Validating Health Economic Models With the Probabilistic Analysis Check dashBOARD.

OBJECTIVES: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making. This study aimed to develop and test a generic dashboard to systematically explore the workings of HE models and validate their model parameters and outcomes. METHODS: The Probabilistic Analysis Check dashBOARD (PACBOARD) was developed using insights from literature, health economists, and a data scientist. Functionalities of PACBOARD are (1) exploring and validating model parameters and outcomes using standardized validation tests and interactive plots, (2) visualizing and investigating the relationship between model parameters and outcomes using metamodeling, and (3) predicting HE outcomes using the fitted metamodel. To test PACBOARD, 2 mock HE models were developed, and errors were introduced in these models, eg, negative costs inputs, utility values exceeding 1. PACBOARD metamodeling predictions of incremental net monetary benefit were validated against the original model's outcomes. RESULTS: PACBOARD automatically identified all errors introduced in the erroneous HE models. Metamodel predictions were accurate compared with the original model outcomes. CONCLUSIONS: PACBOARD is a unique dashboard aiming at improving the feasibility and transparency of validation efforts of HE models. PACBOARD allows users to explore the working of HE models using metamodeling based on HE models' parameters and outcomes.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNFi in JIA patients. METHODS: Retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were either immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalisation) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9,165/patient on active treatment (pre-withdrawal) and decreased significantly to €5,063/patient (-44.8%) and €6,569/patient (-28.3%) in the first and second year post-withdrawal, respectively (p< 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1,180/patient, and €1,320/patient, in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first, and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs are decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdraw decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

The societal impact of implementing an at-home blood sampling device for chronic care patients: patient preferences and cost impact.

BACKGROUND: Diabetes mellitus, cardiovascular diseases, chronic kidney disease, and thyroid diseases are chronic diseases that require regular monitoring through blood tests. This paper first investigates the experiences of chronic care patients with venipuncture and their expectations of an at-home blood-sampling device, and then assesses the impact on societal costs of implementing such a device in current practice. METHODS: An online survey was distributed among chronic care patients to gain insight into their experience of blood sampling in current practice, and their expectations of an at-home blood-sampling device. The survey results were used as input parameters in a patient-level monte carlo analysis developed to represent a hypothetical cohort of Dutch chronically ill patients to investigate the impact on societal costs compared to usual care. RESULTS: In total, 1311 patients participated in the survey, of which 31% experience the time spent on the phlebotomy appointment as a burden. Of all respondents, 71% prefer to use an at-home blood-sampling device to monitor their chronic disease. The cost analysis indicated that implementing an at-home blood-sampling device increases the cost of phlebotomy itself by €27.25 per patient per year, but it reduces the overall societal costs by €24.86 per patient per year, mainly due to limiting productivity loss. CONCLUSIONS: Patients consider an at-home blood-sampling device to be more user-friendly than venous phlebotomy on location. Long waiting times and crowded locations can be avoided by using an at-home blood-sampling device. Implementing such a device is likely cost-saving as it is expected to reduce societal costs.

Costs of Hospital-Associated Care for Patients With Juvenile Idiopathic Arthritis in the Dutch Health Care System.

OBJECTIVE: The aim of this study was to quantify costs of hospital-associated care for juvenile idiopathic arthritis (JIA), provide insights in patient-level variation in costs, and investigate costs over time from the moment of JIA diagnosis. Results were reported for all JIA patients in general and by subtype. METHODS: This study was a single-center, retrospective analysis of prospective data from electronic medical records of children with JIA, ages 0-18 years, between April 1, 2011 and March 31, 2019. Patient characteristics (age, sex, JIA subtype) and hospital-based resource use (consultations, medication, radiology procedures, laboratory testing, surgeries, emergency department [ED] visits, hospital stays) were extracted and analyzed. Unit prices were obtained from Dutch reimbursement lists and pharmaceutical and hospital list prices. RESULTS: The analysis included 691 patients. The mean total cost of hospital care was €3,784/patient/year, of which €2,103 (55.6%) was attributable to medication. Other costs involved pediatric rheumatologist visits (€633/patient/year [16.7%]), hospital stays (€439/patient/year [11.6%]), other within-hospital specialist visits (€324/patient/year [8.6%]), radiology procedures (€119/patient/year [3.1%]), laboratory tests (€114/patient/year [3.0%]), surgeries (€46/patient/year [1.2%]), and ED visits (€6/patient/year [0.2%]). Mean annual total costs varied between JIA subtypes and between individuals and were the highest for systemic JIA (€7,772/patient/year). Over the treatment course, costs were the highest in the first month after JIA diagnosis. CONCLUSION: Hospital care costs of JIA vary substantially between individuals, between subtypes, and over the treatment course. The highest annual costs were for systemic JIA, primarily attributable to medication (i.e., biologics). Costs of other hospital-associated care were comparable regardless of subtype.

