetes patients requiring escalation from metformin monotherapy. MATERIALS AND METHODS: The Clinical Practice Research Datalink database was used to inform a retrospective observational cohort study of patients with type 2 diabetes treated with metformin monotherapy requiring escalation (addition or switch) to a second-line oral regimen from January 1, 2008 to December 31, 2014. Primary outcomes included time to first event (any event, myocardial infarction [MI], stroke, or composite of MI/stroke [major adverse cardiovascular event; MACE]) and total event rate. The health economic consequences associated with the choice of second-line treatment in older patients were assessed using the CORE Diabetes Model. RESULTS: A total of 10 484 patients were included; the majority escalated to second-line treatment with metformin + sulphonylurea (SU; 42%) or switched to SU monotherapy (28%). In multivariate adjusted analyses, total event rates for MACE with metformin + dipeptidyl peptidase-4 (DPP-4) inhibitor were significantly lower than with metformin + SU (0.61, 95% confidence interval [CI] 0.39-0.98), driven by a lower MI rate in the metformin + DPP-4 inhibitor group (0.52, 95% CI 0.27-0.99). Economic analyses estimated that metformin + DPP-4 inhibitor treatment was associated with the largest gain in health benefit, and cost-effectiveness ratios were favourable (<£30 000 per quality-adjusted life-year) for all second-line treatment scenarios. CONCLUSIONS: With respect to treatment choice, data from the present study support the notion of prescribing beyond metformin + SU, as alternative regimens have been shown to be associated with reduced outcomes risk and value for money.