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.

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.

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.

Efficacy and safety of intensive versus conventional glucose targets in people with type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. METHODS: We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA1clevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95). CONCLUSION: Targeting HbA1c levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.

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.

Factors Predictive of Weight Gain and Implications for Modeling in Type 2 Diabetes Patients Initiating Metformin and Sulfonylurea Combination Therapy.

INTRODUCTION: The objectives of this study were to (a) assess the factors associated with weight gain in a population of type 2 diabetes patients escalating from metformin (M) to M+ sulfonylurea (M + S) and (b) evaluate whether healthcare resource utilization associated with being overweight or obese is underestimated in typical health economic evaluations. METHODS: The study was a retrospective cohort study using UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (CPRD/HES) data. The association between baseline phenotypic factors and weight gain was assessed using logistic regression. Hospitalization incidence rates per 1000 person-years for major diabetes-related complications according to body mass index (BMI) at baseline were estimated from the data (observed) and compared to those obtained from a validated diabetes model (predicted). RESULTS: 11,071 patients were included in the analysis; approximately 40% gained weight in the first year following escalation to M + S. Baseline age, HbA1c and gender were found to be predictors of weight gain [odds ratios 0.99 (1-year increment), 1.11 (1% increment) and 0.81 (female vs male), respectively, p < 0.001]. Observed vs predicted incidence rates of hospitalization were 265 vs 13 (normal), 297 vs 31 (overweight), 223 vs 50 (obese) and 378 vs 41 (severe obese). CONCLUSION: This analysis suggests there are identifiable patient characteristics predictive of weight gain that may be informative to clinical and economic decision making in the context of patients escalating from M to an M + S regimen. Hospital admissions in people with type 2 diabetes were generally under-predicted. A particular focus of future research should be the need for diabetes models to make the likelihood of experiencing an event conditional on BMI. FUNDING: Takeda Development Centre Europe Ltd., UK.

Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohn's disease: a systematic review and clinician surveys.

OBJECTIVES: Comparative outcomes of patients with ulcerative colitis (UC) and Crohn's disease (CD) prescribed a biologic therapy are inconclusive. The aim of this research was to characterize the degree of unmet medical need in patients with UC or CD and to identify the potential role for new therapies. METHODS: A systematic literature review was undertaken of studies reporting outcomes associated with the use of existing biologic therapies in patients with UC or CD, focusing on the nature and rate of treatment failure. To complement the systematic review, contemporaneous data were obtained from a survey of practising gastroenterologists in the UK and France. Data were qualitatively combined in a narrative framework to evaluate the degree of unmet medical need among patients with UC or CD. RESULTS: Studies identified in the systematic review (n = 120) were heterogeneous, particularly with respect to the definitions of treatment failure; estimates of treatment failure were high but uncertain. On the basis of standardized definitions, estimates of treatment failure provided by clinicians (n = 102) were high, and they were higher for second-line treatment failure (primary: ≤ 37%; secondary: ≤ 41%) compared with first-line treatment failure (primary: ≤ 26%; secondary: ≤ 28%). The majority of the systematic review and survey data were reflective of outcomes with infliximab and adalimumab. CONCLUSION: High treatment failure rates associated with existing biologics, identified by the review and clinician surveys, indicate a need for other biologic treatment options to improve the management and outcomes for people with UC and CD. Outcomes associated with existing and new biologic treatments should be investigated in head-to-head randomized trials in the context of their likely uses in clinical practice.

Assessing the relationship between computational speed and precision: a case study comparing an interpreted versus compiled programming language using a stochastic simulation model in diabetes care.

BACKGROUND: Simulation techniques are well suited to modelling diseases yet can be computationally intensive. This study explores the relationship between modelled effect size, statistical precision, and efficiency gains achieved using variance reduction and an executable programming language. METHODS: A published simulation model designed to model a population with type 2 diabetes mellitus based on the UKPDS 68 outcomes equations was coded in both Visual Basic for Applications (VBA) and C++. Efficiency gains due to the programming language were evaluated, as was the impact of antithetic variates to reduce variance, using predicted QALYs over a 40-year time horizon. RESULTS: The use of C++ provided a 75- and 90-fold reduction in simulation run time when using mean and sampled input values, respectively. For a series of 50 one-way sensitivity analyses, this would yield a total run time of 2 minutes when using C++, compared with 155 minutes for VBA when using mean input values. The use of antithetic variates typically resulted in a 53% reduction in the number of simulation replications and run time required. When drawing all input values to the model from distributions, the use of C++ and variance reduction resulted in a 246-fold improvement in computation time compared with VBA - for which the evaluation of 50 scenarios would correspondingly require 3.8 hours (C++) and approximately 14.5 days (VBA). CONCLUSIONS: The choice of programming language used in an economic model, as well as the methods for improving precision of model output can have profound effects on computation time. When constructing complex models, more computationally efficient approaches such as C++ and variance reduction should be considered; concerns regarding model transparency using compiled languages are best addressed via thorough documentation and model validation.

Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy.

OBJECTIVES: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis. METHODS: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field. RESULTS: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (approximately .2 percent) for devices costing as much as 60,000 pounds. Sensitivity of the conclusions to both device cost and QALY valuation is examined. CONCLUSIONS: In the event that the price of the device in use would reduce to 40,000 pounds, the value of the survival information can readily justify investment in further trials.