Evaluation of Real-World Healthcare Resource Utilization and Associated Costs in Children with Juvenile Idiopathic Arthritis: A Canadian Retrospective Cohort Study.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease, whose multifaceted care path can lead to significant expenditure for the healthcare system. We aim to assess the real-world healthcare resource use (HCRU) and associated cost for children with JIA in a single center in Canada. METHODS: A single-center consecutive cohort of newly diagnosed patients with JIA attending the pediatric rheumatology clinic from 2011 to 2019 was identified using an administrative data algorithm and electronic medical charts. HCRU was estimated from six administrative health databases that included hospital admissions, emergency, outpatient care, practitioners' visits, medication, and laboratory and imaging tests. Costs were assigned using appropriate sources. We reported the yearly overall and JIA-associated HCRU and costs 5 years prior to and 6 years after the first visit to the pediatric rheumatologist. The Zhao and Tian estimator was used to calculate cumulative mean costs over a 6-year timeframe. Results were stratified by disease subtype. RESULTS: A total of 389 patients were identified. The yearly total overall mean costs per patient ranged between $804 and $4460 during the 5 years prior to the first visit to the pediatric rheumatologist and $8529 and $10,651 for the 6 years after. Medication cost, driven by use of biologic therapies, and outpatient visits were the greatest contributor to the total cost. The overall cumulative mean cost for 6 years of care was $48,649 per patient, while the JIA-associated cumulative mean cost was $26,820 per patient. During the first year of rheumatology care, systemic onset JIA had the highest cumulative mean overall cost, while oligoarticular JIA had the lowest cumulative mean cost. CONCLUSION: The care pathway for children with JIA can be expensive, and complex-and varies by JIA subtype. Although the yearly total mean cost per patient was constant, the distribution of costs changes over time with the introduction of biologic therapies later in the care pathway. This study provides a better understanding of the JIA costs profile and can help inform future economic studies.

Costs of medication use among patients with juvenile idiopathic arthritis in the Dutch healthcare system.

Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype.Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, subtype) and medication use were extracted. Medication use and costs were reported as: 1) mean total annual costs; 2) between-patient heterogeneity in these costs; 3) duration of medication use; and, 4) costs over the treatment course.Results: The analysis included 691 patients. Mean total medication costs were €2,103/patient/year, including €1,930/patient/year (91.8%) spent on biologicals. Costs varied considerably between subtypes, with polyarticular rheumatoid-factor positive and systemic JIA patients having the highest mean costs (€5,020/patient/year and €4,790/patient/year, respectively). Mean annual medication costs over the patient's treatment course ranged from <€1,000/year (71.1% of patients) to >€11,000/year (2.5% of patients). Etanercept and adalimumab were the most commonly used biologicals. Cost fluctuations over the treatment course were primarily attributable to biological use.Conclusions: Polyarticular rheumatoid-factor positive and systemic JIA patients had the highest mean total annual medication costs, primarily attributable to biologicals. Costs varied considerably between subtypes, individuals, and over the treatment course.

Health State Utility Values in Juvenile Idiopathic Arthritis: What is the Evidence?

OBJECTIVES: The objectives of this systematic review were to identify health state utility values (HSUV) of children and adults with juvenile idiopathic arthritis in the literature and to assess whether HSUV were appropriately reported and could be used to inform parameter inputs for a model-based cost-utility analysis to inform decision making. METHODS: MEDLINE, EMBASE, PsycINFO, EconLit and CINAHL databases were searched in July 2019. Inclusion criteria were studies using preference-based instruments, targeting children or adults with juvenile idiopathic arthritis, and in the English language. The quality of studies was assessed using a modified checklist that included relevant sources of bias and assessment of quality of HSUV valuation and measurement. A descriptive analysis was conducted, including assessment on reporting of population characteristics and stratification of HSUV by potential health states or population subgroup. RESULTS: From 620 identified articles, ten reported HSUV. Seven studies reported HSUV of children with juvenile idiopathic arthritis, and three of adults with a history of juvenile idiopathic arthritis. Population disease activity status and drug treatment were reported in less than half of the studies. Six (out of ten) studies stratified HSUV results for at least one of the potential health state categories, but they represent very specific situations or interventions (e.g. patients receiving different types of physiotherapy or treated with etanercept over time). CONCLUSIONS: We have identified critical gaps in the literature reporting HSUV in patients with juvenile idiopathic arthritis including a lack of HSUV measures for distinct health states, particularly in adults with a history of juvenile idiopathic arthritis. The current reported HSUV data in juvenile idiopathic arthritis are insufficient for a full cost-utility analysis with a short or lifetime horizon.

Seeking the state of the art in standardized measurement of health care resource use and costs in juvenile idiopathic arthritis: a scoping review.

BACKGROUND: This study aims to describe current practice in identifying and measuring health care resource use and unit costs in economic evaluations or costing studies of juvenile idiopathic arthritis (JIA). METHODS: A scoping review was conducted (in July 2018) in PubMed and Embase to identify economic evaluations, costing studies, or resource utilization studies focusing on patients with JIA. Only English language peer-reviewed articles reporting primary research were included. Data from all included full-text articles were extracted and analysed to identify the reported health care resource use items. In addition, the data sources used to obtain these resource use and unit costs were identified for all included articles. RESULTS: Of 1176 unique citations identified by the search, 20 full-text articles were included. These involved 4 full economic evaluations, 5 cost-outcome descriptions, 8 cost descriptions, and 3 articles reporting only resource use. The most commonly reported health care resource use items involved medication (80%), outpatient and inpatient hospital visits (80%), laboratory tests (70%), medical professional visits (70%) and other medical visits (65%). Productivity losses of caregivers were much more often incorporated than (future) productivity losses of patients (i.e. 55% vs. 15%). Family borne costs were not commonly captured (ranging from 15% for school costs to 50% for transportation costs). Resource use was mostly obtained from family self-reported questionnaires. Estimates of unit costs were mostly based on reimbursement claims, administrative data, or literature. CONCLUSIONS: Despite some consistency in commonly included health care resource use items, variability remains in including productivity losses, missed school days and family borne costs. As these items likely substantially influence the full cost impact of JIA, the heterogeneity found between the items reported in the included studies limits the comparability of the results. Therefore, standardization of resource use items and unit costs to be collected is required. This standardization will provide guidance to future research and thereby improve the quality and comparability of economic evaluations or costing studies in JIA and potentially other childhood diseases. This would allow better understanding of the burden of JIA, and to estimate how it varies across health care systems.

Understanding the adoption and use of point-of-care tests in Dutch general practices using multi-criteria decision analysis.

BACKGROUND: The increasing number of available point-of-care (POC) tests challenges clinicians regarding decisions on which tests to use, how to efficiently use them, and how to interpret the results. Although POC tests may offer benefits in terms of low turn-around-time, improved patient's satisfaction, and health outcomes, only few are actually used in clinical practice. Therefore, this study aims to identify which criteria are, in general, important in the decision to implement a POC test, and to determine their weight. Two POC tests available for use in Dutch general practices (i.e. the C-reactive protein (CRP) test and the glycated haemoglobin (HbA1c) test) serve as case studies. The information obtained from this study can be used to guide POC test development and their introduction in clinical practice. METHODS: Relevant criteria were identified based on a literature review and semi-structured interviews with twelve experts in the field. Subsequently, the criteria were clustered in four groups (i.e. user, organization, clinical value, and socio-political context) and the relative importance of each criterion was determined by calculating geometric means as implemented in the Analytic Hierarchy Process. Of these twelve experts, ten participated in a facilitated group session, in which their priorities regarding both POC tests (compared to central laboratory testing) were elicited. RESULTS: Of 20 criteria in four clusters, the test's clinical utility, its technical performance, and risks (associated with the treatment decision based on the test result) were considered most important for using a POC test, with relative weights of 22.2, 12.6 and 8.5%, respectively. Overall, the experts preferred the POC CRP test over its laboratory equivalent, whereas they did not prefer the POC HbA1c test. This difference was mainly explained by their strong preference for the POC CRP test with regard to the subcriterion 'clinical utility'. CONCLUSIONS: The list of identified criteria, and the insights in their relative impact on successful implementation of POC tests, may facilitate implementation and use of existing POC tests in clinical practice. In addition, having experts score new POC tests on these criteria, provides developers with specific recommendations on how to increase the probability of successful implementation and use.

Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands.

BACKGROUND: Procalcitonin (PCT) testing can help in safely reducing antibiotic treatment duration in intensive care patients with sepsis. However, the cost-effectiveness of such PCT guidance is not yet known. METHODS: A trial-based analysis was performed to estimate the cost-effectiveness of PCT guidance compared with standard of care (without PCT guidance). Patient-level data were used from the SAPS trial in which 1546 patients were randomised. This trial was performed in the Netherlands, which is a country with, on average, low antibiotic use and a short duration of hospital stay. As quality of life among sepsis survivors was not measured during the SAPS, this was derived from a Dutch follow-up study. Outcome measures were (1) incremental direct hospital cost and (2) incremental cost per quality-adjusted life year (QALY) gained from a healthcare perspective over a one-year time horizon. Uncertainty in outcomes was assessed with bootstrapping. RESULTS: Mean in-hospital costs were €46,081/patient in the PCT group compared with €46,146/patient with standard of care (i.e. - €65 (95% CI - €6314 to €6107); - 0.1%). The duration of the first course of antibiotic treatment was lower in the PCT group with 6.9 vs. 8.2 days (i.e. - 1.2 days (95% CI - 1.9 to - 0.4), - 14.8%). This was accompanied by lower in-hospital mortality of 21.8% vs. 29.8% (absolute decrease 7.9% (95% CI - 13.9% to - 1.8%), relative decrease 26.6%), resulting in an increase in mean QALYs/patient from 0.47 to 0.52 (i.e. + 0.05 (95% CI 0.00 to 0.10); + 10.1%). However, owing to high costs among sepsis survivors, healthcare costs over a one-year time horizon were €73,665/patient in the PCT group compared with €70,961/patient with standard of care (i.e. + €2704 (95% CI - €4495 to €10,005), + 3.8%), resulting in an incremental cost-effectiveness ratio of €57,402/QALY gained. Within this time frame, the probability of PCT guidance being cost-effective was 64% at a willingness-to-pay threshold of €80,000/QALY. CONCLUSIONS: Although the impact of PCT guidance on total healthcare-related costs during the initial hospitalisation episode is likely negligible, the lower in-hospital mortality may lead to a non-significant increase in costs over a one-year time horizon. However, since uncertainty remains, it is recommended to investigate the long-term cost-effectiveness of PCT guidance, from a societal perspective, in different countries and settings.

Toward Alignment in the Reporting of Economic Evaluations of Diagnostic Tests and Biomarkers: The AGREEDT Checklist.

OBJECTIVES: General frameworks for conducting and reporting health economic evaluations are available but not specific enough to cover the intricacies of the evaluation of diagnostic tests and biomarkers. Such evaluations are typically complex and model-based because tests primarily affect health outcomes indirectly and real-world data on health outcomes are often lacking. Moreover, not all aspects relevant to the evaluation of a diagnostic test may be known and explicitly considered for inclusion in the evaluation, leading to a loss of transparency and replicability. To address this challenge, this study aims to develop a comprehensive reporting checklist. METHODS: This study consisted of 3 main steps: 1) the development of an initial checklist based on a scoping review, 2) review and critical appraisal of the initial checklist by 4 independent experts, and 3) development of a final checklist. Each item from the checklist is illustrated using an example from previous research. RESULTS: The scoping review followed by critical review by the 4 experts resulted in a checklist containing 44 items, which ideally should be considered for inclusion in a model-based health economic evaluation. The extent to which these items were included or discussed in the studies identified in the scoping review varied substantially, with 14 items not being mentioned in ≥47 (75%) of the included studies. CONCLUSIONS: The reporting checklist developed in this study may contribute to improved transparency and completeness of model-based health economic evaluations of diagnostic tests and biomarkers. Use of this checklist is therefore encouraged to enhance the interpretation, comparability, and-indirectly-the validity of the results of such evaluations.

Early health technology assessment of future clinical decision rule aided triage of patients presenting with acute chest pain in primary care.

The objective of the paper is to estimate the number of patients presenting with chest pain suspected of acute coronary syndrome (ACS) in primary care and to calculate possible cost effects of a future clinical decision rule (CDR) incorporating a point-of-care test (PoCT) as compared with current practice. The annual incidence of chest pain, referrals and ACS in primary care was estimated based on a literature review and on a Dutch and Belgian registration study. A health economic model was developed to calculate the potential impact of a future CDR on costs and effects (ie, correct referral decisions), in several scenarios with varying correct referral decisions. One-way, two-way, and probabilistic sensitivity analyses were performed to test robustness of the model outcome to changes in input parameters. Annually, over one million patient contacts in primary care in the Netherlands concern chest pain. Currently, referral of eventual ACS negative patients (false positives, FPs) is estimated to cost €1,448 per FP patient, with total annual cost exceeding 165 million Euros in the Netherlands. Based on 'international data', at least a 29% reduction in FPs is required for the addition of a PoCT as part of a CDR to become cost-saving, and an additional €16 per chest pain patient (ie, 16.4 million Euros annually in the Netherlands) is saved for every further 10% relative decrease in FPs. Sensitivity analyses revealed that the model outcome was robust to changes in model inputs, with costs outcomes mainly driven by costs of FPs and costs of PoCT. If PoCT-aided triage of patients with chest pain in primary care could improve exclusion of ACS, this CDR could lead to a considerable reduction in annual healthcare costs as compared with current practice.

The cost-utility of point-of-care troponin testing to diagnose acute coronary syndrome in primary care.

BACKGROUND: The added value of using a point-of-care (POC) troponin test in primary care to rule out acute coronary syndrome (ACS) is debated because test sensitivity is inadequate early after symptom onset. This study investigates the potential cost-utility of diagnosing ACS by a general practitioner (GP) when a POC troponin test is available versus GP assessment only. METHODS: A patient-level simulation model was developed, representing a hypothetical cohort of the Dutch population (>35 years) consulting the GP with chest complaints. All health related consequences as well as cost consequences were included. Both symptom duration, selection of patients in whom the POC troponin test is performed, and test performance at different time points were incorporated. Health outcomes were expressed as Quality-Adjusted Life Years (QALYs). The main outcome parameters involve the effect of POC troponin testing on (in)correct hospital referrals, QALYs, and costs. RESULTS: The POC troponin strategy decreases the referral rate in non-ACS patients from 38.46% to 31.85%. Despite a small increase in non-referral among ACS patients from 0.22% to 0.27%, the overall health effect is negligible. Costs will decrease with €77.25/patient (95% CI €-126.81 to €-33.37). CONCLUSIONS: The POC troponin strategy is likely cost-saving, by reducing hospital referrals. The small increase in missed ACS patients can be partly explained by conservative assumptions used in the analysis. Besides, current developments in POC troponin tests will likely further improve their diagnostic performance. Therefore, future prospective studies are warranted to investigate whether those developments make the POC troponin test to a safe and cost-effective diagnostic tool for diagnosing ACS in general practices.

Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine.

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair - such as autologous chondrocyte implantation (ACI) - plus increasing healthcare costs, and market competition, are forcing a shift in focus from two-stage to single-stage interventions that are more cost-effective. Early health economic models are expected to provide essential insight in the parameters driving the cost-effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost-effectiveness ratio (ICER) of a new investigator-driven single-stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost-effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One-way sensitivity analysis was performed to identify those parameters that drive the cost-effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost-effective treatment option for smaller defects, a single-stage tissue engineering procedure can replace ACI to improve the cost-effectiveness for treating larger defects, especially if clinical non-inferiority can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.

A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis.

OBJECTIVE: Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice. METHODS: A decision tree was developed to estimate the health economic consequences of the PCT algorithm for antibiotic discontinuation from a Dutch hospital perspective. Input data were obtained from a systematic literature review. When necessary, additional information was gathered from open interviews with clinical chemists and intensivists. The primary effectiveness measure is defined as the number of antibiotic days, and cost-effectiveness is expressed as incremental costs per antibiotic day avoided. RESULTS: The PCT algorithm for antibiotic discontinuation is expected to reduce hospital spending by circa € 3503 per patient, indicating savings of 9.2%. Savings are mainly due to reductions in length of hospital stay, number of blood cultures performed, and, importantly, days on antibiotic therapy. Probabilistic and one-way sensitivity analyses showed the model outcome to be robust against changes in model inputs. CONCLUSION: Proven safe, a PCT algorithm for antibiotic discontinuation is a cost-effective means of reducing antibiotic exposure in adult ICU patients with sepsis, compared to current practice. Additional resources required for PCT are more than offset by downstream cost savings. This finding is highly important given the aim of preventing widespread antibiotic resistance.

Health Economic Evaluation of a Strict Glucose Control Guideline Implemented Using Point-of-Care Testing in Three Intensive Care Units in The Netherlands.

BACKGROUND: Point-of-care testing of blood glucose (BG-POCT) is essential for safe and effective insulin titrations in critically ill patients under glucose control with insulin. The costs associated with this practice are considered substantial, especially when more frequent blood glucose (BG) testing is needed, as with more strict glucose control (SGC) aiming for lower BG levels. OBJECTIVE: The objective of this study was to estimate, from a hospital perspective, the incremental cost effectiveness of an SGC guideline, aiming for BG levels of 4.4-6.1 mmol/L, compared to the situation before implementation of that guideline (aiming for BG levels <8.3 mmol/L), both using BG-POCT. METHODS: This is a secondary analysis of a guideline implementation project aiming for implementation of a guideline of SGC in three intensive care units in The Netherlands. A Markov model including the four health states 'target glucose', 'hyperglycaemia' (defined as BG levels >6.1 mmol/L), 'hypoglycaemia' (defined as BG levels <4.4 mmol/L) and 'in-hospital death' was developed to compare expected costs, number of patients within target and number of life-years saved before and after implementation of the SGC guideline. The effectiveness estimates are based on empirical data from 3195 patients 12 and 24 months before and after implementation of the guideline, respectively. All costs have been converted to price year 2013, and are estimated based on hospital data, the literature and available price lists. RESULTS: The number of BG-POCT increased from 4.8 [interquartile range (IQR) 2.6-6.7] to 8.0 [IQR 4.1-11.2] per patient per day, accruing 58% higher costs for BG-POCT (€13.56 vs. €8.57 per patient) in the SGC protocol versus the situation before implementation. When taking total hospital costs and clinical effects into account, implementation of the SGC guideline increased total hospital costs per patient by 1.8%, i.e., €355 (from €20,617 to €20,972) during the inpatient stay, while the number of patients in target glucose levels increased by 1.4% (i.e., from 881 to 895 per 1000 patients). This translates to an incremental cost-effectiveness ratio of €25 per additional patient within the target glucose level. The model outcomes are most sensitive to changes in ICU length of stay. CONCLUSION: The increase in the number of patients and time within target glucose levels is achieved with a small increase in total direct hospital costs.